POSTER SESSION II Thursday, February 8, 2001, 3:30 pm – 5:30 pm

P O S T E R S E S S I O N II Thursday, February 8, 2001 3:30 pm - 5:30 pm Reno Room

CATEGORIES Diabetes

Hypertension Infectious Diseases Physiology/Endocrinology POSTER NUMBERS 180-304

Judges:

Michael C. Gordon, MD Mark B. Landon, MD Kimberly K. Leslie, MD

$64 SMFM Abstracts 0180

0181

J a n u a l y 2001 Am J Obstet Gynecol

ANTENATAL DIAGNOSIS OF FETAL CARDIAC ANOMALIES IN WOMEN W l T H DIABETF~ 1~.I J.ITUS Nihal Naccasha j , Susan Berman '2, Ivan Zador'-', Areal Awwad 2, Mark R e d m a n 3, Stanley Berry'l; IWayne State University, Department of O b / G y n , Detroit, MI; -'2Wayne State University, Departuleut of O b / G y n , Detroit, MI; SWayne State University, D e p a r t m e n t of O b / G y n , Detroit, MI; 4Wayne State University, Department of Ob/Gy~L Detroit, MI OBJECTIVE: To d e t e r m i n e w h e t h e r the routine use of formal fetal echocardiography (FFE) increases the diagnostic yield in insulin-dependent (ID) diabedc padents for whom a routine fetal anatomic survey (FAS) revealed a normal 6--chamber cardiac view (ie, the 4-chamber view phLs the pulmouary a n d aortic outflow tracts). STUDY DESIGN: Diabetic p r e g n a n t women wbo underwent prenatal care a n d delivered at o u r institution from 1995 to 1999 were identified using our prospectively collected computerized perinatal database. Reports of FASs were reviewed a n d c o m p a r e d to FFE results. Neonatal records for those FASs a n d FFEs that were suspicious for cardiac anomalies were reviewed. RESULTS: Two h u n d r e d eight women with ID pregestational diabetes (Group 1) including 2 with twin gestations (total 210 fetuses) and 105 women with ID gestational diabetes (Group 2) including 1 with a twin gestation (total 106 fetuses) were identified. No FAS record was found for 12 patients in G r o u p 1 a n d 9 in G r o u p 2. T h e rates of FAS suboptimal cardiac views were 9.6% (19/198) in G r o u p 1 a n d 17% (16/97) in G r o u p 2. The rates of abnormal views were 1.5% (3/198) and 0%, respectively. A subsequent FFE was obtained in 127 patients in Group 1 a n d 37 in G r o u p 2. All anomalies in Group 1 were confirmed on FFE. O n e fetus in G r o u p 1 had suboptimal cardiac views on FAS at 17 weeks, a VSD on FFE at 19 weeks, a n d neonatal ecbocardlography (NE) which revealed tetrology of Fallot. In a second G r o u p 1 patient, FAS revealed VSD at 28 weeks, and no VSD was found on NE. In G r o u p 1, the sensitivity of FAS for detecting anomalies noted on FFE is 75%, specificity is 100%, PPV is 100%, a n d NPV is 99%. C O N C L U S I O N : O u r data suggest that FAS can adequately screen ID diabedc women for fetal cardiac anomalies. FFE can be resecved for patients where cardiac structures are suboptimally visualized or cardiac anomalies are suspected d u r i n g FAS. Also, NE is essential for c o n f i r m a t i o n of antenatal diagnosis.

0182

DEVELOPMENT OF A COST-EFFECTIVE SCREEN F O R GESTATIONAL DIABETES Katharina Stewart I, Linda Neidhart, MD ~, Helen Kayl; IUniversity of Wisconsin-Madison, Obstetrics a n d Gynecology, Madison, WI; 2University of Wisconsin-Madison, Obstetrics a n d Gynecology, Madison, WI OBJECTIVE: The largest laboratory cost incurred in our perinatal office is generated by the universal screening for gestational diabetes (GDM) using O'Sullivan's criteria. O u r goals were to assess our current method of screening a n d to develop recommendations to improve cost-effectiveness. STUDY DESIGN: A review of records from J a n u a r y 1998 to J u n e 1999 was performed. Padents were included if they received r o u d n e prenatal care with delivery at >28 weeks' gestation a n d excluded if they had an early pregnancy loss or pregestational diabetes. D e m o g r a p h i c data were o b t a i n e d a n d screening results recorded. Descriptive statistics as well as Student t test were used for analysis. Patient cost for a 1-hour, 50-g glucose screen (1 ° GTT) is $'29.73, $143.63 for a 3-hour, 100-g screen (3" GTT), a n d $14.45 for a serum glucose. RESULTS: T h r e e h u n d r e d eighteen patients were screened with mean p o p u l a t i o n values of: age 26.8 years, gravity 2.9 pregnancies, parity 1.1 deliveries, 1 ° GTT 125 m g / d L , a n d BMI 30.9. T h e r e was no statistically significant difference in d e m o g r a p h i c s between patients with GDM versus those without; 22.5% (71) h a d an abnormal 1" GTT a n d 7.2% (23) h a d an abnormal 3* GTT. No statistically significant threshold was identified above which an abnormal 1" GTT value identified an abnormal 3" GTI'. A m o n g the four values in the 3* G'Fr, the fasting blood sugar (FBS) demonstrated some predictive value for refining o u r screen. After a positive 1° GTT, a FBS of > 100 h a d a 93% positive predictive value (PPV) for the diagnosis of GDM (56% sensitivity, 97% specificity) a n d a FBS o f > 105 had a 100% PPV (50% sensitivity, 97% specificity). CONCLUSION8: In o u r study population, using a 1° G'I~I" followed by a FBS for GDM screening would save $129.18 per screen (current cost $173.36). Further prospective evaluations need to be performed to test the validity of using a FBS to exclude patients from further testing.

0183

THE RELATIONSHIP BETWEEN BODY MASS INDEX AND GLUCOSE TOLERANCE TESTING IN MULTIFETAL GESTATIONS Brian BrostI,Jana Ellings ~, Roger Newman-~; 1Medical College of Ohio, Department of Obstetrics a n d (;ynecology, Toledo, OH; 2Medical University of South Carolina, Obstetrics a n d Gynecoloh~', Charleston, SC; :~Medical University of South Carolina, Department of Obstetrics and Gynecolo~,, Charleston, SC OBJECTIVE: Multiletal gestations are reported to be at increased risk of gestatiomd diabetes due to the larger placental mass. This study investigates the relationship of body mass index (BMI) and oral glucose tolerance testing (OGTT) in multifetal gestations. METHODS: Women followed in the Medical UniveL'sity Twins clinic (n = 112) were evaluated with a 50-g one-hour glucose load test ((,IX) at 28 weeks gestation. Values _> 135 m g / d L were further evaluated by OGTT. Any 2 glucose determinants _> established NDDG criteria constituted gestalional diabetes. BMI (weight [ k g ] / [ h e i g h t (cm] 2) was calculated Ior each wmnau. RESULTS: Women with multifi:tal gestations with an abnormal GLT and a positive O G T T were categorized by BM1. C O N C L U S I O N S : Tbe frequency of a positive GLT a n d an a b n o r m a l O G T T is strongly related to BMI in twin gestations. Approximately 20% of GLTs can be eliminated by excluding women carrying muhit~:tal gestations with a BMI < 25.

Fetal GLT and OGTT by BMI BMI 25 25-29.9 30-34.9 35-39.9 40

+ GLT 1/22 7/44 7/23 5/12 5/11

(4.5%) (15.9%) (30.4%) (41.7%) (45.5%)

+ OGTT 0/22 1/44 1/23 1/12 1/11

(0%) (2.3%) (4.3%) (8.3%) (9.1%)

P R E G N A N T WOMEN LACKING CIRCULATING RELAXIN HAVE DECREASED I N S ~ S E N S I T M T Y Lisa Gittens, MD I , Gerson Weiss, MD I, Laura Goldsmith, PhDI; IUniversity of Medicine & Dentistry of Newjersey, Obstetrics, Gynecology and Women's Health, Newark, NJ OBJECTIVE: To determine ffcirculating relaxin modifies insulin response to glucose a n d insulin sensitivity during h u m a n pregnancy. STUDY DESIGN: Aluteal women, with p r e m a t u r e ovarian failure who achieved singleton pregnancy via egg donation a n d wbo lacked circulating relaxin, were study subjects. Women who couceived a singleton pregnancy after spontaneous menstrual cycle were controls. Patients with diabetes in self or family, athletes, a n d medical illnesses or complications of p r e g n a n c y were excluded. Controls took exogenous steroid hormones until placental steroid production began. At 28 to 32 weeks' gestation, after 3 days of unrestricted physical activity, a >150-g carbohydrate diet a n d overnigbt fast, all subjects underwent 100 g glucose tolerance test. Serum obtained from each subject at fasting, 1, 2, and 3 hours was assayed for glucose, HgbAIC, insulin, and relaxin. Area u n d e r the insulin, glucose a n d relaxin curves, a n d insulin sensitivity indices were compared between groups using t test and Wilcoxon rank sum test. RESULTS: Five aluteal a n d 14 control patients participated. Gestational ages a n d body mass indices were similar. Gestational diabetes was not diagnosed. Study patients h a d u n d e t e c t a b l e relaxin levels (<35 p g / m L ) . Controls had a significantly different mean relaxin level of 0.93 n g / m L (P = .0001). No differences were noted in mean glucose, mean insulin, integrated glucose, or integrated insulin. Subjects without circulating relaxin had lower insulin sensitivity indices compared to those subjects with circulating relaxin. These differences did not reach statistical significance (P = .18). Twenty study subjects a n d 30 controls would be required for 87.5% power to detect a significant difference between these 2 groups. CONCLUSION: Absence of circulating relaxin in pregnancy is associated with decreased insulin sensitivity. This supports in vitro evidence that relaxin increases the "~inity of insulin binding to its receptor in adipocytes.

SMFM Abstracts $65

Volunte 184, N u m b e r 1 Am J O b s t e t G y n c c o l 0184

THE FASTING PLASMA GLUCOSE IN EARLY PREGNANCY: A SCREENING TEST FOR GESTATIONAL DIABETES David Sacks, MD t, Wansu Chen, MS'-', Girma Wolde-Tsadik, PhD '2, T h o m a s A. B u c h a n a n , MD3; IKaiser Foundation Hospital, Obstetrics a n d Gynecology, Bellflower; CA; '-'Southern Calilornia Permanente Medical Group, Department of Research, Pasadena, (;At; :~University of Southern Calilbrnia, Internal Medicine and Obstetrics and Gynecology, Los Angeles, (LA. OBJECTIVE: To investigate whether the lasting plasma glucose (FPG) is a sensitive, reproducible, a n d clinically useful screening test Ior gestatiunal diabetes (GDM). STUDY DESIGN: For 1 yeaL all prenatal patients were ofl'ered an FPG at the time of their routine blood tests. Results were blinded if < 100 m g / d L . They were unhlinded if->1 O0 m g / d L , a n d followed by a 75-g, 2-hoar glucose tolerance test (G'I'I') if between 109 m g / d L and 125 m g / d L . GDM was defined either by an FPG _> 126 m g / d L or if >_9 of the fi~llowing GTT values were equaled or exceeded: fasting 100 m g / d L . 1-hour 195 m g / d L , and 2-hoar 160 m g / d L . Patients not identified `as having diabetes in the initial series of testing were requested to take a G'Iq" at their first visit after 23 weeks. RESULTS: O f 4305 women, 3496 (81%) complied with tile protocol. Of the latter, .931 (6.6%) had GDM, of which 8 had an initial FPG >126 m g / d L . An FPG threshold of 85 m g / d L had a sensitivity of 76% and a specificity o1"51% for detection of GDM. A m o n g the 82 women who had 2 GTTs the median diflerence between the second and first fasting plasma glucose was 1 m g / d L (P = NS): the differences in 1- and 2-hour post-glucose conceutnttions were each 10 m g / d L (P< .001). C O N C L U S I O N S : Tile FPG early in gestation offers early detection of GDM and him good padent acceptance. At a threshold of 85 m g / d L , the FPG has a sensitivity similar to that reported for the 50-g glucose screening test. At this th reshnld, 51% of all patients would require a Gq"l" to detect 76% of GDM. T h e FPG is more r e p r o d u c i b l e than the post-glucose challenge test in pregnancy.

0186

FETAL FAT TISSUE G R O W T H IN PREGNANCIES COMPLICATED BY GESTATIONAL DIABETES Serena Rigano l, Tatjana Radaelli~, Madalena Bozzo '2, Emannela Taricco ~, Irene Cedn 2, Georgio Pardi 2, Enrico FerrazziS; tISBM L.Sacco, Obstetrics a n d Gynecology, Milano; 2DMCO San Paolo, O b / G y n , Milano; 31SBM L.Sacco, O b / G y n , Milano OBJECTIVE: To examine sonographic growth of fat tissue in fetuses of gestational diabedc (GDM) pregnancies. STUDY DESIGN: 56 patients with GDM (abnormal 3-hour GTT) a n d 30 normal patients h a d ultrasound examinations every 4 weeks starting at 20 weeks' gestation or at the time of GDM diagnosis (mean = 30.6 ± 0.57 weeks). GDM was well-controlled. Reference ranges were obtained from nonsmoking, nondiabetic pregnancies with a normal p r e p r e g n a n c y BMI (mean = 21.3 ± 0.64). Biparietal diameter, h e a d circumference, a n d f e m u r length were assumed as indicators of lean body mass. Fat mass was measured by ultrasound: abdominal wall subcutaneous tissue thickness (FA), subscapular SQ thickness (FS), a n d SQ area of the mid-arm (FMA) a n d mid-thigh (FMT) (total crosssectional area minus bone and muscle areas). Measurements were made offline at m a x i m u m magnification. Fetal S Q mass c o m p a r i s o n s were m a d e between GDM a n d control patients at diagnosis a n d after treatment. Data shown as mean ± SE and analyzed with t tests. RESULTS: GDM fetuses h a d significandy higher values for all fetal SQ measurements at diagnosis (26 to 32 weeks) compared with 30 normal fetuses of c o m p a r a b l e gestational age. No significant differences were observed between normal a n d GDM fetuses for fat mass indices after treatment. CONCLUSIONS: These data support the hypothesis that untreated GDM causes an early increase in fetal fat mass. Differences in fat mass between normal a n d GDM fetuses are r e d u c e d to nonsignificant levels d u r i n g the course of proper treatment. Subcutaneous measurements

FA FS FMA FMT

0185

PATIENTS WITH A FALSE POSITIVE 1-HOUR GLUCOSE CHAI.I.ENGE TEST (GCT) ARE AT INCREASED RISK F O R PERINATAL COMPLICATIONS David Stamilio I, Tandy Olsen I, Harish Sehdev '2, George Macones3; :David Grant USAF Medical Center, Obstetrics & Gynecology, Travis AFB, CA; '-'Pennsylvania Hospital, Obstetrics & Gynecology, Philadelphia, PA; .~University of Pennsylvania, Obstetrics a n d Gynecology Philadelphia, PA OBJECTIVE: To determine ifa false-positive GCT (FPGCT) is independently ,associated with developing perinatal complications. STUDY DESIGN: We p e r t b r m e d a retrospective c o h o r t study on 1871 p r e g n a n t women. Patients were screened for gestational diabetes mellitus (GDM) using the 1-hour GCT at 24 to 28 weeks' gestation. Abnormal GCTs were followed by a 3-hour glucose tolerance test (GTT). A FPGCT was defined as a result >134 m g / d L followed by a normal GTT. We compared the GCTnegative (negGCT) a n d FPGCT cohorts for perinatal outcomes. Unadjusted, stratified, a n d multiple logistic regression analyses were used to identify interactions a n d c o n f o u n d i n g between mnhiple variables and the association between a FPGCT a n d perinatal complications. With an anticipated 7% baseline rate of any perinatal complication, a 10% rate o f a FPGCT et = .05, this study has 80% power to detect a relative risk (RR) of 2.0 for perinatal complications. RESULTS: O n e h u n d r e d sixty-four patients had a FPGCT a n d 50 patients had GDM. C o m p a r e d to the negGCT cohort, the FPGCT cohort on average was older a n d of h i g h e r parity, h a d a h i g h e r body mass index, a n d m o r e frequently h a d hypertension, sickle trait, a n d elevated midtrimester h u m a n chorionic g o n a d o t r o p i n levels. After controlling for c o n f o u n d i n g variables, the FPGCT cohort had higher perinatal complication rates than the negGCT cohort (adjusted RRs a n d confidence intervals [CI] reported in the Table). CONCLUSION: These data suggest that a FPGCT is an i n d e p e n d e n t risk factor for s h o u l d e r dystocia, macrosomia, stillbirth, a n d cesarean delivery. Patients with a FPGCT may benefit from therapy such as nutritional counseling a n d fetal testing. Perinatal outcomes

Shoulder dystocia Stillbirth Macrosomia Cesarean

FPGCT (%)

NEGGCT (%)

ADJUSTED RR

4.9 1.2 3.0 23.8

1.7 0.4 1.0 17.3

2.7 3.4 3.5 1.4

95% CI 1.2, 6.2 0.7, 17.0 1.2, 9.6 1.0, 1.9

0187

NORMAL

GDM

26-32 wk 0.32 + 0.01 0.28 ± 0.01 1.97 ± 0.12 3.12 ± 0.2

26-32 wk 0.38 ± 0.01 0.36 ± 0.17 2.55 + 0.19 4.1 ± 0.37

P

NORMAL

GDM

P

.001 .001 .001 .01

32-36 wk 0.45 + 0.02 0.41 ± 0.36 3.83 ± 0.33 5.91 ± 0.42

32-36 wk 0.47 + 0.02 0.44 ± 0.02 4.24 ± 0.21 6.94 ± 0.43

NS NS NS NS

N O ASSOCIATION BETWEEN FETAL MACROSOMIA AND MATERNAL GLYCEMIC VALUES IN PREGNANCIF_,S WITH GESTATIONAL DIABETES Ute M. Schaefer-C,raf, MD l, Rosalie Heuer, MD 2, Holger Jahnke, MD s, KaiJ. Buhling, MD 4, Martin Brauer, MD I, Siri L. Kids, MD s, J o a c h i m W. Dudenhausen, MDt; ICharite, Campus Virchow-Klinikum, Obstetrics, Berlin; ~Hospital Neukoelln, Obstetrics, Berlin; 3Hospital Neukoelln, Obstetrics, Berlin; 4Charite, Campus Virchow-Klinikum, Charite, Berlin; 5University o f Southern California, Maternal-Fetal-Medicine, Los Angeles, CA OBJECTIVE: Reduction of the macrosomia rate is an important goal in the m a n a g e m e n t of pregnancies with gestational diabetes (GDM). The c u r r e n t strategies are focused on the maintenance o f maternal euglycemia. The aim of the study was to determine the association of fetal macrusomia a n d maternal glycemic variables in pregnancies with GDM with adjustment for gestational age (GA) a n d maternal body mass index (BMI). STUDY DESIGN: In 431 w o m e n with GDM, values o f the o G T T a n d H b A l c were c o m p a r e d between p r e g n a n c i e s with a n d without fetal macrosomia at diagnosis. An abdominal circumference (AC) > 9Oth percentile (Hadlock) defined macrosomia. Glucose values o f the daily profiles in different categories of gestational age were c o m p a r e d with the AC obtained by serial u l t r a s o u n d m e a s u r e m e n t s (n = 937). To c o n s i d e r the influence o f maternal adiposity (BMI ~ 25 k g / m 2) adjustment for BMI was performed. RESULTS: T h e r e was n o significant difference in the oG'Vr values between pregnancies with a n d without fetal macrosomia independently o f the maternal BMI. In all categories of GA there was n o significant difference in the daily glucose profile between pregnancies with a n d without fetal macrosomia at the time of the profiles. Women with BMI > 25 k g / m 2 h a d slightly higher glucose values in the oGTT a n d in the profiles in all categories o f GA than women with BMI < 25 k g / m ~t. Women with BMI > 25 k g / m = h a d a higher rate of fetal macrosomia in every category of GA (eg, 25% vs 10% at diagnosis, 25% vs 9% at 28 to 31 weeks, 25% vs 5% at 36 to 40 weeks; P < .0001 for each comparison). CONCLUSION: In GDM there is n o association between fetal macrosomia and maternal glycemic values at any time of the pregnancy; In contrast, maternal adiposity is an important risk factor for fetal macrosomia. Maternal glucose values are not useful to assess the risk o f fetal macrosomia. Therefore repeated fetal biometry is r e c o m m e n d e d to identify pregnancies with n e e d for intensive treatment.

$66 SMFM Abstracts

J a n u a r y 2001 Am J Obstet Gynecol

0188

PERINATAL OUTCOMES IN GESTATIONAL DIABETES: A COMPARISON O F CRITERIA F O R DIAGNOSIS Robert Egernmn, MD I, Erin Penn:son, MD2; lUniversity of Tennessee Health Science Center, Obstetrics a n d Gynecology, Memphis, TN; 2University of Tennessee Health Science Center, Obstetrics a n d Gynecology, Memphis, TN OBJECTIVE: To compare per:natal outcomes of women diagnosed with gestational diabetes (GD) by c u r r e n t American College of Obstetrician Gynecologists ( A C O G ) / N a t i o n a l Diabetes Data G r o u p (NDDG) recommendations to those of the American Diabetes Association (ADA). STUDY DESIGN: Two h u n d r e d forty-two women (1995 to 1999) had the standard 3--hour oral glucose tolerance test. Patients were categorized into 3 groups: euglycemic controls (n = 69), GD by NDDG (n = 130), or ADA (n = 43) criteria. Maternal a n d infant charts were reviewed. Primary outcomes included frequencies of cesarean delivery (CSD), preeclampsia (PE), a n d macrosomia. In univariate analysis g 2 was used to c o m p a r e g r o u p differences a n d in multivariate analysis stepwise logistic regression controlled for c o n f o u n d i n g factors. RESULTS: No differences existed between the 3 groups r e g a r d i n g maternal race, body mass index (BMI), history of PE, or family history of diabetes. Frequencies of overall CSD, CSD for macrosomia or arrest disorder, PE, a n d macrosomia were not significandy different between the 3 groups. Neonatal hypoglycemia was more frequent in the ADA (23.3%) a n d NDDG (I6.2%) groups than in the controls (7.2%), reaching near significance, P = .057. In the multivariate analysis, CSD for macrosomia or an arrest disorder correlated negatively with parity a n d positively with BMI. PE was associated with African American race a n d BMI; macrosomia correlated with a previous history of macrosomia a n d familial diabetes. Neonatal hypoglycemia was more c o m m o n in the ADA g r o u p (OR 2.45; 95% CI 1.004 to 5.97) a n d in the insulinrequiring NDDG category (OR 3.71; 95% CI 1.20 to 11.44). CONCLUSION: Benefits of defining a high-risk population of GD women by ADA criteria are unclear. Further large-scale prospective clinical trials are required.

0190

ONE- VERSUS T W O - H O U R POSTPRANDIAL GLUCOSE MEASUREMENT IN GESTATIONAL DIABETES--A PROSPECTIVE STUDY Ahm Shrim l, Boaz Weisz2, Eyal Schifi~, O h a d Cohen 4, Carol H o m k o 5, Eyal Siwan¢i; tSheba Medical Center, O b / G y n , Ramat-Gan; ~Sbeba Medical Center, O b / G y n , Ramat-Gan; :~Sheba Medical Center, O b / G y n , Ramat-Gan; 4Sheba Medical Center, Endocrinology, Ramat-Gan; 5Temple University, GCRC, Philadelphia, PA; 6Sheba Medical Centel; OI)/Gyn, Ramat-Gan OBJECTIVE: To compare the rate of adverse per:natal outcome between women with gestational diabetes (GDM), monitored by one-hour versus twoh o u r postprandial glucose (PPG) measurements. METHODS: O n e htmdred twelve (112) women with GDM. by criteria of Carpenter-Coustan, were included. Women were treated at two centers by the same g r o u p and allocated according to HMO affiliation. Glucose levels were measured by memory-based glucometers d u r i n g fasting, a n d either 1-hour (group l - - n o r n m l values <140 rag%) or 2 hours (group 2 - - n o r m a l wtlues <120 mg%) postprandially. Epidemiologic a n d per:natal data were collected from medical records. RESULTS: Sixty-six women were assigned to g r o u p l (Ih-PPG) and 47 women to g r o u p 2 (2h-PPG). There was no difference in age, parity, family history of diabetes, GDM in previous pregnancies, weight, a n d pre- or postgestational BMI. Both groups had similar 50-g GCT a n d 100-g O G T T assays. As expected, there was a significant difference in mean blood glucose levels between the two g r o u p s (108.1 ± 19.2 a n d 94.9 ± 21.2, 1- a n d 2-bouts, respectively, P < .0001); however, HbAI C levels were similar in both groups. Per:natal outcome as gestadonal week at delivery, fetal weight (3325 ± 471 vs 3309 :l: 608, respectively), a n d percentile (47.2 ± 27 vs 49.6 ± 30, respectively) were similar for both groups. Insulin therapy was in:dated in 28% and 40% (P = .257), respectively. Rate of macrosomia was 7.5% a n d 10.6% (P = .813), respectively. The g r o u p monitored by 2-hour PPG had a 6% (24% vs 30%) higber rate of CS, bowever nonsignificant (P= .624). C O N C L U S I O N : Controlling blood glucose levels by 1 vs 2 hours postprandially does not affect per:natal o u t c o m e in women with GDM. However, there is a trend toward reduction in insulin usage, macrosomia, and CS rate when using the l-hour postprandial criteria.

0189

SPONTANEOUS PRETERM BIRTH IN TYPE I DIABETIC PREGNANCY: M R O L E O F GLYCEMIC C O N T R O L Oormila Kovilam I, J a n e Khoury 2, M e n a c h e m Miodovnik 3, Tariq Siddiqi 2, J o s e p h Spinnato l, B a h a Sibai2; lUniversity o f Cincinnati, Obstetrics a n d Gynecology, Cincinnati, OH; 2University of Cincinnati, Obstetrics a n d Gynecology, Cincinnati, OH; 3St. Luke's-Roosevelt Hospital Center, Obstetrics & Gynecology, New York, NY OBJECTIVE: To determine the role of glycemic control in spontaneous preterm delivery in type I diabetic pregnancy. STUDY DESIGN: Subjects were women who were part of the Diabetes in P r e g n a n c y P r o g r a m project who enrolled p r i o r to 20 weeks' gestation. Spontaneous p r e t e r m delivery (SPTD) was defined as delivery < 37 weeks' gestation excluding all medically indicated PTD. Degree of glycemic control was measured by glycosolated hemoglobin A1 obtained serially t h r o u g h o u t pregnancy. Analysis of variance, X2, a n d multiple logistic regression were used for analysis. RESULTS: O f the 310 patients available, 110 (36%) h a d p r e t e r m deliveries, 47 (43%) were spontaneous, a n d 63 (57%) indicated. Glycemic control in the 2 n d trimester a n d close to delivery was better in term gestation than the preterm g r o u p (Table). After controlling for duration of disease a n d microvascular disease, glycemic control was still a factor in SPTD. C O N C L U S I O N : Less than ideal glycemic control d u r i n g p r e g n a n c y is associated with increased risk for spontaneous preterm birth.

0191

C O R R E C T I O N F O R INSULIN DEPENDENT DIABETES IN ALPHAFETOPROTEIN TESTING HAS OUTLIVED ITS USEFULNESS M. 1. Evans 1, H. Harrison 2, J. E. O'Brien 2, E. Dvorin 3, X. H u a n g 2, E. L. Krivchenia '1, E. A. ReeceS; :Wayne State University, Reproductive G e n e t i c s / O B G Y N / C M M G / Path., Detroit, MI; 2Quest Diagnostics, lnc, Teterboro, NJ; 3Quest Diagnostics, Inc, Auburn Hills, MI; 4Wayne State University, O b / G y n , Detroit, MI; 5Temple University, O b / G y n & Reproductive Science, Philadelphia, PA OBJECTIVE: Historically, AFP levels in insulin d e p e n d e n t diabetics (IDDM) have shown an approximately 20% decrement with a correction factor used to standardize MoMs. With new laboratory methodologies a n d improved precision, we sought to reevaluate the correctness of this approach. STUDY DESIGN: A total of 60,287 nondiabetic a n d 307 IDDM consecutive biochemical screens from o n e laboratory were c o m p a r e d using standard formula weight adjustments, a n d a 20% correction factor for IDDM. Padents were then stratified by maternal weight. RESULTS: Nondiabetic padents averaged 1.0 MuM, IDDM patients 0.91 using no adjustments, 0.96 adjusting for weight only, a n d 1.20 adjusting for weight a n d DM. To explain the "overcorrecdon," analysis by maternal weight shows significant overrepresentadon of IDDM patients at 2175 lb. Mean weight for nondiabetics was 151 + 35, and IDDM 174 + 52 (P< .001). CONCLUSIONS: With current methodologies, the 20% correction factor for IDDM erroneously overcorrects. Using an u p p e r limit weight cutoff of 200 lb, results are within 4% of normal. Hence, corrections for the diabetic status should be a b a n d o n e d .

T E R M ( N = 200) Age at diagnosis o f diabetes HbA1 at entry HbA1 Trimester 2 HbA1 Delivery Nephropathy Polyhydramnios Gestation at delivery LGA >90th percentile

13.2 ± 6.9 9 . 6 ± 2.3 7.7 ± 1.4a 7.4 ± 1.2a 28 (14)a 26 (23) 38.4 ± 1.2a 67 (34)a

SPTD(N=47) 13.3 ± 6.2 10.1 ± 1.8 8.0 ± 1.4ab 8.1 ± 1.3b 12 (26)a 12 (26) 33.6 ± 3. I b 26 (55)b

P NS NS .002 .002 NS NS .001 .001

Nondiabetic Diabetic

NO.

% <175

% 176200

% 201225

% 226250

% 251+

60,287 307

81.0 58.2

10.4 16.7

4.5 8.2

2.2 6.5

1.9 8.8

SMFM Abstracts S67

V o l u m e 184, N u m b e r 1 AmJ Obstet Gynecol 0192

0193

FASTING INSULIN AND GLUCOSE-TO-INSULIN RATIO IN T H E DIAGNOSIS OF GESTATIONAL DIABETES MELLITUS Vivien Pan t. Paniti Sukmnvanicht. Mar!iane K r o h n i R. Phillips Heine:: t University of Pittshurgh School of Medicine, Obstetrics, (;ynecology, a n d Reproductive Sciences, Pittsburgh, PA OBJECTIVE: Fasting serum insulin levels (FI) a n d fasting ghtcose-toinsulin ratios (FBS/FI) are a h e r e d in n o n p r e g n a n t patients with glucose intolerance. We sought to deterntine if FI or FBS/FI are different in pregnant patients with a positive versus a negative .",-hour glucose tolerance test (GTT). STUDY DESIGN: Fasting blood samples were collected from an unselected population of 147 women with singleton gestation u n d e r g o i n g a GTT after a positive l-hour gincose challenge. Insulin levels were deternfiued by ELISA. FBS/FI were calctdated a n d expressed as r a g / 1 0 -t units. Median values of FI and FBS/FI were compared between patients with a positive versus a negative GTT by nonparametric techniques. Receiver operating characterisdcs curves were generated to deterntine the ideal values of FI and FBS/FI for the diagnosis of gestational diabetes mellitus. RESULTS: The GTT was positive in 25 women and negative in 122 women. The median FI in patients with a positive GTT was 10.25 U / m L (range 3.1% 98.73) c o m p a r e d to 6.74 U / m L (range 0.41 to 99.47) in patients with a negative GTT (P= .007). The median FBS/FI was 9.74 r a g / 1 0 -t U (nmge 1.2(1 to 34.99) in patients with a positive GTT compared to 12.32 r a g / 1 0 - : U (range 1.51 to 197.56) in patients with a negative GTT (P= .132). An FBS/FI < 18.23 m g / 1 0 -I U was 90% sensitive in predicting a positive G'I'I" but the specificity was only 26%. By itselL an FI > 5.16 i n U / m L was 90% sensitive for the detection of a positive GTT but the specificity improved to only 32%. C O N C L U S I O N : Fasting insulin levels but not lasting glucose-to-insulin ratios are different in pregnant patients with a positive versus a negative GTI'. Neither test accurately predicted gestational diabetes mellitus a.s defined by a positive GTI'.

PRECONCEPTION VS EARLY PREGNANCY CARE AND ADVERSE PREGNANCY O U T C O M E IN TYPE I DIABETES Michael H n a 0 , Mark Chames t, Menachem Miodovnik ~, Jane Khoury:~, Tariq Siddiqi 4, Baha Sibail; I University of Cincinnati, Obstetrics and Gynecology, Cincinnati, OH; -"St. Luke-Rooseveh Hospital Center, Obstetrics & Gynecology, New York, NY; SUniversity of Cincinnati, Environmental Health, Cincinnati, OH; 4University of Cincinnati, Department of Obstetrics a n d Gynecology, Cincinnati, O H OBJECTIVES: We have previously shown that preconcepdonal care can reduce the rates of malformation a n d abortion. O u r objective was to compare adverse perinatal o u t c o m e in w o m e n with Type I diabetes who received p r e c o n c e p t i o n a l c o u n s e l i n g to those who were initially seen in the first trimester (<14 weeks). STUDY DESIGN: This study was a secondary analysis of women who were enrolled in a mnlddisciplinary program at the University Medical Center. Only pregnancies extending beyond 20 weeks were included. O u t c o m e s studied were the rates of preeclampsia, SGA (<10 percentile), PTD (<35 weeks), and polyhydramnios. These outcomes were correlated to degree of glycemic control as m e a s u r e d by glycohemoglobin A1 (HgbAI) using analysis of variance a n d X~. RESULTS: O n e h u n d r e d seventy-two w o m e n were studied. Adverse p r e g n a n c y outcomes for the 2 groups are listed in the Table. Women who received preconceptional care had lower HgbAl t h r o u g h o u t pregnancy, but adverse perinatal outcomes were not different. C O N C L U S I O N : Type I diabetic patients who e n t e r care in the first trimester but achieve opdmal glycemic control subsequent to enrollment do not have increased adverse perinatal outcome when compared to women who enter care preconceptionany.

0194

PERINATAL O U T C O M E IN WOMEN WITH RECURRENT PREECLAMPSIA COMPARED T O T H O S E W H O DEVELOP PREECLAMPSIA AS NULLIPARA Michael H n a t for MFMU Network, Bethesda, MD; University of Cincinnati, Obstetrics a n d Gynecology, Cincinnati, O H OBJECTIVE: To compare the rate of preeclampsia (PE) a n d perinatal o u t c o m e in women who experience PE for the second time c o m p a r e d to women who develop PE as nullipara. STUDY DESIGN: This is a secondary analysis from data of women who had PE in a previous pregnancy (n = 598) and nulliparous women (n = 2934) era'oiled in 2 separate multicenter trials o f aspirin for prevention of PE. Outcome variables were rates of PE, PTD < 37 a n d < 35 weeks, SGA, abruptio, and perinatal death. Data were analyzed using Xe. RESULTS: The rate of PE and the rate of severe PE were higher in the previous preeclamptic g r o u p as compared to the nulliparous g r o u p (17.9% vs 5.3%, P < .0001, a n d 7.5% vs 2.4%, P < .0001, respectively). However, in both groups the proportion of preeclamptics who developed severe disease was similar (42% vs 45%). Over-all, women who experienced r e c u r r e n t PE h a d more adverse perinatal outcomes than nulliparous women (Table). In addition, a m o n g women who developed severe PE, those with recurrent PE had higher rates ofPTD < 37 (67% vs 33%, P= .0004) and < 35 (36% v,s 19%, P = .041), a n d higher rates o f a b r u p t i o (6.7% vs 1.5%) and fetal death (0.7% vs 1.4%). CONCLUSION: Compared to nulliparous women, women with previous PE h a d h i g h e r rates of PE a n d adverse perinatal outcome. This adverse outcome was mainly related to earlier delivery in the recurrent PE group. Perinatal outcome in women with preedampsla PREVIOUS PREECLAMPSIA (N = 107)

0195

OUTCOME

N O . (%)

N O . (%)

RR

95% CI

PTD <37 wk PTD <35 wk Weight <10th percentile Abrupdon

46 (43.0) 22 (20.6)

35 (22) 15 (9.6)

1.92 2.14

1.33-2.76 1.16-3.93

8 (7.5) 5 (4.7)

16 (10.4) 1 (0.7)

0.73 7.06

0.32-1.64 0.84-59.5

RESPIRATORY DISTRESS SYNDROME (RDS) IN PREITAtM INFANTS OF DIABETIC AND NONDIABETIC M O T H E R S Z o h a r N a c h u m I, Nazik Khateeb l, Dan Reich 2, Raed Salim I , Eliezer Shalev3; IHaEmek Medical Center, Obstetrics a n d Gynecology, Afula; 2HaEmek Medical Center, Neonatology, Afula; SHaEmek Medical Center, Obstetrics a n d Gynecology, Afula OBJECTIVE: To compare the rate of RD8 in infants b o r n to diabetic vs nondiabetic mothers prior to 37 weeks. STUDY DESIGN: All infants of diabetic m o t h e r s delivered before 37 weeks, 1991 to 1997, were matched with infants of nondiabetic mothers (ratio, 1:2). Sample size was calculated assuming a double rate o f RDS (50% vs 25%) in the diabetic g r o u p with ~ = .05, power = 90%. Matching was by gestational age, fetal number, ethnicity, parity, a n d maternal age. The pediatrician who assigned the diagnosiswas blinded to the maternal diabetic status. RESULTS: A total o f 55 a n d l l 0 infants o f diabetic a n d nondiabetic mothers, respectively, were included. The diabetes mellitus (DM) a n d the nonDM groups included 5 a n d 9 pairs o f twins, respectively. Five patients h a d pregestational DM and 45 had gestational DM, 23 treated with insulin a n d 22 with diet only. The diabetic women were well controlled: mean ± SD plasma glucose was 95.9 ± 12.1 m g / d L , H b A l c was 5.8 ± 1.1% (norm: 4% to 6%), fructosamine was 188 ± 37 lamol/L (norm: u p to 230). Delivery type, obstetrical complications, a n d neonatal morbidity were similar, as well as those in the Table. CONCLUSIONS: O u r results show n o increase in respiratory morbidity a n d consequent mortality in infants of well-controlled diabetic mothers. This calls for reconsideration of the need for amnincentesis n e a r a n d at term to detect pulmonary maturity in welt-controlled diabetic patients.

