Poster session II

Poster Session II Thursday, February 8, 1996 3:30 p.m.- 5:30 p.m. Kohala Ballroom

CATEGORIES Maternal-Fetal Physiology Medical Complications of Pregnancy POSTER NUMBERS: 197-316

Judges:

Thomas J. Garite, MD Eleanor L. Capeless, MD Larry C. Gilstrap, III, MD

SPO Abstracts 367

Volume 174, Number 1, Part 2 Aru J Obstet Gynecol

197

EARLY ONSET NEONATAL GROUP B STREP (EOGBS) INFECTIONS: DO RISK FACTORS EFFECT LONG TERM X x OUTCOME? M Pearlman, R. Faix, TRB Johnson. Dept. Ob/Gyn and Pediatrics, Univ of Mich Med Ctr (UMMC), Ann Arbor, MI OBJECTIVE: Several nsk factors have been identified which increase the likelihood of acquisition of EOGBS infection, but little information ts available about whether those risk factors effect early mortality and long term morbidity. STUDY DESIGN. A retrospective observational study of all infants born at UMMC with culture proven EOGBS infections from February 1972 to February 1994 was conducted Labor vanables known to be associated with increased likelihood of GBS infection were identified in the mothers, prior sib with GBS, fever in labor (>100.4 F.), prolonged ROM (> 18 hours), and delivery < 37 weeks Mortality and long term neurologic sequelae was stratified based on risk factors. RESULTS. A total of 74 infants with EOGBS infections born at UMMC during this time period with an average follow-up of 49 months (range 18168 months).. Among these 74 infants, there were 19 deaths (25.7%). Of the 55 survivors, long term outcome was available for 44. The effect of preterm delivery on outcome is noted in Table 1. Table 1. Prematurity as a Predictor of Outcome in Early Onset GBS Infection PRETERM DIED NEURO NORMAL BEFORE D/C SEQUELAE Yes 17/42 (40.5%) 7/24 (29.2%) 17/24(708%) No 2132 (6.3%) 1/20 (5%) 19/20 (95%) p < 0 005 p = 0.043 p<0 1 Neither fever, prolonged ROM or a mor sib with EOGBS, either alone or m combination, was sigmficantly associated with higher mortality or long term morbidity CONCLUSION' Preterm delivery is the best predictive factor of beth short term and long term outcome in infants born with EOGBS infections.

198 MATERNAL AND FETAL CARDIOVASCULAR EFFECTS OF A NICOTINE-PATCH VERSUS MATERNAL SMOKING. H Hardardottir.C Oncken*, VR Lupo*, C Daraglab*, R Chang*, JS Smeltzer. Universityof ConnecticutHealthCenter,Farmington,CT. OBJECTIVE: To prospectively evaluate nicotine levels and the maternal and fetal cardiovascular effects of a transdermal nicotinepatch compared to maternal smoking in a randomized cross-over study. STUDY DESIGN: Pattents who were _>18 years old, at 24-36 weeks gestation, with an uncomplicated pregnancy, who smoked _>15 cigarettes/day for the past year were ehgtble. All patients had salivary levels of the nicotine metabolite cotinine (SC) measured prior to randomization, to confirm cigarette use. Subjects were ehgible for the study if SC was >85ng/ml. They were randomized to either wear a 21 rng nicotine patch or smokead libltum after 12 hours of abstinence from smoking. One week later they were crossed over to the other rnodahty. Maternal vital signs, serum nicotine levels, fetal heart rate (FHR) and resistance index (RI) of the uterine artery (UA), umbilical artery (UMB) and middle cerebral artery (MCA) were obtained at 0900 (baseline), 1100, 1200, 1300, 1500 and 1700 hours. Results were analyzed by ANOVA and paired t-tests for differences from baseline, with p<0.05 considered significant. RESULTS: Seven patients, of 13 enrolled, have completed the study. Maternal systolic, diastolic, and mean arterial pressure (MAP) increased significantly during patch days when compared to baseline and to smoking days (p<0.01, n=7). The maternal heart rate, FHR, UA, UMB and MCA RI did not dtffer between smoking and patch days (n=7). Serum nicotine levels dtd not differ between the groups (p=0.08, n=5). CONCLUSION: These preliminary results show higher maternal BP's during transdermal nicotine patch use when compared to smoking, at comparable mcotine levels. No differences were found m fetal cardiovascular effects when comparing patch use to smoking, as measured by FHR and RI of the UMB and MCA, at comparable nicotine levels.

199

REFERENCE VALUES AND INFLUENCE OF SMOKING ON MATERNAL MIDDLE CEREBRAL ARTERY BLOOD FLOW VELOCITIES. O. lrion°*x,JM. Moutquin°, IC Williams+, JC. Forest*. Dept Ob-Gyn, °Laval Univ, +Univ. of BC, Canada; *Univ. of Geneva, Switzerland OBJECTIVE: To determine the values of systolic, diastolic and mean maternal middle cerebral artery flow velocities (MCAV) at 18 and 26 pregnancy weeks and the potential effect of smoking on MCAV. Data available to answer these two questions are derived from small samples of women (<25). STUDY DESIGN: As part of a prospective cohort study carried out in oormotensive nnlliparas to determine performances of MCAV to predict preeclampsia, women were evaluated in left lateral decubitus, then sitting at 18 (n=305) and at 26 weeks (n=279); 212 were examined at both periods. Left and right MCAV were measured using a 2-MHz pulsed-wave Doppler (Medasonics CDS, CA) and averaged for report. Statistics included paired and unpaired t-tests, and regression analysis. RF~ULTS: MCAV are reported in the table. Sitting resulted in a statistically although not clinically significant decrease in diastolic and mean velocities. Systolic velocities decreased significantly at 26 weeks, but diastolic velocities remained unchanged. Thirty % of women smoked 11 cigarettes per day, on average. Systolic, diastolic and mean MCAV were significantly higher in smokers in both positions at both gestational ages (p_<0.01). The amount of cigarettes smoked correlated positively with higher MCAV. C O N C L U S I O N S : normal MCAV values appear to be higher than previously reported on small series of pregnant women. This could be due to the unintentional measurement of carotid artery end-portion in an earlier study (Obstet Gyneeol 1994;84:445-8), or in the larger proportion of smokers in our population (Br J Obstet Gynaecol 1993;100:85-91). Our data confirm an important increase of MCAV in smokers, exceeding changes due to posture or gestational age. TABLE: 18 weeks 26 weeks MCAV cm/s (:I:SD) decubitos sitting decubitus sitting systolic 113 (18) 112 (18) 109 (17) 109 (18) diastolic 47 (g) 43 (7) 46 (8) 42 (8) mean 69 (11) 66 (11) 67 (10) 64 (11)

200 ABSTRACT WITHDRAWN AT AUTHOR'S REQUEST

368

SPO Abstracts

lalUlal3, 19q6 Am ] Obstet (;vnecol

201

202

INTRAHEPATIC CHOLESTASIS OF PREGNANCY IS ASSOCIATED WITH ABNORMAL ESTROGEN EXCRETION K. K. Leshe. L Reznlkov Dept. of Ob/Gyn, Unlv of Colorado Health Sciences Center, Denver, CO OBJECTIVE Intrahepatlc cholestasls of pregnancy (ICP) defines a group of thseases which include the milder pruritus gravldarum and the more severe recurrent jaunthce of pregnancy ICP Is an extreme example of the subclinical cholestasis experienced by most pregnant women during the third trimester The disease affects as many as 1 in 100 women in the U S , and IS associated with relatively high perlnatal morbidity Numerous lines of evidence ]mphcate estrogen as a primary causative agent for cholestasls m these conditions The large estrogen load produced by the fetal/placental unit is metabolized and conjugated primarily In the maternal hver for final excretion in the urine We explored potential abnormahtles in liver-associated metabolism and excretion of estrogens in women with ICP STUDY DESIGN Urine and plasma samples were collected from 85 normal women at varying gestauonal ages throughout pregnancy, and postpartum Plasma and urine was also collected from women with mild and severe intrahepatlc cholestasis of pregnancy from the United States and from Chde (n=23), representing the largest number of patients with ICP studied to date An array of steroid hormones was measured in each sample by gas chromatography mass spectrometry (GCMS). RESULTS Urinary excretion of the most actwe, cholestanc estrogens was significantly decreased in the urine of women with ICP compared to normal controls Plasma levels of estrogen precursors were not different between groups, indicating that abnormally hlgh estrogen producuon by the placenta and the fetus does not occur in ICP However, the low concentrations of estrogens in the urine of patients with ICP suggests that hepatocytes of affected women may be unable to adequately excrete the normal large estrogen load produced by the fetus and the placenta during pregnancy. CONCLUSION A necessary step prior to urinary hormone steroid excretion is conjugation m the hver Our working hypothesis IS that conjugation of estrngenlc compounds is impaired in [CP, lack of excretion of active estrogens from the hver may result in a viscous cycle of worsening cholestasis set in play by high mtracellular hepatocyte estrogen content

203 MATERNAL SERUM INTERLEUKIN-6 LEVELS ARE

CIRCULATINGMATERNAL SERUM GNRIt AND CRH IN NORMAL AND ABNORMAL PREGNANCIES. K A Sorem, C B. Smlkle', D K Spencer', C Lunt', E Yoder, D. Braget', J. Ramos', M. Gravson', T.M SlierKhodr~ Departments of OB/GYN, University of Texas Health Science Center, San Antonio, and Wilford Hall Medical Center, Lackland AFB, San Antonio, TX OBJECTIVE: GnRH and CRH are produced by the placenta and fetal tissues and have been measured in maternal circulation during pregnancy, however, a longitudinal study of GnRH and CRH in normal pregnancy and in early pregnancy loss has not been reported Our objective was to determine the normal values of these hormones throughout the pregnancy and to determine whether abnormal levels or ratios were predictive of abnormal pregnancies STUDY DESIGN: Fitly-one pregnancies were followed prospectively, with levels of GnRH and CRH measured at 8,10,12,14,16,28,36 weeks gestation and during labor Specific and sensitive RIAs were used to determine the levels of hormones in the samples RESULTS: Thirty-three pregnancies, with samples at multiple time points and outcome data available, were completed to term without complication In the normal group, CRH increased from low or undetectable levels at 8 weeks to 32 5 + 2 3 pg/ml at 16 weeks. Thereal~er, there was a significant increase in maternal CRH to 1609 + 113 pg/ml in labor GnRH levels demonstrated a blmodal distribution increasing from 8 to 14 weeks, decreasing at 16 weeks, and increasing from 28 weeks to term. The ratio of CRH to GnRH In the normal group was 0 198 at 8 weeks, increased slgmficantly at 16 weeks, and peaked at 5 847 in labor. In eight cases of early pregnancy loss, GnRH and CRH levels and ratios were normal at 8 weeks In two cases of premature delivery and one case of severe preeclampsla, these GnRH levels and ratios were within the normal range, CRH was either normal (n=2) or elevated (n=l) CONCLUSIONS: Maternal levels of CRH and GnRH in normal pregnancies and m labor at term were defined In this group, neither concentrations of GnRH and CRH nor the ratio of CRH to GnRH were useful In predicting early pregnancy loss

204 THE EFFECT OF M A T E R N A L SERUM ON B O N E M A R R O W

ELEVATED IN TERM AND PRETERM LABOR. P. Greta x~, A Murtha 1, C. Jimmerson 1, W. Herbert1, B. Roltman-Johnson2, J Allen2, Dept. Ob/Gyn, Duke University1, Durham, NC and R&D Systems 2, Mpls., MN. OBJECTIVE: Pravious work has found elevated amniotic flutd (AF) Interleukm-6 (IL-6) in patients with term labor and preterm labor (PTL) with intrauterine infection. The arm of this study was to determine if maternal serum IL-6 also mcraased wflh these conditions. STUDY DESIGN: Serum samples were obtained from patients who were 22-34 weeks, not in labor (n=59); term, not in labor (n=62); term, in labor (n=149); In PTL at 22-34 weeks who delivered after failed tocolys~s (n=14); and 22-34 weeks in false labor who delivered at term (n=26). Placentas from patients who dehvered preterm were examined for histologic chorioamnionltls, which was used to define infectton. Maternal serum was measured in pg/ml using a specific ELISA kit (R&D systems). Comparisons of IL-6 levels between patient groups was performed using the Mann-Whitney U test RESULTS: At term, pattents m labor had significantly higher serum IL-6 than wtthout labor ( median- 4.7 vs 2.2, p<0.0001) Preterm patients who failed tocolysis and delivered early had significantly higher maternal IL-6 compared to those in false PTL who delivered at term (median=12.5 vs 1.9, p<0.000t). Patients in false PTL had slmtlar IL-6 levels to praterm pattents without labor (median-1.9 vs 1.6, p=.18). Of patients dehvermg preterm who had placentas available for study, 89% (8/9) had histologic chorioamnionitis. A value of _>7pg/ml gave a sensitivity of 100%, specificity of 97%, PPV of 91% and NPV of 86% for refection and tocolyttc farlure. CONCLUSION: Like AF IL-6, maternal serum IL-6 is elevated dunng term and preterm labor and may have a physiologic role in parturition. Elevated serum IL-6 is a very sensitive and specific marker for patients m PTL who are infected and fail tocolysts.

H E M A T O P O I E S I S . T. Nesbitt x, H. Kay, J Kurtzberg x. Depts Ob/Gyn and Pediatncs, Duke Unwersdy Medical Center, Durham, NC. O B J E C T I V E : Pregnancy is associated with known hematologic alterations, but regulation of these changes are not well understood. Our objective was to determine if humoral factors in pregnant women directly affect hematopoiesls in human bone marrow progenitor cells STUDY DESIGN: Human Progenitor Cell Assays (HPCA) used in this study allow analysis of hematopoiesis at an earlier and more accurate level than that of standard morphological and htstochemical techniques HPCA m tnphcate were performed on normal human bone marrow (n=6) to determine the hematopoietic response in the presence of 10% by volume maternal sera (n=40) for each bone marrow sample or 10% by volume growth media (controls) Colony Forming UnitsGranulocyte/Macrophage(CFU-G M),Granulocyte/Erythroid/Monocyte/ Megakaryocyte (CFU-GEMM) and Burst Forming Units-Erythroid (BFUE) were scored after a two week mcubation Data were analyzed with respect to trimester of pregnancy and the presence or absence of labor Continuous variables were compared by paired t-test, and categorical vanables were compared by Fischer's exact test RESULTS: Sera from non-laboring pregnant women had no effect on granulocyte or macrophage growth at any stage of gestation. A sigmhcant stimulatory effect m erythroid precursors was observed with first trimester sera (p=<.0001); this effect was not seen in later gestation. Both myeloid and erthyroid HPC growth were profoundly =nhtbtted by sere from laboring women; no erythrocyte, macrophage, granulocyte or lymphocyte growth was demonstrated in any culture (p=<.000t). C O N C L U S I O N S : Cimulatmg factors present in maternal sera have marked effects on hematoporesis First trtmester sera stimulated erthropoietlc actiwty of human progenitor cells, while sera from laboring patients, regardless of gestational age, demonstrated profound inhibitory effects on both myelord and erythroJd precursors Phystologm hormonal changes, either direct or medmted through cytokme acttvity, are hkely to be responstble for these observat=ons.

Volume 17-t, Nuinbel I, Pall <2 Am I ()b~,tet (¢<<'ne,~ol

205 FETAL SERUM CYTOKINE LEVELS ARE CORRELATED WITH

PRESENCE OR SEVERITY OF HISTOLOGIC ACUTE INTRAUTERINE INFLAMMATION. C.M. Salaha*, J.M. Lage*, S LenckG G S Eghnton, V. Parkash*. Permatal Research Facdlty, Departments of Pathology & OB/GYN, Georgetown Univ Medical Center, Washington, DC, Yale University School of Medlmne, New Haven, CT OBJECTIVE: To study relationships of histologlc acute inflammahon to maternal and fetal serum levels of interleukins (IL)145, 6 and IL 2-receptor (IL-2

SPO Abstracts

207 MPOPROTEIN(a) IN SPIRALARTERIESAT TERM AND AFTER PLACENTAL DELIVERY: CAN INVOLUTION-RELATED PROCESSES BEGIN BEFORE PARTURITION? C M Salafia*, K. Starzyk*, J. Lage*, M Ossandon*, L. Vercruysse*, V. Parkash*, C. Y. Spong, R. Pllnenborg. Departments of Pathology & OB/GYN, Georgetown University Medical Center, Washington DC, Yale University School of Medicine, New Haven CT, Unwerslty Hospital, Leuven Belgium. OBJECTIVE: Lipoproteln(a) (Lp(a)), a marker of vascular damage, is deposded rarely in the normal placental bed and commonly in the preeclamptlc placental bed, but basal plate and involuting arteries have not been studied. We studied I_p(a)in basal plate uteroplacental artenes in term normal and preeclamptlc placentas and in uteroplacental vessels within 5 months after placental delivery STUDY DESIGN: From a consecutive senes of pregnancies dehvered in March and June, 1995, basal plate swal artenes were identihed for 13 cases of uncomphcated term birth of appropnately grown infants, 6 preeclampsia cases dehvered 36-40 weeks, and 4 cases of involutional implantabon sites (2 removed by curettage at 2 weeks and 2 months after delivery, 2 by hysterectomy at 3 and 5 months post partum). Spiral arteries identified on hematoxyhn and eosin preparations of formalin fixed matenal were stained for Lp(a) (Organon Technlka, 1'500) Immunoreactlvity was identified as present (+) or dense (++). Image analysis recorded circumference with reactivity and its location (endothehal, intimal, mural) was recorded. RESULTS: Of thirty-five artenes in the 13 uncomplicated term deliveries, 14 (40%) had at least one artery with Lp(a) reactivity (maximum 5/7 (+) arteries), compared to 20/21 (95%) of arteries in term preeclampsia, and 25/26 (96%) of involuting arteries (p<0.0001) No features of immunoreactivity were correlated with presence/extent of physiologic changes, or w~thterm normal v. term preeclampsia. CONCLUSIONS: Lp(a), associated with atheroma formation and inhibition of flbnnolysls, Ls present in basal plate arteries in many normal term births, and in 95% of basal plate artenes in term preeclampsia and involuting artenes Processes cnhcal to normal uterine vascular Involution may play a role in term preeclampsia. Our data suggest that invoMion-related changes may develop before partunhon even in normal term dehvenes and persist for months post partum. Th~s process may explain decreased late third trimester fetal growth, trophoblast ischemia proposed as the cause of preeclampsia, and the poor prognosis associated with subseuqent pregnancies within one year of partunhon.