Outcomes

Initial HgbAl (normal range 5.5-8.5) HgbA1 first trimester HgbA1 second trimester HgbA1 third trimester Preeclampsia SGA <10th percentile PTD <35 wk Polyhydramnios

PRECONCEPTIONAL COUNSI~J.1ING (N = 47)

FIRST TR]MF~TER ENROLLMENT (N = 129)

P

9.0 ± 1.9 8.4 ± 1.2 7.2 ± 0.8 7.1 ± 0.7 9 (21%) 2 (5%) 8 (19%) 11 (27%)

9.6 ± 2.0 9.1 ± 1.7 7.6 ± 1.1 7.5 ± 1.1 25 (19%) 4 (3%) 23 (18%) 24 (20%)

.082 .024 .030 .030 .825 .641 .909 .247

NULLIPARA (N = 156)

Mean GA at delivery (wk) Mean birth weight (g) Antenatal steroids RDS RD8 <33 wk RDS >33 wk Respiratory support >24 h Supplementary oxygen Surfactant treatment Mortality

DM (N = 55)

NON-DM (N = 110)

34.2 ± 2.4 2314 ± 758 8 (15%) 5 (9%) 5 / 1 3 (38%) 0 / 4 2 (0%) 7 (13%) 12 (22%) 2 (4%) 3 (6%)

34.2 ± 2.3 2306 ± 686 18 (16%) 16 (15%) 10/25 (40%) 6 / 8 5 (7%) 17 (15%) 21 (19%) 11 (10%) 4 (4%)

$68 SMFM Abstracts 0196

J a n t t a l T 2001 Ant J Obstet Gynecol

CHANGE OF MACROSOMIA RATE IN PREGNANCIES WITH DIABETES W H E N I N C L U D I N G NEONATAL AND MATERNAL A N T H R O P O M E T R Y Ute Schaefer-Graft, Manfred Voigt, MD 2, Siri L. Kjos, MD -~, J o a c h i m W. Dudenhausen, MDI; ICharite, Campus Virchow-Klinikum, Obstetrics, Berlin; 2University of Rostock, Obstetrics a n d Gynecology, Rostock; -~University of Southern California, Maternal-Fetal Medicine, Los Angeles, CA OBJECTIVES: The macrosomia rate is a m a j o r o u t c o m e p a r a m e t e r in p r e g n a n c i e s with diabetes. T h e s t a n d a r d definition of macrosomia, 90th percentile of the birth weight for gestational age, does not consider the asymmetric diabetic growth pattern or the maternal anthropometry. The aim o f the study was to d e t e r m i n e the c h a n g e of the m a c r o s o m i a rate when n e o n a t a l a n d m a t e r n a l a n t h r o p o m e t r y were included in the diagnosis of macrusomia. STUDY DESIGN: Maternal d e m o g r a p h i c a n d antenatal parameters a n d n e o n a t a l o u t c o m e p a r a m e t e r s are prospectively collected in a nationwide database for Germany. Percentiles for gestadonal age of several indicators for neonatal growth were calculated from data of 935,746 deliveries (1995 to 1997): (1) birth weight (standard definition), (2)ratio birth w e i g h t / l e n g t h (BW/Length) ( k g / m ) , (3) neonatal body mass index (BMI) (kg/m2), a n d (4) birth weight adjusted for different categories of maternal p r e p r e g n a n c y weight a n d height (BW/Mat). In 845 pregnancies with diabetes (5.6% type I, 94.4% GDM), the rate of macrosomia using the standard definition was compared with the macrusomia rate (~'90th percentile) using the other indicators. RF~ULTS: The macrosomia rate was 34.0% when applied the standard definition, 42.3% for BW/Length, 30.1% for the BMI, and 15.9% for BW/Mat. CONCLUSION: When newborns from diabetic mothers were classified as n o r m o s o m i c by the s t a n d a r d definition "birth weigbt for gestational age," there was a g o o d agreement with the classification by growth indicators which include neonatal or maternal anthropometry. In contrast, when newborns were classified as macrosomic by the s t a n d a r d definition, only 47% of the newborns would be assessed to be macrosomic when considering maternal anthropometry

Ab,r e e m e n t a n d ~ m e n t BW <90th > 90th

0197

0198

FETAL MACROSOMIA: IS IT LIPID PROFILE O R LEVEL OF GLYCEMIA? O d e d Langer, MD; :St. Luke's-Rooseveh Hospital Center, Obstetrics and Gynecology, New York, NY OBJECTIVES: To deternfine if macrosolnia is maternal lipid- or glucosed e p e n d e n t in the infants of diabetic mothers. METHODS: A total of 1129 women with gestational diabetes mellitus (GDM) participated in the study. Excessive fetal growth included large for gestatioual age (>90th percentile) and macrosomia (>4000 g). Lipid prolile (triglycerides, cholesterol, HDL, LDL, a n d HDL ratio) was obtained from all mothers at euUT and after 37 weeks' gestation. Blood glucose was evalnated utilizing self-monitoring (memory-based) blood glucose determinations, H b A I C (early a n d late in the third trimester), a n d variability of level of control. RESULTS: No significant differences was f o u n d in lipid profile a n d HbAIC while a significant dilt~rrence was h m n d in the level of glycemia heft)re a n d after initiation of therapy. Sin:liar levels of siguificant association were found with both hirth weight (mean 3249 _+522) and birth percentile (54 _+23) and cbolesternl (r= 0.22, P= .03), triglycerides (r= 0.25, P= .01), mean blood glucose (r = 0.33, P = .000), a n d fetal cord insulin (r = 0.60, P = .003). Additionally, a posidve correlation was found between maternal obesity and weight gain in pregnancy (r= 0.17, P = .002). Further stratification by level of glycemic control ( p o o r vs g o o d ) revealed that only for the g o o d control subjects did weight gain during pregnancy and trigl.vceride level maintaill a significant correlation (r= 0.12 and r= 0.15, P = 003). CONCLUSION: O u r data suggest that the stimulation for fetal growth in the p r e g n a n t diabetic is multifactorial. Howevel, the impact of these contributors can be minimized by achieviug good glycemic control in these women.

0199

DIABETF~ IN PREGNANCY: DOES G O O D GLYCEMIC C O N T R O L AND N O R M A L NEONATAL SIZE P R O T E C T T H E FETUS FROM HIGHER RATES O F S H O U L D E R DYSTOCIA? O d e d Langer, MD t, Menachem Langerx, Mr'-', Lois Brnstman, MD2; ISt. Luke's-Roosevelt Hospital Center, Obstetrics a n d Gynecology, New York, NY; 28t. Luke's-Roosevelt Hospital Center, Obstetrics a n d Gynecology, New York, NY OBJECTIVES: It is yet u n d e t e r m i n e d if g o o d glycemic control in the diabetic p r e g n a n t w o m a n decreases tbe rate of s h o u l d e r dystocia in comparison to the general population. METHODS: A total of 1546 diabetic women a n d 5036 nondiabetic subjects were evaluated for the rate of shoulder dystocia. Diabedc padents were further stratified by level of glycemic control (good < 100 m g / d L ; p o o r > 99 mg/dL), fetal weight, a n d birth percentile. All d e m o g r a p h i c data for mother, labor characteristics, a n d neonatal outcotne were recorded into o u r computerized database during the study period. RESULTS: (1) Overall incidence of s h o u l d e r dystocia was 3% for the diabetic a n d 0.6% for the nondiabetic population. (2) 17% of padents with previous shoulder dystocia had repeat shoulder dystocia (P = .03). (3) The incidence of shoulder dystocia was 1.9% in the g o o d conu'ol a n d 2.5% in the poorly controlled g r o u p (P = .66). (4) W b e n patients were stratified by neonatal size into macrosomia > 4000 g a n d n o n m a c r n s o m i a , in the good glycemic control g r o u p , the incidence of s h o u l d e r dystocia was 2.0% and 16.0%, respectively, P = .005. (5) Stratification by birth percentile for good glycemic controlled subjects revealed a 1.2% shoulder dystocia for the group below the 25th percentile; 1.9% for the g r o u p between 26th a n d 89th percentiles; and, 15% for the g r o u p > 90th percentile, P = .000. C O N C L U S I O N : O u r data suggest that the diabetic fetus, even when glycemic control is adequate, has a 2- to 3-fold higher risk for the development of shoulder dystocia. Tile risk increases as neonatal size increases. We can speculate that this finding can be explained by the a n t h r n p o m o r p h i ¢ characteristics of the infant of the diabetic mother.

in diabmosis of macrosomia

BW/ LENGTH

BW/ LENGTH

BMI

BMI

BW/ MAT

BW/ MAT

<90th 87% 1.6%

>- 90th 13% 98.4%

< 90th 91.1% 29%

-> 90th 8.9% 72%

< 90th 100% 53%

-> 90th 0% 47%

THE RATE OF PREECLAMPSIA IN WOMEN w r r H GESTATIONAL DIABErF~ IS COMPARABLE T O T H E GENERAL P O P U L A T I O N O d e d Langer, MD l, M e n a c h e m Langerx, MD 9, Lois Brnstman, MD 2, Amos G r u n e b a u m , MDS; tSL Luke's-Roosevelt Hospital Center, Obstetrics a n d Gynecology, New York, NY; 9St. Luke's-Roosevelt Hospital Center, Obstetrics a n d Gynecology, New York, NY; sSt. Luke's-Rooseveh Hospital Center, Obstetrics a n d Gynecology, New York, NY OBJECTIVES: Controversy exists on the precise incidence of preeclampsia (PE) in gestational diabetes mellitus (GDM). We sought to ascertain the rate of PE in GDM women. METHODS: A total o f 9074 GDM a n d 6471 n o n d i a b e d c w o m e n were evaluated. PE was defined as the presence of proteinuria a n d / o r e d e m a a n d blood pressure > 30 m m H g systolic or > 15 m m H g diastolic relative to blood pressure before the 90th week o f gestation or readings > 140/00 m m H g after 90 weeks. All diabetic patients were treated with the intensified m a n a g e m e n t a p p r o a c h . Blood glucose data were obtained utilizing m e m o r y reflectance meters. For purpose of analysis, patients were further stratified based on level o f glycemic control: g o o d glycemic control defined as mean blood glucose < 105 m g / d L ; p o o r glycemi¢ control -> 105 m g / d L . RESULTS: The incidence of PE was 9.6% in the GDM a n d 9.2% in the nondiabefic groups. Further stratification of GDM padents by glycemic control level revealed a rate of 9.0% a n d 11.0% for the g o o d a n d poorly controlled women, respectively (P = .24). Logistic regression revealed that there was no significant difference for the net effect o f obesity, parity, insulin dose, maternal age, treatment modality, a n d the incidence o f PE. CONCLUSION: T h e incidence of PE in GDM is similar to the rate in the general population.

SMFM Abstracts $69

V o l u m e 184, N u m b e r l Am J Obstet Gynecol 0200

0201

DOES LISPRO INSULIN CROSS THE HUMAN PLACENTA? Barak Rosenn ~, Wilhelm Kosssenjans x2, Annie Eis x-a, Diane Brockman x3, Leslie MyattX4; :St. Luke's-Rooseveh Hospital Center, New York, NY; 2University of Cincinnati, Obstetrics & Gynecology, Cincinnati, OH; :3University nf Ciuicinuati, Cincinnati, OH; 4Uuiversity of Cincinnati, Obstetrics & G~aecology, Cincinnati, O H BACKGROUND: Insulin lispro is a rapid acting insulin analog in which the positions of the amino acids lysine and proline have been switched at the eud of the B chain of the insulin molecnle. Clinical studies have suggested that in w o m e n with gestatiooal diabetes who were treated with lispro d u r i n g pregnancy a n d labor, lispro does not cross the placenta. OBJECTIVE: This study was designed to test the hypothesis that insulin lispro does not cross the h u m a n placenta in vitro. STUDY DESIGN: Six h u m a n placentas were obtained from normal term pregnancies immediately following deliver3, and prepared for dual perfusion of an isolated cotelydon. After an initial washout period of 30 minutes, each placenta was perfhsed for an additional 3 hours with lispro enriched media on the maternal perfnsion side: 2 placentas with 10 nniLs/dL, 2 with 50 uniLs/dL, a n d 2 controls with no lispro. Two-mL aliquots were collected from the maternal and fetal perlhsates every 3(/ minutes, and radioimmunoassay was perfhrmed to determine the concentrations of lispro insulin. Placental samples were obtained before a n d after perfl:sion a n d hnmunohistochemistr), was performed using anti-human ins:din antibody. RESULTS: Time-dependent transfer of insulin lispro across the perfused cotelydons was demonstrated, with fetal perfosate concentrations of lispro reaching up to 59% of maternal concentrations, hnmunohistochemistt T of postperthsion cotelydous demonstrated mild staiuing for insulin in mesench}lne of large stein villi, but no significant staining of terminal villi. CONCLUSIONS: Insulin lispro in high concentrations (greater than 50fold normal therapeutic doses) appears to crnss the iu vitro perfused ht:man placenta, but the mechanism of snch transfer is unclear. Further studies are needed to determine how the placenta handles therapeutic concentrations of" lispro.

COMPLICATIONS IN GESTATIONAL AND PRE-GESTATIONAL DIABETIC WOMEN L a m a Tolayma0, Victor Gonzalez-Quintero 2, Shadi Tolaymats, Nina Emko 4, Mary O'Sullivan~; IUniversity of Miami, Obstetrics & Gynecology, MFM, Miami, FL; ~University of Miami, Obstetrics & Gynecology, Miami, FL; :~University of Miami, Coral Gables, FL; 4University o f Miami, Miami, FL; 5University of Miami, Obstetrics & Gynecology, Miami, FL OBJECTIVE: To c o m p a r e p r e g n a n c y complications in women with gestational diabetes (GDM) a n d women with pre-gestational diabetes (PGDM). STUDY DESIGN: This retrospective study was based on 361 women with GDM a n d 105 women with PGDM who delivered at Jackson Memorial Hospital from J a n u a r y 1st 1998 to December 31st 1999. The two groups were compared with respect to discrete variables using chi square tests. For c o n t i n u o u s variables, differences between means were assessed using i n d e p e n d e n t samples Student t tests a n d 95% confidence intervals. Statistical significance was defined as a P value < .05. RESULTS: A total of 361 women witit GDM a n d 105 women with PGDM delivered at Jackson Memorial Hospital during the study period. There was no statistically significant difference with respect to maternal age (mean + SD: 30.4 + 7.0 vs 31.2 + 6.3 years, P = .15), gravidity (3.4 + 2.6 vs 3.3 + 2.1, P = .25), living babies (1.4 + 1.9 vs 1.2 ± 1.4, P = .168) a n d abortoses (0.89 + 1.4 vs 0.89 + 1.2, P = .168) in PGDM vs GDM women. There were significant differences in the two groups with respect to gestationai age at delivery (37.0 + 3.1 vs 37.9 + 2.6 weeks, P= .001) a n d birth weight (3218 + 860 vs 3503 + 783 g, P< .001), but when adjusted to gestadonal age, there was no significant difference between the mean birth weight. The proportion of women with preeclampsia was much higher (X2 Pvalue =0.038) in women with PGDM (23%) compared to women with GDM (14%). O f those who had preeclampsia, the proportion of women with severe preeclampsia was not statistically significant between the two groups (P = .21 ). C O N C L U S I O N : C o m p a r e d to gestationai diabetics, pre-gestationai diabetic women are at an increased risk of preeclampsia, a n d are more likely to deliver at an earlier gestational age.

0202

DIIq,t-sRENCES IN NEONATAL OUTCOMES IN CLASS C / D AND CLASS R / F DIABETES J u n e Murphy I, Tulin Ozcan2,Joshua Copel s, Nancy Nickless4, Urania MagriplesS; :Yale University, Obstetrics a n d Gynecology, New Haven, CT; '-"YaleUniversity, Department of Obstetrics a n d Gynecology, New Haven, CT; "~Yaie University, Obstetrics a n d Gynecology, New Haven, CT; 4yale New Haven Hospital, Maternal fetal Medicine, New Haven, CT; SYale University, Maternal Medicine, New Haven, CT OBJECTIVE: To compare the maternal a n d neonatal outcomes of Class R / F and Class C / D diabetic pregnancies. STUDY DESIGN: Retrospective cohort study of 43 pregnancies complicated by Class R / F diabetes (DM) and 66 Class C / D DM from a total of 827 diabetic padents delivered over a 10-year period. RF~ULTS: Comparison of neonatal outcomes are presented in the table. The overall Cesarean section (C/S) for Class R / F DM was signhqcandy higher than Class C / D (79.5% vs 51.6%, P = .01). C / S were due to non-reassuring fetal testing and arrest disorders in 45 a n d 17% of Class R / F vs 27 a n d 39% of Clas,s C/D, respectively. CONCLUSIONS: Class R / F DM has a significantly higher risk of C/S, small for gestadonal age fetuses a n d preterm deliveries than Class C / D DM. This should be incorporated into counseling women in pregnancy. Neonatal outcome CLASS C / D GA BIRTHWEIGHT %SGA %LGA 5 MIN APGAR

0203

37.1 ± 3.5 3475 + 727.8 5.1 28.3 8.5 ± 1.4

~ S

R/F

35.1 :t: 3.9 2860 ± 912.4 31.6 7.9 8.1 ± 1.8

P .0009 .0004 .0004 .01 NS

END TIDAL CARBON M O N O X I D E LEVELS ARE L O W E R IN WOMEN WITH GESTATIONAL HYPERTENSION AND PREECLAMPSIA D o r o n Kreiser l, Daniel Seidnam S 2, Avroy Fanarofl~, D. Shah 4, Mieha Baum 2, Israel H e n d l e r 2, David Stevenson 5, Eyai Schif~, Maurice DruzinT; IStanford University, Obstetrics a n d Gynecology, Division of Maternal-Fetal Medicine, Stanford, CA; 2Sheba Medical Center, Obstetrics a n d Gynecology, Rarnat Gan; 3Case Western Reserve University, Pediatrics, Cleveland, OH; 4MacDonald Women Hospital, Reproductive Biology, Cleveland, OH; 5Staoford University, Gynecology a n d Obstetrics, Paio Alto, CA; 6Sheba Medical Center, Obstetrics a n d Gynecology, R a m a m t Gan; 7Stanford University, Gynecology a n d Obstetrics, Stanford, CA BACKGROUND: The possible role of heme oxygenase a n d its by-product c a r b o n m o n o x i d e (CO) in the regulation o f b l o o d pressure is u n d e r investigation. CO can activate guanylate cyclase a n d affect smooth muscle tone, similar to nitric oxide. OBJECTIVE: To compare End Tidal breath C O (ETCO) levels in women with gestadonal hypertension (GH) o r preeclampsia m die levels in healthy nonsmoking pregnant a n d non-pregnant women. MATERIALS AND METHODS: We prospectively p e r f o r m e d ETCO measurements corrected for a m b i e n t CO (ETCOc) in two medical centers (Stanford, CA a n d Cleveland, O H ) . A Natus CO-Star E n d Tidal Breath Analyzer (Natus Medical Inc, San Carlos, CA) was used. Study g r o u p included 31 women with GH/preeclampsia. Control groups included 46 n o n - p r e g n a n t healthy women, 44 first trimester a n d 48 third trimester p r e g n a n t healthy women. RESULTS: Mean + SD ETCOc measurements were significantly lower in the GH/preeclampsia g r o u p c o m p a r e d to first trimester ( P = .004) a n d third trimester ( P = .001) normoteusive p r e g n a n t women a n d n o n - p r e g n a n t women ( P = .002), (1.36 + 0.30 vs 1.76 ± 0.47, 1.72 ± 0.42 a n d 1.78 ± 0.54 p p m , respectively). The ETCOc values were < 1.6 p p m in 89% of G H / p r e e c l a m p s i a women c o m p a r e d with, respectively, only 45%, 54%, 46% o f non-pregnant, first a n d third trimester normotensive p r e g n a n t w o m e n (P < ,06), ETCOc measurements were not influenced by maternal age, parity, ethnicity, b o d y mass index, gestadonal age or presence of h o u s e h o l d smokers. In the two centers the controls h a d a similar mean ETCOc a n d t h e d i t f e r e n c e s f o u n d remained significant when results for each center were analyzed separately. CONCLUSIONS: ETCOc levels were f o u n d to be significantly lower in women with GH/preeclampsia. Further investigation is required m d e t e r m i n e if the lower CO levels reflect a deficient compensatory response to the increase in blood pressure or whether these are primary changes o f significance to o u r understanding of die pathogenesis of GH/preeclampsia.

$70 SMFM Abstracts 0204

Janua,y 2001 A m J O b s t e t Gynecol

SIDE-TO-SIDE Dt~t~t~q,EN CES IN TRANSCRANIAL DOPPLER PARAMETERS IN NORMOTENSIVE AND PREECLAMPTIC PREGNANT WOMEN Shlomit Riskin-Mashiah, MD 1, Asma Masood. MPH 2, Michael A. Belfort. MD 3, George R. Saade, MD 4, AlanJ. Herd, MDS; IBaylor College of Medicine, Department of Obstetrics and Gynecology, Houston. TX; ~-Baylor College Of Medicine, Department of Obstetrics and Gynecology, Houston, TX; -~University Of Utah, Department of Obstetrics and Gynecology, Provo, UT; 4The Univex~ity of Texas Medical Branch, Department of Obstetrics and Gynecology, Galveston, TX; 5Baylor College Of Medicine, Department of Medicine. Houston, TX OBJECTIVE: To determine if brain blood flow velocity changes, previously reported in preeclampsia, result in larger side-to-side velocity differences in preeclamptic (PET) versus normotensive (NORM) pregnant women. STUDY DESIGN: 50 NORM and 41 PET pregnant women without cerebral symptoms were studied, in the left lateral position, during the third trimester. Transcranial cerebral Doppler was used to measure peak. end diastolic and mean (Vm) velocities in both right (Rt) and left (Lt) middle cerebral arteries (MCA). An asymmetry index was calculated as I00 x (Rt Lt)/(Rt + Lt)/2, for each of the following parameters: Vm, pulsatility index (FI) and estimated cerebral perfusion pressure (eCPP). Student t test, Pearson's correlation and regression analysis were used as appropriate (statistical significance: P< .05). RESULTS: Both NORM and PET showed good correlation between Rt and Lt MCAVm (R> .8, P< .001), PI (R> .6, P< .001) and eCPP (R> .8, P< .001). There were no differences .] in the asymmetry 3 ° ~ ' t el " PRE'¢LAMPT'¢ 1 index forVm, Pl or ~ . o NORMOTENSIVE eCPP between the 2s two groups. How- Z m ever, among PET ~ 2o oOo'o.: 'k women the Vm •u • showed negative correlation with 1o mean blood pres- ~ sure (R=-.344, P< m .03). There was no ~ correlation

pressure among

nor-

motensive women (R = - . 0 2 , P = .87)

(Figure).

C O N C L U I O N S :

a', -

,

between

Vm asymmetry indexandmeanblood

S

..0 ~

so

so

~

/ : . a , . . =" a "h "" " " ~ . o o o| " ..

a ~ "~ • • °o~o o q,, ,'• o m o=a~ • 7o

eo

so

•

Cardiorespiratory and middle cerebral artery data N O R M (N = 20)

MBP HR PI RI CPP

BASELINE 75±2 77±2 0.83 + 0.03* 0.54 ± 0.01" 55.7+3.6

PET (N = 10)

5% C O s

HANDGRIP

BASELINE

5% CO s

HANDGRIP

73+2 78±2 0.71 + 0.02"i0.49 ± 0.01j56.7±4.7

74+2 79+2 0.73 ± 0.03"10.50 ± 0.01J54.4±2.8

79+3 77+3 0.73 ± 0.03* 0.50 ± 0.01" 57.1-+7.6

81 +4 79+3 0.67 ± 0.04~ 0.47 ± 0.02T 68.5±11.5

79_+3 81+2 0.67 ± 0.03"1" 0.47 ± 0.0It 57.1±5.9

*P< .05 PET compared to NORM tP<.05 compared to baseline

** • "-. ....

•

•

•

~oo ~*o ,20 t30 ~,o iso

MEAN ELOOD PRESSURE

R e l a t i o n s h i p b e t w e e n m e a n velocity a s y m m e t r y index and mean arterial pressure.

Preeclampsia does not appear to induce any side-to-side velocity differences in the MCA distribution. The negative correlation between Vm asymmetry index and mean blood pressure in preeclamptic women suggests that as blood preSsure increases cerebral autoregnlation becomes abnormal and increasingly ineffective in the differential regulation of side-to-side velocity-flow differences. 0205

TRANSC, RANIAL DOPPLF~ MEASUREMENT OF CEREBRAL VELOCITY INDIC, F_~ A S A P R E D I C T O R O F PREECLAMPSIA? Shlomit Riskin-Mashiah, MD l, Michael A. Belfort, MD 2, George R. Saade, MD ~, Asma Masood, MPH I, AlanJ. Herd, MD4; IBaylor College of Medicine, Department of Obstetrics and Gynecology, Houston, TX; 2University Of Utah, Department of Obstetrics and Gynecology, Provo, UT; 3The University of Texas Medical Branch, Department of Obstetrics and Gynecology, Galveston, TX; 4Baylor College Of Medicine, Department of Medicine, Houston, TX O B J E C T I V E : We have shown that preeclamptic women demonstrate cerebral hyperperfusion and abnormal cerebrovascular autoregulation. This study tests the hypothesis that pregnant women develop abnormal cerebrovascular function prior to clinical symptoms. S T U D Y D E S I G N : During the second trimester, transcranial Doppler was performed on 166 women to measure velocities in the middle cerebral arteries (MCA). Preeclampsia developed in 10 initially normotensive patients (PET). In a nested case-controlled design, each PET patient was matched for gestational age at exam, maternal age and parity with 2 pregnant women who remained normotensive (NORM). Measurements were pei'formed in the left lateral position at baseline, during 5% CO 2 inhalation and during isometric handgrip test. Pulsatility index (P1), Resistance index (RI) and Cerebral Perfusion Pressure (CPP) were calculated. (Data: mean ± SE; Significance: P < .05). R E S U L T S : Preeclampsia developed 13.6 ± 1.0 weeks after the study in the PET group. Baseline mean BP was similar, but MCA PI and RI were lower in the PET compared to the NORM group. Both maneuvers caused significant reduction in PI and RI. Using baseline values as covariates, no significant differences were noted in the response to either test between NORM and PET. T h e r e was a small increase in CPP after 5% CO s inhalation in PET group (Table). C O N C L U S I O N S : Normotensive pregnant women who later develop preeclampsia demonstrate lower baseline PI and RI but normal vasodilatory responses to both maneuvers. These findings suggest that women who are destined to develop preeclampsia have cerebral hemodynamic changes that predate the development of o v e r t preeclampsia symptoms.

0206

MATERNAL SERUM PLACENTA GROWTH FACTOR AND VASCULAR ENDOT]4RIJAL GROWTH FACTOR IN PREGNANCIES COMPLICATED BY PREECl.,AMPSIA Tsang-Tang Hsiehl; tChang Gung Memorial Hospital, Taipei OBJECTIVE; To determine I, maternal serum placenta growth factor (PLGF) and vascular endothelial growth factor (VEGF) concentrations in preeclamptic and normal pregnancies in the third trimester and, 2, the relationship between maternal serum PLGF and VEGF concentrations. STUDY DF~IGN: Forty-one patients with preeclampsia and 123 normal pregnancies matched for gestational age in the third trimester. For the detection of serum concentrations of PLGF and VEGF, a quantitative sandwich enzyme immunoassay technique (R & D Systems Inc, Minneapolis, MN, USA) was performed. RESULTS: Maternal serum PLGF and VEGF levels were significantly decreased in preeclamptic patients compared with normal pregnancies (InPLGF 4.7 ± 0.8 vs 5.5 ± 0.6 pg/mL, P < .001; VEGF 9.7 ± 2.7 vs 11.6 ± 2.9 pg/mL, P< .001). In the third trimester of normal pregnancy, maternal serum PLGF and VEGF concentrations did not change with increasing gestational age. Maternal serum InPLGF and VEGF levels were highly correlated in normal pregnancies (r = .387, P < .001) but not in preeclampsia (r = .082, P = .612). Further analyzing with logistic regression model, PLGF was the only significant determinant for the occurrence of preeclampsia (P < .001) when VEGF (P= .058), maternal age (P= .423), parity (P= .627) and gestational age (P= .472) were taken into consideration altogether. CONCLUSIONS: In the third trimester, the risk of preeclampsia increased approximately five times when maternal serum PLGF concentration decreased every one lnPLGE Markedly decreased maternal serum levels of PLGF and VEGF and their dissociation in preeclampsia may imply that impaired placental vascular development might play an important role in pathogenesis of preeclampsia.

SMFM Abstracts $71

V o l u m e 184, Ntttnl>er 1 Am J O b s t e t G e n t e e l

0207

ELEVATED CELLULAR ADHESION MOLECULE CONCENTRATIONS IN MID-PREGNANCY MAY PREDICT RECURRENT PREECLAMPSIA Kristine l,ain I, Steve ('aritisl: tNI('HD, Bethesda, MD OBJECTIVE: Prceclampsia is associated with endothelial activation, and circulating cellular adht-sion molecules have heen proposed as predict~rs fi'~r development of disease. We measttred intracelhdar adhesion melee:tie (ICAM) and vascnlar cell adhesion rnolecule-1 (VCAM) to determine if concentrations were elevated in WOlnen win) developed preeclampsia, and determined cntoffs predictive of disease. STUDY DESIGN: This secoodarv analvsis is from a multi-center trial which evahmted the use of aspirin in high-risk women to prevent preedampsia. The study enrolled 6116 womeo with a I*tistory of preeclampsia. Our cohort of 160 women (125 heahhy and 35 with :'ecurrent preeclampsia) received placeho and had out' or lnore plasma samples collected. Salnples were obtained at mean gestational ages of 19.28. and 36 weeks, and were assayecl Ior l(~kM and VCAM by ELISA. Data were anal)Tt!d I()r dillt-rences among groups hy logistic regression ~md changes over time hy )'-' test of trends. Descriptive statistics were genet'ated with cutoll~ to analyze predictive value. RESULTS: 375 samples were analyzed. Median ICAM and VCAM concentrations at baseline were 237 n g / m L and 677 n g / n l l , respectively. Median values Ibr I('AM aod VCAM did not change over time and were not diffcret~t belweert the twt~ groups. Patietlt.S with ICAM concentrations > 350 n g / m L or VCAM conceotrations -> 130(/ng/mL at 28 weeks had a signiticandy increased risk of developing recnrrent preeclampsia (RR = 2.3, P = .(1% RR = 3.fi, P= .02). Change in VCAM ctmcentratiml from I t) to 28 weeks, an ahsolnte change of > 20 n g / m L or a > 25% iocrease, was also associated with an increased risk of developing preeclampsia (test of trend P = .1.)2and P = .04). CONCLUSIONS: These data indicatc that ICAM and V(L'kM may predict the development of preeclampsia in women with a histo D' of tile disease. Ftuther study is needed to determine if these markers would be clinically useful in the prediction of preeclampsia.

0209

CORRELATION OF QUANTITATIVE PROTEIN MEASUREMENTS IN 8-, 12- AND 24-HOUR URINE SAMPLES FOR THE DIAGNOSIS OF PREECLAMPSIA Amy Adelberg 1, Meg Doerzbacher'-', Jeff Miller ~, Donna Lambers3; tGood Santaritao Hospital, Fort Wright, K'Y; "-'Good Samaritan Hospital, Cincinnati, OH; 3Good Sanmritan Hospital, Obstetrics, Cincinnati, OH OBJECTIVE: Preeclampsia is diagnosed by hypertension with proteinuria, edema or both. Tile standat'd for diagnosing proteinuria is a 24-hoot urine sample tot total protein. Each patient's 8- and 12-hour collections were analyzed for total protein to determine a correlation with their 24-hour sample. STUDY DESIGN: Patients' urine was collected over 24-hours with the first 8 honrs, next 4 hem's and remaining 12 hours collected in separate containers. The total proteio, volume and creatinine were measured from the 8-hour sample. The nrine was comhioed to get tile same measurements from the 12and 24-hour samples. Serum creatinine was obtained. T h e creatinine clearance and total protein in rag/time of collection were calculated. The 8and 12-hour urine results were compared to the 24-hour sample by simple regression analysis to determioe a correlation coefficient. RESULTS: A total of 30 urine samples were collected from 30 patients. Nine patients had no preeclampsia, 15 padents had mild preeclampsia and 6 patients had severe preeclampsia. Tile mean proteinuria between the 8-, 12and 24-hour samples was significantly different (220:1:40 mg vs 1237:1:1132 mg vs 11,657 + 5506 nag) respectively. Tile 8-hour sample correlated with the 24hour sample for patients with mild and severe disease (P= .0004 and P= .031 ). The 12-hour correlated with tile 24-hour sample for patients with no disease, mild and severe preeclampsia (P= .039, P= .0007 and P= .005). There was no diurnal variation noted betweeo samples. Total protein values greater than 91 nag and 1030 rag, in the 8-hour sample, could predict mild and severe proteinuria with positive predictive values of 91.7% and 87.5%. CONCLUSION: Eight and 12-hour urine samples for total protein correlate significantly with 24-hour samples for patients with preeclampsia. A 12-hour and 24-hour sample correlates for patients without disease. These results may aid in earlier diagnosis and management of preeclampsia.

0208

RELATIONSHIP OF TWIN ZYGOSITY AND PREECI..AMPSIA Cynthia Maxwell L, Ellice Lieberntan'-'. Mary Norton 3, Ellen Seely t, Aviva Lee-Parritz4; :Brigham and Wotnen's Hospital, Har~u'd Medical School, Ob/Gyn, Boston, MA; '-'Brigham and Women's Hospital. Ohstetrics and Gynecology Boston, MA; 3University of California, San Francisco, Obstetrics, Gynecology and Reproductive Sciences, San Francisco, CA; tBrigham and Women's Hospital, Boston, MA OBJECTIVE: Twin gestations are known to be at higher risk for preeclampsia. One thee] 3, suggests that maternal recognition of fetal and trophoblastic tissues as foreign may be a tactor. If that hypothesis were true, :no:hers carrying monozygons (MZ) gestations (ie, a single fetal graft) would have a lower rate of preeclampisa than those eat'tying dizygous (DZ) twins. To evaluate this hypothesis, we compared tile rate of preeclampsia in mothers with MZ and same-sex DZ twin gestations. STUDY DESIGN: 768 twin deliveries from 1994 to 1999 were reviewed. Placental patholog3, reports were reviewed to determine chorionicity. Monochorionic placentas were assumed to be MZ. Dichorionic placentas were categorized as DZ if the oeonates were of different sexes or blood types. Maternal data including age, parity, complications of pregnancy and risk factors for preeclampsia (previous preeclampsia, hypertension, renal disease, or lupus) were ahstracted from the medical records. Fetal data included gestational age at delivery, sex. birth weight, and blood group. Only pregnancies over 30 weeks' gestation were included in the analyses. P:'eeclampsia was defined by standard criteria. RESULTS: The overall rate of preeclampsia ~as 9.6% (74/768), There were 337 DZ pairs and 175 MZ pairs (256 pairs with unknown zygosity). Among ntdliparas the rate of preeclampsia was 15% (7/45) for same sex DZ twins versos 20% (15/75) for MZ twins (P = .54). Among multiparas the rate was 12% (4/33) for same sex DZ twins and 5% (4/79) for MZ twins (P = .23). Nuniparas with same sex DZ twins had a rate of preeclampsia of 15% (7/45) versus 14% (18/125) for those with discordant sex twins (P= .85). Tile rates were 12% (4/33) versus 6.5% (7/107) for muldparas (P= .29). CONCLUSIONS: These results do not support the hypothesis that zygosity significantly impacts tile rate of preecla:npsia in twin gestations.