R). STUDY DESIGN: In 1992, 32 consecutwe patients at 20-36 weeks with actwe progressive labor and failure of tocolysls were recruited. Maternal serum sampled during the active phase of labor, and fetal serum from the umbdical vein at birth were assayed by ELISA for levels ([pg/ml or IU/ml]), expressed as mean + S.E.) of soluble IL-2 R, IL-6, and IL-18 if-Cell Diagnoshcs) bhnded to clinical data Acute inflammahon of maternal origin (e g., amnlon, AI) and fetal origin (umbdlcal vascuhtis, UV) were scored by 2 independent groups blinded to clln=cal data on a 0-4 scale. Nonparametric tests, contingency tables, ANOVA and regression corrected for multiple comparisons with p<0 05 as significant RESULTS: Fetal [IL-1B] were elevated in the 14 cases with grade 3-4 UV compared to the 5 cases with no UV (114+24pg/ml v. 19.2+ 9 pg/ml, p=0.02). Fetal serum [IL-2 R] were elevated in the 17 with grade 3-4 AI (1203+166 U/ml) versus either the 3 with grade 1-2 AI (483+101 U/ml), or the 7 cases without AI (685 +104U/ml, p=0.02).Fetal [IL-2 R] were elevated in the 16 with grade 3-4 UV (1247+172 U/ml) vs. the 7 with grade 1-2 and the 5 with n6 UV (686+111 U/ml, and 590+_25 U/ml, respectively, p<0.002) Elevated fetal [IL-6] were correlated with higher maternal antepartum temperature (p=0.01), and a trend to increased rate of maternal taohycardia (p=0 05) Increased maternal ILL-2 R] were associated with increased incidence of maternal tachycardia (p=0 01) Clinical diagnosis of chorioamnionitls was not related to presence/severity of any hlstologic markers of acute inflammation. Maternal cytokine levels were not associated with measures of histologic inflammation in maternal or fetal tissues. CONCLUSIONS: The lack of correlation of maternal serum cytokine levels in preterm labor with any hlstologlc markers of maternal or fetal inflammation may explain the generally poor correlahon between the clinical diagnosis of chorioamnionit=s and histologic inflammation If fetal cytokine levels are correlated with maternal clinical symptoms, fetal cytokine levels may be more stable and reflechve of the inflammatory process than maternal levels.

206

QUANTITATIVE VASCULAR CHANGES OF THE U T E R O P L A C E N T A L A N A T O M Y IN P L A C E N T A L BED BIOPSY DEFINE P R E E C L A M P S I A K Starzyk*, ~ , L. Vercruysse*, J M. Lage*, J.C. Pezzullo*, R. Pijnenborg*. Departments of Pathology and OB/GYN, Georgetown University Medical Center, Washington DC, Umversity Hospital, Leuven Belgium O B J E C T I V E : To determine quanmatwe markers to distinguish normal and .~eeclam.£!tic (PE) uteroplacental vasculature. S T u u Y DE~IGN: From an established data set of placental bed biopsies (PBBs), 6 samples obtained from uncomplicated term dehverles and 4, samples from severe protelnunc PE were selected Mvometrial vessels were identified and characterized as having com p'lete physiologic changes ( c P C ) , o a r t i a l ohyslololzic changes (pPC), no physlologlc change nPC), and'as spiral or basal'arteries 5v a single observer (RP). An image of each vessel was analyzed tiP Lab Spectrum) to calculate mean wallthickness a lumen area an effective diameter (the diameter of a circle of the same perimeter as the measured vessel), and a relative wallto-lumen ratio Erastlc stains (Sigma Chemicals) were performed on matched tissue sections. Elastic was assessed as intact, fragmented or absent. Contm,g ency tables and ANOVA considered.K<0.05 significant R E S U L T S : ~z arteries were identified in nomal viaBS a n n 6 6 m PE PBBs 13 (16%) of the 82 normal PBB arteries showed cPC and 15(18%) had oPC, compared to 17/66 (26%) PE PBB arteries with cPCand 8/66 {12%), PE P BBarteries wlt.h pPC (p=0 19) None of normal PPB arteries nap iinrlnmn necrosis or attierosis, versus 3/25 (12%) of PE PBB arteries (p=0.22). Lumen areas and effective diameters of all types of vessels were smaller m PE as compared to normal PBB (each p
208

COMPONENTS O F T H E BIOPHYSICAL P R O F I L E SCORE IN T H E PREDICTION OF HISTOLOGICAL ACUTE ASCENDING I N F E C T I O N IN P R E M A T U R E R U P T U R E O F T H E M E M B R A N E S (PROM) DELIVERED AT <32 W E E K S GESTATION. C.M Salafia*, V.K. Minlor*, J.C. Pezzullo*, A. Ghldlni, D.M. Sherer, L M. Ernst*. Permatal Research Facility, Deptartments of Pathology & OB/GYN, Georgetown Univ Medical Center, Washington DC, UCONN Medical Center, Farmmgton CT OBJECTIVE: To assess the performance of components of the biophysical profile score (BPP) performed within 24 hours of dehvery in the prediction of severe hlstologlc acute inflammation in premature rupture of the membranes (PROM) dehvered <32 weeksgestation. STUDY D E S I G N : An established consecutive series o f non-anomalous hveborn singleton births at <32 weeks gestation contained 193 cases of PROM, of which 166 (86%) had a BPP within 24 hours of birth Histologic acute inflammation (AI) m amnion ( e g maternal inflammation), and in umbilical and chorionic vessels (e.g. fetal inflammation) was scored by a single pathologist on a numerical scale blinded to clinical data "Severe" AI (SAI) was scored 3-4 on a scale of 04. The diagnostic indices of each component of the BPP (amniotic fluid volume [AFV
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C O N C L U S I O N S : The sensitivities of BPP components are higher for maternal than fetal histologlc inflammation, even though fetal Al and SAI are more prevalent than maternal SAI in very preterm PROM Our data suggest that altered fetal bchavior lS more often a manifestation of maternal inflammation m very preterm PROM.

369

370

SPO Abstracts

.lanu.tr~ t996

Am,] Obstet (,ynecol

209

INTERLEUKIN-6: PLACENTAL IMMUNOREACTIVITY IS PRIMARILY LEUKOCYTE-ASSOCIATED IN ACUTE INFLAMMATION, BUT IS SYNTHESIZED BY CYTOTROPHOBLAST INDEPENDENT OF ACUTE INFLAMMATION C. M. Salafia*, J. F. Mtll*, K.A. Starzyk*, M. Ossandon*, D Spicer*, C Lester*. Pennatal Research Facility, Departments of Pathology & OB/GYN, Georgetown Untverstty Medical Center, Washington DC OBJECTIVE: To study Interleukin-6 (IL-6) synthes~s and tmmunoreacttvtty m placenta and thetr variance w~th gestattonal age (GA), labor, and hstolog~c evtdence of acute ascending ~nfectton(AI). STUDY DESIGN: Etghteen cases dehvermg 37-40 weeks GA and 8 cases dehvermg singleton, nonanomalous infants between 26-33 weeks GA were selected. 10 at term and 3 preterm with spontaneous labor, 7 at term wtth reduced labor, 3 preterm with spontaneous but augmented labor, and 1 term and 2 preterm wtthout labor for preeclampsia Diabehc pahents were excluded. Htstologic AI was diagnosed blinded to chnlcal data. Wtth anhbody to IL-6 (Biosource Int'l, 1.100), ~mmunoh~stochemlcal(IHC) reactw~tym formalin-fixed extraplacental membranes, chonon~cand basal plate, and choriontc vdh was graded as weak (+) or intense (++) In cases with AI, maternal and fetal leukocytss (WBCs) were also assessed. In situ hybndtzat~on (ISH) was performed on senal sechons uttlizing digoxtgenm-labelled nboprobes from a human IL-6 cDNA, and etmtlar intensity scale was used to score ISH staining. RESULTS: In all cases, apmal aspects of amnton ep~thehumwere focally IHC (++). By ISH, amnton was untformly (++) and chonodec~dua(+) at all GA, but decreased to 0/(+) In AI cases at all GA. Subchonontc and basal cytotrophoblast (CT) were IHC (+) reactwe in an annular pattern dehm~tmg cell membranes ISH confirmed presence of IL-6 message ~nthese cells. In AI cases at all GA, maternal WBCs m amnion, chonodectdua, chonomc plate and intervillous space, and fetal WBCs in choriontc vascuhhs were uniformly IHC (++), but were nonreacttve on ISH. ISH and IHC react~wtleswere independent of labor or labor type CONCLUSIONS: IL-6 synthesis (by ISH) and Iocahzatton (by IHC) m amnton (and to a lesser extent m chonodecidua) ~s down-regulated by AI. Non-vtllous (subchonon¢ and basal plate) CT showed low levels of IL-6 message at all GA and no vanance w~th AI or labor. In non-AI, IL-6 assayed in amntotic fluid may be placentally denved, but ~n AI IL-6 is likely to be denved from WBCs Negattve regulation of extraplacental membrane IL-6 expresston may provide a fetal defense agatnst pctenttal deletenous effects of excess IL-6.

211

INCREASEDINTERLEUKIN-1-ALPHA(IL-I-~) IMMUNOREACTIVITYIN BASAL CYTOTROPHOBLASTRELATED TO HISTOLOGIC ACUTE INTRAAMNIOTIC INFECTION. C. Salafia*, J Mdl*, K. Starzyk*, M. Ossandon*, D. Spinet*, C Lester'. Perinatal Research Factlrty, Departments of Pathology & OB/GYN, Georgetown Unlverstty Medical Center, Washington DC. OBJECTIVE:To examine ~f IL-l-et tmmunoreactivtty in placenta is gestattonal age related and affected by hlstologic evidence of acute ascendtng refection. STUDY DESIGN: Sixteen non-anomalous singleton, nondlabet¢ cases were selected, including 8 dehvered 37-40 weeks, and 8 dehvered between 26-33 weeks for prmclpal indcatton of preterm labor/premature rupture of membranes. Four of each group had moderate hlstologtc acute margmahng choriodecrduit~s Usmg antibody to IL-l-o~ (S~gma Chemicals, 1.100), relative ~mmunoreact~vityof frozen ttssue samples was graded as weak (+), moderate (++), and intense (+++) Cells assessed included syncyttotrophoblasl (ST), cytotrophoblast (CT, of basal plate, placental septae, subchononic fibrm, and m penvillous fibrin) vascular smooth muscle, endothelial and stromal cells, and edematous and non-edematous vtlh RESULTS: In pretarm cases w~thout acute Inflammation, approxtmately 25% of basal plate and chonon~c plate CT were (+). Most endothelial cells and septal CT were (+++). Less than 50% of villous stromal cells, and scattered stromal and vascular smooth muscle cells m the chonontc plate and fetal vessels were (++) Preterm cases with acute inflammation showed >75% basal CT (+++), and Increased numbers of subchorionic CT and chorionto plate cells (+++). in term noninflamed cases, >75% of basal plate, septal and interv~llous CT were (+++), most endotheha and vtllous stroma and vascular smooth muscle cells were (++); but few subchonomc CT were (++). In inflamed term cases, no consistent patterns of react~wtywere seen. In basal plate, IL-I-~ reacttwty was also seen m extracellular matrix independent of gestattonal age or inflammation. IL-l-(x was not dtfferent in edematous will compared to non-edematous vtllt CONCLUSIONS: IL-I-~ reactwtty m preterm placental endothehum ~s intense and may quantltattvely decrease by term CT (and dec~dual extracellular matnx) is a malor locus of IL-I-~ both preterm and at term. Intense IL-I-~ react~vttywas seen in preterm ~nflamedcases, and in all term cases independent of acute mflammat~on. IL-I-~, the pnmary species contamed m trophoblastic cells, has been suggested to modulate placental development. IL.l.o~ expression at the maternal/placental interface may contnbute to normal parturttton, and may be a component of preterm mflammatton-relatedparturttton.