0210

THE ANGIOTENSIN II RECEPTOR I 1166A TO C/~H.FJJC VARIANT IS N O T ASSOCIATED WITH PREECLAMPSIA Christine Johns t, Joshua Kalowlton 2, Lesa Nelson l, Kenneth Ward I; IUniversity of Utah, Obstetrics and Gynecology,, Salt Lake City, UT; 2Universtiy of Utah, Obstetrics and Gynecology. Salt Lake City, UT OBJECTIVE: Preeclampsia is a familial disorder. The mode of inheritance has not been fully established, but genes of the renin-angiotensin system have been implicated. A polymorphism at nucleotide 1166A to C of the angiotensin 11 receptor I (AGTR1) gene has been associated with essential hypertension. We investigated whether there was an association between this polymorphism and preeclampsia in our population. STUDY DESIGN: A case-control study was conducted in a group of 471 patients who had developed preeclampsia, 380 patients who remained normotensive throughout pregnancy and 100 patients with hypertension antedating pregnancy. Genotypes were determined through a polymerase chain reaction followed by allele-specific digestion with Ddel. Digested PCR products were size fractionated and visualized on an agarose gel stained with ethidium bromide. RESULTS: (Table). CONCLUSION: Genotype and allele frequencies for the two groups did not deviate from Hardy-Weinberg equilibrium. Although there is a strong ,association between angiotensinogen variants and preeclampsia, there is no association between the 1166A to C polymorphism in the angiotensin II receptor I gene and preeclampsia or early onset chronic hypertension in our population.

Preeclamptic group (n = 471) Normal controls (n = 380) Chronic hypertension (n = 100)

CC GENOI~zFPE

C ~T.T.'I~.TJR

7.6% 7.9% 4.0%

27% 27% 24%

$72 SMFM Abstracts 0211

GENETIC SUSCEt-rIBILrrY TO PREECLAMPSIA: ROLES OF Asp9Asn MUTATION, -95G PROMOTER MUTATION, Asn291Ser MUTATION IN THE LIPOPROTEIN LIPASE GF-,N~ Young Ju Kiml; IEwha Womans University, MokDong Hospital, Obstetrics and Gynecology, Seoul OBJECTIVE,: The objective of this study was to evaluate the association between preeclampsia and the Asp9Asn mutation, the -93G promoter mutation, the Asn291Ser mutation in the lipoprotein lipase gene, STUDY DESIGN: DNA was extracted from whole blood or cheek swabs of 250 preeclamptic patients, 265 controls, and 106 babies from preeclamptic patients. All samples were genotyped for all polymorphisms using PCR of known allelic variants. Sequences were confirmed on an Applied Biosystems 373 DNA Sequencer. Results were analyzed with an X2 contingency table. RF~ULTS: The prevalence of the LPL AspgAsn mutation, the LPL-93G promoter mutation were not significantly different among the preeclamptic patients, severe preeclamptic patients, and HELLP syndrome patients and controls, and also not significantly different between the babies born from preeclamptic mothers and controls (P = NS). Between nulliparous HELLP syndrome patients and controls, there was a significant difference in the prevalence of the LPL Asn291Ser mutation(16.7% vs 3.0%, P= .01 ). CONCLUSION: In this population, the LPL Asp9Asn mutation, the LPL -93G promoter mutation are not associated with an increased risk for preeclampsia and HELLP syndrome. The LPL Asn291Ser mutation shows a significant association with an increased risk for nulliparous HELLP syndrome.

J a n u a r y 2001 AmJ Obstet Gynecol 0213

PREECLAMPSIA: WILL IT HAPPEN AGAIN? Dorothea Mostello I, Liana Roman ~, Tegan Catlin 2, Terry LeeO, William Holcomb, J 0 : ~St Louis University, Obstetrics, Gynecology and Women's Health, St Lottis, MO; "St Louis University School of Public Health, St Louis, MO; .~St Louis University School of Public Health. Community Heahh, St Louis, MO OBJECTIVE: To identify risk factors for preeclampsia in the second pregnancy and to determine whether the risk of recurrent preeclampsia is related to gestational age at deliver), (GAD) in the first pregnancy. STUDY DESIGN: Birth certificate data from the Missouri maternallylinked cohort were used to identifi.' 4616 cases diagnosed with preeclampsia during the second pregnancy and 4986 controls between 1990 and 1997. Logistic regression analysis was used to estimate relative risks, with appropriate adjustments for confounding bias. RESULTS: Risk factors (crude odds ratio) for preeclampsia in the second pregnancy include chronic hypertension (5.3), diabetes (2.8), renal disease (4.0), obesity (4.4), maternal age > 35 (1.5), black race (1.6), birth interval > 24 months (1.7), prior low birth weight (LBW) (2.6) or very-LBW infant (3.9), and change in paternity (1.2). Smoking is protective (0.74). A history of preeclampsia confers the highest risk (7.7, 95% confidence interval [C1] 6.59.1). This risk of recurrent preeclampsia was dependent on the GAD in the first pregnancy (Table); odds ratios were adjusted (aOR) for birth interral and body mass index (BMI). The relationship to GAD did not change when other risk factors were added to the model. CONCLUSIONS: The risk of recurrent preeclampsia increases with earlier GAD for the lirst pregnancy. Further study is needed to clarity, the relationship between BMI and preeclampsia recurrence. R i s k o f r e c u r r e n t p r e e c l a m p s i a b y G A at d e l i v e r y o f f'wst b i r t h

0212

GENETIC POLYMORPHISMS WITHIN THE INTERLE I N - I t PATHWAY AND PREEGLAMPSIA Lukas A. Hefler I, Clemens B. Tempfer 2, Anthony R. GreggS; IBaylor College of Medicine, Obstetrics & Gynecology, Houston, TX; 2Baylor College of Medicine, Obstetrics & Gynecology, Houston, TX; 3Baylor College of Medicine, Houston, TX OBJECTIVE: It is theorized that an inflammatory response with subsequent endothelial dysfunction is involved in the pathogenesis of preedampsia (PE). Interleukin-l[~ (IL-I~) is a potent pro-inflammatory agent, ID1 receptor antagonist ilL-IRA) is its natural inhibitor. IL-II3 and IL-IRA are both up-regulated in PE. We searched for associations between gene polymorphisms within the IL-l[3 cluster and the PE phenotype. STUDY DESIGN: We genotyped a Hispanic population for 2 polymorphisms of the IL-1[3 gene (exon 5 and promoter region) and 1 polymorphism of the IL-1RA gene (intron 2). Data for all 3 polymorphisms were available for 59 women with PE and 38 controls. Clinical data were obtained from patient records. We compared clinical data in 2 ways: 1, for each polymorphism separately, 2, PE patients with at least 3 polymorphisms in the cluster vs all others with PE. RESULTS: The bi-allelic polymorphisms (exon 5 and promoter) were found to be in Hardy-Weinberg equilibrium. No association between any single polymorphism and the occurrence of PE was found. Women with PE and at least $ mutant alleles (n = 8) had higher systolic blood pressure at admission (182 vs 160 mm Hg, P = .009) and increased ALT (67 vs 20 IU/L) and AST (119 vs 24 I U / L ) . Blood pressure at admission in the control group was independent of the number of polymorphisms identified. CONCLUSION: These data do not support a role for the IL-I[~ and IL-RA polymorphisms we tested in the pathogenesis of preeclampsia among Hispanic women. Our data do suggest polymorphisms within this gene cluster may influence the severity of PE at the time of presentation.

0214

GA (WEEKS)

aOR

CI

< 33 33- 34 35- 36 37+,non-obese 37+,obese

22.4 16.6 13.3 8.0 4.9

9.7, 52.0 6.6, 42.2 7.7, 22.9 6.3,10.1 2.6,9.4

HEAT SHOCK PROTEIN 70 CONCENTRATIONS ARE NOT INCREASED IN SEVERE PREECI.AMPSIAJeffrey Livingston, MD I, Reem Awaad2, Robert Ahokas, PhD s, Robert Egerman, MD 4, Bassam Haddad, MD 2, Bill Mabie, MD 3, Baha Sibai, MD2; IUniversity of Tennessee Health Science Center, Memphis, TN; 2University of Tennessee Heahh Science Center, Obstetrics & Gynecology, Memphis, TN; 3University of Tennessee Healtlt Science Center, Obstetrics & Gynecology, Memphis, TN; 4University of Tennessee Health Science Center, Memphis, TN INTRODUCTION: Heat shock protein 70 (hsp 70) plays a vital role in mechanisms of cellular protection during episodes of stress. Hsp 70 may be induced by the production of oxygen free radicals at times of hypoxia, ischemia/reperfusion, or as part of the inflammatory response. There are currently no studies evaluating hsp 70 in preeciampsia. The purpose of this case control study was to compare hsp 70 concentrations in plasma of women with severe preeciampsia to normotensive pregnant controls. MATERIAI~ AND METHODS: Study groups were women with singleton pregnancies with severe preeclampsia (n = 46) and normotensive pregnant controls in = 52). Patients with HELLP syndrome in = 2) or eclampsia (n = 1) were also included. Exclusion criteria were chronic hypertension, renal disease, diabetes, autoimmune disease and infection. Plasma was obtained at the time of diagnosis of severe preeclampsia. Hsp 70 concentrations were determined by a quantitative sandwich immunoassay. Data analysis was with the Mann-Whitney U test. Clinical characteristics were compared using the Student t test. A Pvalue of less than .05 was considered significant. RESULTS: The groups were similar regarding maternal age and parity. Clinical findings and plasma values are compared in the Table. There were no differences in maternal plasma hsp 70 concentrations between the two groups. Twenty-eight samples from preeclamptics and 31 from controls had undeteetable concentrations of hsp 70 (assay detection limit was 0.2 ng/mL). These were considered as 0.2 n g / m L in the analysis. CONCLUSION: The inflammatory process of preeclampsia does not include elevation of maternal plasma hsp 70 concentration. Since the primary role of hsp 70 is protection of intracellular proteins, plasma hsp 70 may be indicative of cell death and release ofhsp 70. Intraeellular levels ofbsp 70 may be more indicative of stress of preeclampsia.

Gest. age at delivery (wks) Birth weight (grams) Systolic BP (ram Hg)* Diastolic BP (ram Hg)* Plasma hsp 70 ( n g / m L ) t

SEVERE PREECLAMPSIA

NORMOTENSIVE

34.3 + 5.6 2289 + 1034 174.5 + 17.3 110.1 + 12.9 32.7 ± 103.7

35.4 + 5.7 2518 + 1103 3126.9 + 23.2 79.8 + 13.0 34.6 ± 96.0

Data expressed as mean ± standard deviation; *p < .001; t p < .05.

SMFM Abstracts $73

V o l u m e 184, N u m b e r 1 Am J Obstet Gynecol

0215

PLACENTAL G R O W T H FACTOR IS N O T AN EARLY MARKER F O R T H E DEVELOPMENT O F SEVERE PREECLAMPSIA Jeffrey Livingston, MD I, Bassam Haddad, MD ], Laura Gorski, DO I, Robert Ahokas, PhD t, Baha Sibai, MDX; tUniversity of Tennessee Health Sciences Center, OB/GYN, Memphis, TN; -°Univet,'sity of Tennessee Heahh Sciences Center; Memphis, TN OBJECTIVE: To evaluate plasma concentrations of placental growth factor (PLGF) as an early pregnancy marker in women who ultimately develop severe preeclampsia (SPE). STUDY DESIGN: Tiffs nested case control study compared PLGF plasma concentrations in SPE women to normotensive pregnant controls. Plasma was collected at < 20 weeks' gestational age (GA) and again in the 3rd trimester. Twenty-two women who developed SPE were matched for GA at delivery to 22 normotensive controls. PLGF c o n c e n t r a t i o n s were m e a s u r e d by ELISA technique and comparisons made using the Mann-Whitney U or Student t test. RESULTS: 2 2 / 8 8 0 developed SPE (incidence = 2.5%). Preeclamptic women had higher blood pressures a n d lower birth weights. Placental weights were similar. PLGF concentrations are in the table. C O N C L U S I O N : In the 3rd trimester, SPE patients have decreased maternal c o n c e n t r a t i o n s of PLGE This difference is not seen earlier in pregnancy.

EARLY PREG. GA (wks) --PLGF (pg/mL) LATE PREG. GA (wks) --PLGF (pg/mL)

SPE

CONTROLS

P

15.0±3.3 (10.9- 197) 98.8 ( 29.3 - 540.6)* 37.3 ± 1.6 (35.1 - 40.9) 125.2 (64- 657)*

15.1_+3.3 (10.4 ~ 19.6) 56.3 ( 11.4 - 298.8)* 37.0 ± 1.5 (34.3 - 40.9) 449 (10Ll 101)*

ns

0217

OBSTETRICAL INTERVENTION, MATERNAL AND NEONATAL O U T COMES O F WOMEN W I T H GESTATIONAL H Y P E R T E N S I O N E.N. Gofton l, V. Capewell I, R. Natale I, RJ. Grattonl; ISt J n s e p h ' s Health Care, Obstetrics a n d Gynecology, London, Ontario OBJECTIVE: To determine the rate of obstetrical intervention a n d the maternal a n d neonatal outcomes of women with gestational hypertension (GHTN) in c o m p a r i s o n to w o m e n with preeclampsia (PE), c h r o n i c hypertension (CHTN) and normotensive controls. STUDY DESIGN: A retrospective review of.the St. Joseph's Health Cafe's Perinatal Database from November l, 1995 - October 31, 1999. Term patients (37 to 41 weeks) were divided into four groups: GHTN (n = 979), PE (n = 165), CHTN (n = 187), a n d controls (n = I 1,434). Rates of obstetrical intervention a n d indices o f maternal a n d neonatal morbidity were d e t e r m i n e d a n d analyzed by ANOVA with Dunnett's Test for Multiple Comparisons, Z2 a n d Fisher exact test. RESULTS: Women with GHTN h a d an induction rate (GHTN 69.2%, PE 79.4%, CHTN 72.7%, controls 37.5%; P < .0001) a n d caesarian section rate (GHTN 21.6%, PE 32.1%) CHTN 26.7%, controls 13.8%; P < .0001) similar to that of women with PE and CHTN a n d almost double that of controls. The length of labor, incidence of p o s t p a r t u m h e m o r r h a g e a n d length o f postpartum stay were greater for women with GTN than controls. There was no difference in the clinical diagnosis of IUGR a n d fetal birth weight between the G H T N a n d control groups. Fetal birth weight was only decreased in women with PE and CHTN (CHTN 3375 ± 579 g, G H T N 3461 ± 506 g, PE 3285 ± 577 g, controls 3500 ± 498 g; P < .0001). There was no difference in umbilical artery pH or base excess between any of the groups. Neonatal intensive care (NIC) involvement was increased in the GHTN a n d PE groups. CONCLUSIONS: Women with GHTN had obstetrical intervention rates m u c h h i g h e r than controls a n d similar to those with PE a n d CHTN. Obstetrical intervention increased maternal morbidity a n d NIC involvement significantly but other markers of neonatal/fetal morbidity were similar to the control population. While G H T N requires h e i g h t e n e d surveillance o f maternal a n d fetal well-being, it may n o t require aggressive obstetrical intervention.

0218

T H E INFLUENCE O F GESTATIONAL AGE O N T H E EFFECWIVENESS O F LOW-DOSE ASPIRIN F O R T H E PREVENTION O F HYPERTENSIVE DISEASE AND G R O W T H REffIIUCTION IN PREGNANCY Barbara Hogg, MD, for the NICHD MFMU Networki; INICHD, MFMU Network, Bethesda, MD OBJECTIVE: To determine whether initi ring daily aspirin (ASA) therapy (60 rag) at a n earlier gestational age (GA) influences the s u b s e q u e n t development of severe pregnancy-induced hypertension (PHI), preeclampsia (PE) or intrauterine growth restriction (IUGR). STUDY DESIGN: This retrospective analysis included d a t a f r o m two multicenter, double-blind, randomized trials designed to determine whether ASA prevents PE in healthy nulliparons women a n d in women at high risk. Women with hypertension a n d / o r proteinuria at baseline were excluded. The primary outcome o f interest was the subsequent development of severe PHI, PE, or IUGR. Women were g r o u p e d based on the GA at randomization. Data were analyzed in Z2 a n d Cochran-Mantel-Haenszel analysis with P < .05 considered significant. RESULTS: O f 4598 women evaluated, 515 (11%) developed P H I / P E a n d 262 (6%) developed IUGR. Maternal demographics were similar between t h e ASA a n d placebo groups. Aspirin therapy did n o t influence the suhev~'quent d e v e l o p m e n t of P I H / P E o r IUGR in w o m e n stratified b a s e d o n GA at enrollment. C O N C L U S I O N : Aspirin therapy does n o t decrease the rate o f severe P I H / P E or IUGR regardless of the GA at initiation.

ns ns .003

mean ± sd, *median, (range)

0216

LONG-CHAIN 3 HYDROXYACYL-COA DEHYDROGENASE DEFICIENCY IS U N C O M M O N IN PREGNANCIES COMPLICATED BY FULL/PARTIAL H E L L P SYNDROME O R ACUTE FATTY LIVER O F PREGNANCY Jeffrey Livingston, MD I, J o h n Barton, MD 2, Vicki Park, MD 1, Bassam Haddad, MD 1, Bill Mabie, MD I, Baha Sibai, MDB; ¿University of Tennessee Health Sciences Center, O b / G y n , Memphis, TN; 2Central Baptist Hospital, Antenatal Diagnostic Division, Lexington, KY; 3University of Tennessee Health Sciences Center, Memphis, TN I N T R O D U C T I O N : A mutation in the long-chain 3 hydroxyacyl-CoA d e h y d r o g e n a s e (LCHAD) g e n e has b e e n linked to acute fatty liver of pregnancy (AFLP) a n d elevated liver enzymes in HELLP syndrome (Ibdah, NEJM 1999). LCHAD acts within the mitochondrial beta-oxidation pathway. A fetal/maternal interaction may be responsible for maternal liver pathology. OBJECTIVE: To determine the G1528C mutation frequency in maternal a n d fetal samples in pregnancies complicated by full/partial HELLP syndrome or AFLP. METHODS: Maternal (n = 36) a n d fetal (n = 17) samples were obtained from pregnancies with maternal AST > 72 U / L . Two patients h a d AFLP. Thirtyfour h a d partial (n = 14) or full (n = 20) HELLP syndrome. DNA was extracted a n d PCR-RFLP was p r e f o r m e d . Genotypes were d e t e r m i n e d by gel electrophoresis. RESULTS: No maternal or fetal samples h a d the G1538C mutation in LCHAD. See table for padent characteristics. CONCLUSION: The G1538C LCHAD mutation is an u n c o m m o n cause of elevated liver enzymes in pregnancy. Contrary to previous reports, screening women or fetuses b o r n to women with HELLP/AFLP for LCHAD mutations is not r e c o m m e n d e d . MAP

(MMHG) Mean ± s d Range

AST (U/L)

130 ± 17 2 7 8 ± 3 9 3 8 9 - 1 7 3 72-2026

LDH (pMOL/L)

PLATELEWS (109/L)

DELIVERY G A (W]KS)

1714 ± 2134 208-12,000

85 ± 57 17-233

31.0 ± 5,2 22-40

P I H / P E (%) ASA Placebo IUGR (%)

ASA Placebo

13-16W6D (N = 1050)

17-19W6D (N = 1129)

20-26W (N = 24S9)

14 15

10 II

9 II

.1

5 6

6

6 6

.3

7

P

$74 SMFM Abstracts 0219

January 2001 Am J Obstet Gynecol

IN PREECLAMPSIA, MACROPHAGES MAY INDUCE TROPHOBLAST IN THE PLACENTAL BED BY DECREASING TRYPTOPHAN CONCENTRATION Frank Reister l, Berthold Huppertz°-,John C.P. Kingdom ], Kiaus Marzusch s, Peter Ruck 4, Weruer Rath 5, Peter Kaufmann 2, Haus-Georg Frank2; tUniversity of Toronto, Obstetrics & Gynecology, Toronto, Ontario: 2University of Technology Aachen, Medical Faculty, Anatomy, Aachen; SUniversity of Tuebingen, Obstetrics and Gynecology, Tuebingen; 4University of Tuebingen, Pathology, Tuebingen; 5University of Technology Aachen, Medical Faculty, Obstetrics and Gynecology, Aachen OBJECTIVE: In situ data provide a hint on macrophage-induced trophoblast apopto*is in preeclampsia (PE), resulting in reduced trophoblast invasiveness. In addition there is in vitro evidence for the impact of tryptophan starvation on induction of apoptusis of extravillous trophoblast hybrid cells as well as for degradation of tryptophan by macrophage-derived Indoleamine 2,3dioxygenase (IDO). Therefore we asked (a) if macrophages might be involved in tryptophan-associated apoptosis of extravillous trophoblast and (b) if changes in cytokine environment might provide activating mechanisms. STUDY DESIGN: (a) The effect of tryptophan supplementation on apoptosis (TUNEL test and nuclear morphology) was studied in a co-culture model (extravillous trophoblast hybrid cells/macrophages). (b) In the placental bed of both PE patients as well as healthy pregnant women (each: n = 6) the distribution of uterine natural killer (NK)-cells was investigated immunohistochemically. RESULTS: (a) The incidence of trophoblast apoptosis was significandy reduced by supplementation of tryptophan in a dose-dependent manner. (b) PE patients showed significandy higher numbers of NK-cells in non-invaded decidua compared to healthy pregnant women. In well-invaded decidua no such differences could be demonstrated. CONCLUSION: (a) Macrophages may decrease trophoblast inva-siveness by secretion of IDO, resulting in tryptophan starvation and trnphoblast apoptosis. This may contribute to iusufficient endovascular trophoblast invasion in PE. (b) NK-cells in the decidua of preeclamptic patients may stimulate IDO secretion in placental bed macrophages via interferon-'/.

0221

ANGIOTENSINOGEN T235 EXPRESSION IS ELEVATED IN FETAL LIVER Francis Song I. Terry Morga n2, Lesa Nelson ~, Kenneth Ward't: [University of Utah, CAMT, Perinatal Genetics Lab, Salt Lake, UT; 2Stanford University, Department of Pathology, Stanlord, CA: -aUniversity of Utah, CAMT, Perinatal Genetics Lab, Salt Lake City, UT; 4University of Utah, Obstetrics and Gynecology & Human Generics, Salt Lake City, UT OBJECTIVE: The T235 variant of angiotensinogen (AGT) is associated with elevated AGT expression in vitro and locally in vivo. It has been suggested that over-expression of angiotensinogen may play an important role in the pathogenesis of pregnancy-induced hypertension. Most circulating AGT is synthesized in the liver, but allele-specific hepatic production has not been examined to date. We hypothesized that there would be relatively elevated expression ofT235 compared to the M allele in the livers of heterozygous fetoses. METHOD: Using an [RB approved protocol, 108 fetal liver samples were obtaioed from normal first or second trimester, electively terminated abortuses. Fetal genomic DNA was extracted from the liver samples and T235/M235 genotypes were determined by mutagenically separated polymerase chain reaction. Fifty-four of 108 (50%) were heterozygotes. Total RNA ~¢as extracted from the 54 heterozygotic fetal liver homogenates using TRI-REAGENT. AGT-Ex2 and AGT-Ex3 primers were used to perform RT-PCR. An allele-specific ligation assay was used to quantitatively analyze the AGT expression. We then compared log T235/log M235 in the cDNA to log T235/log M235 in tile genomic DNA controls using the Nonparametric Wilcoxon Signed Rank Test. RF.SULTS: All fetal livers showed AGT expression (from 6 to 18 weeks' gestation). The T235/M235 ratio was significantly increased in the RNA compared to the matched genomic DNA controls. CONCLUSION: In heternzygous individuals, T235 is preferentially expressed in the liver compared to M235. These allele-specific differences in expression may explain the higher circulating angiotensinogen levels in individuals who are homozygous for T235. The implications of elevated prenatal expression need to be explored.

INCRF2tSF.,D ER~rHROCY'rE ADHESIVENESS/AGGREGATION IN THE PERIPHERAL VENOUS BLOOD OF WOMEN WITH PREGNANCY IND U G K U HYPERTENSION Ronni Gamzu l, Ariel Many l, David Pauzner I, Abraham Berliner 2, Rivka Rotstein 9, Renato Fusman 2, Joseph Lessing j, Michael KupfermincS; tTel Aviv Sourasky Medical Center, Lis Maternity Hospital, Tel Aviv; ITel Aviv Sourasky Medical Center, Internal Medicine D, Tel Aviv; STel Aviv University, Obstetrics and Gynecology, Tel Aviv OBJEL-WIVE: We have adopted a simple slide test and image analysis to reveal the state of erythrocyte adhesiveness/aggregation (EAA) in the peripheral blood of women with pregnancy induced hypertension (PIH) as well as in matched controls. b-WUDY DESIGN: We recruited 25 pregnant women with PIH. Age- and gestadonal age-matched 25 normotensive volunteers rook part in the study and served as controls. Blood smears were evaluated by an image analysis system (INFLAMET). Quantitative measures of erythrocyte aggregation were used to describe the state of erythr(myte adhesiveness/aggregation such as vacuum radiue, ( V R ) which measures the spaces between the aggregated erythrocytes. ~'I'S: A significant (P= .002) increment in the state of EAA was noted in the study group as opposed to the controls, the VR values being 16.1 + 1.3 and 10.3 ± 1,9, respectively. Erythrocyte sedimentation rate but not fibrinogen concentration was significandy elevated in the study group. The increased aggregation correlated significantlywith fibrinogen concentration, systolic and diastolic blood pressures. CONCLUSIONS: We observed increased aggregability of red blood cells in hypertensive conditions of pregnancy. Our findings are significant in that they reveal blood pressure related increment in red cell adhesiveness/aggregation despite there being no significant increment in clotable fibrinogen concentrations.

0222

OF A RANDOM PROTEIN TO CIEF~TININE RATIO AS A PREDICTOR OF SIGNIFICANT PROTEINURIA Diana Rodriguez-Thompson, MD l, Ellice Lieberman, MD~; IBrigham and Women's Hospital, Mammal Fetal Medicine, Boston, MA; 2Brigham and Women's Hospital, Boston, MA OBJECTIVE: To evaluate whether a random protein to creatinine ratio (P:C R) is a clinically useful predictor of significant proteinuria (SP) (300 m g / 2 4 hours). STUDY DESIGN: The medical records of 104 women who completed both a P:C R and a 24-hour urine collection for evaluation of preeclampsia were reviewed. All random samples were collected prior to the 24-hour urine collection. The sensitivity and specificity of the P:C R as a predictor of SP was determined using a range of cutoffs. RESULTS: Forty-five percent of the study population had SP. The data suggests that a level below 0.16 ruled out SP. The best cutoff of >/0.19 yields a sensitivity of 91% and a specificity of 70%. Two thirds of the false + ranged from 250 to 300 mg protein while all of the false negatives were below 400 mg. • CONCLUSIONS: The P:C R is strongly associated with SP. A level below 0.1B can rule out SP. With further study, the P:C R may represent a simpler method for detecting SP.

APOPTOSIS

0220

ROC Crave for R a n d o m P:.¢ fl81~o em a Predictor o f S P

i+i I 0" o+,.

ConViction between 24 hourTPE and R a n d o m P:C R a t i o *

* LI 1.~3

1.14 FIIse

TreePodqvm •

"

0.SS Pmltlwe 0.7S Tree

" °

• •

•

0~7 Nega~ivm

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0 0.1 0.2 0.3 0.4 0.8 0.6 0.7 0.8 0.9 1

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. . . . . . . o ,iramo~ra4mll~. m4 ~ll i0oim -,i~,I~ al0otim 24 hourTotal Protein Excretion ~8 b'ue pmlttve outlers not shown

SMFM Abstracts S75

V o l u m e 184, N u m b e r 1 Am J Obstet Gynecol 0223

UNBOUND A C T M N A, INHIBIN A, AND FOLLISTATIN IN SERUM AND URINE OF WOMEN WITH PREECI..AMPSlAJeanne O'Brien, MD I, Patrick Sluss. PhD 2, Teresa Woodruff, P h D '~, Eileen Wang, MDI; INorthwestern University, Obstetrics and Gynecolog3,, Chicago, IL; '-'Massachmetts General Hospital, Reproductive Endocrine Unit, Boston, MA; 3Northwesteru University, Neurobiology and Physiolog); Evanston, IL OBJECTIVE: Activin and inhibin hm'e recently been examined ,as markers for preeclampsia. However; neither u n b o u n d activin A (UactA), the biologically active form, not" follistatiu (FS), a protein that binds a n d neutralizes the bioactivity of UactA, have ever been studied in preeclampsia. We investigated if UactA a n d inhibin A are iocre~tsed in term preeclampdc patients a n d e x a m i n e d the relationship between serum c o n c e n t r a t i o n s of UactA, inhihin A, FS, a n d urinal y FS. STUDY DESIGN: Using a case-control design, we compared patients with preeclampsia and norlnotensive controls with respect to their serum levels of UactA, inhibin A, FS, and urinary. FS. Patients were term, nulliparons with singleton pregnancies who presented at the hospital before tile onset of labor. Women with underlying medical conditions or fetal abnorumlities were excluded. The diagnosis of preeclampsia required standard blood pressure criteria a n d new onset proteinuria > 100 m g / d L . Serum concentrations of UacLA a n d inhibin A were measured ruing ELISA assays and total FS in serum a n d urine by a double-antibody, competitive RIA. Statistical analyses of normally distributed UactA, inhibin A, FS, a n d urinary FS were p e r f o r m e d using parametric tests. RESULTS: Fifteen women with preeclampsia were identified and matched for gestational age and parity with 1.5 controls. Mean UactA a n d inhibin A levels were significantly elevated in preeclamptic patients compared to controls (8644 ± 3818 p g / m L versus 2362 ± 872, P= .000 and 1991 ± 1656 p g / m L versus 801 ± 532, P = .012). The mean serum and urine FS levels were not statistically difli~rent between the two groups. CONCLUSION: UactA, the biologically active form, and inhibin A are both elevated in term preeclamptics c o m p a r e d to gestational age matched controls. These statistically significant results have potential clinical significance. In the future, UactA a n d inhibin A may help identify term preeclamptics before the classic signs of disease.

0225

LIPIDE PEROXIDATION AND TOTAL PEROXYL RADICAL-TRAPPING ABILITY OF UMBILICAL VENOUS B L O O D PLASMA IN NORMAL PREGNANCY AND PREECLAMPSIA Yoon Kim YHK I , Bong Ahn '2, Tae-Bok SongS,Ji ByunS; I C b o n n a m National University Medical School, O b / G y n , Kwangju; -°Chonnam National Univerity Medical School, Biochemistry, Kwangju; 3Chonnam National University Medical School, O b / G y n , Kwangju OBJECTIVE: O u r purpose was to investigate lipid peroxides levels a n d total peroxyl radical-trapping antioxidative p a r a m e t e r (TRAP) of umbilical venous blood plasma in normal pregnancy a n d preeclampsia. STUDY DESIGN: Lipid peroxides levels of umbilical v e n o m blood plasma in nornaal pregnancy (n = 20) a n d preeclampsia (n = 16) were measured by thiobarbituric acid reaction. The TRAP of umbilical v e n o m blood plasma was analyzed in 28 women with normal pregnancies a n d 16 pregnant women with preeclampsia. The TRAP value of amniotic fluid was measured by Wayner's method, although some reaction conditions were modified. RESULTS: Lipid peroxides levels of umbilical venous blood plasma in women with preeclampsia were significantly higher than those in women with normal pregnancy (10.03 ± 4.30 vs 5.85 ± 2.47 n m o l / m g protein, P < .01). TRAP values of umbilical venous blood plasma were f o u n d to increase progressively with advancing normal p r e g n a n c y d u r i n g 26 to 41 weeks' gestational age (n = 28, r= .72, P< .01 ). TRAP values of umbilical venous blood plasma in women with preeclampsia (n = 20) were significantly lower than those in women with gestational age-matched normal pregnancy (n = 16) (0.45 ± 0.07 vs 0.39 ± 0.06 mMoI/L, P< .05). CONCLUSIONS: We suggest that the imbalance of increased lipid peroxidation and decreased antioxidant activity in placenta is involved in the pathogenesis of preeclampsia, and it may also have effects on the antioxidant status of the fetus.

0224

VEGF GENE EXPRESSION IS INCREASED IN THE DECIDUA OF PRETERM PREECLAMPTIC PATIENTS Matthew Kim, MD t, Maryam Tarsa, MD 2, Thomas Moore I, Ljubica BOGIC, PhDS; IUniversity of California, San Diego, Reproductive Medicine, San Diego, CA; '-'University of California, San Diego, Reproductive Medicine, San Diego, CA; SUniversity of California, San Diego, Reproductive Medicine, San Diego, CA OBJECTIVE: Vascular endothelial growth factor (VEGF) is a multifunctional cytokine expressed in h u m a n fetal m e m b r a n e s t h r o u g h o u t normal pregnancy. O u r previous reports have noted a differential regional expression of VEGF in the maternal decidua of patients with p r e t e r m premature rupture of membranes. The objective of this study was to quantify the level ofVEGF mRNA expression in preterm pregnancies with preeclampsia but without complicating preterm labor or rupture of membranes. STUDY DESIGN: Full-thickness membranes were obtained from patients delivering preterm by c-section either with preeclampsia (n = 10) or without (n = 8). These patients were delivered for indications not related to labor, rupture of membranes or overt chorioamnionitis. Membranes were sampled from two regions: near the site of placental attachment a n d in a more distal region. Quantitative in situ hybridization was p e r f o r m e d to determine the level of VEGF expression. Student t test a n d two factor ANOVA were used for statistical comparison. RESULTS: VEGF mRNA expression in the maternal decidua was significandy greater in preeclamptic patients compared to controls (563 ± 20 FR vs 248 ± 13 FR, P < .000001 ). A differential regional expression of VEGF mRNA with distal zone greater than proximal peri-placental zone was observed in control patients (P< .0045) but not in the preeclampsia group. CONCLUSION: This study provides evidence of an abnormality in VEGF gene expression in the decidual layer of pregnancies complicated by preterm preeclampsia. Elevated VEGF expression, which is a hypoxia-inducible cytokine, suggests a potential role o f the d e c i d u a in the pathogenesis of preeclampsia. We speculate that the high decidual VEGF mRNA expression may be a reflection of dysregulation of placental hypoxia inducible factor associated cytokine activity.

0226

NITRIC OXIDE OF THE UTERINE, UMBILICAL, AND ANTEGI.~ITAL VENOUS BLOOD IN WOMEN WITH PREECLAMPSIA Yoon Kim YhkI,jongUn Lee 2, Tae-Bok SongS,Ji ByunS; IChonnam National University Medical School, O b / G y n , Kwangju; 2Chonnam National University Medical School, Physiology, Kwangju; SChonnam National University Medical School, O b / G y n , Kwangju OBJECTIVE: The aim of this study was to measure circulating levels of nitric oxide metabolites (nitrites) in the uteroplacental, fetoplacental, a n d peripheral circulation in women with normal pregnancy a n d preeclampsia. STUDY DESIGN: Sixteen women with preeclampsia were compared with 10 women with normal pregnancy. At cesarean, blood samples were taken from the antecubital vein a n d uterine vein draining the placental site before delivery of the baby, a n d the umbilical vein after delivery of the baby. Plasma nitrites were measured using the Greiss reaction after conversion of plasma nitrates to nitrites using nitrate reductase. RESULTS: Nitric oxide metabolites were significantly higher in the uterine venous b l o o d plasma a n d umbilical venous b l o o d plasma o f w o m e n with preeclampsia c o m p a r e d with those of normal pregnancy (85.0 ± 31.8 vs 42.9 ± 22.1 m m o l / L , P < .01,122.6 ± 75.0 vs 41.2 ± 19.4 mMol/L, P < .01). There was no significant difference in nitric oxide metabolites of the antecubital venous blood plasma between w o m e n with n o r m a l p r e g n a n c y a n d p r e e c l a m p s i a (178.2 ± 67,9 vs 223.0 ± 84.2 m m o l / L , P = NS), But, nitric oxide metabolites of the antecubital v e n o m blood plasma in women with severe preeclampsia (n = 8) were significantly h i g h e r than those in w o m e n with n o r m a l p r e g n a n c y (282.1 ± 54,5 vs 178.2 ± 67.9 mMol/L, P < .01). CONCLUSIONS: We observe higher levels of nitric oxide metabolites in the uteroplacental, fetoplacental, a n d peripheral circulation in women with preeclampsia than in normal pregnancy. We suggest that these increased nitric oxide metabolites may be results of a compensatory mechanism against the pathologic effects of preeclampsia.

$76 SMFM Abstracts 0227

T-12.1~.IJ. ZETA CHAIN EXPRESSION IN WOMEN W I T H P R E E ~ S I A COMPARED T O N O R M O T E N S I V E P R E G N A N T C O N T R O L S Paul W h i t e c a r l, Kim Boggess2, Michael McMahon 2, J o h n T h o r p , J r 2, Douglas TaylorS; ]University of North Carolina at Chapel Hill, Department of Obstetrics a n d Gynecology, Chapel Hill, NC; 2University of North Carolina at Chapel Hill, D e p a r t m e n t of Obstetrics a n d Gynecology, Chapel Hill, NC; SUniversity of Louisville School of Medicine, D e p a r t m e n t o f Obstetrics a n d Gynecology, Louisville, KS' OBJECTIVE: An immunlogical etiology of preeclampsia has long been suspected. T-cell CI~3 zeta plays a critical role in signal transduction ofT-helper cells. Recent studies have shown that a soluble circulating factor produced in p r e g n a n c y decreases T-cell zeta chain production. The resulting T-cell suppression may play a role in protection of the fetal allograft. The aim of this study is to investigate the modulation ofT-cell zeta expression by sera of pregnant women with preeclampsia c o m p a r e d to normotensive controls at term. STUDY DESIGN: Sera obtained at 24 to 28 weeks' gestation from 16 nulliparous women who later developed preeclampsia a n d 32 normotensive, gestational a g e - m a t c h e d controis were incubated with 100 Z e t a C h a i n Expression * cultured T cells that possess a functional T c R / CD3 complex. Cell lysates 80 were analyzed for CD-3 I [ Zeta chain expression by '~ 6 0 I Western immunoblotting a n d quantified by densit- = ometry. Results were ~ 4 0 • c o m p a r e d by the rank- nO sum test for differences between groups. 20 ~TS: CD-3 Zeta chain suppression a m o n g • w o m e n with preeclamp0 • sia was significantly lower Controls Preedamptics c o m p a r e d to n o r m o t e n sire p r e g n a n t controls (P< .0001). CONCLUSIONS: Nulliparous women who develop preeclampsia exhibit less suppression of T-cell zeta chains than normotensive controls. This appears to o c c u r long before clinical evidence of disease a n d suggests an i m m u n e d e r a n g e m e n t as a n etiologic factor in preeclampsia. S u p p o r t e d by g r a n t NICHD-HD28684.

0228

ROLES O F NITRIC OXIDE AND POTASSIUM CHANNELS IN T H E VASCULAR EFFECT O F V A S O P ~ IN PREGNANCY Mohammad Anwar I , Eva Fulep 2, Yuri Vedernikov 1, G e o r g e Saade t, Robert Garfieldl; IUniversity of Texas Medical Branch at Galveston, O b / G y n , Galveston, TX; 2Univiersity of Texas Medical Branch at Galveston, O b / G y n , Galveston, TX OBJECTIVE: To determine the roles of nitric oxide (NO) a n d potassium channels in the effect ofvasupressin (VP) on the isolated aorta from pregnant rats~ STUDY DESIGN: Aortic rings (with a n d without endothelium) from late p r e g n a n t Sprague-Dawiey rats (day 21, n = 6) were m o u n t e d for isometric tension recording in 10 m L organ baths containing modified Krebs-Henseleit solution (5% CO9 in air, p H o f 7.4, at 37°C, optimal resting tension 2 g). Cumulative concentration response curves toVP (10-H to 10"e M) were obtained in the absence a n d presence of NG-ultro-L-arginine methyl ester (L-NAME, 10-4 M), i n d o m e t h a c i n (INDO, 106 M), gfibenclamide (GLIB, 4 x 10-6 M), tetrabutylammonium (TBA, l 0 s M). Effects of V1 (10"6 M), V2 ( l o s M) a n d V2 plus L-NAME antagonists on responses to VP in aortas with intact endothelium were also examined. Responses were expressed as % of reference tension to 60 mM KCI. One-way ANOVA was used for analysis (significance: P < .05). R]g~LILTS.. TBA a n d L-NAME, but not INDO or GLIB, e n h a n c e d the VP• i n d u c e d increase in tension in intact vessels. In d e n u d e d vessels, only TBA significantly e n h a n c e d the effect o f VP. The response to VP in the presence of TBA was n o t significantly different in intact versus e n d o t h e l i u m - d e n u d e d rings. Initial application o f TBA a n d L-NAME resulted in rise in tension o f arteries in the two,sets of experiments. Contractions to VP were obtained in the presence o f the V'2 antagonist, but not in the presence o f V1. CONGt,USION: VP acts through the V1 receptor to increase vasomotor t o n e in the isolated aorta o f p r e g n a n t rats, an effect that is attenuated by the endothelium-derived nitric oxide, a n d possibly by hyperpolarizatlon of the smooth muscle by the calcium-gated a n d inward rectifier potassium channels. This knowledge may have clinical implication in preeclampsia, a condition with known increase in vascular response to VP.

J a n u a r y 2001 AmJ Obstet Gynecol

0229

0230

REPEAT POSTPARTUM MAGNESIUM SULFATE ADMINISTRATION FOR SEIZURE PROPHYLAXIS: IS THERE A PATIENT PROFILE PREDICTIVE OF NEED F O R ADDITIONAL THERAPY? ChristT lsler, MD t, P. Barfilleaux, MD 2, Brian Rinehart, MD I, Everett Magann, MD -s, J a m e s Martin, Jr, MD4; IUniversity of Mississippi Medical Center, D e p a r t m e n t of Obstetrics and Gynecology Jackson, MS; 2University of Mississippi Medical Ceuter, O b / G y n Div. of MFM, Jackson, MS; SUniversity of Mississippi Medical Center, D e p a r t m e n t of Obstetrics a n d Gynecology, Jackson, MS; "tUniversity of Mississippi Medical Center, Graduate Medical Education,Jackson, MS OBJECTIVE: To profile patieuts with hypertensive disorders of pregnancy whose p o s t p a r t u m disease worsens a n d reinstitution of magnesium snlfate therapy due to exacerbation of disease is required. STUDY DESIGN: A prospective clinical trial utilizing clinical symptoms a n d signs to signal safe cessatiou of intravenous magnesimn stdfate postpartum in gravidas diagnosed with preeclampsia, eclampsia, a n d HELLP syndrome. Patients who r e q u i r e d reinstitution of m a g n e s i u m sulfate therapy d u e to exacerbation of b l o o d pressure (sustained blood pressure > 160/110) associated with headache or visual changes are profiled. RESULTS: Five-hundred three patients were enrolled a n d classified according to hypertensive disease using ACOG criteria. Thirty-eight patients (7.6% of total) required reinstitution of magnesium sulfate therapy for 24 hours. No patieut with eclampsia required reinstitutlon of seizure prophylaxis c o m p a r e d with 6.3% (18/284) o f patients with mild preeclampsia, 5.7% (6/105) with severe preeclampsia, 18.0% (11/61) with chronic hypertension with superimposed preeclampsia, a n d 6.7% (3/45) with HELLP syndrome. Patients who required reinstitution of magnesium therapy, when compared with patients r e q u i r i n g no additional therapy, had a significantly lower gestational age (32.4 + 4.3 versus 36.3 ± 4.2 weeks respectively, P < .001), a higher mean arterial pressure during their initial magnesium course (113.2 ± 11.2 versus 105.6 ± 11.2, mm Hg, P < .001), and a longer initial postpartum course of magnesium prophylaxis (11.2 :t 13.4 versos 6.7 ± 7.5 hours, P= .049). C O N C L U S I O N : Suboptimal candidates for a clinically d e t e r m i n e d duration of postpartum m a ~ l e s i u m sulfate seizure prophylaxis course include patients with chronic hypertension with superimposed preeclampsia, patients delivered at less than 34 weeks' gestation a n d patients with l o n g e r initial periods of disease resolution.

FIRST TRIMESTER MATERNAL SERUM URIC ACID, LIPIDS, LIPOPROTEINS AND OBESITY IN RELATION T O T H E RISK O F PREECLAMPSIA. Michelle Williams, ScD 1, David Luthy, MD 1, Cuilin Zhang, MD I, Irena King, PhD 2, Daniel Welsh, MPH l, Tanya Sorensen, MDt; ISwedish Medical Center, Center for Perinatal Studies, Seattle, WA; ~Fred Hutchinson Cancer Research Center, Public Health Sciences, Seattle, WA OBJECTIVE: Metabolic anomalies, including hyperuricemia, dyslipidemia a n d obesity are observed in p r e g n a n t women with preeclampsia (PE). The relationship o f these characteristics with the o c c u r r e n c e o f PE, however, remains uncertain. We studied the association of maternal first-trimester serum uric acid (UA), lipids, a n d obesity with file risk of PE. STUDY DESIGN: From a prospective cohort of 449 women, we studied 24 women with PE a n d 241 who remained normotensive t h r o u g h o u t pregnancy. Serum UA, lipid a n d lipoprotein concentrations were measured using samples collected at an average of 13.2 gestational weeks. RESULTS: Mean serum UA a n d triglyceride (TG) concentrations were 10% a n d 25% higher, respectively a m o n g PE cases as c o m p a r e d with normotensive subjects. Cases h a d 10% lower mean high density lipoprotein (HDL) c o n c e n t r a t i o n s than normotensive women. In univariate analyses, women with UA concentrations > 3.1 m g / d L experienced a 3.2-fold increased risk of PE (95% confidence interval [CI] 1.3 to 7.7). Elevated serum TG (> 93.0 m g / d L ) was associated with a 5-fold increased risk of PE (95% CI 1.7 to 15.1); high HDL (> 67.1 m g / d L ) was associated with an 80% reduced risk o f P E (RR = 0.2; 95% CI 0.1 to 0.6). Maternal pre-pregnancy obesity (body mass index [BMI] > 22 k g / m 2) was associated with a 7-fold increased risk (95% CI 2.0 to 24.2). In a multivariate logistic regression model, only maternal obesity (RR = 3.6; 95% CI 1.0 to 13.4), a n d elevated TG (RR = 3.2; 95% CI 1.0 to 13.3) remained statistically significant risk factors of PE. Although the association between PE risk a n d serum HDL was only slightly attenuated, the RR did not reach statistical significance (RR = 0.4; 95% CI 0.1 to 1.2). In the multivariate model, the RR for UA was greatly attenuated (RR = 1.4; 95% CI 0.5 to 3.8). C O N C L U S I O N S : O u r results suggest that obesity a n d hypertriglyceridemia are i n d e p e n d e n t predictors of PE.

V o l u m e 184, N t t m b e r 1 Am J O b s t e t G y n e c o l 0231

ELEVATED FIRST TRIMESTER SERUM C-REACTIVE PROTEIN AND SUBSEQUENT RISK OF PREECLAMPSIA David Luthy, MD I, Michelle Williams, ScD '2, Cuilin Zhang, MD t, Scott Walsh, PhD :~, Daniel Welsh, MPH I, Tanya Sorensen, MDI; ISwedish Medical Center, Center fur Perinatal Studies, Seattle, WA; '-'Swedish Medical Ceute:', Center tor Perinatal Studies, Seattle, WA; 3Virginia Coinmnnweahh University, Richmond, VA OBJECTIVE: Elevations in p r o i u t l a m m a t o r y cytokines such as t u m o r necrosis l]tctor-Ot have been shown to be predictive of preeclampsia (PE) risk. These observations coupled with clinical a n d epidemiologic data suggest that inflammation may play a prominent role in the etiology of PE. High sensitivi~' assays for the acute-phase reactant C, reactive protein (hs-CRP) have been used to d e m o n s t r a t e that even mild elevations of this clinical m a r k e r of inflammation are predictive of vascular disease. We sought to d e t e r m i n e whether elevations of hs-CRP in the first trinaester are predictive of PE. STUDY DESIGN: We used a prospective study design to study maternal senun hs-CRP concentrations in 24 women who developed PE compared with 241 normotensive pregnant women. Study subjects were selected from a cohort of 449 women. Serum hs-CRP was measured using an immunoturbidimetrie

SMFM Abstracts S77 0

0233

~Lssay.

RESULTS: Mean serum c o n c e n t r a t i o n s of hs-CRP were significantly increased a m o n g w o m e n who developed PE as c o m p a r e d to those who remained normotensive (9.4 ± 1.8 vs 5.3 ± 0.4 rag/L, mean + standard error of mean, P = .031 ). The relative risk (RR) of PE for women in the u p p e r quartile of hs-CRP (> 5.7 rag/L) as compared with those in the lower three quartiles was 4.3 (95% confidence interv-al [CI] 1.8 to 10.0). Alier adjusting for c o n f o u n d i n g by maternal pre-pregnancy obesity, parity a n d a history of c h r o n i c hypertension, we found that an eles~tion of hs-CRP was associated with a 3.3told increased risk of PE (adjusted RR = 3.3; 95% CI 1.2 to 9.0). CONCLUSIONS: O u r results are consistent with findings indicating that chronic systemic inflammation precedes the clinical diahmosis of PE. Studies designed to identi~ the dete:aninants of chronic inflammation in pregnancy are warranted.

0232

A PROSPECTIVE STUDY O F MATERNAL DIETARY AND PLASMA FOLATE, VITAMIN BI2 AND HOMOCYSTINE STATUS IN RELATION T O PREECLAMPSIA RISK Tanya Sorensen, MD 1, M. Rene Malinow, MD 2, Cuilin Zhang, MD ], h'ena King, PhD -~, David Luthy, MDI, Michelle Williams, ScD4; tSwedish Medical Center, Center for Perinatal Studies, Seattle, WA; 2Oregon Regional Primate Research Center. Beaverton, OR; -SFred Hutchinson Cancer Research Center, Public Health Sciences, Seattle, WA; 4Swedish Medical Center, Center for Perinatal Studies, Seattle, WA OBJECTIVE: H y p e r h o m o e e s t i n e m i a in p r e g n a n c y is a risk factor for preeclampsia (PE). The relationship between dietary a n d plasma folate and vitamin BI2 status with the risk of PE, however, is less well characterized. We measured maternal first trimester plasma folate, vitamin B12, a n d homoeestine (tHee) in 24 women who developed PE a n d 241 normotensive women. We also studied the relation between PE risk a n d dietary folate intake using a foodfrequency questionnaire. STUDY DESIGN: A case-control study nested within a prospective cohort of 449 pregnant women. RESULTS: After adjusting for maternal parity a n d history o f c h r o n i c hypertension, low plasma folate (< 0.11 n m o l / L , the lowest quartile) was associated with a 66% increased risk of PE, though the relative risk (RR) did not reach statistical significance (95% confidence interval [CI] 0.6 to 4.6). The ,association was not as evident for dietary folate intake a n d PE risk. The relative risk of PE for women in the lowest quartile of dietary intake (< 185.4 lag/day) as compared to those in the u p p e r three quartiles was 1.3 (95% CI 0.4 to 4.1). There was some suggestive evidence of a weak association between low plasma vitamin B12 (< 292.0 p m o l / L ) a n d PE risk (RR = 1.6; 95% CI 0.6 to 4.1). Elevations in tHe e (> 6.5 lamol/L) were strongly related with PE risk. After adjusting for confounders, women with elevated tHee experienced a 4.1-fold increased risk of PE (95% Cl 1.4 to 12.1) as compared with those with lower values. CONCLUSIONS: These findings confirm the strong association between tHey a n d PE risk. O u r findings also suggest a tendency of slightly increased risk of PE a m o n g women with relatively low plasma a n d dietary folate. Although our results must be confirmed in a larger population, there is some suggestion that public h e a h h efforts to increase dietary a n d s u p p l e m e n t a r y intake of folate may serve to reduce the occurrence of PE.

0234

N I C O T I N E INHIBITS INTERCELLULAR A D H E S I O N M O L E C U L E EXPRESSION O N ENDOTI4E.I JAL CI~I J.q IN VITRO Paul Speer, MDt, Yan ping Zhang I, Yang Gu I, Yuping Wangl; ILSU Health Sciences Center, Obstetrics and Gynecology, Shreveport, LA OBJECTIVE: We previously reported that nicotine decreases leukocyte adhesion to uterine vascular endothelial cells (ECs) in vivo u n d e r ischemia conditions in p r e g n a n t rabbits. To f u r t h e r investigate the m e c h a n i s m of decreased leukocyte-endothelial adhesion by nicotine exposure, the effect of nicotine on EC intercellular adhesion molecule (IGAM) expression was • studied. STUDY DESIGN: ECs were isolated from h u m a n umbilical cord veins (n ='8) from normal pregnancies in non-smoking women immediately after delivery. The first passage of ECs was grown on 48 well/cell culture plates. When ECs were confluent, the cells were incubated in an absence or presence of nicotine at concentrations of 0.01, 0.1, 1.0, 10 a n d 100 IxM for 1 h o u r at 37"C C O 2 incuhator. Then, the expression of ICAM-1 was determined. All experiments were p e r l o r m e d in triplicate. The relative expression of ICAM-I was analyzed by Spectra Microplate A n : t r e a d e r at 450 nm. Data were expressed as mean of OD 450 + SE, and analyzed by ANOVA and Student-Newman-Keuls post-hoc test. A Pless than .05 was considered statistically different. RESULTS: 1) Nicotine at a lower concentration of 0.01 ltM had no effect on EC ICAM-1 expression compared to controls (0.19 + 0.04 vs 0.20 + 0.01), P = .614; 2) Nicotine at a higher concentration of 10 a n d 100 gM completely inhibited EC ICAM-I expression; 3) The inhibitory effect by nicotine on EC ICAM-I expression was in a dose-dependent m a n n e r between dose of 0.01 to 10 ~M: 0.19 ± 0.04 (0.01 ttM); 0.18 + 0.02 (0.1 gM, P= .005); 0.15 + 0.01 (1.0 taM, P< .0001 ); 0.01 + 0.01 (10.0p.M, P< .0001); 0.01 + 0.01 (100 gM, P < .0001) vs control, respectively. C O N C L U S I O N : Nicotine inhibits endothelial cell surface adhesion molecule expression of ICAM-1 in vitro. SPECULATION: The inhibitory effect of nicotine on endothelial adhesion molecule expression may affect the biological function of vascular endothelial cells during pregnancy a n d contribute to the lower incidence of preeelampsia in smoking women.

MA~AL FIRST-TRIMESTER PLASMA ~ C O I ( B I C ACID (VlT,O/IN C) CONCENTRATIONS IN R E I ~ T I O N T O RISK OF PREECLAMPSIA Cuilin Zhang, MD I, David Luthy, MD I, lrena King, PhD 2, Scott Walsh, PhD s, Tanya Sorensen, MD I, Mark Kestin, PhD 4, Michelle Williams, ScDI; tSwedlsh Medical Center, Center for Perinatal Studies, Seattle, WA; ~Fred Hutchinson Cancer Research Center, Public Health Sciences, Seattle, WA; SVirginia C o m m o n w e a l t h University, R i c h m o n d , VA; 4University o f Washington, Epidemiology, Seattle, WA; 5Swedish Medical Center, C e n t e r for Perinatal Studies, Seattle, WA OBJECTIVE: Oxidative stress plays a n i m p o r t a n t role in the pathophysiology of preeclampsia (PE). Vitamin C is known to function as a first-line antioxidant defense against oxidative stress by scavenging reactive oxygen a n d nitrogen species, as well as antioxidant-derived radicals. We sought to investigate t h e association of maternal first-trimester plasma ascorbic acid (AA) concentrations with the subsequent occurrence o f PE. STUDY DESIGN: Nested in a prospective cohort study, 24 w o m e n with proteinuric pregnancy-induced hypertension (PE) a n d 241 normotensive pregnant women (controls) were studied. Blood samples were collected at 13 gestational weeks on average. Samples were protected from ultraviolet light, kept on wet ice a n d processed within 50 minutes of phlebotomy. Plasma decanted into cryovials was preserved with metaphosphoric acid/dithiothreitol solution and frozen at -70°C until analysis. Plasma AA concentrations were determined using an enzymatic assay. RESULTS: Mean plasma AA concentrations were approximately 10% lower for cases than controls (58.1 vs 64.7 p.mol/L). T h e r e was n o evidence o f a linear trend in PE risk across successively lower quardles o f plasma AA concentrations (relative risks [RR] were 1.0, 0.7, 0.5, a n d 1.8, with the highest quartile as the referent). After adjusting for maternal smoking, pre-pregnancy obesity, parity a n d a history of c h r o n i c hypertension, w o m e n with AA c o n c e n t r a t i o n s in the lowest 10% of the p o p u l a t i o n d i s t r i b u d o n (< 48.8 ttmol/L) as c o m p a r e d to those with h i g h e r values, experienced a 3.1-fold increased risk of PE (adjusted RR = 3.1, 95% confidence interval 1.1 to 9.4). CONCLUSIONS: These early findings are consistent with the hypothesis that a n t i o x i d a n t status is a d e t e r m i n a n t o f PE risk. Studies that assess simultaneously maternal dietary a n t i o x i d a n t intake, as well as plasma a n d tissue enzymatic a n d non-enzymatic antioxidant status are warranted.

i

$78 SMFM Abstracts 0235

0236

.]anuary 200 I Am.] Obstet (,ynecol

VASCULAR RF.,ACTIVITY DURING PREGNANCY IN TRANSGENIC MICE LACKING E N D O T H E L I A L NITRIC OXIDE SYNTHASE Monica L o n g o I , Venu Jain'-', Lyn Mackay2, Yuri Vedernikov 2, Fabio Facchineni "~,George Saade e, Robert Garfieldt; I University of Texas Medical Branch at Galveston. O b / G y n , Galveston, TX; 2The University of Texas Medical Branch at Gah'eston, O b / G y n , Gah,eston, TX; 3UniversiD' of Modena, O b / G y n , Modena, Italy OBJECTIVE: To examine the effect of absence of a functional endothefial nitric oxide synthase (eNOS) on vascular reactivity during preguancy. STUDY DESIGN: Two-ram segments of aorta were obtained from nonp r e g n a n t and timed-pregnant (mid-pregnant day 14 a n d term day 19) female eNOS knockout mice (KO, C57BL/6J-NOS3 - / - from Jackson Laboratory) a n d age matched wild-t3pe controls (WT, NOS3 +/+) (n = 8-10 in each group). T h e rings were m o u n t e d in a small vessel m y o g r a p h for m e a s u r e m e n t of isometric force a n d responses to contractile a n d relaxant agents were stndied. Contractile responses were normalized to 60 laM KC1 contraction. Student t test was used for statistical analysis (P< .05 denoted significance). RESULTS: Contractile response to pheoylephrine (PE) was significantly increased in non-pregnant, mid-pregamnt a n d term KO mice compared to WT mice. In presence of NOS inhibitor L-NAME, PE responses were signiticantiy increased in all groups in WT but only at term in KO, and were greater in WT versus KO in mid a n d term pregnant, but not non-pregnant, animals. In rings contracted with PE, aeetylcholine produced relaxation in V(I" in contrast to a small contractile response in KO. Relaxant responses to nitric oxide (NO) d o n o r sodium nitroprusside were not significantly different in non-pregnant WT compared to KO mice, but were greater in KO c o m p a r e d to WT at mid and term pregnancy. In both groups relaxation by SNP was decreased at term compared to mid-pregnant3,. CONCLUSION: NO is the p r e d o m i n a n t endothelium-derit'ed relaxant in p r e g n a n t mouse aorta. Compensator), changes occur in the absence of eNOS a n d a p p e a r to be m o r e i m p o r t a n t d u r i n g p r e g n a n c y when additional NO production from other sources (inducible NOS) a n d an increase in response to NO occur. The role of eNOS a n d NO in vascular function is gestationally regulated.

0237

UTERINE CONTRACTILITY IN P R E G N A N T MICE LACKING AN INDUCIBLE NITRIC OXIDE SYNTHASE Monica L u n g o t, Weuu Jain 1, l.vn Mackay I, Ynri Vedernikov I, Fabio FacchinettF-', (;eorge Smlde 1, Robert Garfieidl; tUniversity uf Texns Medical Branch at (,alveston, O b / ( ; y n , Galveston, TX; '-'Univel~ity of Modena, O b / G y n , Modeua, hah' OBJECTIVE: To study the role of nitric oxide (NO)-cGMP svstem in the maintenance of uterine quiescence using transgenic mice lacking ~nl inducible NO synthase (iNOS). STUDY DESIGN: Uterine ring obtained from n o n p r e g n a n l (n = -I-6) and timed-preglmnt (n = 6-8, mid: day 14 and term: day 19) female iNOS knockout mice (KO, B 6 / 1 2 q F J N O S 2 - / - , Jackson Laboratory) a n d their wild-type controls (~,VI'. NOS2+/+) were motmted in organ chambers in Krebs solution for isometric tension recording. Uterine contractility was stimulated with o~'tocin ( 10-9 M) and the effects of cumulati`.,e concentrations of NO d o n o r sodium nitroprusside (SNP, I 1~ -10.4 M), cGM P analogue 8-hr-cGMP ( 1(I'~-10-t M). NOS substrate l,-arginine (10t;-10 -3 M), ATP-dependent K+-channel opener, pinacidil (10"s-10 "4 M), and Mg2 ÷ (2-16 raM) were studied. RESULTS: Responses to the agents studied were not significantly difli:rent in non-pregnant ~rI" and KO mice. At term. inhibition of uterine contractility by L-arginine. SNP and 8-br.-cGMP was decreased compared to mid gestation in WT but not KO. Effects of L-arginine and SNP were significantly greater in Mrl" compared to KO in mid-pregnanQ' and ",'ice versa at term. Effect of 8-hrcGMP was significantly greater in KO compared to WT at term. Inhibition lay pinacidil was lower; albeit not sigrfificantly, in p r e g n a n t c o m p a r e d to n o n p r e g n a n t KO and WT. Responses to Mg2* were not different berweerl the groups. C O N C L U S I O N S : The NO-cGMP system is present in the uterus in n o n p r e g n a n t and pregnant mice and is dowrn'egulated at term. Lack of iNOS during pregnancy is a~sociated with changes in NO production at'td sensiti`.'ity of the m y o m e t r i u m to NO a n d cGMP. The effects of ATP-depeudent K+channel and Mg2 + on uterine contl-actility are independent of iNOS.

VASCULAR EFFECT OF MAGNESIUM SULPHATE IN TRASGENIC MICE LACKING E N D O T H E L I A L NITRIC OXIDE SYNTHASE Monica L o n g o t, VenuJain I , Lyn MackayI , Yuri Vedemikov 2, Fabio Facehinetti s, George Saade L. Robert Garfieldl; IUniversity of Texas Medical Branch at Galveston, O b / G y n , Galveston, TX; 2University of Texas Medical Branch at Galveston, O b / G y n , Galveston, TX; SUniversity o f Modena, O b / G y n , Modena, Italy OBJECTIVE: To investigate the role of endothelial nitric oxide (NO) in the vascular effect of magnesium sulphate (MgSO 4) in pregnancy using mice lacking a functional endothelial nitric oxide synthase (eNOS). STUDY DESIGN: Two-ram segments of aorta were obtained from timedp r e g n a n t (mid-pregnant day 14, term day 19) female eNOS knockout mice (KO, C57BL/6J-NOS3 - / - from Jackson Laboratory) a n d their corresponding wild-type controls (WT, NOS3 +/+) (n = 4-6 in each group). The rings were mounted in a small vessel myograph for measurement of isometric tension. After pre-contraction with phenylephrine, relaxation responses to Mg2+ and voltage-gated Ca2+-channel blocker nifedipine were studied. Student t test was used for statistical analysis a n d P < .05 denoted significance. RESULTS: In rings c o n t r a c t e d with PE, relaxation by Mg2+ was significantly greater in WT compared to KO mice at mid-pregnancy, but was not significantly different between the two groups at term. In both WT and KO mice, Mg2+ responses were significantly decreased at term compared to midpregnancy. Responses to nifedipine were not significantly different between the various groups. CONCLUSIONS: T h e vasorelaxant effect of Mg2+ is gestational age d e p e n d e n t a n d decreases at term. A c o m p o n e n t of Mg2+ action in midpregnancy is N O d e p e n d e n t a n d may be absent at term. Voltage-gated Ca2+c h a n n e l activity is not altered by gestational age o r absence of eNOS expression. This may be an i m p o r t a n t consideration in w o m e n with preeclampsia, a condition characterized by endothelial dysfunction.

0238

THE SEVERITY OF PREECLAMPSIA AND THE TIMING OF DELIVERY INFLUENCES T H E SEVERITY AND RECURRENCY RATE OF PREECLAMPSIA A M O N G PRIMIPAROUS WOMEN WITH PREECLAMPSIA Offer Erez j , Doron Dukler, MD ], Asher Bashiri, MD'-', Boris Furman, MD'-', Moshe Mazor, MDI; ISoroka University Medical Center, Faeuhy of Health Sciences, BenG u r i o n University of the Negev, O b / G y n , Beer-Sheva; '-'Soroka University Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, O b / G y n , Beer-Sheva, OBJECTIVE: To evaluate the impact of the severity of preeelampsia and the time of delivery in the first pregnancy on its recurrence rate. METHODS: A population-based retrospective cohort study was designed: The study g r o u p consisted of 380 primiparous women with preeclampsia. The r e c u r r e n c e a n d severity of preeclampsia in subsequent p r e g n a n c i e s were evaluated a c c o r d i n g to the severity of preeclalnpsia and gestational age at delivery of the index pregnancy. RESULTS: In the study g r o u p 82% 1314/380) had mild preeclampsia, 17% (66/380) h a d severe preeclampsia, a n d there was 1 case (0.3%) of eelampsia. Primiparous with severe preeclampsia had a significantly higher rate of pretenn delivery than those with mild preeclampsia (34.4% vs 10.7% respectivel); P < .0001). Patients that developed preeelampsia in the second p r e g n a n c y h a d a significantly h i g h e r rate for its r e c u r r e n c e in later p r e g n a n c i e s [89% (76/85) vs 20% (50/240) respectively, P < .0001]. Primiparous patients with preeclampsia who delivered preterm did not have an overall higher risk for recurrence of preeelampsia. However, they h a d a significantly h i g h e r risk for m o r e than single r e c u r r e n t episode of preeclampsia in subsequent pregnancies [16% (9/54) vs 7.5% (24/320) P = .037, respectively]. Primiparous with severe preeclampsia had a significantly higher rate of severe preeclampsia in the second pregnancy in comparison to primiparous with mild preeclampsia [9.6% (5/52) vs 2.3% (6/263), P = .021; O R 4.56, 95% CI 1.15 to 17.78] CONCLUSION: 1. Primiparous women with preeclampsia that delivered preterm have a significantly higher risk to develop preeclampsia in more then o n e o f their s u b s e q u e n t pregnancies. 2. Primiparons women with severe preeclampsia had a significantly higher risk for preterm delivery and to have severe preeclampsia in their subsequent pregnancy.

SMFM Abstracts S79

\ ; o h m a e 184, N u m b e r I Am J Obstet Gvnecol 0239

0240

MATERNAL ECHOCARDIOGRAPHIC ALTERATIONS IN ASYMPTOMATIC 24 WEEKS UTERINE ARTERY BILATERAL NOTCHES H e r b e r t Valensise I. Barbara Vasapollo I, (_;iampanlo Novelli '2, Giovanni Larciprete I, Alberto Galante '2. Carlo Rolnaninil; IUoiversity of Rome Tor Vergata, Obstetrics and (;ynecolngQ; Rome, '-'UniversiW of Rome Tor Vergata, School of Cardiology, Rome OBJECTIVE: To identify the ntaternal cardiac a d a p t a t i o n throttgh a c o m b i n e d M-mode a n d Doppler intracardiac evaluation in a ldgh risk asynq)tomatic poptdation with hilateral ootcbes iu uterirte artery Doppler WaVeI~,)I'IUS. STUDY DESIGN: Ten patients nut of 128 consecutive beahhy normntensive bigh risk patients (7.8%) sbowed nterine artery bilateral notcbes a n d elevated resistance index (RI) at 24.2 ± 1.1 weeks of gestation. Maternal diastolic cardiac indices derived from transmitral a n d p u h n o n a r y vein [low pattern (Left Ventricular lsovolumetric Rel~L'~atitm Time [IVRT]), Deceleration time of the E wave [DtE]. E / A ratio, systolic, diastolic a n d reversal wave velocity of p u h n o n a r y vein flow), systolic cardiac fnnction (stroke vohnne, cardiac output, CO), total ~mscnlar resistance (TVR) and maximal and minimal left atrial area (LA max, LA rain) were calculated at the same time. Longitudinal clinical tollow-up was set up h)r all the patient.s. R.F.,SULTS: Four of 10 patients developed gestatinnal Itypertension. These patients showed at 24 weeks lower CO (3.4 ± 0.3 L/rain vs 6.0 ± 1.8 L/rain, P< .05); lower LA rain (7.6 ± 0.8 cm 2 vs 6.3 ± 0.9 cm'-', P < .05); higher IVRT (92.5 ± 6.4 msec vs 74.2 ± 6.6 msec, P< .001) tban the patients with bilateral notcbes and uneventful pregnancy. CONCLUSIONS: These preliminary data snggest tbat maternal e c b o c a r d i o g r a p h i c parameters m i g b t be altered in patients witb bilateral nntcbes in uteriue artery Doppler waveforms that will subsequently develop p r e g n a n c y complications. The absence of central cardiac adaptation might explain tbe differences in maternal outcome.

0241

MILD GESTATIONAL HYPERTENSION: RACIAL DII,'Iq~IRE,NCES ARE ASSOCIATED WITH ALTERED OUTCOMES IN WOMEN U N D E R G O I N G OUTPATIENT MANAGEMENT J o h n R. Barton, MDI,John M. O'Brien, MD 2, C. Brent Barton, MD I, Niki IC Bergauer, RN -~, Debbie L. Jacques, MPH "s, Baha M. Sibai, MD4; ]Centi'al Baptist Hospital, Perinatal Diagnostic Center, Lexington, Ix'Y; 2Central Baptist Hospital, Perinatal Diagnostic Center, Lexington, KY; ~Matria Healthcare, Clinical Research, Marietta, GA; 4University of Cincinnati, Obstetrics a n d Gynecology, Cincinnati, O H OBJECTIVE: To evaluate the impact of race on outcome in women with mild gestadonal hypertension. STUDY DESIGN: Nulliparuus women with mild gestadonal hypertension participating in an outpatient monitoring program beo,veen J a n u a r y 1995 and December 1999 were candidates. Patients had a singleton gestation < 37 weeks a n d were followed for a minimnm of 2 days as an outpatient. Maternal a n d perinatal outcomes were compared between groups by ANOVA a n d Pearson's X" analyses. RESULTS: 1182 women were included in the analysis. No differences in gestadonal age (GA) or incidence of proteinuria at start of observation were noted. Newborns of Hispanic and African American women had sigafificandy smaller birth weights (BW) compared to Caucasians (Table). African American women h a d a higher incidence of a b r u p d o n (n = 5), stillbirths (n = 3), a n d neonatal deaths (n = 4) vs the other groups (n = 0 for all). The frequency of progression to t h r o m b o c y t o p e n i a / H E L L P syndrome a n d cesarean delivery rates were similar between groups. CONCLUSION: Differences in outcomes are observed between races even when u n d e r g o i n g the same intensive o u t p a t i e n t m o n i t o r i n g for mild gestational hypertension.

0242

O u t c o m e s by r a c e in w o m e n w i t h ~ e s t a t i o n a l h y p e r t e n s i o n

GA del (wk) Birth wt (g) BW < 1500 g BW < 2500 g Abruption HELLP/Dec. platelets C / S delivery

HISPANIC (N = 92)

AFRICAN-AM. (N = 476)

CAUCASIAN (N = 614)

PVALUE

36.8 + 2.6 2711 ± 768 5 (5.4%) 41 (45%) 0 4 (2.1%)

36.5 ± 2.4 2736 + 807 41 (8.6%) 169 (36%) 5 (I.1%) 10 (2.1%)

36.9 ± 2.3 2846 ± 738 28 (4.6%) 181 (33%) 0 18 (2.9%)

.022 .038 .023 .005 .042 .416

38%

48.3%

45%

.163

SUBSEQUENT PREGNANCY OUTCOMES IN WOMEN WrI'H A HISTORY OF I-II7.IJ.P SYNDROME _< 30 WlV.I~.~¢,Elizabeth T. McKinney, MD l, Bassam Haddad, MD t,John R. Barton, MDe,Jeffrey C. Livingston, MD I, Baha M. Sibai, MDI; IUniversity of Tennessee Health Science Center, O b / G y n , Memphis, TN; '-'Central Baptist Hospital, Antenatal Diagnostic Division, Lexington, KY There is limited or no data to counsel women with a history, of HELLP at -< 30 weeks' gestation. OBJECTIVE: To describe pregnancy outcomes in women with previous HELI.P at < 30 weeks' gestation. METHODS: O n e h n n d r e d eighteen women with previous HELLP at < 30 weeks' gestation followed for > 2 years were stndied; 69 b a d at least l s u b s e q u e n t pregnancy. O u t c o m e variables were: HELLP r e c u r r e n c e rate, preeclampsia, abruptio placenta, SGA < 10th percentile, a n d delivery < 37 weeks. RESULTS: The median follnw-up w-as5 years (range: 2 to 14). Padents had 113 subseqnent pregnancies at > 20 weeks. See table for ensuing pregnancy outcomes. These were also analyzed for presence or absence o f c h r o n i c hypertension (CHTN) during the index pregnancy. Seven women with CHTN had 12 pregnancies; 9 (75%) preeclampsia, 1 (8%) HELLP, a n d 2 (17%) abruption. CONCLUSION: Women with a history of HELLP at -< 30 weeks" gestation bare an increased rate of adverse p r e g n a n c y outcomes in s u b s e q u e n t pregnancies; bowever, HELLP r e c u r r e n c e is only 5%. This data should be usefnl in patient counseling.