210 INTERLEUKIN-6 RECEPTOR SYNTHESIS: DOWN-REGULATED BY ACUTE

212

NEONATAL NUCLEATED ERYTHROCYTES IN PRETERM PREECLAMPSIA MARK FETAL ACIDOSIS AND PLACENTALtSCHEMIA. (~,M. Salafia*, V.K. MInlor*, J.C. Pezzullo*, L M. Ernst*, A Ghidint, D M. Sherer. Permatal Research Facdlty, Departments. of Pathology & OB/GYN, Georgetown University Medical Center, Washington DC, UCONN Medical Center, Farmington CT. OBJECTIVE:To determine relationships among neonatal nRBCs, assessment of fetal well-being, umbihcai artenal and venous (UA, UV) blood gases and placental lesions in preterm preeclampsia (PE). STUDY DESIGN: From an established data set of non-anomalous singleton Itvebtrths dehvered 22-32 weeks gestational age (GA) without cases of maternal diabetes mellitus or chronic hypertension, there were 78 cases of PE, and 70 (89%) had a complete blood count by 3 hours of hfe. The biophysical profile (BPP) component scores within 24 hours of birth, fetal heart rate (FHR) abnormalities, neonatal anthropometric data and placental lesion scores were collected. Placental lesions in categories of (1) uteroplacental vascular and related villous lesions including tiistologic abruption (2) chronic inflammatory lesions and (3) coagulation related lesions as well as vdlous edema, were scored on a 0-4 scale, nRBC/dl (= WBCo nRBC/100WBC), normalized by log transformation, was analyzed by ANOVA and regression with p<0.05 slgmficant. RESULTS: Mean nRBCs was 5.4/dl-(range 0.03-57.7). nRBCs/dl was independent of GA (p=0.7, mean GA 29+2 wk, range 22.8-32 wk). The following were associated with TnRBCs/dl: Stotal BPP (p,0.04), .l. fetal movement score on BPP (p=0.005), greater inctdence 9f SFHR vartabiltty (p=0.027), SUA and UVpH(p=0.02, p=0~0002)and ,I,UA and UV base excess (p=0..008,p=0.006). Each 10-fold Tin nRBC/dl is associated with an average .1. in UV pH of 0.02. Maternal maximum blood pressure and degree ofproteinuria, and mfant weight or length centdes were not related to nRBCs/dL Placental lesions of Tcytotrophoblast (X-cell) proliferation (p=0.04), abruption related histoDgy~p=0.015), and severe vtllous edema (p=0.0002) were also related to ,1, nRBCs/dl. CONCLUSIONS: In preterm PE, nRBCs/dl are correlated with ,1. fetal wel!-be~ng laboratory evidenc e .of fetal aci,dost,s; chronic ~cytotrophoblast pro,reratlon) ano more acute (aoruption-relateo tesionsj placental lesions reflectmgabnormal uteroplacental perfusion. This suggests that tn preterm PE, nRBCs/dl can be used as a marker of abnormal uteroplacental perfusion sufficient to cause fetal hssue hypoxta. The association of severe villous edema with nRBCs/dl suggests in certain cases w[Ious edema may be a marker of fetal hypoxia.

INFLAMMATION IN AMNION, CHORION, DECIDUA AND VILLI AND IN SPONTANEOUSLABOR IN THE BASAL PLATE. C. M. Salafia*, J F. Mdl*, K A Starzyk*, M Ossandon*, D. Sptcer*, C. Lester*. Perinatal Research Faclhty, Departments of Pathology & OB/GYN, Georgetown Untvers=ty Med=cal Center, Washtngton DC OBJECTIVE: To examine if placental interleukm-6 receptor (IL-6R) synthesis and tmmunoreactivtty is related to gestatlonal age at birth (GA), labor (spontaneous/no augmentatton [SL], augmented [AL], tnduced [IndL] with v~tgmaldelivery) and acute ascending mfect~on. STUDY DESIGN: 18 cases delivermg 37-40 weeks GA and 8 cases delwerlng singleton, nonanomalous mfants between 26-33 weeks GA were selected: 10 at term and 3 preterm with SL, 7 at term with IndL, 3 preterm with SL+AL, and 1 term and 2 preterm without labor for preeclampsla. Dtabetic patients were excluded. ,H~st~og¢ acute inflammation (AI) was dJagnosed (0-4 scale. ,With antibody to IL-6R u~o:~ource, 1'100), immunontstoncemtca[(IHC) reacttwty m frozen ttssue samples was graded as 0, weak (+) or mtense (++) In situ hybridizatlon(ISH) was performed on adlacent hssue sechons fixed m formalin uttl~zm~ dtqox~qemn-labelled nboprobas from a human IL-6R cDNA, and scored on a slm[rar int'ens~¥ scale. RESULTS: ISH demonstrated complex IL6-R patterns of expression rn amnion and its subjacent stroma, chonon stroma, scattered chorion c~otrophoblast (C~ and dec~dual stromal and leukocyt~c cells Th~s pattern was aDohshed to 0-focatiy~+ by AI at all GA. ISH also demonstrated IL-6 R mRNA umformly in syncytiotrophoblast (ST), fetal endothelm, many villous stromal and vascular smooth muscle cells, and basal CT at all GA In AI, endothehal and smooth muscle stammg was absent, subchonon~cCT stammg was tncreased and ST showed large areas 6! nega,tive staming assoctated with vnlous edema Basal CT ISH reactivity was inaepenoent of AI Ron-vtllous CT were the only IHC (+) cells in all cases. Subchorlontc CT reactiwty mcreased in AI, and did not vary wtth labor. In term SL and IndL wLth no AI, basal CT was 0- focally (+) by IHC, but was >50% (++) in AI, both m term without labor, preterm SL, and in preterm no labor w~thoutAI. Preterm SL+AL had negatwe <25%(++) basal CT. In all cases, IL-6 R IHC reactivity was kdentff~edm extracellular sttes CONCLUSIONS. IL-6 R expresston in extraplacental membranes is complex and modulated by AI at all GA. In basal plate, CT IL-6 R may vary with labor type and GA A phystologteeffect of labor augmentatLonm preterm birth ~s modulation of IL-6 R function Many cells intensely ISH reactive leg, ST, vtllous stroma and endothehal cells) are IHC non-reactive. TNs combmedwlth IHC suggests that CTassociated IL-6 R may be soluble rn the CT enwronment, and may be produced by CT or by another cell-type tn the intrauterine mdieu.

Volume 174, Nunrber 1, P,ut '2 Am ] Obstet Gynecol

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KINETICS OF NUCLEATED ERYTHROCYTE NUMBER (nRBCs) IN NEONATAL CIRCULATION IN THE FIRST DAY OF LIFE ARE RELATED TO UNDERLYING P A T H O P H Y S I O L O G Y OF nRBC RELEASE IN PRETERM BIRTH. C.M Salafia*, J.C Pezzullo*, C. Spong, A. Ghldmt. Pertnatal Research Facility, Departments of Pathoqogy & OB/GYN, Georgetown Umverstty Medtcal Center, Washington DC. O B J E C T I V E : nRBCs have been proposed to mark fetal hypoxta. Inflammatory cytokrnes are related to release of mature and tmmature myelotd cells as well as nRBCs from hematoporetlc sites Are processes of antenatal nRBC release dlstrugutshed by kmettcs of nRBCnumber in the neonatal ctrculat~on? STUDY DESIGN: From a data base of consecutrve non-anomalous singleton hvebirths at 22-32 weeks m 1989-94 (excluding maternal d~abetes melhtus, chromc hypertension, and non-hypertensive abruptmn), 125 cases had a complete blood count and nRBC count obtamed w~thm 3 hours of hfe, and a 2nd complete blood count and nRBC count wtthm 24 hours after the first value [92(74%) premature membrane rupture {PROM} and preterm labodmtact membranes {PTL}, 33 (26%) preeclampsm {PE}]. Neonatal data regarding volume expansion and transfusion was recorded Lesmns m 4 categories (lesions of utero-placental vascular pathology, chronic mflammation, coagulation, and placental vaso-occluston) were scored and summed to g~ve t o t a l p a t h o l o g i c burden nRBCs/dl was calculated as WBC. nRBC/100WBC, and a relative rate of decrease m nRBC/dl over the t~me interval of the 2 complete blood counts calculated (AnRBC) ANOVA and regression analyses corrected for multiple comparisons (p<0.05). R E S U L T S : No one placental lesion was relatedto AnRBC m e~ther PROM/PTL or PE In PROM/PTL, mcreasmg total burden of uteroplacental vaso-occlusmn was inversely related to AnRBC (p=0 009). Increasmg total myeloid number rn mtttal complete blood count was posmvely correlated w~th AnRBC (p=0.007). Both factors remained independently significantly related to AnRBC m a multiple regression that included neonatal volume therapy (overall p=0.003) They were not related to AnRBC in PE (p>0 50). Other placental lesmns or categories were not related to AnRBC in PROM/PTE or PE C O N C L U S I O N S : Uteroplacental vascular lesmns (shown to impair fetal oxygenation) would be hypothesized to be related to AnRBC vm chromc erythropo~etm sumulation. Acute mflammation-related AnRBC wa cytokmes might be expected to be more transient. Our data are consistent w~th these hypotheses. Patterns of AnRBC in the early newborn period vary with the underlying associated fetal d~sease process(es), and are mdependent of neonatal ddutional effects