P r e ~ n a n c y o u t c o m e i n w o m e n w i t h p r e v i o u s I - t F J L P (n = 113)

HELLP Preeclampsia Abruption SGA Delive~ < 37 weeks Delivery < 30 weeks

#

%

6 51 5 23 46 12

5 45 4 20 41 11

SERUM LEVELS OF ESTROGENS IN WOMEN w r I ' t l PREECI.,&MPSI.A Harald Zeisler t, Peter Husslein l, Clemens Tempfer 1, Stefan Jirececk t, Elmar Armin J o u r a l, Maria H o h l a g s c h w a n d m e r l, H a r a l d Zeislerl; IUniversity of Vienna, Obstetrics a n d Gynecology, Vienna OBJECTIVE,S: Altered profiles of serum estrogens may be associated with preeclampsia, however previous findings are discussed controversially. We ev-aluated the serum levels of estriol a n d estradiol in patients with mild a n d severe preeclampsia a n d healthy pregnant controls. STUDY DESIGN: Group A consisted of 30 women with mild preeelampsia, g r o u p B of 30 women with severe preeclampsia. Thirty normotensive p r e g n a n t women serving as control g r o u p (group C) were matched for gestational age and parity at the dme of blood sampling. Serum levels of estradiol a n d estriol were determined using a sandwich enzyme-linked immunosorbent assay. RESULTS: The median serum levels of estradiol were 3679 (2518-4199) p g / m L in g r o u p A, 3596 (2587-4176) p g / m L in g r o u p B a n d 3722 (2587-4176) p g / m L in g r o u p C. The differences between g r o u p A a n d C a n d g r o u p B a n d C were statistically not significant (P =. 13 a n d P = .33, respectively). The median serum levels of estriol were 118 (13-617) n g / m L in g r o u p A, 112 (16-212) n g / m L in g r o u p B and 150 (12-700) n g / m L in g r o u p C. The differences between g r o u p A a n d C and g r o u p B a n d C were stadsdcally nnt significant (P= .19 a n d P = .12, respectively). CONCLUSIONS: O u r data do not indicate that alterations o f estrogen serum levels are associated with preeclampsia.

$80 SMFM Abstracts

J a n u a r y 2001 Am J Obstet Gynecol

0245

17[~ ESTRADIOL IMPROVES FLOW-MEDIATED DILATATION IN MYOMETRIAL RF-RISTANCE ARTERIES FROM WOMEN W I T H PREECtAMPSIA Eimantas Svedas I , Karolina Kublickiene 2, MarjaJ. VanWijk 3, Yorgos Nikas'2, Charlotta G r u n e w a l d 4, H e n r y Nisell2; IKarolinska Institutet, Stockholm; 2 H u d d i n g e University Hospital, Obstetrics a n d Gynecology: 3University of A m s t e r d a m , Academic Medical Center, Obstetrics a n d Gynecology, Amsterdam; 4Karnlinska Institutet, Soder Hospital, Dept. Obstetrics a n d Gynecology, Stockholm ,OBJECTIVE: To evaluate bradykinin (BK)-and flow-mediated dilatation in isolated mynmetrial arteries from w o m e n with preeclampsia (PE) a n d to d e t e r m i n e w h e t h e r p r o l o n g e d incubation with 17[3 estradiol (17-13-E2, 0.01 g m o l / L ) may e n h a n c e flow a n d BK-mediated dilatation in these arteries. STUDY DESIGN: Arteries (approx. 200 m m ) were dissected from myometrial biopsies at cesarean section because o f P E . a n d from normal p r e g n a n t (NP) w o m e n u n d e r g o i n g p l a n n e d cesarean section. Vessels were m o u n t e d in a pressure arteriograph (60 m m Hg). Concentration response curves to BK (1 n m o l / L to 3 g m o l / L ) a n d flow responses were obtained after preconstriction with n o r e p i n e p h r i n e (NE, 1 I.tmol/L) in physiological salt solution (PSS) a n d c o m p a r e d in arteries from NP a n d PE women. Furthermore, BK a n d flow-mediated responses were determined before a n d after i n c u b a t i o n with 17-1~E2 (3 hours) in arteries from w o m e n with PE. Scanning electron microscopy (SEM) was applied to compare endothelial cell morphology in arteries from women with PE (n = 5) a n d NP (n = 5). RESULTS: Flow-mediated dilatation was impaired in arteries from women with PE (n = 5) compared with NP (n = 9) (% change in diameter at max flow rate - 1 6 % + 6% vs 33% + 9%, respectively, P < .01) The maximal BK-mediated dilatation was impaired in arteries from women with PE (dilatation at 3 lamol of BIL 73% + 39% PE (n = 6) vs 141% ± 17% NP (n = 30), P < .05). Prolonged incubation with 17-l~-E2 did not affect BK-mediated dilatation in arteries from women with PE, but reversed impaired flow-mediated dilatation (% change in diameter at max flow rate of 204 p.L/min: -16% ± 6% vs 32% ± 9%, n = 5, P< .01). SEM demonstrated symptoms of endothelial dysfunction in arteries from women with PE. CONCLUSIONS: I m p a i r e d flow-mediated dilatation in isolated myometrial arteries from women with PE might be improved by estrogens.

0245

MATERNAL HEMOLYSIS, ELEVATED LIVER ENZYMES AND L O W PLATELETS (I-tFJ.LP) SYNDROME: PERINATAL AND NEONATAL OUTCOMES Nalini SinghaP, Harish Amin t, .left Pollard ~, Suzanne Tough 1, D e b o r a h Clark 1, Reg Sauve-~; IUniversity of Calgary, Paediatrics, Calgary, Alberta; 2University of Calgary, Obstetrics and Gynecology, Calgary, Alberta; 3University of Calgary, Community H e a h h Sciences, Calgary, Alberta OBJECTIVE: To study the mortality a n d short term morbidity of infants horn to women with pregnancies complicated by HELLP syndrome a n d to compare the long term neurodevelopmental morbidity of a subgroup of these infants with birth weight < 1250 g with weight matched controls. STUDY DESIGN: All cases o f HELLP syndrome at the University of Calgary - Foothills Hospital between 1990 a n d 1995 were identified a n d verified by a single author. Perinatal a n d neonatal data on the infants born to mothers with HELLP syndrome were analyzed and the subgroup with weight < 1250 g (H) were c o m p a r e d to a g r o u p of weight m a t c h e d controls (C) followed through the Perinatal Follow-up Program. RESULTS: Ninety-one infants were b o r n to 87 m o t h e r s with HELLP syndrome. Mean gestational age at delivery was 33 weeks a n d mean umbilical artery pH was 7.22. Apgar scores were 6 at one minute a n d 8 at five minutes. Mean days on intermittent positive pressure ventination (IPPV) 3.9, and mean days on supplemental oxygen (05) 9.8. Twenty-seven percent of infants were small for gestational age. Three (4%) infants developed sepsis. Twenty-three infants were < 1250 g and were compared to controls. There were no differences in Apgar scores, cord pH, perinatal mortality (3 H vs 5 C), mean days on IPPV (10.7 H vs 15.1 C), days on 0 2 (28 H vs 32 C), confirmed sepsis (3 H vs 5 C), necrotizing enterocolitis (4 H vs 4 C), and O~. at discharge (7 H vs 6 C). At 3 years corrected age 2 H and 5 C had weights < 2 SD below the mean. Disabilities at 3 years were cerebral palsy (0 H vs 2 C) and hearing loss (0 H vs 1 C). Mean scores for cognitive development were 100 H ~ 92 C. CONCLUSIONS: There were no significant differences in the outcome of premature infants < 1250 g bo:'n to women with HELLP syndrome compared to controls. This study did not show these children are at increased risk for morbidity or mortality.

0244

I N D U C T I O N O F L A B O R VS PLANNED CESAREAN DELIVERY < 34 WRing.g, GESTATION W I T H SEVERE GESTATIONAL HYPERTENSION Jeff Pollard t, Alina Iosif2, Rebecca Simrose 1, Nalini Singhal s, G r e g o r y Connorsl; :University o f Calgary, Obstetrics a n d Gynecology, Calgary, Alberta; 2University o f Calgary, Obstetrics a n d Gynecology, Calgary, Alberta; 3University o f Calgary, Pediatrics, Calgary, Alberta OBJECTIVE: To compare maternal a n d perinatal outcomes by intended delivery route in pregnancies delivered for severe gestadonal hypertension (GHTN) < 34 weeks' gestation. STUDY DESIGN: Records o f all women delivered between 1988 a n d 1998 at the authors' institution for G H T N from 24 to 33 weeks a n d their infants were reviewed. Those who u n d e r w e n t cesarean delivery without labor (CS) were c o m p a r e d with those who h a d labor induced (IND). Comparisons were m a d e with lr~her exact test or Student t test. RESULTS: O n e h u n d r e d ninety-two w o m e n were delivered for GHTN. F'tt~een were excluded d u e to fetal demise (8), estimated weight < 500 g (6), or m a j o r congenital anomalies (1). O f the r e m a i n i n g 177 women, 101 (57%) u n d e r w e n t CS a n d 76 (43%) IND. Thirty-two (42%) of 76 of IND required a cesarean delivery d u r i n g the induction (IND-CS). There were no differences in gestational age (29.8 weeks C~, 30.1 weeks IND) or birth weight (1221 g CS, 1264 g IND). No differences were noted in maternal mortality (1 CS, 0 IND), chorioamnionitis/endometritis (3 CS, 2 IND), o r major maternal morbidity. Postpartum hospital stay was greater in CS vs IND (6.5 days vs 5.4 days, P= .02). T h e 177 pregnancies yielded 195 live b o r n neonates (111 CS, 84 IND). No differences were noted in neonatal mortality (4/111 CoS,3.6%; 4 / 8 4 IND, 4.8%), (14 CS, 8 IND), grade III/IV intraventricular hemorrhage (2 CS, 5 IND), or necrofizing enterocolitls (12 CS, 9 IND). Bronchopulmonary dysplasia (28 C~, 11 IN-D, P = .03), a n d neonatal hospital stay (33.9 days C~, 22.0 IND, P < .01) were significantly less in IND vs CS. Comparing only the CS a n d IND-CS groups, n o differences were noted. CONCLUSION: Induction of labor in women with G H T N is associated with a reasonable rate of vaginal delivery (58%), no increase in maternal or perinatal morbidity or mortality, a n d a decrease in maternal a n d neonatal hospital stays a n d b r o n c h o p u i m o n a r y dysplasia c o m p a r e d with p l a n n e d cesarean delivery.

0246

ANGIOTENSINOGEN IS EXPRESSED AND T235 EXPRESSION IS PREFERENTIALLY EXPRESSED DURING HUMAN RENAL DEVELOPMENT Francis Song l, Terry Morgan 2, Lesa Nelson s, Kenneth Ward4; IUniversity of Utah, CAMT, Perinatal Genetics Lab, Salt Lake City, UT; ~Stanford University, Department of Pathology, Stanford, CA; 3University of Utah, CAMT, Perinatal Genetics Lab, Salt Lake City, UT; 4University of Utah, Obstetrics a n d Gynecology & H u m a n Genetics, Salt Lake City, UT OBJECTIVE: We recently demonstrated that angiotensinogen (AGT) is expressed in the proximal tubule of mice a n d adult h u m a n s . In o r d e r to determine the role of AGT, especially the T235 allele, in renal development a n d possibly in the pathogenesis o f hypertension, we studied the AGT expression in fetal kidney. We hypothesized that there would be elevated expression of T235 c o m p a r e d to the M allele in the kidneys of heterozygous fetuses. METHOD: Using an IRIS approved protocol, 183 fetal kidney samples were o b t a i n e d from n o r m a l first or second trimester, electively t e r m i n a t e d abortuses, Fetal genomic DNA was extracted from the kidney samples. Fetal DNA was g e n o t y p e d for the T 2 3 5 / M 2 3 5 p o l y m o r p h i s m by mutagenically separated polymerase chain reaction. Eighty of 183 (44%) were heterozygotes. Total RNA was extracted from the 80 heterozygous fetal kidney homogenates using TRI-REAGENT. AGT-Ex2 a n d AGT-Ex3 primers were used m perform RT-PCR. An allele specific ligation assay was used to quantitatively analyze the AGT expression. We then c o m p a r e d log T235/Iog M235 in the cDNA to log T 2 8 5 / l o g M235 in the g e n o m i c DNA controls using the N o n p a r a m e t r i c Wilcoxon Signed Rank Test. RESULTS: All 80 fetal kidneys showed AGT expression (from 6 to 18 weeks' gestation). The T235 allele was preferentially expressed. CONCLUSION: Based on this preliminary study, we suspect that AGT has a role in fetal renal development. The observed preferential expression of the T allele may have developmental effects on the kidney. These observations may help to explain how prenatal events can have an effect on the occurrence of hypertension a n d o t h e r adult onset diseases.

SMFM Abstracts $81

V o l u m e 184, N u m b e r 1 Am J Obstet Gynecol 0247

IS A POLICY O F P R O P H Y L A C T I C MAGNESIUM SULFATE F O R ALL PREECLAMPTIC PATIENTS IN LABOR WORTHWHILE? A m a n d a Cotter, DR t, Sean 17. Daly'2-; ICoombe Women's Hospital, Dublin 8, Ireland, Dublin; 2Coombe Women's Hospital, Dublin OBJECTIVE: Anticonvulsants are administered to women with preeclampsia (PET) to prevent eclampsia a n d improve maternal a n d fetal outcome, Magnesium sulfate is a proven anticonvulsant in the m a n a g e m e n t of eclampsia but its role in prophylaxis is undetermined. O u r objective was to determine if a policy of prophylactic magnesium sulfate for all women with PET in labor would be effective in o u r population. STUDY DESIGN: An individual chart review was performed of all cases of eclampsia which occurred in o u r hospital during the interval 1980-1999. PET was defined by a blood p r e ~ u r e -> 140/90 mm H g a n d +1 protein on dipstick urinalysis or > 300 mg proteinuria. RESULTS: O f 134,591 deliveries there were 3000 cases of PET but only 50 cases of eclampsia (0.037%). There were 21 antepartum seizures hence these women would not have received prophylaxis. O f 12 intrapartum seizures, 4 women did not have a diagnosis of PET. Similarily of the 17 women who seized postpartum, 8 had undiagaaosed PET. Therefore 33 women (66%) were not recognized to have PET until they seized a n d so would not have received prophylaxis according to the proposed policy. O f known PET patients, 99.4% would have received m a g n e s i u m sulfate unnecessarily. Despite lack of anticonvulsant prophylaxis, there were no maternal deaths a n d no serious maternal sequelae. T h e r e were 4 i n t r a u t e r i n e deaths which o c c u r r e d in patients who seized antenatally a n d one neonatal death due to prematnrity at 25 weeks' gestation in a patient who seized antenatally. CONCLUSION: The rate of eclampsia was low in o u r population despite lack of auticonvulsant prophylaxis while maternal a n d fetal outcomes did not deteriorate. A policy of prophylactic magnesium sulfate for all PET patients in labor would have prevented 44% o f seizures while exposing 99% of preeclamptics to this therapy tmnecessarily.

0249

DO WOMEN AT HIGH RISK DEVELOP PREECLAMPSIA E A R l . r t ~ IN GESTATION T H A N T H O S E AT L O W RISK? Leslie Myattl; tNICHD MFMU Network, Bethesda, MD OBJECTIVE: To d e t e r m i n e if time of diagnosis of preeclampsia is different a m o n g patients at high risk of d e v e l o p m e n t o f disease: n o n hypertensive, non-proteinuric pregestational diabetics (PD), multffetal gestations (MF) a n d previous preeclamptics (PP) vs a low-risk g r o u p of nnlliparuus patients, a n d if distinct early onset versus late onset disease occurs. STUDY DESIGN: S e c o n d a r y analyses f r o m d a t a sets u s i n g low-dose. aspirin for p r e v e n t i o n of preeclampsia. Study g r o u p s were low-risk nulliparas (n = 2947), a n d high-risk women: PD (n = 335), MF (n = 678) a n d PP (n = 600). RESULTS: Rates of preeclampsia in high-risk groups (PD = 17.6%, MF = 13.7% a n d PP = 17.8%) were significantly higher than low-risk groups (5.3%). Preeclampsia developed in all groups as early as 26 weeks with a significant difference (P < .0001) between groups in c h a n g e in occurrence rates with gestational age. There was no evidence for separate early onset a n d late onset disease. In low-risk and PP groups the rate of occurrence increased in a linear m a n n e r to 40+ weeks. Twenty-five percent of the low-risk a n d 65% of the PP patients developing preeclampsia did so before 37 weeks. In PD a n d MF groups the rate increased exponentially up to 37 weeks by which time 78% o f PD a n d 79% of MF patients who developed PE h a d d o n e so. After 37 weeks the rate of preeclampsia in PD and MF groups decreased probably due to their high rate of induction a n d / o r c-section (78% a n d 03% of e a c h g r o u p respectively). Correction for this high rate o f delivery gave overall preeclampsia rates of 23.2%, 33.0% a n d 19.5% for PD, MF a n d PP groups. CONCLUSION: In nuiliparous women a n d PP the rate of PE increases in a linear fashion t h r o u g h o u t gestation, whereas in PD a n d MF gestations it increases exponentially, suggesting a different etiology. T h e high rate of delivery of these patients prior to term may mask their true rate of PE.

0248

R E L A T I O N S H I P O F VASCULAR E N D O T H E I J A L G R O W T H FACTOR (VEGF) AND PLACENTAL G R O W T H FACTOR (PLGF) IS ALTERED IN PREECLAMPSIA J a s o n Evans, MD l, a n d D o n n a D. J o h n s o n , MD 1, D o n n a J o h u s o n l ; IMedical University of South Carolina, Obstetrics a n d Gynecology, Charleston, SC OBJECTIVE: VEGF is a p o t e n t permeability factor. VEGF must form VEGF-VEGF h o m o d i m e r s or less potent VEGF-PLGF h e t e r o d i m e r s to be biologically active. The objective of this study is to determine if the relationship between VEGF a n d PLGF is altered in p r e g n a n c i e s complicated by preeclampsia. METHODS: The study was approved by the IRB a n d informed consent was obtained from patients p r i o r to enrollment. Maternal serum was collected from u n c o m p l i c a t e d n o n s m o k i n g patients a n d f r o m previously healthy n o n s m o k i n g patients diagnosed with severe preeclampsia based o n A C O G criteria. All patients were at term a n d were not in labor when the serum sample was collected. Maternal serum was stored at - 8 0 ° C. Blood levels of VEGF a n d PLGF were d e t e r m i n e d by enzyme-linked i m m u n o s o r b e m assay. Data were analyzed using Student t test a n d are presented as mean a n d standard error. RESULTS: VEGF is present in equivalent concentrations in the serum of normal a n d preeclamptic patients (46.7 + 10.9 vs 43.0 + 17.6 p g / m L , P = .9). However, PLGF is significantly decreased in the serum from preeclamptic patients compared to controls (80.7 + 20.5 vs 415.8 + 99.0 p g / m L , P < .01). In control patients, PLGF concentration is 10-fold greater than VEGF (46.7 + 10.9 ~ 415.8 + 99.6 p g / m L , P < .01). In contrast, PLGF a n d VEGF concentrations are similar in preeclamptic patients (89.7 ± 20.5 vs 43.0 ± 17.6, P = .15). CONCLUSIONS: PLGF is decreased in the serum of patients with severe preeclampsia. Less PLGF is available to f o r m less p o t e n t VEGF-PLGF heterodimers. This difference may c o n t r i b u t e to the increased vascular permeability seen in severe preeclamptic patients.

0250

A COMPARISON OF I N D U C T I O N T O DFAJVF.~Y INTKRVAI~ IN PATIENTS WITH PKEECI.AMPSIA VS NORMOTENSIVE C O N T R O I ~ J o a n n e Stone, MD t, Michelle Morgan. MD2; t M o u n t Sinai School o f Medicine, O b / G y n , New York, N'Y;2Mount Sinai Medical Center, O b / G y n , New York, NY OBJEC'I'IVE: To c o m p a r e the duration o f labor in nulliparous patients induced secondary to preeclampsia with uormotensive controls. STUDY DESIGN: A retrospective case-controlled study was p e r f o r m e d using a computerized perinatal database encompassing the years 1995 to 1999. The study patients included 83 nulliparous patients admitted for induction secondary to preeclampsia. The controls were 83 nuUiparous patients induced for other indications. Cases a n d controls were m a t c h e d for gestational age, initial cervical exam a n d birth weight. Statistical analysis included McNemar Test for Correlated proportions, t test a n d logistic regression analysis. RESULTS: No differences were detected in the use o f cervical ripening agents, oxytocin, delivery route or neonatal outcomes. T h e r e was significantly longer induction to active labor interval in the preeclamptics vs controls (12.9 vs 10.5, P = ,009), b u t n o differences in interval from active l a b o r to full dilatation (FD), or FD to delivery. This difference was n o longer significant after controlling for c o n f o u n d i n g factors. C O N C L U S I O N : This study does n o t s u p p o r t the clinical b e l i e f t h a t preeclamptics are more easily induced, or have shorter labors, than m a t c h e d controls.

$82 SMFM Abstracts 0251

DIURNAL VARIATION IN B L O O D PRESSURE AND SUBSEQUENT RELAT I O N T O o l f r C O M E S IN WOMEN WITH GESTATIONAL HYPERTENSION George Saade, MDI,John Barton, MD", DebbieJacques, MPH 3, Niki Bergauer, RN ~', Gary Stanziano, MD 3, Baha Sibal, MD4; t Univ. of Texas Medical Brancb at Galveston, O b / G y n , Galveston, TX; "Central Baptist Hospital, Perinatal Diagnostic Center, Lexington, KY; aMatria H e a h h c a r e , Clinical Research, Marietta, GA; 4Univ. of Cincinnati, O b / G y n , Cincinnati, O H OBJECTIVE: To evaluate diurnal variation (DV) in blood pressure (BP) in women with mild gestational hypertension (GHTN) a n d its relationship to pregnancy outcome a n d subsequent need for delivery. STUDY DESIGN: W o m e n with G H T N a n d a singleton gestation participating in an outpatient monitoring p r o g r a m between 4 / 9 5 a n d 1/99 were eligible. Patients had a minimum of 4 days of automated BP data hefore delivery, with measurements between 8 A~l a n d noon and 6 and 10 era. Data were divided into women delivered because of a worsening condition (group 1, n = 55) a n d women stable at delivery (group 2, n = 101). Statistical analyses included Student t a n d repeated measures regression (SPSS, Chicago, Ill; P < .05 considered statistically significant). RESULTS: Maternal age, marital status, percent smokers, a n d p e r c e n t nulliparous were not significantly different between the groups. Women in g r o u p 1 h a d significandy earlier gestational age at delivery, a greater percent small-for-gestational-age infants, newborn intensive care unit admission, a n d a h i g h e r rate of cesarean delivery. Overall, g r o u p 1 h a d h i g h e r AM a n d PM systolic, diastolic, a n d mean arterial pressures than g r o u p 2 (P < .001). Within each g r o u p DV in systolic BP (VM > AM) was present (P< .001 for g r o u p 1 and P = .001 for g r o u p 2). T h e p e r c e n t difference in systolic DV was marginally significant between the groups (P = .051) with a greater percent difference in g r o u p 1. Diastolic DV was not f o u n d in g r o u p 1 (P = .963) but was present in g r o u p 2 (AM > PM, P = .033). CONCLUSION: Women in g r o u p 1 had higher AM a n d PSi BP than those in g r o u p 2. Systolic DV was present in both groups. Additional research is n e e d e d to d e t e r m i n e w h e t h e r a widening of systolic DV is predictive of a worsening clinical condition in women with GHTN.

January 200 l Am J Obstet Gynecol 0253

IMPACT OF DIFFERENT PREVENTION STRATEGIES O N NEONATAL G R O U P B S T R E P T O C O C C A L DISEASE: AN ITALIAN EXPERIENCE Patrizia Vergani I, Luisa Patane q, Camilla Andrentti ~, Carla Colombo'-', ('ecia Borroni 2, Alessandro Ghidini:~; Univ. Milano-Bicocca, I O b / G y n a n d 2Neonatology, Monza; 3Georgetown Univ., Washington, DC OBJECTIVE: We performed a retrospective cohort study to estimate the effect of different prevention strategies on the rate of early-onset neonatal g r o u p B streptococcal disease (EONGBSD). STUDY DESIGN: The mortality and morbidity associatcd with EONGBSD in 4 periods characterized hy dilferent prevention stnttegies were compared by Fisher exact test with a l-tailed Pvalue <.05 considered significant. Frnm I / 8 7 to 12/90 (group A) wnmen were not screened for g r o n p B streptococci (GBS) during pregnancy a n d there was no standardized treatment for risk factors during labor. Between 1/91 and 12/94 (group B) women were not screened for GBS d u r i n g pregnancy, but those with risk factors received antibiotic prophylaxis d u r i n g labor. Between 1/95 a n d 1 2 / 9 7 (group C) a universal screening for GBS d u r i n g pregnancy was p e r f o r m e d at 26 to 28 weeks and women with positive c u h u r e s a n d risk factors in the presence of negative cultures or cultures not performed received antibiotic prophyh'Lxis. Between 1/98 and 12/99 (group D) the gestational age at screening was changed to 35 to 37 weeks. RESULTS: The prevalence of positive GBS anogenital cultures was similar in all study periods (mean 17.8%, range 16%-19%). Neonatal outcomes are summarized in the table. C O N C L U S I O N : T b e prevalence of positive GBS anogenital cultures remained stable across the study periods (17.8% in our population). Universal screening for GBS a n d i n t r a p a r t u m prophylaxis is associated with a more significant effect on the mortality rate than otl EONGBSD.

Neonatal outcome of study periods GROUP A (N = 8573) Mortality rate 4 (0.04%) EONGBSD 8 (0.09%)

GROUP B (N = 10,303) I (0.01%) 8 (0.07%)

GROUP C/D PVALUE* (N = 13,754) .1 .8

PVALUEt

O (0%) 6 (0.04%)

.02 .1

*Comparison of risk factor g r o u p vs no s c r e e n i n g / n o treatment group. ~Comparison of universal screening vs no s c r e e n i n g / n o treatment.

0252

PRETERM PREECLAMPSIA W1TH FETAL GROWTH RESTRICTION IS A MORE SEVF.,RE PLACENTAL DISEASE THAN PRETERM PREECLAMPSIA ALONE Alessandro Ghidini l, Carolyn M. Salatia2, Luisa Pamne'3; IGeorgetuwn Univ., O b / G y n , Washington, DC; 2Columbia-Presbyterian College of Physician a n d Surgeons, Pathology, New York, NY; 3Early Path, Larchmont, NY I N T R O D U C T I O N : Placental histology a n d uterine artery D o p p l e r velocimetry findings suggest that fetal growth restriction (FGR) a n d preeclampsia [PE) often share a similar pathophysiology (ie, faulty placental implantation with consequent abnormal placental perfusion). It is unknown, however, w h e t h e r p r e g n a n c i e s with PE alone have distinguishing features c o m p a r e d with cases o f PE associated with FGR. STUDY DESIGN: From a database .of 465 consecutive deliveries o f singleton, liveborn, n o n a n o m a l o u s infants at <32 weeks, we extracted all cases o f P E (n = 78, 17%). Maternal, neonatal, a n d placental histologic findings were c o m p a r e d between cases of PE with FGR (birth weight below 10th percentile, n = 47) a n d cases o f PE with birth weight above 10th percentile (n = 31 ) by 1-way analysis of variance, Fisher exact test, Z2, a n d regression analysis with 2-tailed P < .05 considered statistically significant. RESULTS: Pregnancies with PE + FGR h a d similar maternal age, rate of nulliparity, a n d male sex, but lower gestational age at delivery (28.9 + 2.3 vs 29.9 + 1.6 weeks, P = .02), birth weight (820 + 43 vs 1224 ± 376 g, P < .01), a n d h i g h e r rate of cesarean delivery (47/47 [ 100%] vs 25/31 [81%], P= .007) than pregnancies with PE alone. A m o n g all women with PE, placental histology showed significant inverse correlations between birth weight percentiles a n d severity o f u t e r o p l a c e n t a l vascular (UPV) lesions (R 2 = 0.08, P = .01), intraplacental vascular (IPV) lesions (_/i'2 = 0.05, P= .04), a n d a combination of UPV a n d IPV lesions (/~2 = 0.12, P = .01). No association was found between severity o f FGR a n d lesions of chronic or acute inflammation. CONCLUSION: T h e presence o f FGR in the context of PE signals a more severe maternal vascular process, with m o r e destructive placental vascular effects, which also tends to become clinically manifest at a lower gestational age.

0254

VASCULAR CELL A D H E S I O N M O L E C U L E AND LOW-DENSITY L I P O P R O T E I N OXIDATION IN PREECLAMPSIA B. Raynor I, S a n d r a Brickman, MD 2, Elizabeth Bonney ~, K.T. J a n g , MD 2, Nalini Santanam'-', Sampath Parthasarathy2; Emory Univ., Divisions of IMaternaI-Fetal Medicine a n d ~Ob/Gyn, Atlanta, GA OBJECTIVE: To evaluate the correlation between low-density lipnprntein (LDL) oxidation a n d vascular cell adhesion molecule (VCAM) in preeclamptic a n d n o r m a l pregnancy. Both VCAM a n d LDL oxidation are increased in preeclampsia a n d VCAM synthesis is stimulated by LDL. STUDY DESIGN: Plasma was drawn from w o m e n diagnosed with preeclampsia by criteria of the American College o f Obstetricians a n d Gynecologists or with normal pregnancy. VCAM was determined by enzymelinked i m m u n o s o r b e n t assay (R&D, Minneapolis, Minn). LDL was determined by Cholestech analyzer. Whole plasma oxidation was p e r f o r m e d by 10 p.mol/L Cu ++ a d d e d to plasma diluted 1:100 continuously m o n i t o r e d for the appearance of conjugated dienes at 234 nm. Statistical analysis by paired t test a n d Pearson correlation. P < .05 was significant. RESULTS: Fourteen healthy a n d 19 preeclamptic women were studied. VCAM was increased in preeclamptics (431.5 [149.6] vs 284.3 [141.1] n g / m L normal), P < .005. LDL was similar. Oxidation lag times a n d maximum change were similar between the groups, whereas m a x i m u m oxidation interval was l o n g e r in preeclampsia (90 [36] a n d 66 [24] rain, P < .04). In n o r m a l pregnancy, LDL correlated with lag time (r = 0.67, P < .01), which also correlated with m a x i m u m oxidation interval (r = .05, P < .02) but not with maximum change. This pattern was different in preeclampsia; the maximum change correlated negatively with the maximum oxidation interval ( r = - 0 . 7 4 7 , P = .000), but none of the other variables correlated. DISCUSSION: Observations confirmed that VCAM is increased in preeclampsia. A l t h o u g h n o difference was seen in lag times, the patterns of oxidation were different; in healthy women m o r e LDL was associated with longer lag times a n d slower oxidation rates. In preeclampsia faster oxidation rates were associated with lower amounts of conjugated dienes produced a n d neither correlated with the a m o u n t of LDL.

SMFM Abstracts $83

V o l u m e 184, N u m b e r 1 Am J Obstet Gynecol 0255

FREQUENCY OF NUCLEOSIDE A IN AFRICAN AMERICAN WOMEN W I T H PREGNANCY-INDUCED HYPERTENSION. J a l p a Shah I, Geetha Pa~jendran, MD'-', Ashok Kumar, MD -~, Uma Verona. MD'-', Nergesh Tejani, MD-'; tNew York Medical College, O b / G v n '-'Westchester Medical Center, O b / G y n , Hawtlmrne, NY; ~New York Medical College, Pathology, Valhalla, NY OBJECTIVE: Pregnancy-induced hypertension (PIH) is a major cause of maternal and infant mortality. Earlier studies have suggested an association of M e t h i o n i n e 2 3 5 T h r e o n i n e ( M 2 3 5 T ) p o l y m o r p h i s m in the a n g i o t e n s i n o g e n gene with PIH. However, these results were not confirmed by recent studies. H u m a n a n g i o t e n s i n o g e n gene has an A / C polymorphism at -20, which is located between the TATA box and the transcriptional initiation site. We have recently shown that nucleoside A at - 2 0 creates an estrogen receptor (ER) binding site in the angiotensinogen gene promotei: Moreover, the p r o m o t e r activity of r e p o r t e r constructs with nucleoside A at - 2 0 is increased on cotrausfection of ER ct followed by estrogen treatment in HepG2 cells. O u r objective was to detemnine whether there is an association between frequency of nueleoside A and PIH in Africau American women. METHODS: G e n o m i c DNA was analyzed from 25 African American women with PIH and 25 Al'rican American women with normal blood pressure during pregnancy. RESULTS: African American women with PIH have an increased frequency of nucleoside A at -20 (0.8) compared women with normal blood pressure during pregnancy (0.5). C O N C L U S I O N : O u r resulLs suggest that nucleoside A at - 2 0 in the angioteusinogen gene is a potential risk factor for PIH in African American women.

0257

ENDOMETRIAL MICROBIAL C O L O N I Z A T I O N IS INCREASED IN WOMEN WITH ASYMPTOMATIC BACTERIAL VAGINOSIS William Andrews I, John H a u t h 1, Suzanne Cliver I, Robert G o l d e n b e r g l ; IUniv. of Alabama at Birmingham, O b / G y n , Birmingham, AL OBJECTIVE: To determine whether endometrial microbial colonization is increased in women with asymptomatic bacterial vaginosis (BV). STUDY DESIGN: Endometrial specimens were obtained in 772 women after preterm and term delivery (mean 82, range 55-137 days). Cultures for' aerobes, anaerobes, T vag~nalis, a n d genital mycoplasmas were performed. Gram stains of vaginal smears were interpreted with use of Nugent's criteria (BV score >7). RESULTS: Endometrial cultures were positive for at least o n e microorganism in 82% of women and 37% had a Gram stain score >7. The mean n u m b e r of micro-organisms isolated from the e n d o m e t r i u m was 1.6 + 1.3 organisms. The frequency of positive endometdal cultures was slightly higher a m o n g women with BV compared with women without BV (88% vs 78%, P = .001 ). However, endometrial cultures positive for BV.-associated bacteria were significantly m o r e c o m m o n in w o m e n with versus those without BV: any anaerobe (38% vs 14%, P < .0001), anaerobic gram-negative bacilli (15% 4%, P < .0001), anaerobic gram-positive cocci (30% vs 7%, P < .0001), M hominis (14% vs 4%, P < .0001), G vaginalis (72% vs 31%, P < .0001), a n d Mobiluncus spp (4% vs 2%, P = .022). T h e study c o h o r t was 71% African American, 63% single, a n d 74% h a d <12 years of education. Adjustment for these demographic characteristics by logistic regression analysis did not alter the univariate results. Isolation o f U urealyticum from the cervix (57% vs 54%, P = .47) a n d endometrium (8% vs 7%, P = .37) was similar in women with a n d without BV. Because U urealyticum was much less commonly isolated from the e n d o m e t r i u m compared with the cervix, the above results do not appear to be the result of bacterial c o n t a m i n a t i o n of the e n d o m e t r i a l specimen with cervical bacteria. CONCLUSION: Endometrial microbial colonization, especially with BVassociated bacteria, is increased in women with asymptomatic bacterial vaginosis.

0256

T H E EFFECT OF BACTERIAL VAGINOSIS TREATMENT O N T H E ACQUISITION O F O T H E R SYMPTOMATIC SEXUALLY T R A N S M r l r r ~ D DISEASES D U R I N G PREGNANCY J e a n n e s. Sheffield I, NICHD MFMU Network2; INICHD MFMU Network, 2NICHD, Bethesda, MD OBJECTIVE: A b n o r m a l vaginal flora has b e e n associated with an increased risk of sexually transmitted diseases (STDs). Eradication of bacterial vaglnosis is presumed to restore the normal vaginal flora. O u r objective was to d e t e r m i n e w h e t h e r the t r e a t m e n t of bacterial vaginosis in p r e g n a n c y decreased the acquisition of other symptomatic STDs. STUDY DESIGN: The NICHD Maternal Fetal Medicine Unit conducted a 4-year double-blind r a n d o m i z e d trial of p r e g n a n t w o m e n d i a g n o s e d with asymptomatic bacterial vaginosis. Women received either metronidazole 2 g x 2 doses or placebo at 16-24 weeks a n d again at 24-30 weeks' gestation. All w o m e n tested negative for g o n o r r h e a , syphilis, a n d trichomoniasis at enrollment. In this secondary analysis, demographic factors, sexual practices, a n d the acquisition o f symptomatic STDs d u r i n g the r e m a i n d e r of the pregnancy were analyzed with respect to treatment regimen. RESULTS: A total of 894 w o m e n with follow-up were r a n d o m i z e d to metronidazole a n d 904 to placebo. Clearance rates of bacterial vaginosis were 77.6% a n d 37.4%, respectively. T h e r e were n o differences between the 2 groups with respect to d e m o g r a p h i c factors, sexual practices i n c l u d i n g c o n d o m usage, HIV status, or social habits. Results are shown in the table. C O N C L U S I O N : T r e a t m e n t of bacterial vaginosis, with p r e s u m e d restoration of normal vaginal flora, did n o t decrease the acquisition of symptomatic chlamydia, syphilis, or gonorrhea.