215

EVALUATION OF ANGIOGENIN IN MIDTRIMESTER AMNIOTIC FLUID AND SERUM AS A PREDICTOR OF INTRAUTERINE GROWTH RESTRICTION. CY Saon~* DM Sherer, A Ghldlm, CB Jenkms*, M Ossandon*, JC Pezzullo*, FD Seyde]*, GS Eghnton Pennatal Research Faclhty, Department of OB/GYN, GeorgetouTnUmversuy Medical Center, WashingtonDC OBJECTIVE Proliferation of villous caplllarres is seen m placentas exposed to chronic oxygen deficrency Markers of compensatory placental neovascularlzatlon may assist m the prediction of mtrautertae growth resmctron (IUGR) Angrogemn,a single-chain polypeptlde, is a potent reducer of neovasculanzatmn This study was designed to evaluate angmgenlnas an antenatal marker for the predictionof IUGR m mldtnmester amnlotlc fluid and maternal serum compared with approprlate-forgestatlonal-age controls matched for gestatmnal age (GA) at dehvery STUDY DESIGN Patients who underwent mldtnmester ammocentesls between 1992 and 1995 with follow-up dehvery data were rdentlfied IUGR was defined as blrthwoght < 10% for GA Control patrenrs were matched for GA, maternal age, race anar parry with at least two controls for each study patient Patients with maternal immune disease hypertension, diabetes, asthma, congenital heart disease, multiple gestation, and fetuses wUh structural or chromosomal anomahes were excluded Mldmmester ammonc fluid and serum samples were assayed by ELISA for angmgenm (R&D Systems Mmneapehs MN) The sensmwty for amnlotlc fluid was 0 078 ng/mL and for serum 0 6 ng/mL Angmgenm values were normalized using naturallog transformation Potential confounders considered were maternal serum alpha-fetoprotern (MSAFP), smoking history, pregnancy induced hypertension, and neonatal gender Statisticalanalysis included Z" and ANOVA with p<0 05 consrdered significant RESULTS: From the ammotlc fired database 18 panents (6%) dehvered neonates with IUGR and were matched with 46 controls (mean GA at samphng 17 3_+29 and 16 6+2 9 wks respectively p=04) From the maternal serum database 13 patients (7%) dehvered neonates wub IUGR and were matched wuh 45 contro s (mean GA at sampling 16 2+1 I and 16 8+1 5 wks respectivelyx p=0 4) Mean _+SD amnlotlc fluid and maternal serum IL-10 levels were not slgmhcantly different m IUGR paoents compared with controls

216

Ln anglogenln (p~mL} Amnlotlc fluid Maternal serum

[ IUGR 3 4_+0 7 (n=lS) 5 8 + 0 2 (n=13)

[ Control (n=46) 3 1+05 5 9 + 0 2 (n=45)

P 006 0 40

No significant differences were identified between maternal age, smoking history, African-American race, nulhpanty, GA, pregnancy induced hypertensmn, or MSAFP >2 0 MOM in pauents dehvenng IUGR neonates compared wuh controls (,each p value >0 05 As expected, btrthwelght was stgmficantly lower in patients dehvenng IUGR neonates compared wah contro s (p<0 00 ) C O N C L U S I O N S : MidtrJmester serum angmgenln is not a predxctor for development of IUGR However, elevated amnlotlc fluzd anglogenm levels do demon~,trnte a trend toward slgnltluaece In the prediction el subsequent IUGR Addtnonal studies are needed to clarity the relatlon~tup

INTERLEUKIN-10 IN MIDTRIMESTER AMNIOT1C FLUID OR SERUM DOES NOT PREDICT SUBSEQUENT INTRAUTERINE GROWTH RESTRICTION. CY Snonu*, DM Sharer, CB Jenkins*, A GhJdml, M Ossandon*. JC Pezzullo*, FD Seydel*, GS Eghnton Pennatal Research Facduy, Department of OB/GYN, Georgetown UmversUyMedical Center, WashingtonDC OBJECTIVE lnterleukln-10 (IL-10), a potent lmmunosuppresstve cytokme, has been shown to be elevated in mldtnmester amnlotlc fluid in patients with subsequent mtrautenne growth resmctmn (IUGR) compared with term controls Ttusstudy was designed to evaluate IL-10 as a potential predictor of subsequent IUGR in either amnlotlc fluid or maternal serum compared with appropnate-for-gestatlonal-age controls matched for gestatlonalage (GA) at delivery STUDY DESIGN Patients who underwent mldtrlmester ammocentesls between 1992 and 1995 with follow-up delivery data were identified IUGR was defined as btrthwoght < 10% for GA Controlpatients were matched for GA, maternal age, race and parity with at least two controls for each study panent Patmnts with maternal immune disease, chronic hypertension, diabetes, asthma, congenital heart disease, multiple gestatron, and fetuses with structural or chromosomal anonlahes were excluded Mldtnmester ammotlc fluid and serum samples were assayed by EL1SA for IL-10 (Endogen Cambridge, MA) The ELISA sensuwuy for ammonc fired was 5 6 pg/mL and for serum _<3 pg/mL IL-10 values were normalized using natural log transformation Potential confoundingvariables considered were maternal serum alpha-fetoprotern (MSAFP), smoking history, pregnancy induced hypertension, and neonatal gender Statlstrcalanalysis included Z2 and ANOVA wah p<0 05 considered significant RESULTS: From the amntotlc fluid database, 18 patients (6%) delivered neonates with IUGR and were matched wUh 46 controls (mean GA at samphng 17 3_+29 and 16 6:L29 weeks respectively, p=0 4) From the maternal serum database, 13 patients dehvered neonates wuh IUGR (7%) and were matched with 45 controls (mean GA at sampling 16 2+1 1 and 16 8_+1 5 weeks respectively, p=0 4) Amnlottc flmd and maternal serum IL-10 levels were not slgmficantly elevated in patients subsequently dehvermg IUGR neonates compared w~thcontrols (Table, mean + SD) Ln IL-10 (pg/mL, Ammottc fired Maternal serum

IUGR 3 0-+0 2 (nitS) 2 9-+ 0 4 (n=13/

J

Control 2 8-+0 5 (n=46) 3 0 + 0 7 (n=45)

I

~ 0 8 060

No significant differences were identified in maternal age, smoking history, African American race, nulhparlty. GA, pregnancy Induced hypertension, or MSAFP >2 0 MOM in patients dehvenng IUGR neonates vs controls respecuvely (each p value >0 05) As expected, btrthwelghtwas s~gmficantlylower in patients dehvenng IUGR neonates compared wUh controls (p<0 001) CONCLUSION After matching for GA at dehvery, m~dtnmester ammotlc fired or maternal serum IL-10 values are not predlctrveof subsequent developmentof IUGR

CORRELATION OF UMBILICAL ARTERY LEVELS OF INTERLEUKIN-6 (IL-6) AND SOLUBLE INTRACELLULAR ADHESION MOLECULE.1 (SlCAM-I) WITH UMBILICAL ARTERIALBLOOD GAS MEASUREMENTS.*JC Smul~an,**WA Campbell, *AM V=n~loos, **JF Rodls *UMDNJ-RobertWood JohnsonMedicalSchool/St Peters MedcalCenter, New Brunswick,New Jersey.**Universdyof CT HealthCenter,Farrntngton,CT OBJECTIVE Umbdlcalafter/(UA) bloodgas statusmay be compromised by advanced fetal sepsis Thisstudywas des=gnedto determine the relationshipof fetal serologicmarkersof =nflammat=on,UA levelsof IL-6and slCAM-1,to UA bloodgas measurements STUDY DESIGN UA blood samples were collected at the brae of dehvery Blood gas determ=nattons[pH, pO2, pCO2, base excess(BE)] were performed on hepann=zedUA specimens Non-hepanmzedserum specimenswere assayedfor IL-6 and slCAM-1 using ELISAassaysadlustadfor ram=mumdetectablelevelsof 7 pg/mL and 7 ng/mL respectively The Spearmanrankcorrelationwas used to determine relationshipsbetween UA levels of IL-6 and slCAM-1with UA bloodgas parameters Analyseswereperformed based on labor status, route of delivery, and presence or absence of neonatal sepsis Blood gas results were compared betweensubgroups using the unpairedt-test Significance p<0 05 RESULTS.UA specimenswere obtainedin 3 term labor, 2 term C-sect=on, 4 preterm labor, 8 preterm rupture of membrane, and 2 tndcated preterm deifier/ patients The median valuesof UA IL-6 and slCAM-1were18 pg/ml (range <745,174) and 159 ng/ml (range 81-4731 IL-6 Correlations pH BE {n) Mean Rho* p Mean Rho* p Total (19) 7 27 -0 389 0 098 -3 6 -0 475 0 044 Labor (11) 7 27 -0 697 0 028 -3 9 -0 761 0 016 No Labor(8) 7 28 0 047 0 902 -3 2 -0 171 0 650 SVD(8) 7 26 -0 575 0 128 -4 8 -0 826 0 029 CS (11) 7 28 -0 147 0 641 -2 8 -0 243 0 443 No Seps~s(13) 7 29 -0 608 0.035 -2 8 -0 373 0 196 Seps~s(6) 7 25 0 143 0 749 -5 3 -0 029 0 949 *Rho=Spearman'scoefficientfor correlat=onof UA IL-6 levelsand pH or BE UA pCO2AND pO2 showedno s~ntficant correlabonswith UA IL-6 levels There were no s~gn~ficantdifferencesbetweenthe meanvaluesof the UA blood gas components for each analyzedsubgroup UA slCAM-1 Levelsshowedno significantcorrelationswith UA blood gas measurementsfor any of the subgroupsanalyzed CONCLUSIONS.1) UA levelsof IL-6 havea s~mficantinversecorrelationw~thUA pH tn the presenceof labor 2) UA levelsof IL-6 have significant inverse correlationswith UA BE for patients undergoJnglaborand who havean SVD 3) The lack of correlationof UA IL-6 wdh pH or BE *n pat*antswith neonatalsepsissuggeststhal low pH and low BE in the presence of lntraamnloUcLnfecttonmay be due to the effectsof labor ratherthan advancedsepsrs