0258

ANTIMICROBIAL SL~Y~u~ImIIATY OF GRAM-NEGATIVE UROPATHOGENS ISOLATED F R O M OBSTETRIC PATIENTS Whitney Jarnie t, Rodney Edwards l, Patrick Duffl; tUniv, of Florida, O b / G y n , Gainesville, FL OBJECTIVE: To evaluate the antimicrobial susceptibility of gram-negative uropathogens in a rural, indigent obstetric population. STUDY DESIGN: Charts of patients enrolled for prenatal care in the University of Florida clinic system as of March 2000 were reviewed to identify subjects with asymptomatic bacteriuria or cystitis. A positive urine culture was defined as >100,000 C F U / m L o f a single gram-negative u r o p a t h o g e n . The antimicrobial susceptibility of the u r o p a t h o g e n was recorded for each case. The ;(2 a n d Fisher exact test were used as appropriate for categorical data. Ninety-five percent confidence intervals were calculated for proportions. RESULTS: A total o f 95 positive cultures were identified. O f these infections, 72% (95% confidence interval [CA] 63-81), 87% (95% CA 81-94), a n d 89% (95% CA 83-96) were susceptible to ampicillin, t r i m e t h o p r i m suffamethoxazole, a n d nitrofurantoin, respectively. Escherichia coil a c c o u n t e d for 71 (75%) cases. When only cases caused by this organism were considered, 100% (95% CI 98-100) o f isolates were susceptible to nitrofurantoin, but only 87% (95% CI 80-95) o f isolates were susceptible to trimethoprimsulfamethoxazole (P < .01). Klebs/d/a pneumon/ae a n d Proteus m/rabi//s caused 8 cases each. T h e p r o p o r t i o n of susceptibility (75%) to n i t r o f u r a n t o i n a n d trimethoprim-sulfamethoxazole was equal a m o n g the Klebsieila isolates. However, all the Proteus isolates were susceptible to t r i m e t h o p r i m sulfamethoxazole, a n d n o n e were susceptible to nitrofurantoin ( P < .01). CONCLUSIONS: Both trimethoprim-sulfamethoxazole a n d nltrofurantoin are superior to ampicillin for empiric treatment o f lower urinary tract infections. Overall, susceptibility of gram-negative u r o p a t h o g e n s is similar for wimethoprim-sulfamethoxazole a n d nltrofurantoin. However, unless P m/mb///,v is the suspected pathogen, nitrofurantoin is a better choice for empiric treatment of lower urinary tract infections in obstetric patients.

SYMPTOMATIC STDS Syphilis Gonorrhea Chlamydia

METRONIDAZOLE (N = 894)

PLACEBO (N = 904)

PVALUE

3 (0.3) 8 (0.9) 44 (4.9)

1 (0.1) 12 (1.3) 42 (4.6)

.37 .38 .78

$84 SMFM Abstracts 0259

A COMPARISON OF AMNIOTIC FLUID IL-12, IL-6, MMP-9, AND GLUCOSE FOR DIAGNOSING SUBCLINICAL CHORIOAMNIONITIS Rodney Edward.s t, Penny Clark l, Gregory Locksmiths, Patrick Dultl; IUniv. of Florida, Ob/Gyn, Gaine.wine, FL; 2Univ. of Texas Medical Branch, Ob/Gyn, Galveston. TX OBJECTIVE: To compare amuiotic fluid (AF) interleukin (IL)-I2, IL-6, matrix metalloproteinase (MMP)-9, and glucuse for diagnosing subclinical chorioamnionitis in women with preterm labor. STUDY DESIGN: Women (n = 44) in preterm labor at 22-35 weeks' gestation underwent amniocentesis if subclinical ehorioamnionitis was suspected. AF was analyzed by Gram stain, glucose, and cuhure. MMP-9 concentrations were determined in a prior study. We tested AF ~ m p l e s for IL6 and IL-12 with commercially available enzyme immunoassays and compared median values with the Mann-Whitney Utest. With positive (+) AF cuhure ms a standard, sensitivity, specificity, and positive (PPV) and negatb,e (NPV) predictive values were calculated for IL-6, MMP-9, and glucose. RESULTS: Six (14%) women had + AF cuhures. For those with + and negative AF cultures, respectively, median IL-6 levels were 53.8 and 0.77 n g / m L (P= .02), and median IL-12 levels were 70.6 and 64.5 p g / m L (P> .05). Below are performance statistics (95% confidence interval) for llfo, MMP-9, and glucose. Each test was negative for a single case who was culture + for X maltophilia, a probable contaminant. This woman was delivered at term, 4 weeks after amniocentesis. All 3 tests were + in 3 patients with negative cultures, all of whom were delivered <24 hours after amniocentesis; one had clinical chorioamnionitis, and another had a + glucose and Gram stain. IL-6 was + in an additional woman who was delivered spontaneously <24 hours after amniocentesis. CONCLUSIONS: AF IL-6, MMP-9, and glucose reliably predict microbial invasion of file amniotic cavity or imminent delivery. In this small study, none of these tests was superior to the other two. AF IL-12 values did not correlate with AF culture results.

SPECIFICITY

PPV

NPV

83 (53-100)

89 (80-99)

56 (23-88)

97 (92-100)

83 (53-100)

92 (84-100)

63 (29-96)

97 (92-100)

83 (53-100)

87 (75-99)

56 (23-88)

97 (90-100)

SIGNIFICANT DECREASE IN EARLY-ONSET NEONATAL SEPSIS CAUSED BY GROUP B STREPTOCOCCUS AND O T H E R PENICILLIN-SUSCEPTIBLE ORGANISMS IN AN ERA OF GROUP B STREVI~COCCUS INTRAPARTUM ANTIBIOTIC PROPHYLAXIS Katherine Chen, MD I, Ruth Tnomala, MD I, Amy Cohen I, Ellice Lieberman, MDI; IBrigham and Women's Hospital, Ob/Gyn, Boston, MA OBJECTIVE: To assess tile impact of a risk-based group B Streptococcus (GBS) screening and treatment protocol on the rates of early-onset neonatal sepsis (EONS) caused by GBS and other organisms. STUDY DESIGN: A prospective cohort study included all neonates born at the Brigham and Women's Hospital between 1990 through 1996. Tile hue of EONS per 1000 births among neonates horn in 1990 to 1992 (period without GBS intrapartum antibiotic prophylaxis) was compared with that of neonates horn in 1993 to 1996 (period with GBS prophylaxis). A case of EONS was defined as a neonate having a positive blood cuhure within 7 days of life, receiving >48 hours of intravenous antibiotics, and having a blood cuhure org~mism not considered a contaminant by tile neonatologists. RESULTS: In the period without GBS intrapartum antibiotic prophylaxis, 28,803 neonates were born with 113 cases of EONS. In the period with GBS prophylaxis, 34,262 neonates were born with 90 cases of EONS. Penicillinsusceptible organisms included GBS, viridans streptococci, Enterococcusfaecalis, Streptococcus boris, Streptococcus pne~tmoniae, Aainomyces sp, and Fusobacterium nurleatum. Non-penicillin-susceptible orgauisms were Escherirhia colt, Staphyoloroceus epidermidis, Staphylococru.~ attreus, Bacteroides sp, Haemophilus influenzae, Candida sp, Acinetobarter sp, Citrobaeter diversus, Flavimonas oo,zihabitians, Morganella mo~;anii, and Proteus mirabilis. CONCLUSIONS: GBS intrapartum antibiotic prophylaxis has signillcantly halved the incidence of EONS caused by GBS and has reduced by 60% tile incidence of EONS caused by other penicillin-susceptible organisms at our instinltion. This decrease has not been accompanied hy an increase in EONS by E edit and other organisms not susceptible to penicillin. N O GBS PROPHYLAXIS (1990-1992)

GBS PROPHYLAXIS (1993-1996)

Overall GBS Other pelticillinsusceptible org-anisms

3.9 2.0 0.6

2.6 1.1 0.2

.004 .005 .024

E colt

0.6 0.8

0.5 0.8

.740 1.000

EONS RATE/ 1000 BIRTHS

Other non-penicillinsusceptible organisms

LOW V I R ~ C E GROUP B STREtrI'OCOCCUS SEROTYPES: A POSSIBLE EXPLANATION FOR THE LOW INCIDENCE OF EARLY-ONSET NEONATAL DISEASE IN SOUTHERN ISRAEL Dror Marchaim~, Mordechai Hallak 1, Pavlo Yagupsk~, Klaris Reisenberg2, Limor Gor~ak-Uzan 4, Nechama Peled s, Fmusisc Schlaeffer2; tSoroka Medical Center, ~lnfectious Diseases, SBacteriology, and 4Ob/Gyn Dept. A, Beer Sheva, Israel OBJECTIVE: In a previous study we found a discrepancy between relatively high prevalence of group B streptococci (GBS) among pregnant women (13.6%) and very low neonatal early-onset disease (EOD) incidence (0.14/1000 births). We initiated this study to evaluate whether the low incidence of EOD is associated with low virulence GBS serotypes distributed in southern Israel. STUDY DESIGN: A prospective study was conducted between January and July 2000 in our 12,000 deliveries per year labor and delivery rooms. Cultures for GBS were obtained and processed as recommended. Samples were cultured on blood-agar plates with and without added gentamicin. GBS was identified by ~hemolysis and positive cyclic adenosine monophosphate test and confirmed by agglutination with specific antiserum. Serotyping was done by the Lancefieid precipitin method, with rabbit monospecific antisera to polysaccharides Ia, Ib, II, III, IV, and V and surface proteins C, R, and X. RF_~ULTS: The serotype distribution of 58 GBS isolates is listed in the table. CONCLUSIONS: The low prevalence of the known, high-virulence serotypes IlI and V, combined with the high prevalence of the polysaccharide It and the proteins C and R (both constitute 83% of samples) found in the current study, is totally different from the serotype distribution reported from industrialized, developed countries. This may explain the discrepancy between the relatively high prevalence of carriage among pregnant women and the very low incidence of EOD in Southern Israel.

No. %

0261

E O N S r a t e d u r i n g p e r i o d s w i t h a n d w i t h o u t GBS p r o p h y l a x i s

SENSITIVITY IL-6 (>8.9 ng/mL) MMP-9 (>351 ng/mL) Glucose (<15 m g / dL)

0260

J a n u a t T 2001 Am J Obstet Gynecol

tit

II

II/C

II/R

IlI

IV/C

V

V/C

V/R

5 8.6

1 1.7

17 29.3

1 1.7

1 1.7

1 1.7

3 5.1

2 3.4

2 3.4

C

R

13 12 22.4 20.7

0262

P VALUE

HIV INFECTION IS A RISK FACTOR FOR ADVERSE PERINATAL OUTCOME Jane Ellis, MD I, Michael Lindsay, M D l, William Graves, PhDI; IEmory Unix,. School of Medicine, Ob/Gyn, Atlanta, GA OBJECTIVE: To ascertain the risk of adverse pregnancy outcome in HIVinfected parturients. STUDY DESIGN: A retrospective cohort study was conducted in a population of pregnant women delivered in a large inner-city hospital between January 1, 1988, and December 31, 1995. The study population consisted of 530 HIV-seropositive women and 2185 seronegative controls. Results were analyzed with descriptive statistics, X2 test, and logistic regression. RESULTS: Seropositive women were more likely than controls to be delivered of low-birth-weight (LBW) infants (29.3% vs 16.4%, odds ratio [OR] 2.11, 95% confidence interval [CI] 1.68-2.64), preterm infants (28.9% vs 18.2%, OR 1.83, 95% CI 1.46-2.28), and intrauterine growth-restricted infants (16.5% vs 10.6%, OR 1.66, 95% CI 1.26-2.19). Seropositive women were also more likely than controls to have perinatal deaths (11.5% vs 8.3%, OR 1.41, 95% CI 1.0.9,-1.95). The risk of fetal malformations, fetal distress, and operative delivery was similar between the groups. After controlling for race, parity, alcohol use, prenatal care, hypertension, diabetes mellitus, 100% ideal body weight, and sexually transmitted diseases, the increased risk of LBW (adjusted OR 1.4, 95% CI 1.14-1.88) and preterm delivery (adjusted OR 1.31, 95% CI 1.04-1.6) persisted. CONCLUSION: HIV-infected parturients in our inner-city hospital are at increased risk of delivery of LBW and premature infants. Selected characteristics of study population

CHARACTERISTIC

SEROPOSITIVE (%)

Black Single Age 20+ Parity 1+ Alcohol Prenatal Care Hypertension History of sexually transmitted diseases

93.6 82.8 86.0 78.0 20.0 60.8 6.8 34.8

SERONEGATIVE (%) 79.5 69.6 73.0 64.0 5.7 70.3 4.5 13.7

SIGNIFICANCE P< .0001 P < .0001 P< .0001 P< .0001 P < .001 P < .000-1 P= .03 P < .0001

SMFM Abstracts $85

V o l u m e 184, N u m b e r 1 Ant J O b s t e t G y n e c o l 0263

MATRIX METALLOPROTEINASE-9 AND APOPTOSIS (FAS/FAS LIGAND SYSTEM) IN INTRA-AMNIOTIC I N F E C T I O N C.D. Hsu, MD l, Hassan Harirah 2, Kristen Aversa, MD3; IDuke Univ., O b / G y n , Durham, NC; °-Univ. of Texas Medical Branch, Galveston, O b / G y n , Galveston, TX; ?'Yale Univ., O b / G y n , New Haveu, CT OBJECTIVE: Matrix metalloproteinase-9 (MMP-9) a n d Fas/Fas ligand (Fas/FasL) have been previously localized on fetal membranes. The aim of this study was to determine whether amniotic fluid MMP-9, soluble Fas (sFas), and sohthle FasL (sFasL) were correlated a n d assoicated with intra-amniotic infectioxl (IAI). STUDY DESIGN: Thirty-six women with singleton p r e g n a n c i e s were studied. Seventeen patients had IAI and 19 did not. Amniotic fluid (AF) was obtained from these patients with either preterm labor or premature rnpture of melnbranes through transabdomina[ amniocentesis. IAI was defined as the presence of a positive AF c u h u r e . AF tests for G r a m stain, glucose, a n d leukocytes were performed. AF MMP-9, sFas, and sFasL were deternfined by enzyme immunoassays. Two-tailed t test a n d linear regression and correlation were used for statistical analyses. Data were expressed as means ± SE. RESULTS: T h e r e were no significant differences in maternal age, gestational age, parity, or race in patients with a n d without IAI. AF MMP-9 (20.5 ± 3.1 vs 0.5 ± 0.3 n g / m L , P< .0001 ), sFas (5.5 ± 0.9 vs 2.0 ± 0.4 U / m L , P< .001), and sFasL (0.5 ± 0.1 vs 0.2 ± 0.0 n g / m L , P < .001) were signifieandy elevated in patients with IAI. AF MMP-9 was positively correlated with AF sFas ( r = 0.743, P < .0001) and sFasL ( r = 0.786, P < .0001). AF MMP-9, sFas, and sFasL were also positively correlated with AF leukocytes (r = 0.858, P < .000 I; r = 0.707, P < .0001; and r= 0.787, P< .0001, respectively). CONCLUSION: O u r results suggest that MMP-9 a n d Fa.s/Fa.sL system are correlated a n d associated with intra-amniotic infection. Although fetal m e m b r a n e s are one of the possible sources, AF leukocytes can be a n o t h e r major sonrce for these findings.

0265

PREMATURE R U P T U R E O F MEMBRANES AFTER 35 WEEKS: A RANDOMIZED CLINICAL TRIAL O F I N D U C T I O N O F LABOR WITH ORAL VERSUS VAGINAL ADMINISTRATION O F M I S O P R O S T O L Oscar Puga 1, j y h Kae Nien I, Ricardo Gomez 1, Luis Medina l, Mario Carstens I, Rogelio Gonzale#, Ivan Rojas 1, Roberto Romero2; ICEDIP, Sotero del Rio Hospital, O b / G y n , Univ. Catolica de Chile, Puente Alto, Santiago, Chile; 2Perinatology Research Branch, NICHD, Bethesda, MD; Wayne State Univ., O b / G y n / Maternal Fetal Med, Detroit, MI OBJECTIVE: To evaluate the safety a n d efficacy o f oral versus vaginal misoprostol for the induction of labor in padents with premature rupture of membranes >35 weeks (PROM). METHODS: Patients with PROM after 35 weeks were r a n d o m i z e d to receive either a misoprostol dose o f 50 ~tg vaginally or 100 p.g orally, administered up to 3 times. Inclusion criteria were the absence of regular uterine contractions, singleton pregnancy, a n d vertex presentation. Patients with a previous classic scar, previous uterine surgery, or with an indication for cesarean section at admission were excluded. Patients receiving oral misoprostol did not u n d e r g o cervical assessment undl they went into labor. L a b o r was c o n d u c t e d by s t a n d a r d surveillance i n c l u d i n g fetal h e a r t rate monitoring, epidural anesthesia, a n d oxytocin augmentation when indicated. Primary outcomes were the frequency of maternal infection a n d the rate of cesarean section. C o n t i n g e n c y tables a n d X2 analysis were p e r f o r m e d for statistical analysis. RESULTS: A total of 270 eligible patients were r a n d o m i z e d to receive either oral (n = 146) or vaginal misoprostol (n = 124). Demographic data were similar between groups. No differences were f o u n d in the rams of maternal infectious morbidity, cesarean section, a n d o t h e r variables (see table). C O N C L U S I O N : Induction o f labor with misoprostol in patients with PROM after 35 weeks can be successfully accomplished by use of either the oral or vaginal route of administration.

Maternal infectious morbidity Cesarean seedon Abnormal fetal heart rate with tachysystole Induction to delivery interval (h) Neonatal infectious morbidity

0264

T H E ROLE OF cYrOKINES AND FAS/FAS LIGAND SYSTEM IN INTRA-AMNIOTIC INFECTION Chaur-Dong Hsu t, Hassan Harirah, MD 2, Kristen Aversa, MD3; IDuke Univ., O b / G y n , Durham, NC; 2Univ. of Texas Medical Branch, Galveston, O b / G y n , Galveston, TX; 3Yale Univ., O b / G y n , New Haven, CT OBJECTIVE: Amniotic fluid (AF) cytokines were found to be associated with intra-amniotic infection (1AI). We hypothesized that AF eytokines, interieukin (IL)-6, IL-8, a n d growth-related protein (GRO)-o., could be associated a n d modulated apoptosis of Fas/Fas ligand system in IAI. Thus we d e t e r m i n e d the AF c o n c e n t r a t i o n s a n d correlations of IL-6, IL-8, GRO-0t, soluble Fas (sFas), a n d soluble FasL (sFasL) in patients with a n d without IAI. STUDY DESIGN: Forty-fuur AF specimens were obtained from an AF bank at o u r institution. IAI was defined as the presence of a positive AF culture. Twenty-one specimens were from padents with IAI and 21 were not. AF IL-6, IL-8, GRO-ct, sFas, a n d sFasL were determined by an enzyme immunoassay. Statistical analyses were performed by 2-tailed t test a n d linear regression and correlation test. Data were expressed as mean ± SE. RESULTS: T h e r e were no significant differences in maternal age, gestational age, parity, a n d race between patients with a n d without IA1. AF concentrations of IL-6, IL-8, GRO-0t, sFas, a n d sFasL were significandy higher in IA1 than without IAI (IL-6:23.5 ± 4.7 vs 7.0 ± 3.2 n g / m L , P = .007; IL-8:11.4 ± 4.5 vs 4.0 ± 2.1 n g / m L , P = .01; GRO-ct: 12.9 ± 2.9 vs 4.8 ± 2.5 n g / m L , P= .04; sFas: 4.9 ± 0.8 vs 2.0 ± 0.3 U / m L , P= .001 ; sFasL: 0.4 ± 0.1 vs 0.2 ± 0.0 n g / m L , P < .001). AF IL-6, IL-.8, a n d GRO-0t were positively correlated with sFas a n d sFasL. AF IL-6, IL-8, a n d GRO-0t were also positively correlated with AF leukocyte counts. CONCLUSIONS: O u r data indicate that AF cytokines, IL-6, II..-8, GRO.-tx, were significantly associated a n d correlated with an increased apoptosis of sFas/sFasL system in IA1. O u r findings also suggest that AF leukocytes can be one of the major sources for the elevation of AF cytokines a n d sFas/sFasL in IAI. The role of cytokines, apoptosis, a n d leukocytes in the pathogenesis of IAI warrants further studies.

0266

ORAL (N = 146)

VAGINAL (N = 124)

PVALUE

5 (3.4%)

5 (4.0%)

> .05

16 (11%) 24 (16.4%)

14 (11.3%) 16 (12.9%)

> .05 > .05

10 ± 6.6

9.9 + 7.2

> .05

4 (2.7%)

3 (2.4%)

> .05

MULTLANTIVIRAL THERAPY F O R HIV IN PREGNANCY IS N O T ASSOCIATED WITH INCREASED ADVERSE PERINATAL O U T C O M E Donna Neale t, Urania Magriples2; Yale Univ., tMaterual-Fetal Medicine, a n d 2Maternal Medicine, New Haven, CT OBJECTIVE: Triple antiviral therapy for the t r e a t m e n t o f HIV d u r i n g pregnancy has been associated with preterm delivery a n d small-for-gestationalage (SGA) fetuses. We studied women during a 10-year period to determine whether treatment with multiple antiviral medications worsened the perinatal outcome. STUDY DESIGN: Retrospective review o f w o m e n with HIV who were followed u p at the Yale H i g h Risk Clinic d u r i n g their p r e g n a n c i e s a n d delivered at the Yale New Haven Hospital from 1990-2000. Maternal demographics, treatment regimens, HIV acquisition risk factors, a n d delivery i n f o r m a t i o n were reviewed. W o m e n were g r o u p e d into 3 categories: n o treatment (group 1), monotherapy (group 2), a n d muldtherapy (group 3). RESULTS: A total of 93 patients were studied (group 1 = 21, g r o u p 2 = 34, a n d g r o u p 3 = 38). The groups were matched for age, race, gravidity/parity, risk factors for HIV, a n d m o d e o f delivery. A total o f 9%, 34%, a n d 15% o f women in groups 1, 2, a n d 3, respectively, h a d AIDS. The inidadon o f andviral therapy was equally distributed between each trimester (34% first trimester, 34% second trimester, a n d 32% third trimester). The mean gestational age at delivery was 37.0 weeks for g r o u p 1, 37.6 weeks for g r o u p 2, a n d $7,0 weeks for g r o u p 3. The mean birth weight was 2707 g for g r o u p 1, 2822 g for g r o u p 2, a n d 2680 g for g r o u p 3 (not significant, ANOVA, P = .05). T h e r e was n o significant difference in the presence o f intrauterine growth restriction o r 5minute A p g a r score <7 between the groups. CONCLUSION: O u r study f o u n d that aggressive antiviral therapy for HIV t h r o u g h o u t the a n t e p a r t u m period does not increase p r e t e r m delivery, SGA, intrauterine growth restriction, o r the n e e d for n e o n a t a l resuscitation at delivery. Earlier c o n c e r n s o f p r e t e r m delivery a n d S G A associated with multiple antiviral therapies should not preclude o n e f r o m using these agents d u r i n g pregnancy. Further study of the reduction in vertical transmission with aggressive antepartum treatment is ongoing.

$86 SMFM Abstracts Am 0267

0268

J a q t t a r y 20(11 Gynecol

J Obstet

STATE-MANDATED PRENATAL SCREENING F O R HUMAN IMMUNODEFICIENCY VIRUS AT A LARGE COMMUNITY HOSPITAL William Cusick '2, Julie Stewart, FNP I, Parry Michael, MD 3, Sullivan Chris, MD'-'; IStamford Hospital, Depts. of 2Maternal Fetal Medicine and 3Infectious Disease, Stamford, CT OBJECTIVE: Evaluate the impact of state-mandated h u m a n i m m u n o deficiency virus (HIV) screening at a large community hospital. STUDY DESIGN: Before October 1, 1999, mandatory HIV counseling and voluntary screening was practiced in the state of Connecticut. After that date, HIV screening of all p r e g n a n t women was mandated by the state legislature. U n d e r this policy, all p r e g n a n t women would be screened twice fox" HIV in p r e g n a n c y unless refused on religious grounds. Newhorns b o r u to mothers who h a d refused or failed to u n d e r g o screening would be tested for H W before hospital discharge. A hospital-based HIV team was organized to manage the transition to m a n d a t o r y screening a n d to ensure fixll compliance with the new law. Results over the first 10 months of screening are px'esented. RESULTS: A total of 2352 infants were b o r n to 2239 women during the study period. Nine cases of HIV were diagnosed during the study period. Seven (0.3%) p r e g n a n t women were screen positive for HIV. Two additional family m e m b e r s were diagnosed with HIV infection (child, spouse) after positive prenatal screening in the mother. It was estimated that 6 of 9 (66.7%) of these cases would have b e e n missed u n d e r a policy of voluntary prenatal HIV screening. Pregnant HIV-posidve women received aggressive antepartum a n d intrapartum therapy. All infants born to tile 6 women delivered to date have tested negative for HIV. Assuming a 30% vertical transmission rate without treatment, two cases of neonatal HIV were prevented. C O N C L U S I O N S : A policy of m a n d a t o r y prenatal HIV screening is practical a n d desirable. Benefits derived fi'om mandatory prenatal screening include (1) diagnosis a n d p r o m p t treatment of affected mothers, (2) early identification and treatment of HfV-infected relatives, and (3) prevention of vertically acquired neonatal HIV infection.

0269

MECONIUM PASSAGE AND RISK O F I N F E C T I O N AT TERM Allahyar Jazayeri I, Kathy Porter, MD '2, Michelle Sahinler. MDt; ITexas Tech Univ.. O b / G y n : '--'TexasTech Univ. Heahh Sciences (;enter, O h / G y n , Lubbock. TX OBJECTIVE: To investigate the association between meconium passage and materual inl~:ctions. STUDY DESIGN: T h r e e h u n d r e d lorry-six patients delivered with meconium and the next patient without meconium who was delivered at the same gestational age were compared over 18 luondls. RESULTS: T h e r e were 11o differences between the m e c o n i u m a n d nomeconium groups in maternal age, gravidity, gestational age, birth weight, duration of rupturecl membranes, length of labor, n u m h e r of wiginal exams. or 5-nlinnte Apgar scores. Meconium p,x~sage was associated with endometritis (odds ratio [OR] 2.87, 95% confidence iuter~"al [CI] 1.23-6.73; P = .012) but not chorioamnionitis. T h e r e was a h i g h e r rate of cesarean sectious in the m e c o n i u m g r o u p (21% vs 13%, P = .03). Logistic regression was used xo statistically correct fox"this potential c o n f o u n d e r and showed meconium to be an i n d e p e n d e n t risk factor (OR 3.2, 95% Cl 1.29-7.96; P= .013). When ~lginal and cesarean deliveries were analyzed separately, meconium was associated with endometrids only in vaginal deliveries (OR 6.15, 95% CI 1.71-22.11: P = .005). There was no difference in chorioamuionitis (8% vs 8%) or nmternal hospital stay (2.16 x~ 2.02 days) between the two groups. The overall rate of endometritis in vaginal deliveries with meconium was I 1%; in this g r o u p the average length of stay was 2.85 days (range 2-5 days) and the average maximuxn temper-ature was 38.3°C (rauge 38.0°C-39.9°C). C O N C L U S I O N S : T h e r e appears to be a clear association between m e c o n i u m passage a n d endometritis in vaginal deliveries. T h e rate of endometritis a n d the materual morbidity associated with it was low in the meconium g r o u p who were delivered vaginally. Observation and treatment of infected women in the postpartum period remains tile best optiun to reduce the risk of antibiotic resistance in the neonate.

THE a..INICAL SIGNII~CJuNCE O F INTR&-AMNIOTIC INFI.AMMATION IN PATIENTS ~ PRETF, RM L A B O R AND INTACT MEMBRANES Bo Hyun Yoont, Roberto Romero~, Gilja Kiml, J e o n g Bin Moonl, j u n g . E u n YangL Miha K i m I , J o o n g Shin P a r k l , J o n g Kwan J u n l ; tSeoul National Univ. College o f Medicine, O b / G y n , Seoul, Korea; '2Wayne State Uni~:, O b / G y n Maternal Fetal Med, Detroit, MI OBJECTIVE: Inflammation is a nonspecific mechanism of host defense. Infection is a leading cause of intrauterine inflammation. Yet the diagnosis of infection requires culture techniques. An alternative a p p r o a c h for clinical m a n a g e m e n t is to rely on the identification of intra..amniotic inflammation (I/d), which is easier a n d faster to diagnose than infection. The purpose of this study was to d e t e r m i n e the frequency a n d clinical significance of IAI in preterm labor. STUDY DESIGN: Amniocentesis was p e r f o r m e d in 206 patients with preterm labor a n d intact membranes. Amniotic fluid (AF) was cultured for aerobic/anaerobic bacteria a n d myeoplasmas. The diagnosis of IAI was made in patients with negative AF culture based on AF interieukln-6 (>2.6 n g / m L derived from receiver--operator characteristic curve). RESULTS: (1) IAI was m o r e c o m m o n than positive AF culture (21% [ 4 4 / 2 0 6 ] vs 10% [ 2 1 / 2 0 6 ] ) ; (2) amniocentesis-to-delivery interval was significantly shorter in patients with IAl than in those without inflammation (P < .0001); (3) spontaneous preterm delivery <37 weeks was more frequent in patients with IAI than in those without inflammation (98% vs 36%, P < .0001 ); (4) patients with IAI h a d a significantly h i g h e r rate o f adverse per:natal o u t c o m e than those without lad (Adverse outcomes included clinical a n d histologic chorioamnionitis, fun:sits, early preterm birth, significant neonatal morbidity, a n d death.); (5) there were no significant differences in the rate of adverse outcomes between patients with IAI a n d intra-amniotic infection. CONCLUSION: (1) Intra-amniotic inflammation/infection complicates o n e third of patients with preterm labor (31%, 65/206) a n d is a risk factor for adverse outcome; (2) the o u t c o m e of patients with positive AF culture is similar to that of patients with 1AI; (3) we p r o p o s e that m a n a g e m e n t of patients in preterm labor be based on the operational diagnosis of IAI rather than the diagnosis o f intra-amniodc infection, which cannot be quickly made.

0270

ASSESSING THE TERATOGENIC POTENTIAL OF ANTIRETROVIRAL DRUGS: DATA FROM THE ANTIRETROVIRAL PREGNANCY REGISTRY Patricia Garcia, MD t, Heather Watts, MD ~, Evelyn Rodriguez, MD 3, Harold Fox, MD 4, Nancy Yuen -~, Charles Shwamlein, MD 6, Peggy Do:7; INorthwestern University, O b / G y n , Chicago, IL; ~NIH, PAMA, and 3FDA, Division of DDRE II, OPDRA, Rocky:lie, MD; 4Johns Hopkins University, O b / G y n , Baltimore, MD; 5Agourun Pharmaceuticals, Drug Information and Safety, Apex, NC; 6Abort Laboratories, Epidemiology, Abbott Park, IL; VPharmaResearch, Wilmington, NC OBJECTIVE: To detect any increased rate or pattern of birth defects from exposure to antiretroviral drugs used in pregnancy. STUDY DESIGN: In 1989 a registry was established of p r e g n a n c i e s exposed to antiretroviral agents prospectively r e p o r t e d by health care providers. Timing of exposure a n d dosage were obtained. Immediate newborn outcome data were solicited at the time of delivery. Birth defects risks were c o m p a r e d with data from the CDC's population-based birth defects surveillance system. RESULTS: As of J a n u a r y 2000, 1123 evaluable, prospective cases have been reported. The prevalence of birth defects a m o n g first-trimester exposures is 1.4/100 live births (6 defects/444 live births, 95% confidence interval [C1] 0.6%-3.1%) for any antiretroviral drug. The greatest n u m b e r of first-trimester exposures has been reported for zidovudine monotherapy, a n d there was one defect a m o n g these 112 live births (0.9%, 9.5% CI 0%-5.6%). This prevalence does not significandy differ from those diagnosed within the first day of life by the CDC surveillance program (2.17%, 95% CI 2.10%-2.23%). No consistent or unique pattern of defects was seen. C O N C L U S I O N : To date, registry data d e m o n s t r a t e no increase in the prevalence of birth defects a m o n g first-trimester zidovudine m o n o t h e r a p y exposures, a l t h o u g h the power to detect such an increase is limited. A c c u m u l a t e d cases o f exposures to o t h e r antiretroviral agents are, as yet, insufficient to make reliable assessments of fetal risk. Prospective reports of antiretroviral exposures are critically important to determine their ter-atogenic potential a n d can be made by calling (800) 258-4263.

V o h t m e 184, N t t m b e r 1 AtnJ Obstet Gynecol

SMFM Abstracts $87

0271

VERTICAL TRANSMISSION O F HIV WITH HAART: R E D U C T I O N IN TRANSMISSION MAY BE INDEPENDENT OF VIRAL LOAD David Seals, MD I, Hank Roqne l, Machelle Allen, MD2; I New York University, O b / G y n , New York, NY; '-'New York Univ. Medical Center; O b / G y n , New York, NY OBJECTIVE: To determine whether HAART decreases the incidence of vertical transmission of H IV. MATERIALS AND METHODS: Retrospective cohort study of 83 obstetric patients with serology positive ibr HIV at Bellevue Hospital (]enter. OVERVIEW: The prevalence of HIV in the parturients at Bellevue Hospital has relnained at I% of the p r e g n a n t population fi):" tile past several vears. Starting in late 1997, patients with HIV and detectable viral loads were 13laced on antenatal muhiantiretroviral d r u g therapy (HAART, highly active antiretroviral therapy). RESULTS: There were 8 neonates positive Ior HIV followed up to at least 6 months post partum tot a vertical tlamsmission ~tte of 9.6%. In the 28 patients compliant with HAART, there were tlo vertical transmissions. Twenty-one patient.s were delivered vaginally, the r e m a i n d e r ahdominally. The average third-trimester viral load of these patients was 4886 c o p i e s / m L (range 5050,000 copies/mL). Compared with data fi'om the Women and Inl~.mts Study G r o u p (Garcia et al, N Engl J Med 1999;341:394-402) there is a significant reduction in vertical transntission (l-sided P~-alue: .0325). C O N C L U S I O N : Transplacental fetal HAART prophylaxis may offer superior protection to vertical transmission than zido~aldine :nonotherapy.

0273

0272

MULTIPLE DRUG ANTIVIRAL THERAPY F O R HIV IN PREGNANCY IS N O T ASSOCIATED WITH INCREASED ADVERSE PERINATAL O U T C O M E Donna Neale I, J o s h u a Copel '2, B. Joyce Simpson 3, Urania Magriples4; Iyale Univ. School of Medicine, Materual-Fetal Medicine, 2Ob/Gyn, 3Pediatrics, and 4Maternal Medicine, New Haven, CT OBJECTIVE: Triple antiviral therapy for HIV d u r i n g pregnancy has been reported to be associated with preterm delivery a n d small-for-gestadonal-age (SGA) fetuses. We studied w h e t h e r t r e a t m e n t with multiple ant:viral medications worsened per:natal outcome. STUDY DESIGN: Retrospective review of women with HIV who received antenatal care a n d were delivered at Yale New Haven Hospital from 1990-2000. Materual demographics, treatment regimens, HIV acquisition risk factors, and delivery information were reviewed. Women were g r o u p e d into 3 categories: no treatment (group 1), monotherapy (group 2), a n d multiple d r u g therapy (group 3). RESULTS: A total of 93 patients was studied (group 1 = 21, g r o u p 2 = 34, a n d g r o u p 3 = 38). There were no significant differences in age, race, gravidity, parity, risk factors for .HIV, or m o d e of delivery between the groups. Nine percent, 34%, a n d 15% of women in g r o u p 1, 2, and 3, respectively, h a d AIDS. The initiation of ant:viral therapy was equally distributed a m o n g trimesters (34% 1st trimester, 34% 2nd trimester, a n d 32% 3rd trimester). There was no significant difference a m o n g the groups in mean birth weight (group 1, 2707 g; g r o u p 2, 2822 g; g r o u p 3, 2680 g) or gestational age (group 1, 37.0 weeks; g r o u p 2, 37.6 weeks; g r o u p 3, 37.0 weeks). There was no significant difference in the presence of intrauterine growth restriction or in 5-minute Apgar score. CONCLUSIONS: In the largest study of this to date, we f o u n d that aggressive ant:viral therapy for HIV t h r o u g h o u t the antepartum period did not inc:'ease preterm delivery, SGA, intrauterine growth restriction, or the need for neonatal resuscitation at delivery. Earlier concerns of preterm delivery a n d SGA associated with mtdtiple ant:viral therapies should not preclude use of these agents d u r i n g pregnancy. F u r t h e r study of the r e d u c t i o n in vertical transmission with aggressive antepartum treatment is ongoing.

0274

SUDDEN cq-ANTITRYPSIN (¢xt-AT) SERUM ELEVATION AS A MARKER OF CHORIOAMNIONITIS Fabio Scarpellini I, Renzo Boccadoro 2, Luciano Scarpellini3; IUniversity of Pavia, Dept. of Internal Medicine & Medical Therapy, Section of Pharmacology, Rome, Italy; 2Colleferro ~Parodi-Delfino" Civil Hospital, 11 O b / G y n Division, Colleferru, Italy; -~University "La Sapienza" of Rome, II O b / G y n Institute, Rome, Italy OBJECTIVE: Chorioamnionitis is o n e of the most dramatic a n d dangerous complications of pregnancy, especially before the e n d of fetal lung maturation. Its sudden onset a n d rapid and uncontrollable progression jusdfy the continuous search of obstetricians to find some diagnostic indicators for preventing, avoiding, or timely treatment of this pathologic condition. The ct Iantitrypsin (cxl-AT) is a ubiquitous protein p r o d u c e d by many cell types, which has the specific function of neutralizing the trypsin enzymes released by the polymorphonnclear neutrophil leukocyte lysosomes. These cells are drawn by chemotaxis eidler during infections or during delivery. The authors tested the usefulness of this protein as a marker of chorioamnionids a n d its predictive value in this condition. STUDY DESIGN: Thirty-nine women with p r e m a t u r e r u p t u r e of m e m b r a n e s r a n g i n g between the 24th a n d 36th weeks were investigated prospectively for the occurrence of chorioamnionitis, confirmed by positive cuhure of amniotic fluid a n d histologic examination of membranes. RESULTS: This condition occurred in 11 women, I0 of whom showed ~xtAT levels above the cutoff standard defined by the authors. The cutoff serum level for cq-AT was >500 n g / d L . Twenty-three of the 28 patients without chorioamniooitis were c o n s i d e r e d negative for 0:l-AT because these were u n d e r the 500 n g / d L marker. The marker so valued showed a sensitivity of 90.9% a n d a specificity of 85%. T h e rise of the 0:i-AT levels o c c u r r e d appruximately 7 hours before the rise o f the body t e m p e r a t u r e a n d the average rate of this marker increase was 43% in the chorioamnionitis group, whereas in the 5 unaffected women posidve for the marker (>500 n g / d L ) the mean elevation rate was only 16%. C O N C L U S I O N : O u r findings suggest that the 0:i-AT can be a useful marker in the early diagnosis of chorioamnionids either by the evaluation o f its blood levels or the observation of its rate of increase, allowing for a preventive or timely therapy when there is a daily control of enzyme blood levels.

NERVE GROWTH FACTOR AND BRAIN-DERIVED N E U R O T R O P H I C FACTOR CONCENTRATION IN MATERNAL SERUM AND A M N I O T I C FLUID Tomoaki lkeda, MD I, Shunichi Noda, MD 1, Y] Xia, MDI, Tsuyomu Ikenoue, MD1; IMiyazaki Medical College, O b / G F a , M i F a T ~ , J a p a n OBJECTIVE: The neurutrophin family includes nerve growth factor (NGF) a n d brain-derived neurotrophic factor (BDNF), which play important rules in the development of the fetal nervous system. It has been postulated that the fetus produces a large amount of these neurotrophins, which may influence the amniodc fluid environment a n d m a m m a l conditions. The purpose of o u r study was to investigate NGF a n d BDNF levels in these two c o m p a r t m e n t s (ie, maternal serum [MS] a n d amniotic fluid [AF]) during pregnancy. STUDY DESIGN: MS was obtained before the 20th week a n d thereafter approximately every 6 weeks from 110 normal p r e g n a n t a n d once from 10 n o n p r e g n a n t women. AF samples were obtained from p r e g n a n t women at 15 to 19 weeks in = 16) a n d at 37 to 41 weeks in = 13) of gestadonal age. NGF a n d BDNF levels were measured by a 2-site enzyme-linked i m m u n o s o r b e n t a.~ay (EmaxTM immunoassay system, Prumega, Madison, WI). RESULTS: T h r o u g h o u t pregnancy NGF a n d BDNF levels in MS were 35 to 270 times a n d 320 to 960 times those of AF levels, respectively. MS NGF levels gradually rose unfit the 28th to 36th week evaluation point a n d then declined sharply to n o n p r e g n a n t values at term. At 28 to 36 weeks of gestafional age they were signiflcandy higher than that o f nonpregnant women (86.1 ± 26.6 vs 64.9 t 15.2 n g / m L , mean ± SD, P < .05). T h r o u g h o u t pregnancy MS BDNF levels were similar to n o n p r e g n a n t values. NGF in AF f r o m p r e g n a n t women at 15 to 19 weeks' gestation was higher than that at 37 to 41 weeks' gestation (2.06 + 0.84 vs 0.23 ± 0.11 ng/mL, P < .001 ). BDNF in AF at 15 to 19 weeks ~ gestation was also higher than that at 37 to 41 weeks' gestation (100.6 ± 13.3 vs 31.8 ± 6.6 p g / m L , P < .001). T h e r e was n o correlation between n e u r o t r o p h i n s n o r between compartments. CONCLUSION: These facts stimulate the f u r t h e r investigation to correlate MS a n d AF neurutrophins with the development of the fetal nervous system.

$88 SMFM Abstracts

J a n t t a r y 2001 Am J Obstet Gynecol

0275

DETERMINANTS OF NUCLEATED RED BLOOD cFJJ~ COUNTS IN TERM NEONATES? Kathleen Hanlon-Lundberg t, Russell Kirby2, Christine Van Mullem s, Fredrik Broekhuizen2; tUniv, of Michigan, Ob/Gyn, Ann Arbor, M1; 9Univerlsty of Wisconsin Medical School, Milwaukee Clinical Campus, Ob/Gyn; SSinai-Samaritan Medical Center, Ob/Gyn, Milwaukee, WI OBJECTIVE: Elevated nucleated red blood cells (NRBC) in fetal circulation are associated with adverse perinatal outcomes. We examined the association between newborn birth weight percentiles, select maternal characteristics, and umbilical cord blood NRBC counts. STUDY DESIGN: We prospectively collected blood from term neonates between 2 / 1 / 9 5 to 7 / 3 1 / 9 5 and 8 / 1 / 9 6 to 2/28/97. Trained hematology technicians performed analyses. Medical records provided correlative maternal and neonatal data. A race- and sex-specific national reference was used for birth weight percentiles: small-for-gestational-age (SGA) <10%, appropriate-forgestational-age 10%-90%, large-for-gestational-age (LGA) >90%. RESULTS: A total of 2599 term singletons met study criteria. The mean gestational age was 39.1 ± 1.17 weeks, birth weight 3305 ± 459 g. NRBC data were strongly skewed. A total of 2580 cases were analyzed. Overall, mean NRBC = 8.36/100 white blood cells (WBC), SD 10.34, median 5, mode 1, and range 098. NRBC increased with increasing gestational age (P = .002). LGA was associated with elevated NRBC (P< .001), but SGA was not (P= .990). Other factors independently associated with elevated NRBC were maternal diabetes (P< .001), primigravidity (P= .006), and black race ( P < . 001). Asian race was associated with lower NRBC (P = .031). When controlled for race, gestational age and birth weight percentile, factors NOT associated with elevated NRBC counts include maternal anemia, tobacco use, and payor status. Analysis of variance confirmed birth weight percentile, gestational age, and race to have significant influence on NRBC ( P < . 0001). However, together they accounted for 0.03 of observed variance. CONCLUSION: LGA, increasing gestational age, primigravidity, diabetes, and black race are independently associated with elevated NRBC in term neonates. Together they account for a small fraction of NRBC variation, suggesting that other, poorly defined factors influence this hematologic parameter in utero.

0277

DOCUMENTATION OF AMNIOTIC FLUID EMBOLUS VIA LUNG HISTOPATHOLOGY: FACT OR FICTION Gary Hankins, MD l, Russell Snyder, MD I, Tung Dinh, MD t, James Van Hook, MD I, Steven Clark, MD2; IUniv. of Texas Medical Branch, Ob/Gyn, Galveston, TX; "-'Univ. of Utah, Ob/Gyn, Salt Lake City, UT OBJECTIVE: To evaluate die reliability of pulmonary histopathology for confirming the diagnosis of amniotic fluid embolism. STUDY DESIGN: This is a large animal stndy using the Catna hirc*~model and fresh homologous amniotic fluid. The fluid was injected through the CVP port of a pulmonary artery catheter in a volume of 2.5 m L / k g animal weight (avg total volume 128 mL). Three types of fluid were injected: raw fluid (n = 8), filtered fluid (n = 14), and meconinm-stained fluid with from 1% to 7% solid debris (n = 7) as determined by microhematocrit tubes. The filtered fluid was placed through a 5-~tm filter. Three hours after embolization animals were killed and specimens were collected. Three to five areas of hmg were sampled, sites selected on the basis of the most abnormal areas by macroscopic examination. Hematoxylin and eosin as well as special stains were used. The study protocol was approved by the Institutional Review Committee and Animal Use and Care Committee. Statistical analysis was by X° with Yates' correction. Significance ~ras deferred as P< .01. RESULTS: Material felt to represent amniotic fluid debris or to include fetal squames, mucin, or foreign pigments was found in 10 of 24 animals (34.5%). Debris was tbund in 7/7 (100%) of the meconium ~'oup, in 2 of 8 (25%) of the raw fluid group, and in 1/14 of the filtered thtid group (7%). The likelihood of finding debris in amniotic fhtid emboli with meconiumstained fluid is much greater than with raw (P< .017) or filtered amniotic fluid (P< .001). CONCLUSION: Except in cases of clinically suspected amniotic fluid embolism involving meconium-stained fluid, histopathologic confirmation of amniotic fluid embolism is an unreliable marker for the event. In the absence of meconium, failure to demonstrate foreign debris in the maternal circulation is the rule and not the exception.

0276

COMPARISON OF ADRENOMEDULLIN AND ADRENOMEDULLIN RECF.,FrOR mlINA EXPRESSION IN PLACENTAS FROM NORMAL AND COMPLICATED PREGNANCIi~.q Christina Apodaca I, Brian Pierce 2, Todd Rossignols, Mary Joe Dehar0, Peter Napolitano 4, Roderick Hume s, Byron Calhoun'l; 1Tripler Army Medical Center, Honolulu, HI; 2Madigan Army Medical Center, Tacoma, WA; Madigan Army Medical Center, SClinical Investigation, 4Ob/Gyn, Ft Lewis, WA OBJECTIVE: To compare adrenomedullin (AM) and adrenomeduflin receptor (AMR) messenger RNA (mRNA) expression in placentas from pregnancies complicated by hypertension or olignhydramnios with placentas from normal pregnancies. STUDY DESIGN: RNA was extracted from amnion, chorion, cotyledon, umbilical vein, and umbilical artery of 14 normal placentas (N), 5 placentas from pregnancies complicated b~oligohydramnius (O), and 5 placentas from pregnancies complicated by hypertension (H). Expression of AM and AMR mRNA was compared between tissues by reverse transcription-polymerase chain reaction (RT-PCR). Results were analyzed by 1-way analysis of variance. RESULTS: RT-PCR data are summarized in the table. There was no difference in total AM mRNA a m o n g the three different placenta types. Placentas from patients with O contained more AMR mRNA compared with placentas from patients with N (P< .008) and from patients with H (P< .03). CONCLUSION: The increased expression ofAMR mRNA in O placentas relative to normal placentas may represent a fetoplacental compensatory response to a vascular insult in an effort to optimize vasodilation, The vasoconstricted state in patients with hypertension may reflect a decrease in AM receptor& Our findings of decreased AMP, mENA in placentas from these patients support this premise.

0278

PROTHROMBINASE EXPRESSION IN THE PREGNANT RAT UTERUS Daniel Rychlik1, Edward Chien t, Mark Phillippel; JUniv. of Chicago, Ob/Gyn, Chicago, IL OBJECTIVE: Thrombin, a component of the coagulation cascade, also activates specific cell surface receptors resulting in cellular effects. Thrombin is derived from prothrombin. Factors Xa and V generate thrombin in the plasma; in contrast, in tissues thrombin can be generated by a novel prothrombinase (fgl2). The activity of fgl2 is stimulated in response to proinflammatory cytoldnes (eg, interleukin [IL]-I, 11.,-2, tumor necrosis factor-a, and interferon gamma). These studies sought to test the hypothesis that fgl2 is expressed in pregnant rat uterine tissues. STUDY DESIGN: For these studies, uterine tissues were obtained from timed-pregnant Spragne-Dawley rats, placed in RNA-Later solution, then used for the isolation of total cellular RNA by the acidic gnanidinium thiocyanatephenol-chloroform technique. Subsequently, the RNA was treated with deoxyribonuclease and then used for reverse transcriptase (RT)-polymerase chain reaction (PCR) studies. PCR primers were generated with use of the reported mouse and human fgl2 sequences. Ethidium bromide-stained DNA gels allowed qualitative estimates of fgl2 expression in the rat tissues. RESULTS: With use of these primers, the predicted 299-bp amplicon was produced; sequence analysis of this amplicon confirmed its identity as the rat form of fgl2. RT-PCR studies performed with uterine tissues isolated during the second half of gestation confirmed expression of fgl2 in the placenta, the pregnant endometrium, and the myometrium. CONCLUSION: Activation of thrombin appears to be an important component of the tissue response m inflammation. Fgl2, a prothrombinase activated in response to proinfiammatory cytokines, appears to provide the mechanistic coupling between inflammation and the generation of active thrombin. Our studies have confirmed the expression of fgl2 in tissues of the pregnant uterus (which are also known to contain prothrombin). Therefore fgl2 could play a key role in the initiation of contractions, especially in response to local or systemic infection. (Supported by the NIHNICHD: HD01232 [E.C.] and HD2850fi [M.P.].)

R a t i o o f a d r e n o m e d u l i i n a n d r e c e p t o r (R) versus [32-microglobulin ~andard AMAM- lqIO NIt (R)CHORI N O H

1.7 1.3 0.9

0.3 0.8 0.I

1.3 0.7 0.8

UMB UMB CHORI COTYL UMB VEIN UMB ART OR) COTYL (R) VEIN ( ~ ART ( ~ 0.8 0.4 0.1

1.1 0.4 0.8

0.8 2.7 0.6

0.7 1.4 0.6

0.8 0.5 0.1

0.7 3.8 0.9

0.2 0.6 0.2

V o h t m e 184, N t t m t ) e r 1 Am J Obstet Gynecol

SMFM Abstracts S89

0279

THE INTRAUTERINE EXPRESSION OF PROTHROMBIN Mark Phillippe t, David Wolfft, Trevatlia Satm(iersl; IUlliV. oi'(;hicago, Oh/(;yrl, Cbicago. IL OBJECTIVE: Thr(,mbin, a conlponeut of tile coagulatiou cascade, activates specilic cell surl~lce receptors resuhing in celhdar elli_'cLs (eg, smooth muscle contractiollS). The ttterotonic effects of throfllbin a p p e a r to underlie cootractions in response to intt~mterine bleediug. Tile iotranteriue expression of tissne pr(,thrombimme (fgl2) suggests that endogenous thrombin production offllrs unrelated t O bleeding. These stndies sottgbt to demorJstrate that pr¢lthrombin is expressed within i'at uterine tissues. STUDY DESIGN: Uterine tissues were from estrus and pregnant Spt~lgueDawlev. rals. For Western hh,Ls, tissue was homogenized in a protease-inhibitor solotiou, proteins quantified by Coonlassic assay a n d immtmoblot.s perfurmed using anti-prothrond)in/thronlbitl antibodies. For immunobistochenlical (IH) stndies, tissue sections were incubated with tile same antibodies a n d then stained with the Vector Elite ABC kit. For RNA studies, total celhdar RNA was isolated with the acidic guanidinium-tbi,,cyanate-pltenol-chlorolbrna technique; reverse transcriptase (RT)-polymerase chain reaction (PCR) studies were perl~ormed with vat prothronlbin-specific P('R primers. RESULTS: Western blots c o n f i r m e d expression of p r o t h r o m b i o a n d Ihrolubin ill myomeu-ionl t]'oln estrus and pregnant rats. ]H studies confirrlled tbe preseoce of prothronlbin in both the circular and Iongitndinal layers of the nlyonlelrinnl, a h m g with expression ill tile endonletrinm below the surface epithelimn. RT-PCR studies confirmed prnthronlbin messenger RNA (mRNA) in the endometrial cells, whereas no prothronlbin mRNA was detectable in the myometriunl. CONCLUSIONS: These studies have c o n f i r m e d tile expression of p r o t h r o m b i n in tile endometrial and myometrial layel~ of the pregnant a n d n o n p r e g n a n t rat uterns. Prothronlbin appears to he syntbesized ill the e n d o m e t r h u n , whereas tile nlyonletriunl appears to sequester the preformed protein. The intt~mterine expression of prothrnmbin, along with lg12, provide support for the hypothesis that e n d o g e n o u s tbrolllbin g e n e r a t i o o is a paracrine nlechanism for tbe regulation of contractile activity. (Snpported by N I H H D28506 and H D32449.)

0281

0280

A DEVELOPMENTAL ANALYSIS OF CELLULAR LOCALIZATION OF ERYTHROPOIETIN mRNA, PROTEIN, AND RECEPTOR IN THE OVINE PLACENTA Matthew Kim, MD I, Ljubica Bogie, PbD I , Cecilia Cheung ~, Robert Brace, PhD2; Univ. of California, San Diego, Reproductive Medicine, ISan Diego a n d '-'LaJolla, CA OBJECTIVE: Curreutly tile role of erythropoietin (EPO) in the placenta is unclear. "Orehypothesized that characterization of the distribution of EPO in the ovine placenta would provide insight into the functional role of EPO in the regulation of maternal-fetal placental function. This study was designed to investigate the cellular localization of EPO messenger RNA (mRNA), protein, a n d receptor in ovine placenta. STUDY DESIGN: Pregnant sheep at 62, 100, a n d 142 days' gestation were studied, In situ hybridization was nsed to determine EPO mRNA distribution. Fluorescent immunocytochemistry was used to localize EPO protein and EPO receptor. RESULTS: At all ages studied, EPO mRNA hybridization signal was concentrated in the maternal portion of the placenta at the interface region between maternal carnncle a n d fetal trophoblast. Fluorescent signal for EPO protein was colocalized with EPO mRNA in the same region. EPO receptor signal was widely distributed in the fetal trophoblast as well as in the maternalfetal interface. This region is found to consist of a high density of binucleate cells. CONCLUSION: The localized expression of EPO in the maternal-fetal interface of the ovine placenta, a region densely populated by binucleate cells, suggests that these cells may be the site of EPO production. A developmental pattern in EPO gene expression was not apparent. Since binucleate cells are migratory steroid-producing trophoblast cells, they may be analogous to h u m a n extravillous trophoblast. Further, EPO was discretely expressed in the maternal-fetal interface, whereas EPO r e c e p t o r distribution was m o r e generalized t h r o u g h o u t the fetal trophoblasts. This may reflect a transport mechanism for EPO within the ovine placenta. We speculate that placental EPO may be involved in local mitogenesis or angiogenesis. Alternatively, EPO p r o d u c e d by the placenta may contribute to the circulating pool of EPO in the maternal a n d / o r fetal systems.

0282

GENE EXPRESSION OF AQUAPORIN 8 IN HUMAN CHORIOAMNIOTIC MEMBRANES: CELLULAR AND MOLECULAR MECHANISM OF INTRAMEMBRANOUS AMNIOTIC FLUID RESORPTION S. Wang t , W. Song l, N.S. Kallichanda t, M.G. Rosst; ]Harbor-UCLA Medical Center, Dept. o f O h / G y n , Torrance, CA Objectives: Anmiotic tluid (AF) is an essential accompaniment of normal pregnancy. AF fluid absorption across the chorioamniotic m e m b r a n e , the i n t r a m e n l b r a o o u s (IM) pathway, is critical for AF homeostasis. Yet th'e underlying mecbanism for the IM path~cay remains unknown. Aquaporins are cell m e m b r a n e watet~chamlel proteins that greatly e n h a n c e m e m b r a n e permeability to water. O u r recent study by reverse transcriptase-polymerase cbain reaction revealed that aquaporin 8 (AQP8) is expressed in both human a n d urine amnion, chorion, a n d placenta. In view o f hypothesis that AF is absorbed acrnss the chorioamnion via AQP8, we sought to determine the cell types in the fetal m e m b r a n e s that express AQP8 a n d filrther illustrate the celhdar mechanism for IM pathway. STUDY DESIGN: Fresh h u m a n placenta a n d fetal m e m b r a n e s were obtained at elective cesarean sections. In situ hybridization (ISH) was used to characterize tile celhdar expression of AQP8. In vitro transcribed antisense cRNA, labeled with biotin, was used as probe. The hybridized p r o b e was detected by streptavidin-alkaline p h o s p h a t a s e conjugate a n d NBT/BCIP detection system. Sense cRNA probe was used as a control. RESULTS: 1SH with antisense p r o b e detected AQP8 gene transcript in epithelium of chorion a n d amnion, as well as trophoblasts of placenta. ISH with sense probe was negative, confirming the specificity of ISH assay. AQP8 expression was highest in chorion a n d lowest in amnion. CONCLUSIONS: This is the first study demonstrating the expression of an aquaporin water channel (AQP8) in h u m a n amnion epithelium. AQP8 may be the major water chamlel mediating AF resorption via the IM pathway and thus a key element in the regulation of AF volume homeostasis.

NONINVASIVE MEASUREMENT OF CERVICAL COLLAGEN IN WOMEN IN ACTIVE VERSUS LATENT LABOR AT TERM Gayle Olson I, Cordula Fittkow, MD l, George Saade, MD l, Lynne Mackayt, Robert Garfieldl; IUniv. of Texas Medical Branch at Galveston, Ob/Gyn and Reproductive Sciences, Galveston, TX OBJECTIVE: To investigate collagen cross-finking in the human cervix during active versus latent labor at t e r m by use of llght-induced fluorescence (LIF). STUDY DESIGN: Cervical collagen was measured in 15 gravidas at 3742 weeks' gestation (9 latent labor, 6 active labor). Women in active labor had regular uterine contractions, cervical change, and cervical dilatation >5 cm. For the measurement of LIF of collagen, an excitation fight source centered at 340-nm wavelength was focused through a fused silica lens at the end of an optical wand that was placed in contact with the ectocervix. The fluorescence emitted from the tissue was collected into a grating monochromator and the spectra signals were directed to an optical multichannel analyzer connected to an on-line computer. The peak wavelength (390 nm) of the collagen spectrum was then determined and analyzed. For standardization, the ratio of count at 390 nm over reference was used as an indicator of collagen content. Data were tested for normality and are presented as mean + SD. Student t test was used for analysis (significance: P< .05). RESULTS: LIF in the group with active labor was significantly lower than in the group not in active labor (0.19 ± 0.1 vs 0.4 • 0.19; P= .029). CONCLUSION: Collagen crnss-finking in the cervix is lower in women in active labor compared with those not in active labor, a change that can be documented and quantified noninvasively by use of LIE Additional studies to determine the value of LIF measurements in differentiating active labor from other forms of uterine activity seems to be justified. (Supported by NIH HD 37480-01.)

$90 SMFM Abstracts Am

Jan u a r y 2001 J Obstet Gynecol

0283

SYNCYTIAL K N O T S ARE T H E S O U R C E O F PLACENTAL C R H Harvey Kliman, MD, PhDt,Juliette McSweet t, Trang La2; :Yale Univ., O b / G y n ; Wale Univ., Yale College, New Haven. CT OBJECTIVE: To identify the cellular source of corticotropin-releasing h o r m o n e (CRH) in the h u m a n placenta. STUDY DESIGN: H u m a n late third-trimester placentas were immunohistochemically stained for CRH (clone 4H9, Biogenesis). H u m a o hypothalamus served as the posidve control tissue while normal mouse ascites (NMA) served as the negative control antibody. RESULTS: The anti-CRH antibody stained the cell bodies of scattered neuronal elements within the hypothalamus while the NMA was negative. AntiCRH staining of the placentas revealed specific staining of syncydal knots of the villous syncytiotrophoblast layer. However, little staining was noted in the fiat, n o n k n o t t e d portions of the syncytiotrophoblast layer. CONCLUSION: Placental CRH is believed to promote fetal maturation by e n h a n c i n g glucocorticoid p r o d u c t i o n by the fetal adrenal gland. Placental CRH expression is f u r t h e r stimulated by the antagonistic b i n d i n g of progesterone a n d cortisol to glueoeorticoid receptors in the placenta. The result is a positive feedback loop between placental CRH and cortisol, wbich is consistent with the increases in fetal cortisol level, CRH level, dehydroepiandrosterone level, a n d fetal adrenal growth observed at the end of gestation. It has b e e n suggested that this regulates the placental clock that drives the increases in the mediators of labor. These stimulatory actions are coupled vAth the glucocorticoid effects on fetal o r g a n m a t u r a t i o n with the timing of parturition. We hypothesize that the adaptive placental response to the intrauterine stresses of term pregnancy or preterm uternplacental iusufficiency is the formation of syncytial knots. The production of CRH by syncytial knots therefore appears to be the critical event that promotes fetal maturation a n d parturition.

0285

CHOLINERGIC STIMULATION OF FETAL UPPER GASTROINTESTINAL M O T I I X r Y J e o n g J a e Lee, MD t, Reinaldo Acosta, MD 1. Masakatsu Sase, IVIDe, TerIT L. Buchmiller-Crair, MD2,James B. Atkinson, MD 2, Michael Ross, lVlD:~: ZHarbor-UCLA Medical Center, O b / G y n , Torrance, CA; '-'UCLA Medical Center, Div. of Pediatric Surgery, Los Angeles, CA; 3Unk; of California, Los Angeles, Harbor-UCLA Medical Center, Torrance, CA OBJECTIVE: Gastrnintestinal (GI) tract t~.mction includes the coordination of digestion, propulsiou, a n d nturient absorption in both the prenatal and postnatal periods. GI motility in the preterm fetus is immature. and it is unknown whether the fetus responds to prokinetic agents. We assessed the effect of bethaneeol, a cholinergic prokinetic agent, in the late-gestation rabbit fetus. STUDY DESIGN: Ten pregnant New Zealand White ~lbbits were studied at day 30 of their normal 31-day gestatkm. In each litter, two fetuses were selected as study (n = 19) a n d two as control (n = 19). U n d e r n h r a s o u n d guidance, a spinal needle was percutaneously inserted into the fetal stomach (mean body weigbt 50 g). Fluorescein, labeled with color-coated microspheres and either bethanechol (0.6 .Ug/gm in 30 ~L) or normal saline (30 IlL) was injected. Two hours after injection, ti~tuses were delivered, the small intestine harvested, and length fluorescein traveled was measured by calculating the UV light optical density. The percent motility, defined as the length of fluorescein traveled divided by the total length of the small intestine, was calculated. Results were analyzed by the paired Student t test. RESULTS: T h e p e r c e n t motility of b e t h a n e c h o l - t r e a t e d fetuses was significantly higher than that of control fetuses (64.6 _+2.8 vs 59.7% ± 3.0%; P < .05). Percent motility was correlated with fetal body weight in control (r2 = 0.53, P = .01) but not bethanechol fetuses (/e = 0.18, P = .23). CONCLUSION: Fetal u p p e r GI modlity is increased in relation to fetal body weight and in response to intragastric bethauechol. In utero stimulation of fetal GI motility may e n b a n c e nutrition of the preterm newborn and offcrs potential for in utero fetal therapy.

0284

ENDOT/4~,IJUM-DERIVED HYPERPOLARIZING FACTOR IN T H E VASCULAR BED O F T H E RAT UTERUS IN PREGNANCY Yuri Vedernikov l, Eva Fulep t, George Saade t, Robert Garfield:; lUniv, of Texas Medical Branch at Galveston, O b / G y n , Galveston, TX OBJEL,-I'IVE: TO define the role a n d n a t u r e of endothelium-derived hyperpolarizing factor (EDHF) in the rat uterine vascular bed (UVB). STUDY DESIGN: The U'VB from n o n p r e g n a n t , mid-pregnant (day 14) a n d term (day 21) female pregnant Spragne-Dawleyrats (n = 6 in each group) were isolated in situ a n d perfused via the iliac artery with Krebs buffer (2% dextran, 10--s m o l / L indomethacin, bubbled with 5% carbon dioxide in air (37"C, p H -7.4). The intraluminal pressure (IP) was monitored with pressure transducer connected to an on-line computer. The effects ofvarious agents on IP at constant flow rate (2 m L / m i n ) and on the flow rate-lP relationship (FRIP) were determined. RESULTS: The nitric oxide synthase inhibitor L-NAME (10 -4 m o l / L , 30 rain) did n o t significantly affect IP or FR-IP in UVB from n o n p r e g n a n t or p r e g n a n t animals. Infusion of p h e n y l e p h r i n e (10 .-6 m o l / L ) a n d L-NAME increased IP, without significant differences in m i d p r e g n a n t , term, a n d n o n p r e g n a n t animals, an effect that was not influenced by neither L-arginine n o r L-citrulline (both at 10-s m o l / L , 30 rain). A 5-minute infusion of acetylcholine (10- ~ m o l / L ) o r bradykinin (10-7 tool/L) decreased IP, an effect that did not d e p e n d on gestational age or the presence of L-NAME. Substance P (10- 7 m o l / L ) p r o d u c e d no significant change in IP either in the absence or presence o f L-NAME. The nitric oxide d o n o r D E A / N O (10 ~tL of 10-4 m o l / L as a bolus) decreased IP, an effect that was more p r o n o u n c e d in term animals a n d was not influenced by L-NAME. Acetylcholine in the presence of indomethacin a n d L-NAME decreased IP at term, an effect abolished by 30 m m o l / L potassium chloride, as well as by inhibitor of epoxygenase (miconazole, 10~ tool/L) but not by inhibitors of lypooxygenase (octa-9, 12dienehydroxamic acid, 10-6 m o l / L ) , or cytochrome P450 (17-octadecynoic acid, $ x 10 ~ m o l / L ) . CONCLUSION: EDHF in the UVB controls uterine perfusion a n d is not a p r o d u c t of lipooxygenase or cytochrome P450 pathways.

0286

TELEMETRIC CHARACTERIZATION OF T H E ELECTRICAL PROPERTIES O F T H E UTERUS DURING GESTATION AND PARTURITION IN C O N S C I O U S , UNRESTRAINED RATS Shao-Qing Shi ), William Maner t, George Saade I, Robert Garfieldl; IUniv. of Texas Medical Branch at Galveston, O b / G y n , Galveston, TX OBJECTIVE: To determine the changes in electrical parameters of uterine activity "bursts" over gestation a n d parturition by use of telemetric electromyography (EMG) in conscious unrestrained rats. STUDY DESIGN: O n day 12 of a 21-day gestation, 4 t i m e d - p r e g n a n t Sprague-Dawley rats (term = 21 days) were outfitted with internal telemetry devices (CS0-PXT models from Data Sciences, St Paul, MN) for measuring uterine EMG through bipolar electrodes sutured to the uterine wall. From day 17 of gestation until 4 h o u r s post partum, uterine EMG activity was continuously r e c o r d e d while the rats were conscious a n d unrestrained. Sampling was d o n e at 10 Hz a n d band-pass filtered from 0.3 to 5 Hz. Data were transmitted by telemetry to an external receiver (RLA 1020 telemetry receivers, Data Sciences) a n d fed to a recording system (MaeLab 16/s, AD Instruments, Castle Hill, Australia). For each burst of electrical activity, Chart software (AD Instruments) was used to generate a PDS peak a n d to determine the frequency a n d magnitude of the peak. RESULTS: Between days 17 a n d 21, the PDS peak frequency (overall mean = 1.13 ± 0.03 Hz) a n d magnitude (overall mean = 1.18 + 0.06 mV) exhibited no significant change from day to day (P > .05). From day 21 to 22 of gestation, the average value of the PDS peak frequency (2.85 + 0.88 Hz) a n d magnitude (2.78 ± 1.01 mV) was significantly higher ( P < .05) than previous days. There was no significant diurnal variability noted at any day. C O N C L U S I O N S : Uterine electrical activity can be accurately characterized t h r o u g h o u t pregnancy in conscious, unrestrained animals. An increase in PDS peak frequency a n d magnitude precedes the onset of labor. Measurement of these electrical parameters may be useful in the detection a n d m a n a g e m e n t of preterm a n d term labor.

SMFM Abstracts S91

V o l u m e 184, N u m b e r 1 AmJ Obstet Gynecol 0287

CHANGES IN BLADDER PRESSURE AND ELECTRICAL ACTIVITY DURING PREGNANCY IN C O N S C I O U S , UNRESTRAINED RATS Shao-Qing

0289

GESTATIONS Roger B. Newman, MD |, Roger Newman l, for the NICHD MFMU Network; INICHD MFMU Network, Bethesda, MD OBJECTIVE: To c o m p a r e on contraction frequency by gestational age between singleton a n d twin gestations. STUDY DESIGN: A total of 59 twin a n d 306 singleton gestations met m i n i m u m c o m p l i a n c e criteria in an observational study of h o m e uterine activity m o n i t o r i n g (HUAM) at 11 centers between 1994 a n d 1996/ Contraction frequency was r e c o r d e d 2 t i m e s / d a y on 2 days/week from enrollment between 22 and 24 weeks until delivery or 36 weeks 6 days. HUAM data were interpreted according to a standard protocol. Mean contraction f r e q u e n c y / h o u r per gestational week was calculated. Repeated measures analyses were performed to determine whether uterine contraction frequency differed between singleton and twin gestations across gestational ages. it was also determined whether differences in contraction frequency existed when twins and singletons who delivered either term or preterm (<35 weeks) were evaluated separately. RESULTS: A total of 34,908 hours of HUAM were recorded by the 306 singleton gestations a n d 5427 hours were r e c o r d e d by the 59 twins. No contractions were seen on 79.2% a n d 67.7% of the monitored singleton a n d twin hours, respectively. Twins have a significantly g r e a t e r c o n t r a c t i o n frequency (P = .002) compared with singletons, regardless of gestational age. The difference in c o n t r a c t i o n frequency between singletons a n d twins remained significant regardless of the type of delivery (preterm or term). Mean contraction f r e q u e n c i e s / h o u r were greatest for twins delivered preterm (<35 weeks). Mean contraction f r e q u e n c i e s / h o u r were nearly identical for singletons who were delivered preterm a n d for twins who were delivered at

Shi t. George Saade t, Robert Garfiehlt: IUniv. of Texas Medical Branch at Gah'eston, O b / G v n , (,alveston. TX OBJECTIVE~ To determine changes in bladder pressure and electrical activity during preguancy in a n u model by use of telemetric methods. STUDY DESIGN: On day 12 of gestation. 5 pregnant t-aLswere outfitted with internal telemetry devices (('50-PXT models, Data Sciences, St Paul, MN) tor m e a s u r i n g b l a d d e r pressure a n d e l e c t r o m y o g r a p h y (EMG) activity. A c a t h e t e r was sutured into the bladder, a n d bipolar EMG electrodes were attached to the bladder wall. Fetal weights were measured in similar animals killed daily (n = 6 for each day). From clay 15 of gestatinn, bladder pressure and EMG of al'l rats were continuously recorded through day 21 of gestation (term = day' 22) while they were conscious and unrestrained. Sampling was done at 10 Hz. Data were n,'ansmitted by telemetry to an external receiver (RLA 1020 model, Data Sciences) a n d recorded (MacLab 16/s, AD Instruments, C,'tstle Hill, Australia). Maximmn pressures at 4-hour intervals a n d EMG power spectra at 12-hour intervals were estimated by use of Chart software (AD Instruments). RESULTS: From day' 15 to 21 of gestation, bladder maximum pressure gradually' and progressively declined fiom 51.96 ± 2.16 to 20.45 ± 1.57 mm Hg (P < .05). EMG power spectrnm peak fi'equency remained relatively, steady; whereas EMG power spectt-um magnitude showed a significant increase (P < .05) from the day 15-16 period (1.26 ± 0.05) to the day 19-21 period (1.85 ± 0.09). Fetal weights rapidly increased from 0.2997 _+0.01 to 5.3996 ± 0.17 g (P< .01). CONCLUSIONS: Pregnancy is associated with a progressive decrease in bladder pressure a n d a marked increase in bladder EMG peak power. These changes are the resuh of tetal growth, which reduces the bladder's volumetric capacity and requires greater muscular exertion to void.