371

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SPO Abstracts

217

THE RELATION OF UMBILICAL VEIN INTERLEUKIN.6 AND SOLUBLE INTRACELLULAR ADHESION MOLECULE-1 TO HISTOLOG~ PLACENTAL INFLAMMATION. *JC Smuhan, **WA Campbell, " L Ernst , *AM Vmtzl~eos, **JF Rodis *UMDNJ-RWJ Medical School/St Peter's Medical Center, New Brunswick, NJ **Umv of CT Health Center, Farmmgton, CT OBJECTIVE Amn¢ot=cfluidlevelsofmterleukm-6 (IL-6) and soluble mtracellular adhesion molecule-1 (slCAM-1) have been shown to have significant associations with acute and chronic inflammation of the placenta, respectively The study was designed to evaluate the relationship of placental Inflammation (acute and chromc) to umbd=calveto (UV) levels of IL-6 and slCAM-1 STUDY DESIGN UV samples were collected after cord clamping tn 26 term and preterm deliveries The serum specimens were assayed in duphcate for IL-6 and slCAM-1 using ELISA assays adjusted for minimum detectable levels of 7 pg/mL and 7 ng/mL respectively Placental specimens were evaluated for maternal (MAI) and fetal (FAI) acute mftammato~ responses (MAI was ~dent~fiedby the presence of chorlodecldu~tts and/or amnlonltrs FAI was identified by the presence of umbilical vascuhtls and/or chononlc vascuhtls ) Both MAI and FAI were graded for severity using a score of 0-4 Chronic Inflammabon (CI) was Indicated by chronic lymphocytic and/or plasma cell infiltraUonsof the membranes, basal plate, vdh, or mtervlllous spaces Mann-Whitney U was used to evaluate levels of IL~ and slCAM-1 in the presence and absence of MAI, FAI, and CI Kruska]-Wallrs test was used to evaluate IL-6 and slCAM-I levels according to seventy of inflammation Sigmficance p
218

CORRELATION BE'i3NEENUMBILICAL ARTERY AND UMBILICAL VEIN LEVELSOF tNTERLEUKIN-6 AND SOLUBLE INTRACELLULAR ADHESION MOLECULE-I. *JC Smullan,'*WA Campbell,*AM Vmtaleos,**.IFRodls.*UMDNJ-RWJMedicalSchool/St Pete"~ Medical Center,New Brunswick,NJ, **Umvof CT HealthCenter, Farmmgton,CT OBJECTIVE The relationshipbetween umbihcalartery (fetal compartment) and umbthcal veto (maternal/placental compartment) inflammatory markers has not been descnbed prevlousq This studywas designedto determine if there are correlationsbetween umblhcal artery(UA) and veto(UV) levelsof edherinterleukm-6 (IL-6) or soluble intracalluleradhesion molecule-1 (slCAM-1)and to assess potential effects of gestahonal age (CA), labor, and route of del~vePJon thesecorrelations STUDYDESIGN UA and UV sampleswere separatelycollected after cord clamping Serum specimenswereassayedm duplicatefor IL-6and slCAM-1 using ELISAassaysadjusted to have mm~mumdetectablelevelsof 7 pg/mL and 7 ng/mL respectively The paired-sign test was usedto compareUA to UV levelsof IL-6 and slCAM-1 The Spearman rank correletlon was used to determinerelationshipsbetweenpaved UA and UV levels of both substances for term gestations(->37weeks), pretermgestatlons (<37 weeks), presence or absence of labor, and routeof dehvery A p<0 05 was consideredsigmficant RESULTS The meanGA at dehverywas 32 4 + 4 3 weeks Themed~anvalues of IL-6 for UA and UV were 18 pg/ml (range <7-45,174) and <7pg/ml (range <7-21,384), (pINS) The medianvaluesof slCAM-1 for UA and UV were 159 ng/ml (range 81-473) and 143 ng/ml (range62413), (pINS) UA levelswere slgmhcantlygreaterthan UV levelsfor both IL6 (p=0039) and slCAM-1 (p=0035) IL.6 slCAM-1 (n) Rho* p Rho* p 0 845 <0 0001 0 806 0 0002 Total (23) 0 818 0 001 0 928 0.0002 Preterm(17) 0 714 0 11 0 786 0 079 Term (6) 0764 00113 0 762 0 012 SVD (12) 0 834 0 0084 cs(fl) 0 911 0 OO4 0 789 0 0031 0 775 0 0037 Labor (15) 0 881 0 02 1 00 0 0082 No Labor(8) "Rho=Spearman'scoefficientfor correlationof UA and UV levels CONCLUSIONS 1) UA levelsof IL-6 and sICAM-1 correlate significantlywdh UV levels regardless of the routeof dekveryor the presenceof labor 2) The UA and UV correlahons are slgmficant for preterm gestahonswith a trend for slgmficancewdh term gestations 3) EdherUA or UV specimenscould be usedfor studiesanalysing cord IL-6 and slCAM-1,but the potentialfor fetal produchonshould be considered if deftnlng parametersfor clinical use

Janua D 1996 Am I Ob~tet (;'~necol

219

220

CORRELATIONOF UMBILICAL ARTERY AND VEIN LEVELSOF INTERLEUKIN-6 AND SOLUBLE INTRACELLULAR ADHESION MOLECULE-I WITH NEONATAL HEMATOLOGIC INDICES AND EARLY SEPSIS. *JC Smuhan, **V Bhandanx, **WA Campbell, *AM Vmtzileos,**JF Rodls *UMDNJ-RobertWood Johnson Medical School/St Peter's MedicalCenter,New Brunswick,NJ **Umvof CT HealthCenter, Farm~ngton,CT OBJECTIVE The relation of umbilicalcord blood markersof ~nflammahonto conventional determinatesof eedy neonatalsepsis has not beendescnbed This study was designed to evaluatecorrelationsof early neonatal hematologiclndlcasand sepsis status wdh umbilical artery (UA) and veto (UV) levelsof intedeuk=n-6(IL-6) and soluble mtracellular adhesion molecule-1(slCAM-1), STUDYDESIGN UA and UV sampleswere collected after cord clamping In preterm (<37 weeks) and term dehvenes The serumspecimenswere assayed in duphcate for IL-6 and slCAM-1 using ELISAassaysadjusted for minimum detectable levels of 7 pg/mL and 7 ng/mL respectively Neonateswere categorizedas havtng e~thersuspected or confirmed sepsis(S} versus no sepsis (NS) wdhm 3 days of birth by din~caland/or laboratorycntena Mann-WhdneyU was usedto evaluatelevelsof IL-6 and slCAM-1 based on sepsis status Neonatal hematologicstudies including absolute neutrophil counts (ANC), absolute band counts (ABC),immature/totalneutrophdratios(I/T), and pleteletcounts (PC) were correlated w~th UA and UV levels of IL-6 and slCAM-1 us=eg the Spearman rank correlahon Significancewas set at p<0 05 RESULTS Therewere 17 preterm(S=7, NS=10)and 6 term (S=1, NS=5) dehvenes There were s~gndlcantd~fterencesof IL.6 levels betweenS and NS infants for specimensfrom the UA (mean rank 17 8 vs 8 9, p=0 0017) and UV (mean rank 18 5 vs 8 5, p<0 0001) IL-6 UA UV (n=18) Rho* p Rho* p ANC -0 105 0 67 -0 203 0 40 ABC O 668 0 006 0 640 O 008 liT 0 650 0 007 0 694 0 004 PC 0 006 0 98 -0 161 0 51 * Spearman'scoeffieentfor correlationof IL-6and hematologicresults Therewereno slgmhcantdifferencesof slCAM-1 between S and NS infants for specimens from either the UA (mean rank 133 vs 11 3, p=052) or UV (mean rank 138 vs 11 1, p=0 37) NeitherUA nor UV levels of slCAM-1 correlated wdh neonatal ANC (p=07), ABC {p=0 8), I/T (p=08), or PC (p=06) CONCLUSIONS 1) UA and UV levels of IL-6 (but not sICAM-1)are significantlyhigher m neonatesdevelopingchmcaland/orlaboratoryevidenceof earlysepsis 2) UA and UV levels of IL-6 (but not slCAM-1) correlatewith neonatalABC and I/T ratios 3) Umbil~alcord blood IL-6 is potentiallyusefulas a markerfor eedy neonatalsepsts

DISCORDANT/CONCORDANT TWINS GROWTH, AND THE LEVELS OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) INSULIN AND GROWTH HORMONE. A. Wizaltzerz, B. Furmanz, R. Gakman~, M, Mazor~, M. M~cachz, A. Koiphmanz, J. Levy~, J.R. Leiberman=, E.A. Reece. Dept. of OB/GYN & Clinical Laboratory of F_,ndccrine, Soroka Medical Cent~/Ben-Ourion Univ., Israel and Dept. of OB/GYN & RS, Temple Univ Sch of Med, Philadelphia, PA, USA OBJECTIVE: To investigate the role of IGF-I, insulin (IN), and growth l~'mon~ (GH), in twin l~rS, with and without growth regaiction~ STUDY DESIGN: Serum samples were olXained froca 27 twin geirs, immediately after delivery. Assignment to discordant twin group (n-16) was based on intertwln birthweight difference >20%, and to ~ a n t twin group (n-ll), by intertwin birdiweight differonce <20%. Maternal serum and cord blood were analyzed for IGF-1, 1N and GH. A receiveroperator characteristiccurve used intertwin IGF-I differences. RESULTS: The larger twin had significantly higher (r=0.66, p <0.(301) IGF-I level in all cases of discordant twin growth comgered with the ~naller twin. A mean intertwin difference in IGF-I cord blood levels of 69,9 ng/ml was consistent with discordant twin gestation. There was no intertwin differences in IGF-I levels in the concordant group (Figures).