0288

DISTINCT EXPRESSION LEVELS OF PROSTAGLANDIN E.2 IN FETAL AND MATERNAL COMPARTMENT IN N O R M A L TERM HUMAN PLACENTA

M a h m u d Huleihel l, Gershon Holcherg'-', Sharon Levi -~, Olga Sapir 4, Miriam Katz5, Avraham Danon 6, Ela Kagan 7, Leslie Myatt8, Moshe Mazorl; ISoroka Univ. Hospital, --Ben Gurion University of The Negev, Dept. of O b / G y n , Beer Sheva; 3Soroka Univ. Medical Center, Ben Gurion 5University of The Nege~; O b / G y n , Beer Sheva, 7University of The Negev, Dept. of Clinical Pharmacology, Beer She~a, Israel; SUnk,. of Cincinnati Medical Center, O b / G y n , Cincinnati, OH OBJECTIVE: To evaluate the levels of prostaglandin E 2 (PGE,2) in fetal and maternal sites of the isolated normal h u m a n placental cotyledon. STUDY DESIGN: Isolated placental cotyledons were dually perfused for 10 hours in 5 n o r m a l term placentas. Perfusate samples from fetal a n d maternal sites were collected every 30 minutes during 10 hours a n d examined by radioimmunoassay for PGE 2 levels. Statistical significance was determined by paired t test and analysis of variance. RESULTS: A significant increase in PGE 2 concentration was observed in maternal a n d fetal circulation within 8 to 10 hours of perfusion in term placentas. The increase Of PGE 2 in perfusate was time-course dependent. The basal levels of PGE 2 were significantly h i g h e r in the fetal c o m p a r t m e n t compared with the maternal c o m p a r t m e n t (127 ± 20 p g / m L vs 20 ± 9 p g / m L , P < .05). A significant increase i n PGE 2 levels was detected in the fetal c o m p a r t m e n t (from 127 ± 20 p g / m L to 480 :t 126 p g / m L , P < .05 within 120 minutes), followed by a significant decrease (from 480 ± 126 p g / m L to 180 ± 9 p g / m L , P < .05). A siguificant increase of PGE 2 was detected in the maternal c o m p a r t m e n t (from 20 ± 9 p g / m L to 286 ± 86 p g / m L , P < .05). After 10 hours of perfusion the fetal PGE 2 levels were significantly lower than maternal (180 ± 19 p g / m L vs 286 ± 86 p g / m L , P < .05). CONCLUSIONS: The results of o u r study demonstrated higher levels of PGE 2 in the fetal c o m p a r t m e n t than in the maternal site. This pattern of expression was conversed after 10 h o u r s of perfusion. It may indicate a production of PGE2 by the maternal site and degradation by the fetal site. Thus PGE,2 may be involved in the regulation of the placental physiologic function during h u m a n parturition.

UTERINE ACTIVITY DURING PREGNANCY: SINGLETON VERSUS TWIN

tel'In.

C O N C L U S I O N : Mean uterine contraction frequency was significantly higher for twin gestations compared with singletons t h r o u g h o u t the latter half of pregnancy. Significant differences persisted when the twins a n d singletons delivered either preterm or term were compared separately.

0290

T H E EFFECT OF A N ELEVATED MATERNAL LYSINE CONCENTRATION O N LYSINE T R A N S P O R T A N D CATABOLISM IN T H E O V I N E M O D E L

Paul Wilkes 1, Yarning Zhu 2, Cecilia Teng 2, G i a c o m o Meschia 2, Randy Wilkening 2, Paul Fennessey, Dr 2, Frederick Battaglia2; IUniv. o f C o l o r a d o Health Sciences Center; 2Univ. of Colorado Health Sciences Center, Pediatrics, Denver, CO OBJECTIVE: O u r goals were to examine whether lysine (Lys) delivery to the fetus a n d placental Lys uptake could be increased by a 4× increase in maternal Lys concentration. STUDY DESIGN: L-[U-13C]Lys a n d 12C-L-Lys were infused into the maternal circulation to increase maternal c o n c e n t r a t i o n to 4x steady-state conditions. T h e c o n c e n t r a t i o n s of 12C-L-Lys a n d 12C-0t-aminoadipic acid (aAAD), a metabolite of Lys catabolism, were measured in maternal baseline a n d experimental (4:< baseline concentration) states. Maternal femoral artery (A), uterine vein (V), fetal hindlimb artery (a), a n d umbilical vein (g) were sampled. Uterine a n d umbilical blood flows were measured by the steady-state diffusion technique. RESULTS: Uterine uptake, fetal uptake, a n d uteroplacental uptake o f Lys were h i g h e r at increased maternal Lys c o n c e n t r a t i o n s (P = .01, .02, .03, respectively). Approximately two thirds of the increase in uterine uptake was used within the placenta a n d o n e third within the fetus (see table, units = g m o l / k g / m i n ) . 12C-aAAD c o n c e n t r a t i o n s increased significantly in the maternal circulation in the e x p e r i m e n t a l period ( P = .002). T h e r e was a significant trend in umbilical ateriovenous difference for 12C-aAAD at elevated maternal Lys concentrations. C O N C L U S I O N : T h e elevated maternal Lys c o n c e n t r a t i o n led to a n increased Lys delivery to the fetus a n d the initiation of net placental Lys use. The 12C-aAAD data clearly establish increased lysine catabolism in the fetus in the experimental period. We were able to d e m o n s t r a t e increased fetal catabolism o f Lys. We hypothesize that placental use o f Lys c h a n g e s as a function of maternal Lys concentration. 12C-Lys u p t a k e

.

UTERINE UI~AKE 12CLYS

BASELINE 2.42 ± 1.05

4x BASELINE 8.54 ± 3.39

UMBILICAL UPTAKE

UTEROPLACENTAL UPTAKE

BASELINE

4x BASE IJNE

B.A.,SEIJNE

4x BASELINE

2.76 ± 0.32

4.25 + 0.85

--0.34 ± 1.19

4.29 + 3.52

$92 SMFM Abstracts

J a n uary 2001 AmJ Obstet Gyuecol

0291

EFFECT OF CRYOPRESERVATION ON UMBILICAL CORD STEM CF.I J.q: PERCENT CD34 + AND VIABILITY IN TERM AND PRETERM CORD BLOOD AFrER FREEZING Lucy A. Bayer-Zwirello, MD I, Despina Hoffman 2, Lorrie Adams 2, Fadi A. Bsat, MD s, Paul Wilde#, Sejal PateP, Margaret Reece, PhD2; :Tufts Univ., Ob/Gyn, 2Baystate Medical Center, Dept. of O b / G y n Research, SBaystate Medical Center, Die. of Maternal-Fetal Medicine, Dept. of Ob/Gyn, Springfield, MA; 4Viacell Inc, Worcester, MA OBJECTIVE: Cord blood intended for transplantation is often cryopreserved in liquid nitrogen. However, the effects of freezing on stem cell populations are not known. The objective of this study was to characterize the white blood cell population in umbilical cord blood by gestational age after cryopreservadon in liquid nitrogen. STUDY DESIGN: Umbilical cord blood was collected from 60 patients after delivery at Bays:ate Medical Center. Blood was collected in heparinized syringes, processed for white blood cells, and frozen in liquid nitrogen within 48 hours of collection. Cells were quick thawed and reconstituted as per standard protocol. White blood cells were counted with trypan blue staining and a hemacytometer. Fluorescence activated cell sorting analysis in accordance with ISHAGE guidelines was used to establish CD34 + concentration and viability. RESULTS: The mean CD34 + cell concentration was 6352.5 4. 6922.1 cells/mL for preterm and 3705.7 :t: 4405.2 cells/mL for term gestational cord blood. The percent CD34 ÷ for preterm and term was 0.08 + 0.09 and 0.17 4. 0.51, respectively. The mean percent cell viability for preterm cord blood was 54.1 ± 16.5 compared with 49.6 4- 16.3 for term blood. Viability after freezing ranged from 13.3% to 93.1% with no significant differences between preterm and term gestations. There was an inverse correlation between CD34 + cells and gestational age (r= -0.396, P = .002). CONCLUSION: Similar to published data reporting CD34 + counts on fresh cord blood, we found that the CD34 + concentration on frozen cord blood decreases with increasing gestational age. However, the percentage of CD34 + cells after freezing appears to be lower than percentages reported by others on fresh cord blood. This suggests that these cells freeze poorly.

0293

132-MICROGLOBULIN LEVELS: A POTENTIAL MARKER OF FETOMATERNAL HISTOCOMPATIBILITY Edward Kuc~,nski l, Nebojsa RadtmovicL Gian Carlo Di Renzo'-', Charles Lockwoodt; INew York Uni`.:, Ob/G,~aL New York, NY; -"University Hospital, Perngia, Center of Reproductive and Perinatal Medicine, Perugia, Italy OBJECTIVE: Pregnancy can he considered a successful allogeneic tissue transplant. Because ]$,rmicroglobulin (B2M) increases during organ rejection episodes and graft-versus-host disease, we studied whether B2M levels change during pregnancy. STUDY DESIGN: We conducted a cross-sectional analysis of 3.5 paired fetal and maternal serum samples obtained between 18 and 38 weeks' gestation at tile time of diagnostic cordocentesis in uncomplicated pregnancies resuhing in normal term delivery, using regression analysis and Stodent t tests. RESULTS: Fetal B2M levels decreased significantly across gestation (r = -0.67, P < .001); mean values were sigafilicantly higher than maternal ",';titles (3.34 [+0.68] m g / L vs 1.50 ,~.0 [4.0.34] mg/L, P < .001). Maternal levels correlated positively with gestational age (r = 0..34, P = . 0 4 ) . There was no correlation +.s . 12":,. .:.., ..... . between fetal and maternal walues (r= -0.21, P= .22). CONCLUSION: Fetal B2M values decrease significandy as gestation progresses and are substantially greater than maternal levels but are not correlated with maternal levels, suggesting fetal production of B2M. The increase in maternal 16 21 26 g' g6 B2M across gestation may e¢:tt:i>n+l n9¢ reflect an immnllomodnlaB2M a n d g e s t a f i o n a l a g e tion process.

0292

OPTIMAL P R O C E S S I N G O F U M B I L I C A L C O R D B L O O D F O R RETRIEVAL OF W l 4 r l ~ BLOOD: A COMPARISON OF METHODS Lucy A. Bayer-Zwirello, MD l, Despina Hoffman 9, Lorrie Adams 2, Fadi Bsat s, Sejal Patels, Margaret Reece, PhD9; lTufts Univ., Ob/Gyn, 2Baystate Medical Center, Dept. of Ob/Gyn Research, SBaystate Medical Center, Dept. of Ob/Gyn, Die. of Maternal-Fetal Medicine, Springfield, MA OBJECTIVE: Most cord blood banks separate white blood cells from red blood cells before freezing and storage. Cell recovery and morphology were evaluated after physical versus chemical separation processes of white blood cells fi'om umbilical cord blood. ~ Y D$'-qIGN: Sixty-two umbilical cord blood samples were collected d u r i n ~ e study period. Samples collected from 10/97 to 2/98 (n = 42) were • physically separated by use of standard Ficoll-Paque technique (Amersham Pharmacia Biotech AB). Those collected between 3/98 and 6/98 (n = 20) were chemically separated by the Puregene Red Blood Cell Lysis Solution (C,entra Systems, Inc.). Cells were counted before and after processing. A mean percent difference in the number of cells before and after processing was calculated. Cytospin-deposited cells after processing were rated for morphology with hematoxylin and eosin. R F . S U L T S : The mean differences for the preprocessing and p o s t p r o c e ~ n g cell counts were 3.8% + 3.7% for the Ficoli-Paque protocol and 1 , 8 % ± 5,3% for Puregene protocol. Ficoll-Paque and Puregene protocols yielded approximately 46% and 51% of intact cells, respectively. CONCLUSION: Both protocols performed equally well. However, the Puregene protocol requires less time and is more cost efficient and thus has greater practical value.

0294

TENSILE STRENGTH OF THE CHORIOAMNION THROUGHOUT GESTATION Eva Pressman |, James Woods I, Gail Bestl; IUniv. of Rochester, Ob/Gyn, Rochester, NY OBJECTIVE: We have shown previously that reactive oxygen species in vitro weakens the chorioamnion, whereas vitamin therapy protects the membrane. The purpose of this study was to determine the tensile strength of the chorioamnion at various gestational ages. STUDY DESIGN: Segments of chorioamnion were obtained from 13 patients delivered at gestational ages ranging from 17 to 40 weeks. Clinical information including gestational age, chorioamnionitis, premature rupture of membranes, and onset of labor was recorded. Tensile strength (grams to burst) was measured on 2 to 4 specimens per patient. RESULTS: Tensile strength increases up to 20 weeks' gestation and then plateaus until after 39 weeks' gestation, when it falls dramatically (see figure). Clinical chorioamnionitis alone did not affect tensile strength but the one twin pregnancy with gross pathologic evidence of membrane inflammation in only one sac did have reduced tensile strength on the inflamed side. CONCLUSIONS: Tensile strength of the chorioamnion varies with gestational age. This baseline information will be useful in assessing the effects of various conditions and therapies on membrane strength and may provide insight into strategies for the prevention of preterm premature rupture of membranes. m

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V o l u m e 184, N u m b e r 1 Am J Obstet Gynecgl 0295

SMFM Abstracts $93

THE EFFECTS OF ORTHOSTATIC CHANGES O N MATERNAL DIASTOLIC FILLING PATTERNS J e a n - C l a u d e Veille l, Dalane Kitzman2; Wake Forest Univ., t O b / G y n and "Cardiology, Winston-Salem, NC INTRODUCTION: Left ventricular diastolic filling patterns (LVDFP) are an essential part of cardiac function. Little is known regarding the effect of p r e g n a n c y (P) on LVDFP including those that o c c u r d u r i n g orthostatic aherations. METHODS: Ten healthy women were followed up longitudinally during each trimester and at 12 weeks post par:ore. Patients were studied by use of pulsed Doppler across the mitra[ valve (1) supine (S), (2) after 15 minutes of 600 head up (HU), and (3) after 15 minutes of 300 bead down (HD). Total time velocity integral (TVI), peak early (E) a n d atrial (A) filling velocities, E / A ratio, E deceleration time (DT), isovolumetric relaxation (IVR), a n d heart rate (HR) were analyzed. Results are expressed as means ± SD. (^ = Difference with S), (P, all 3 trimesters were polled together). RESULTS: (l) HU significantly decreased TVI, E peak, a n d DT a n d increased HR a n d IVR, (2) HD did not affect LVDFP, (3) P did not alter LVDFP. C O N C L U S I O N : Orthostatic gravitational stresses affect LVFDP but P *does not alter this response.

0297

D i a s t o l i c f'dling c h a n ~ e s w i t h o r t h o s t a t l c s t r e s s e s HR

TVI

NP-S 65.7 ± 6 18,9 ± 3 P-S 76.4 ± 11 18.8 + Np-AHU +4,6 -2.8 p-AHU +6.8 -2.5 NP~HD -1.7 +0.5 P-AHD --0.8 +0.2

E PEAK A PEAK 77.4 ± 87.9 ±* -11.6 -14.1 +3.5 +4.5

47.4 + 57.9 ± -2,7 +1.6 +0.5 -3.5

E/A

DT

IVR

1.69 ± 1.60 ± -0.13 -0.26 +0.1 +0.3

249 ± 205 ± -22 -10 -35 -13

91.1 ± 80.6 ± +13 +5.6 -2.6 -2.5

O R A L MAGNESIUM DOES N O T ALTER BRAIN LEVELS O F IONIZRD MAGNESIUM IN P R E G N A N T RATS Cynthia Standley, PhD t, Michelle D a u g h e r t y l Jessica Lohff, BSI; I Midwestern Univ., Physiology, Glendale, AZ OBJECTIVE: We have previously shown that oral magnesium alters blood a n d brain levels of magnesium a n d calcium in n o n p r e g u a n t rats. The purpose of this study was to examine oral magnesium versus an acute treatment with magnesium on brain levels of ionized magnesium in p r e g n a n t rats. STUDY DESIGN: Forty-four Long-Evans p r e g n a n t rats were used in the. study. Pregnant rats were placed on special diets fed ad libitum with free access to water on gestadonal day 6 a n d remained on these diets until postpartum day 1 (10 high-magnesium diet, 10 low-magnesium diet, 10 basal diet). The only difference a m o n g the diets was the content of magnesium. O n postpartum day 1, rats were killed a n d blood, cerebrospinal fluid (CSF), a n d b r a i n were obtained and processed for determination of sodium, potassium, calcium, a n d magnesium levels. Pups were weighed a n d measured. An additional set of rats received intraperitoneal magnesium sulfate for 2 hours on gestational day 21 or an equivalent a m o u n t of saline (7 magnesium treated, 7 saline controls). After 2 hours, rats were killed, a n d blood, CSF, a n d brain were obtained, processed, and analyzed. RESULTS: Although blood levels were altered with the diets, CSF levels were not. CSF levels were higher in the 2-hour magnesium group, suggesting some a d a p t a t i o n of the brain u n d e r c h r o n i c dietary conditions. P u p measurements were not affected by the low- o r high-magnesium diets. C O N C L U S I O N : Although dietary manipulations of m a g n e s i u m alter brain levels in n o n p r e g n a n t rats, this does not a p p e a r to be the case in pregnant rats. The brain of pregnant rats may adapt to chronic changes as a protecdve measure. I o n i z e d m a g n e s i u m levels BLOOD Low magnesium Basal High magnesium 2-Hour saline 2-Hour magnesium

CSF 1.45 + 0.02 1.46 ± 0.02 1.58 ± 0.07 1.35 ± 0.08 1.71 ± 0.071.

0.85 ± 0.06* 1.51 ± 0.14 2.20 ± 0.11" 1.67 ± 0.11 4.99 :t: 0.42t"

Values in milligrams per deciliter. *P< .05 compared with basal diet. 1.P < .05 compared with saline group.

0296

CONTRACTILE ACTIVITY OF OVINE FETAL C O L O N : MECHANISM F O R MECONIUM PASSAGEJeongJae Lee, MD l, Reinaldo Acosta, MD I, Masakatsu Sase, MD 2, Terry L. Buchmiller-Crair, MD 2, Michael RossS; IHarbor-UCLA Medical Center, O b / G y n , Torrance, CA; 2UCLA Medical Center, Div. o f Pediatric Surgery. Los Angeles, CA; 3Univ. of California, Los Angeles, HarborUCLA Medical Center, Torrance, CA OBJECTIVE: Meconium is believed to be passed in utero in response to fetal maturation or "stress." Aldlough colon motility is required for meconium passage, It:de is known of the regulation of fetal colonic motility. We examined the normal patterns of contractile a n d myoelectric acdvity of the colon in the late-gestation ovine fetus. STUDY DESIGN: Five near-term (135-day) singleton ovine fetuses were chronically p r e p a r e d with three sets of miniature strain gauges a n d bipolar electxomyogram (EMG) electrodes implanted on the serosa of the transverse a n d descending colon. After 5 days of recovery, contractile a n d myoelectrical activity were r e c o r d e d a n d stored digitally. Data were analyzed a n d colon activity defined by both strain gauge a n d EMG. RESULTS: Colon activity periods were divided into active a n d resdng states. As defined by the strain gauge, active states a c c o u n t e d for 14.1% ± 12.6% a n d resting states for 85.9% ± 12.6% of time. Active states were composed of bursts o f high amplitude contractile activity with a mean duration of 10.9 ± 3.4 seconds a n d an average of 8.2 ± 4.5 spike bursts. Resting states displayed low-amplitude contractions of both short (SDC) a n d long d u r a d o n (LDC). SDC had a mean duration a n d frequency of 6.4 ± 2.7 seconds a n d 87.3 ± 9.3/10 minutes, respectively, a n d a p p e a r e d continuously. LDC had mean duration of 44.5 ± 6.9 sec a n d 12.9 ± 2.8/10-minute frequency. EMG acdvity distinguished two kinds of activity. An EMG short-duration spike burst lasted 1.5 ± 1.7 seconds a n d was usually rhythmic and grouped. EMG long-duration spike bursts (9.8 ± 6.7 seconds) were intermittent a n d irregular. CONCLUSION: The fetal colon displays marked EMG a n d myocontractile activity n e a r term. A l t h o u g h resting states may r e p r e s e n t colonic c o n t e n t mixing, active states are consistent with colonic propagation. Identification of regulators of colon activity may aid in u n d e r s t a n d i n g a n d prevention o f meconium passage in umro.

0298

ANGIOTENSINOGF,N "r235 IS ASSOCIATED W I T H ABNORMAL SPIRAL ARTERIES IN TERM M O R P H O L O G Y Ling Zhao I, Terry Morgan ~, Kenneth WardS; IUniv. of Utah, CAMT, Perinatal Genetics Lab, Salt Lake City, UT; 2Stanford Univ., Dept. of Pathology, Stanford, CA; SUniv. o f Utah, O b / G y n & H u m a n Genetics, Salt Lake City, LIT OBJECTIVE: Preeclampsia is associated with a c o m m o n molecular variant o f a n g i o t e n s i n o g e n (AGT) (M235T). We have shown t h a t the AGT T235 variant is associated with a b n o r m a l spiral artery r e m o d e l i n g in first- and second-trimester decidua. For this study, we hypothesized t h a t AGT 1"235related failure of physiologic changes will be observed in placental b e d biopsy specimens at term. METHODS: By use of a n Institutional Review B o a r d - a p p r o v e d protocol, 280 myometrial blood vessels from 25 control a n d 4 p r e e d a m p f i c women at term were examined. And-0t-smooth muscle acfin a n d anti-yon Willebrand factor were used to highlight arterial walls. Quantitative histology was accomplished with Image-Pro Plus. Blood vessel aspect, lumen diameter, a n d area were measured. Incomplete cross-sections a n d tangential cuts with aspects larger than 2 were excluded. Mutagenically s e p a r a t e d pol~merase c h a i n reaction was used m determine the AGT genotype. Vessel m o r p h o l o g y was compared with genotype with the Student t test. RF.,SULTS: In women homozygous for ACT T2B5, the average l u m e n area (P= .001) a n d diameter (P= .0001) of spiral arteries at term were significantly smaller compared with those of women homozygous for AGT M235. Average diameter is significantly greater in term spiral arteries f r o m healthy padents compared with those of women with p r e e d a m p s i a ( P = .002). CONCLUSION: We have now shown the T235 is associated with a b n o r m a l vessels in each trimester o f pregnancy. We conclude that T2~5 is a risk factor for preeclampsia a n d o t h e r p r e g n a n c y complications resulting f r o m failed maternal responses. NO. OF VE~ELS MM TM TT Preeclampsia

Control

59 124 97 58 222

LUMEN AREA $264 3363 999

' LUMEN D~r~,K 48 SS

26 ~7 40

$94 SMFM Abstracts 0299

J a n u a r y 2001 Ant J O b s t e t G y n e c o l

ANGIOTENSINOGEN T235 RELATED TO ABNORMAL SPIRAL ARTERY REMODELING IN THE SECOND TRIMESTER Ling Zhao t, Terry Morgan'-', Kenneth Ward3; |Univ. of Utah, CAMT, Perinatal Genetics Lab, Salt Lake City. UT; 2Stanford Univ., Dept. of Pathology, Stanford, CA; -aUniv. of Utah. O b / G y n & H u m a n Genetics, Salt Lake City, UT OBJECTIVE: Preeclampsia is associated with a c o m m o n molecular variant of angiotensinogen (ACT) (T235). We have shown that the AGT T235 variant is associated with a b n o r m a l r e m o d e l i n g of spiral arteries in first-trimester decidua. For this study, we hypothesized that T235-related failure of physiologic change will persist in second-trimester decidua. METHODS: With use of an Institutional Review Board-approved protocol, 1226 decidual blood vessels from 43 pregnancies electively aborted at 11 and 12 weeks' gestation were examined. Anti-0t-smooth muscle artin was used to highlight the arterial walls. Qnantitative histology was a c c o m p l i s h e d with Image-Fro Flus. Blood vessel aspect, lumen diameter, and area were measured. Incomplete c r o ~ e c t i o n s a n d t a n g e n t a l cuts with aspects larger than 2 were excluded. Mutagenically separated polymerase chain reaction was used to determine the AGT genotype. Vessel morphology was compared with genotype with a Student t test. RF_~ULTS: In women homozygous for AGT T235, the average htmen area is significandy smaller in second-trimester spiral arteries (P = .03). CONCLUSION: O u r results show that AGT T235 plays a role in abnormal spiral artery remodeling in decidua not only in the first trimester but into the second trimester as well. We conclude that AGT T235 is likely to be one of the multiple factors in the cause(s) of preeclampsia. GENOTYPE

MM TM TT

N O . VESSELS

L U M E N ARE&

308 541 377

751 672 509

0301

INTRAVENOUS 1-DESAMINO-[8-D-ARGININE] VASOPRESSIN (DDAVP) WITH ORAL WATER LOADING DOES N O T AFFECT OVINE UTERINE ARTERY B L O O D FLOW (UABF) Stephanie Mann 1, Todd Roberts 2, .]tong Lee'-'. Michael Ross~; IUniversity of ('alil~n'nia, San Francisco, O b / G y n , San Francisco. CA; 2Harbor-UCLA Medical Center, O b / G v n , Torrance, CA; 3University of California. Los Angeles, H a r b o r - U C l ~ Medical ('enter, Torrance, CA OBJECTIVE: O l i g o h y d r a m n i o s is associated with significant perinatal morbidity a n d lnortality. Studies in both ovine models a n d Iluman patients with oligohydramnios have demonstrated that maternal ol,'al water loading and intravenous administration of tile vasopressin-selecth,e antidiuretic agonist, dDAVP, induce maternal a n d fetal physiologic responses that increase AF volume. Althuugh water hydration/dDAVP increases amniotic fluid vohnue, ill part, via reduction in maternal a n d fetal plasma usmolality, we hyp()thesized that water hydration/dDAVP may increase UABE STUDY DESIGN: Six ewes with singleton f~ftoses (128 ± 2 clays) were prepared with a uterine artery ultl~lsonic flow probe and bladder, ~kscnlaL and amniotic cavity catheters. After 5 days' recovery, 2000 mL DsW was administered orally to the ewe together with dDAVP (20-Bg bolus, 2 Bg/min) to maintain nlaternal plasma Na 10 to 12 mEq below baseline for 6 hours. UABF ~"a.smeasured before a n d after dDAVE RESULTS: There were no significant changes in maternal or fetal blood pressure or heart nile (Tal31e). Mean maternal Na decreased from 135 + 3 to 123 + 4 mEq/L. UABF decreased by 5% fi'om baseline. CONCLUSIONS: dDAXrp with a continuous water infusion does m)t affect UABE We speculate that maternal plasma expansion using dDAVP a n d water hydration results in an increase in amniotic fluid vohnne as a restih of increased trausplacental water movement. Cardiovascular parameters MAP (MM H G ) Maternal Fetal

300

FJ..ECTROMYOGRAPHY AS AN ALTERNATIVE T O TOCODYNANOMETRY FOR M O N I T O R I N G PREGNANT PATIENTS William Maner l, Gayle Olson I, George Saade I, Robert Garfieldl; lUniv, of Texas Medical Branch at Galveston, O b / G y n , Galveston, TX OBJECTIVE: To determine if transabdominal uterine electromyography (EMG) identifies uterine activity that is clinically useful a n d correlates with conventional tocodynanometry (TOCO). STUDY DESIGN: Uterine electrical activity was simultaneously recorded for at least 30 minutes with T O C O a n d bipolar electrodes placed on the abdominal surface of gravidas with preterm labor (group 1: n=8), term labor (group 2: n=6), a n t e p a r t o m no labor (group 3: n=6), a n d term, rnle-out labor <24 h o u r s (group 4: n=3) o r >24 hours (group 5: n=10) of delivery. EMG signals were acquired at 100 Hz, band-pass filtered from 0.2 to 4 Hz, stored a n d analyzed with Chart software CAD Instruments, Casde Hill, Australia). Only patients with a high EMG signal/n0ise ratio a n d discernible contractions on T O C O were included. A contraction was defined as pressure activity lasdng >20 seconds a n d a n increase over baseline of>_5 mm H g in n o n l a b o r a n d ->10 m m H g f o r the l a b o r i n g patients. Contractions identified o n T O C O were paired with EMG burst activity at the temporal begin a n d e n d points. Correspondence between EMG a n d T O C O was noted as present if the peak of a particular contraction on T O C O fell within the established time range of the EMG burst. ~ T S : The correspondence between T O C O a n d EMG was 90.1% ± 9;3% with n o significant differences between the groups (1:90.1 :t: 9.3 vs 2:86.8 ± 9.6 vs 3:95.6 ± 7.7 vs 4:90.6 ± 12.1 vs 5:89.8 :t: 9.5; P = .8). CONCLUSION: EMG bursts recorded from the abdominal surface show a high degree o f correlation with contractions recorded by T O C O across various categories o f p r e g n a n t patients. In addition to frequency o f uterine contractions, EMG provides information regarding uterine electrical acdvity a n d may supplant conventional T O C O . (Supported by NIH HD37480-01 .)

0302

77 + 10 51 + 5

HR (BEATS/MIN) 100 + 9 147+ 10

INFLUENCE OF POLYAROMATIC HYDROCARBON O N F O O D INTAKE AND FETAL W E I G H T Cheryl A l b u q u e r q u O , Fred Royce2, Kim Stepheus s, Marzieh Shaft: 3, Kent Pinkerton 4, Michael RossS; I H a r b o r UCLA Torrance, Obstetrics a n d Gynecology, Torrance, CA; 21nstitute of Toxicology a n d Environmental Health, Department of Obstetrics and Gynecology, Davis, CA; 31nstitute of Toxicology a n d Envirnnmental Health, Davis, CA; 4University of California, Davis, Anatomy, Physiology & Cell Biology, Davis, CA; 5University of California, Los Angeles, Harbor-UCLA Medical Center, Torrance, CA OBJECTIVE: Maternal cigarette use is associated with decreased birth weight, although the mechanism of fetal growth restriction is not clear. A m o n g the nearly 100 c o m p o u n d s , polyarnmatic hydrocarbons (PAH) are a major c o m p o n e n t of cigarette smoke. O u r objective was to investigate the influence of a PAH, ~-naphthoflavone (BNF) on food intake, maternal a n d fetal weight, amniotic fluid, a n d placental weight. STUDY DESIGN: Eighteen p r e g n a n t Sprague-Dawley rats were randomly assigned to 3 groups. BNF rats were administered intraperitoneal BNF (80 m g / k g ) in corn oil 72 a n d 48 hours before delivery. Restricted-food rats were fed a restricted food intake (12 g) 72 a n d 48 hours before the examination, determined by the a m o u n t of food consnmed by BNF-treated p r e g n a n t rats in a pilot study. Control dams were fed ad libitum t h r o u g h o u t the experiment. Pregnant rats were weighed daily a n d food intake measured. All pups were delivered on gestadonal day 21 a n d placental a n d fetal weight a n d amniotic fluid volume measured. RESULTS: BNF treatment significantly decreased maternal food intake at 24 (8.8 ± 6.5 g vs 30.0 ± 4.4 g) a n d 48 hours (6.3 ± 1.9 g vs 24.9 ± 3.5 g) after administration c o m p a r e d with control rats. Maternal (327.0 ± 13.8 g vs 429.5 ± 18.7 g; P< .05) a n d fetal (3.7 ± 0.1 gvs 4.5 ± 0.1 g; P< .05) weight a n d amniotic fluid volume (0.6 ± 0.1 mL vs 1.1 ± 0.1 mL; P < .05) were significantly decreased c o m p a r e d with control fetuses. Food-restricted rats d e m o n s t r a t e d a significantly reduced maternal (329.9 ± 3.9 g; P < .05) a n d fetal weight (3.7 ± 0.1 g; P < .05), although there was no difference in amniodc fluid volume (0.9 ± 0.1 mL) c o m p a r e d with control fetuses. The placental weight was similar a m o n g BNF, control, a n d food-restricted rats (1.1 ± 0.1, 1.3 ± 0.1, 1.2 ± 0.1). CONCLUSION: Polyaromatic hydrocarbons present in cigarette smoke may decrease fetal weight, in part, by decreasing maternal food intake. However, the significant r e d u c t i o n in amniotic fluid volume indicates an additional toxic a c d o n on the developing fetus.

SMFM Abstracts $95

V o l u m e 184, N u m b e r 1 Am J Obstet Gvnecol 0303

METABOLIC ADAPTATION TO PLACENTAL DYSFUNCTION DURING LATE PREGNANCY: EARLY ORIGINS OF INSULIN RESISTANCE Ricardo (;omez I, Rogelio (;onzah.z L. Rodrigo Bazaes ~, R~d)et-to Romero :~, I.ttis Medina I. Em-ica I)iltaluga ~, Angelica Alegria a, (,. Inigucz'-'. Veronica Mericq'-'; I(:EDIP, Soten'o del Rio He,spiral, Ol~-(;yn. Univ. (;atolica de Chile. Puente Aho. Santiago, Chile; '-'IDIMI. Univ. cIe Chile, Santiago, Santiago; :~Perinatolog)" Research Branch, NICHD, Bethcsda, MD; ICEDIP, Sotero del Rio Hospital. Unidad de Neonatologia, Pueute Alto. Santiago OBJECTIVE: Large retrospeclive cohort studies indicale that small-tbx~ gestational-age (S(;A) inlhnts are at increased risk for the development o l diabetes, hypertension, and premamn-e death from cardiovascular disease in aduh life. However, the 111echilnislll responsible 6~r this phenomenon remains to be chtcidated. The pttrpose of this study WtLSto examine the relationship between placental dvsfunction as deternlined I)v abnormal Doppler velocimetxT of the umhilical anenT (UA) and insulin sensitivity after birth. STUDY DESIGN: A cohort study was designed to inchtde term newborns diagnosed as S(;A without congenital ahnormalities wire had u n d e r g o n e Doppler examinaticm (hu-ing pregnancy and were followed in onr neonatal trait. Plasma insulin, C-peptide, insulin growth tactor binding protein-l, sex hormone binding glolmlin, and leptin levels were mettsured by imnnunoassays. The metabolic and endocrine proliles of inhmts with and withot|t Doppler abllornlalities were determined. Ncmparametric statistical methods ",*.'eretlsed. RESULTS: The endocrine profiles of I 1 SGA cases were determined. Of these, 3 had abnormal UA Doppler velocimet~' during the third trimester. Cases with abnormal UA had higher plasma leptin concentrations than newhorns without it (0.25 n g / m l , [0.21-0.28] vs 0.(15 u g / m L [0.05-(I.13], respectively, P< .05). There were m) differences in other analytes, hirth weight. or poD(lel'a[ index betweell die 2 groups. CONCLUSION: Placental dysD.mction (assessed by Doppler velocimetD') is associated with changes in leptin concentrations, a hl)rlnone implicated in the regulaticm of l~etal metabolism. O u r findings provide a link between uterol)lacental insufficiency, the development of S(;A iulants, and metabolic adaptations that could resuh ill aduh disease.

0304

EFFECT OF MATERNAL ANEMIA A N D / O R MALNUTRITION ON FETAL THYROID FUNCTION Shailini Singh I, Supriya Mahajan ~, N. Kochupillai3; n('-eorgetown University, O h / G y n , Livingston, Nj; 2SUNY at Buffalo, Department of Allen'g)' and hnmunolog); Amherst, NY; 3All India Institute of Medical Sciences, Department of Endocrinology, New Delhi, India OBJECTIVE: To study the effect of maternal anemia a n d / o r malnutrition on fetal thyroid I'tmction. STUDY DESIGN: In a cohort study. 525 pregnant women were enrolled prospectively in a hospital in India. Maternal materialized venous samples and neonatal paired uu'nbilical arte D' and vein samples were obtained simuhaneously at normal deliver3'. The samples analyzed for hemoglobin (Hb) g/nnL and TSH, T I, T:~, and rT 3. Anemia classified according to W H O guklelines: severe anemia, hemoglobin 4 to 6.9 g/dL; moderate, hemoglobin 7 to 10.9 g/dL; no anemia, hemoglobin >1 I g/dL. Malnutrition `'~-asdefined as BMI of 17 to 19. RF_~ULTS: Of the 525 pregnant women studied, anemia was present in 482, malnutrition with and without anemia in 43 patients. Severe anemia wa.s present in 18/482 (3.7%), moderate in 361)/482 (74.7%), and in 104/482 (21.6%) was normal; 36/43 (83.7%) women were anemic/malnourished, and 7/43 (16.3%) were unalnourished. By univariate anal~is, in severe maternal anemia there was sigalificant decrease in T4, T 3 (P < .001 ) levels in maternal and fetal sernm. Maternal and neonatal TSH elevated and rT 3 decreased hut did not reach siga]ificance. Similarly, in unnderate maternal anemia, significant decreases in rT:~ (P < .009), increase in levels of TSH (P < .001), and in the fetus there were increases in TSH (P < .001) and decreases in T 4, rT 3 (P < .001 ). In malnourished women, there were increased levels of T 3 (P < .001) and T 4 (P< .001), and similarly their fetuses had significant association with elevated T 4 (P < .001), but T 3 elevation did not reach significance. In mahlourished women with moderate to severe anemia, there was increased T.,, (P< .067), T4 (P< .001 ), and their fetuses had increased levels o f T 4 (P< .001), decreased levels of T 3 (P < .013), and rT.~ (P < .017). TSH levels, although elevated, did not reach a level of significance. DISCUSSION: Both moderate and severe maternal anemia show an association with primary, fetal hypothyroidisnL Malnutrition with anemia has effects on thyroid functions. Its long-term effects based on Barker hypothesis will be discussed.