15e

i= . | " s o

'

s t

19o

po~t I

too

2o0

)to

Addttionslly, there was no co.elation between birthweight and cord blood level of IN and GH. CONCLUSIONS: Our data demonstrate thai IGF-I is an important in-utero growth promoter, and seems to play a crucial role in normal and deviant fetal growth.

Volume 174, Number 1, Part '2 Am ] ()bstet (,yne~ol

221

SPO Abstracts

GLUCOSE AND AMINO ACID TURNOVER IN UNTREATED GESTATIONAL DIABETICS. D. Zlmmer. A. Golichowski, A. Baronx, S Denne x, lndlana Umversity Medical Center, Indpls., IN. OBJECTIVE: Although gestatlonal diabetes (GDM) affects as many as 3% of all gravldas, its spemfic effects on glucose and protein metabolism have not been clearly dehneated It is proposed that GDM results m increased glucose productmn and proteolysis dunng fasting STUDY DESIGN: The rates of appearance (Ra) of glucose (GLU), leuclne (LEU) and phenylalanine (PHE) were determined m 10 patients with GDM within 2 weeks of diagnosis and prior to lmtlatmn of dmt or insulin treatment. Eight healthy, nondiabetic gravidas served as controls (C). GDM and C had a mean age of 25+8 and 25+6 yrs, gestational age of 32+3 and 32+2 wks, weight of 85+24 and 78_+9 kg and body mass index of 33+7 and 28+3 kg/m2, respectively. After an overmght fast, a prime constant intravenous infusmn of L-[I-13C]-LEU, L-[nng-ds]-PHE, and D-[6,6,d2]-GLU was administered for 5 hrs. RESULTS: (*p<0 05) GLU Ra

LEU Ra

mg/kg/min GDM

2 2+0.6

PHE Ra

INS

I.tmole/kg/hr 148+29

40+7*

223

LONGITUDINAL STUDY OF Oo2 ADRENERGICRECEPTORNUMBERAND FUNCTION DURING PREGNANCY RichardM Smileyx, Carol B. Pantuckx, Dept. of Anesthesiology,Columbia Univ New York, NY. OBJECTIVE. To determine if o-adrenergic receptor (oAR) number or function is alteredduring human pregnancy STUDY DESIGN: Platelets were isolated from blood (30 ml) obtained from 21 healthypregnantwomenat weeks 1O,20, 30, and 37 of gesta~on, and 10-12weeks postpartum (PP). The func'donalstatus of 02ARs was assessed (in the presence of propranolol) by epinephrine inhibition of PGE-stimulated cAMP produc*aon (PGE/02) and expressedin pmoles cAMP/IOs colls/lO min 02-inhibd]onof PGEstimulated CAMPproductionwas also expressed as a percentage decrease (% o 2 inhib.). 02AR num~r (Bmax,receptorsper cell) and binding affinity (KD, nM) were determined using H-yohimbine (1-20 nM) and Scatchard analysis. Data were analyzedusing repeatedmeasuresANOVA. RESULTS: The table includes mean data obtained thus far. SEMsare omitted for readability. Data from 20 subjects should be available by the time of the mealing No statistically significant changes over the course of pregnancyhave yet been detected. PLATELET oAR CHARACTERISTICS 10 wks 20 wks 30 wks 37 wks PP n 15 19 14 11 9 PGE cAMP 2.0 2.8 3.1 37 3.9 PGE/o2 cAMP 0.8 1.0 1.0 16 0.9 % O2 mhib. 60 64 68 57 77 Bmax 227 229 231 253 253 KD 2.6 29 3A 3.0 3.2 CONCLUSIONS: oARs are involved in uterine confraction, vascular tone, and neural signalling and modulation, Platelet o2ARs appear to reflect uterine %ARs veff closely (1). KnowledgeregardingoAR function dudng normal pregnancymay lead to better understanding of the molecular physiology of pregnancy, Improve managementof hemodynamicallycompromised pregnantwomen, and conlnbute to understandingalterationsin pain toleranceand otherCNS changes In pregnancy This work was supportedin part by a Clinical ScholarGrant from the Intemabonal Anesthesia ResearchSociety. REFERENCES:1. Eur J Pharmaco1150 403-404,1988.

224

LONGITUDINALSTUDYOF 8-2 ADRENERGIC RECEPTORNUMBERAND FUNCTION DURING PREGNANCY. Rchard M. Smileyx, Carol B Pantockx, Dept. of Anesthesiology,Columbia Umv New York, NY OBJECTIVE. To determine if 8-adrenergic recepfor(BAR) number or function is altered during human pregnancy STUDY DESIGN: BARswere studied on lymphooytesduring pregnancy. Blood (30 ml) was obtainedfrom 21 healthypregnantwomen at weeks 10, 20, 30, and 37 of gesteSon,and 10-12weeks postpartum(PP) Lymphocyteswere isolated and cyclic AMP (CAMP)produc'don(pmoles/lO° cells,'lO min ) determinedin the basal state (BAS)and in responseto b'ealmentwith isoproterenol(ISO),forskohn (FSK), and prostaglandm E1 (PGE1). BAR number (Bmax, receptors per cell) and binding affinity (KD, pM) were determined with125I-iodopindolol,and evaluated by Scatchardanalysis Data were analyzedusing repeatedmeasuresANOVA RESULTS: The table includes mean data obtained thus far. SEMsare omitted for readability. Data from 20 subjects should be available by the bme of the meating No statisticallysignificant changes haveyet been detected LYMPHOCYTE BAR CHARACTERISTICS 10 wks 20 wks 30 wks 37 wks PP n 15 19 14 11 9 BAS cAMP 6.2 4.5 4.4 5.6 5.6 ISO cAMP 17.4 11A 11.0 13.5 13.8 PGE cAMP 87.3 67.4 69.8 87A 712 FSK CAMP 9.5 10 0 8.2 8.6 80 Bmax 1530 1265 1220 1162 1344 KD 42 41 21 16 32 CONCLUSIONS: The lymphocyteBAR has been shown to be a good model for flARs on otherorgans, and correlates par~cularly well with myomeb'ial BARs (1). Understanding BAR function during normal pregnancy may increase the understanding of the molecular physiofugyof pregnancy,improvemanagementof hemodynamically compromised pregnant women such as those with preeclampsia or pre.existingcardiacvalvular disease and ralJonalize the use of 82agonists for proterm labor. Thts work was supported m part by a Clinical Scholar Award from the Intema~onalAnesthesia Research8oclety. REFERENCE& 1. Clin Pharmacol Ther fg8g; 45' 1.8

GLU

~tU/ml

mg/dl

26+1"

76+8*

Control 2 4_+0.5 135+ 18 47+6 5+_2 70+2 CONCLUSIONS. GLU concentrations throughout the study were increased m GDM, but there was no increase m GLU Ra There was no difference m LEU Ra, and PHE Ra was actually decreased m GDM. Normal GLU turnover m the face of 5-fold higher prevailing msuhn (INS) concentratmns suggest GDM Is associated with both hepatic and penpheral INS resistance. Elevated INS levels probably contribute to the fact that proteolysis rates are not increased m GDM.

222

C O M P A R I S O N O F F E T A L L U N G M A T U R A T I O N IN WELL DATED DIABETIC AND NON-DIABETIC PREGNANCIES K Berkowitz. M.D.. C. Reyes, M.D., P. Sadaatx & S. Kjos, M.D. University of Southern California School of Medicine, Los Angeles, CA O B J E C T I V E : To compare fetal lung maturation in diabetic and non-diabetic pregnancies and to evaluate the influences of diabetic class, third trimester glycemic control and hypertension. STUDY DESIGN: Prospective cohort study of well-dated diabetics (n=585) and non-diabetics (N=628) delivering between 1987-1992. RESULTS: 96% of diabetics and 90% o f non-diabetics had mature L/S ratios at 39 weeks. PG% was mature in 93% of diabetic and 100% of non-diabetics at the same gestational age. Neither diabetic classification, glycemic control or hypertension affected the rate of maturation in the diabetic patients.

~,~ ,,:,o

27

31

32

WEEKS

33

34

35

36

37

GESTATIONAL

3B

39

40

41

AGE

C O N C L U S I O N S : Lung maturation is not delayed in well-dated diabetic pregnancies compared to non-diabetics. Neither diabetic elassfieation, glyeemm control or hypertension affect the rate of fetal lung maturation among diabetic pregnancies.

373

374

SPO Abstracts

I,muaD' 1996 A m J ()bstet (,ynecol

225 POST PARTUM CHANGES IN RAT UTERINE ARTERY VASCULAR TONE ARE DUE TO WITHDRAWAL OF NITRIC OXIDE. *GD Helmbrecht, **MY Farhat, '*L Lochbaum, **HE Brown, *GS Eglinton, '*PW Ramwell Dept. 'Ob/Gyn, and **Physiology, Georgetown UniversityMedicalSchool,Washington,DC OBJECTIVE: Endothelium derived nitric oxide (EDNO) is thought to contribute significantly to the decrease in vascular tone during pregnancy. We evaluated the effects of inhibitionof EDNO synthesison vascular reactivity during the post partum transition. STUDY DESIGN: Pregnant Sprague-Dawiey rats received chronic infusions of saline (S) or the EDNO synthase inhibitor L-nitro arginine methyl ester (L)(LNAME 50 mg/day) from mid gestation to term. Uterine arteries (internal diameter 250 - 500m) were harvested on day 18-20 (P)(n=10) or 24 hours post partum (PP)(n=10). Vessels were mounted on a microvascular isometric myograph for determination of vascular reactivity in response to prostaglandin-F2~ (PGF2c0, acetylcholine (ACH), and sodium nitroprusside (SNP). Data were analyzedusing two way ANOVA and Newman-Keulstest for multiple

227

A PROSPECTIVE LONGITUDINAL STUDY OF TRANSFORMING GROWTH FACTOR - i3 1 (TGF- 13 1) LEVELS DURING FIRST, SECOND AND THIRD TRIMESTER, LABOR, POST PARTUM AND WITH CORD BLOOD AND LABOR ANESTHESIA F. Rigby, E Bowenx, D. Clavin, D Powers~, C. Campbellx, T Nolanx, S Greenbergx, Dept of OB/GYN, LSU Medical Center, New Orleans, LA Objective. TGF- 13 1 Is a multlfunctlonal polypeptide growth factor for which the vast majonty of human cell types have receptors It has been imphcated m the first trimester decldual immunoregulatory response This ts the first prospectNe longitudinal study of the levels of this growth factor in pregnancy Study Design Peripheral venous blood was obtained during first, second and third trimester, m labor, wtth anesthesm admmlstratmn and post partum Cord blood was also obtained Resulte Please see graph. VerUcal axts is plasma TGF- 13 1 m ng/ml and horizontal axts ts number of samples in each trimester

compariscrls.

80

RESULTS: The maximumtension developed(Tmax) in responseto PGF2 a was greatest for saline treated P compared to PP (3.25 v t.60mN) (p<.01). LNAME attenuated the contractile force to a greater extent in P than in PP vessels (49% v 20%). Among the saline treated groups, relaxation response to ACH was greater tor P than for PP (98% v 65%)(p<.01) reflecting greater EDNO activity in the former. LNAME significantly inhibited ACH induced relaxation. All vessels responded similarlyto SNP. CONCLUSIONS: These data support a role for EDNO in the maintenanceof the loweredvascular tone duringpregnancy. Post partum changes in uterine artery vascular tone result from the abrupt withdrawalof the influenceof EDNO on vascularsmco~ muscle.

g0

226 C H A R A C T E R I Z A T I O N

OF AMBULATORY BLOOD PRESSURE IN NORMOTENSIVE PRENGNANCY. G Btal~, M. Ruddyx, E Malka*, F Ctoffi Section of Hypertension, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ. OBJECTIVE. The purpose of the present study was to estabhsh the normal ambulatory blood pressure (ABP) profile for normotensive, healthy pregnant women. STUDY DESIGN: A total of 84 pregnant subjects with normal clinic blood pressures were reermted for this study. O f these, 18 were fast trtrnester, 29 were second trimester, and 37 were third trmaester Each subject underwent 24-hour Ambulatory Blood Pressure Monitoring using a Spacelabs 90204 ABP apparatus There were no differences among the groups with regard to age and height RESULTS Mean±SE lat T r i m 2nd T r i m 3rd Trim Clinic SBP mmHg 110±2.2 1184-35 1144-26 Clinic DBP 684-22 714-27 704-1.9 Awake SBP 1144-15 1134-16 1194-21" Awake DBP

67 4- 1 3

66 + 1.0

70 4. 12"

Awake HR bpm 864-18 904-12 914-1.4 Sleep SBP 103 4- 2 4 103 4- 2 1 109 4- 2 5 Sleep DBP 58 ± 1 8 55 4- 1.0 61 4- 1.8" ,Sleep ItR bpm 74 4- I 8 79 ± 1 5 79 + 1 6 % Nocturnal Decline [= (awake-sleep BP) + awake BP) x 100)] SBP mmHg 91±1.3 9,1+12 764-09 DBP mmElg 144±1.6 16.1 ± 1.3 124±1.4 "Statistically stgmficant dtfference by ANOVA (p £ 0 05) fi'om 2nd trtm CONCLUSIONS' Ambulatory &astolie BP was highest m the third trimester, and lowest m the second, for both awake and sleep Awake SBP was also highest m the third and lowest m the second trimester. There was a similar tendency m sleep SBP

[] Rrst Trimester

I

[] Second Trimester 1Third Trimester

40

[] Labor mAnasthesla • Cord Blood 29 15 15 25 14 20 25

[] Post Partum

These values represent the first prospecttve Iongttudmal study of TGF- I1 1 levels throughout pregnancy. The statistically s=gmficant lower levels noted m second and thtrd tnmester and m labor may represent down regulation of this important immuno-regulatory pepUde by the placenta Conclusion'

228 E R Y T H R O C Y T E

INSULIN R E C E P T O R BINDING IN RS Eeerman. ES Umstot, x RN Andersen,s PR Casson, x and BM Sibai, I~epartment of Obstetrics and Gynecology, University of Tennessee, Memphis. OBJECTIVES: Insulin resistance may contribute to hypertension during pregnancy. Therefore, we compared insulin binding to erythrocytes by means of competitive radioreceptor assay in patients with preeclampsia and normotensive pregnancies. STUDY DESIGN: Blood was obtained after an overnight fast from eight patients with preeclampsia and from eight normotensive controls. All patients had normal glucose screening and no familial history of diabetes. Erythrocytes were used as an indicator of peripheral insulin receptor expression Erythrocytes were isolated by densit~ gradient centrifugation, washed, and reconsUtuted with buffer at 4uc. Serial dilutions of biosynthetic human insulin were prepAw~.edand incubated overnight wtth an aliquot of red cells and an "~'Jl insulin tracer. Erythrocytes were centrifuged through oil and counted in a gamma counter. Scatchard analysis determined maximal % binding, number of binding sites/cell, and affinity Ka. RESULTS: There were no differences between the two groups regarding maternal age, BMI, gestational age, and fasting glucose and insulin levels at time of sampling (Table). As expected, preeelamptic patients had significantly higher mean arterial pressures (MAP) than controls (P=0.006). However, there were no differences regarding any insulin binding studies {Table). PREECIAMPSIA NORMOTENSIVE Maternal Age (yr) 21.8 ± 1.1 22.4 :t: 1.2 Body mass index (kg/m2) 29.0 ± 1.8 28.1 ± 0.4 MAP(~waHg) 99.7 + 3.7 81.9 ± 4.8 GAatsamphng(wk) 35.4 ± 1.0 364 ± 06 Fasting glucose (mg/dl) 82.3 + 3.6 78.0 ± 2.3 Fasting insulin (mu/ml) 7.5 + 1.6 10.5 + 1.0 Maximal bmding (%) 15 2 ± 2 3 1 4 3 ± 1.0 Receptor sites per cell 8.6 ± 0.8 7.5 ± 1.2 Affinity Constant/Ka x1091 4 7 ± 0.8 4.0 ± 0.5 CONCLUSION: Erythrocyte insulin receptor expression is not altered in preeclampsla. However, these findings need confirmatmn in target tissues of insulin activity such as adipocytes and myooytes. PREECLAMPSIA:

SPO Abstracts

Volume 174, Number 1, P,nt 2 Am [ O b s t e t (;ynecol

229

230

IMMUNOHISTOCHEMICAL LOCALIZATION OF PHOSPHOLIPASE A= ISOFORMS IN HUMAN MYOMETRIUM DURING PREGNANCY AND PARTURITION. D Skannal, X A Eis,X D Brockman,= T Siddiq=, L. Myatt = Dept. Ob/Gyn, Univ of Cinti Coil Med, Cincinnati, OH OBJECTIVE: Distract =soforms of phosphohpase A= including 14kDa secretory (sPLA2) and 85kDa cytosolic (cPLA~ have been demonstrated. The isoforms have different substrates specificities and cellular Iocalizations which may define their roles m signal transduction pathways involving arachidonic acid mobilization and prostaglandin synthesis, The purpose of this study was to ident=~ and determine changes m expression and localization of sPLA2 and cPLA2 in pregnant human myometnum w=th gestat=onal age or partuntion STUDY DESIGN: Myometrlum was collected at cesarean section at term (>37 weeks) or preterm (<37 weeks) from patients who were or were not =n labor (n = 5 each group), flash frozen in liquid nitrogen and tissues sectioned on a cryostnt at 7 I~m, Secttons were incubated wcth specific monoclonal antibodies against sPLA= or cPLA2 and biotinylated anti-mouse IgG second antibody and visuahzed with the Vectastain ABC ehte method Control sections had no pnmary antibody Intensity of immunostalnmg in different cellular Iocahzattons was scored by an investigator bhnded to ttssue identity and compared between tissues using students 't' test RESULTS: Secretory PLA2 immunostaining was dispersed rn the perinuclear regton throughout the myometnel smooth muscle fibers and tn vascular smooth muscle Variable mtenstty of staining was seen between samples Cytosohc PLA2 immunostalning was predominantly Iocahzed to endothehal cells of myometnal blood vessels and weakly throughout myometrial fibers Overall sPLA= ~mmunoslammg was more intense than cPLA2 No differences m mtens=ty or tocafizat=on of sPLA2 or cPLA2 could be determined with respect to gestational age or parturition CONCLUSION: Both sPLA= and cPLA2 isoforms are present in pregnant human myometrium but at different locations suggesting distinct physiologic roles The apparent lack of change Dn expression with gestation or labor suggests changes in myometrial PLA2 activity and, hence, local arachidonic acid mobilization and prostaglandin synthesis may not mediate parturition.

CHANGES IN C I R C U L A T I N G L O N G C H A I N ESSENTIAL FATTY ACIDS (LCEFA) IN N O R M A L H U M A N PREGNANCY. P. Oebum. M. Kanayamax, J. Van Winter x, K. Schwarz x, R. Holman x. Dept. Ob/Gyn, Mayo Clinic, Rochester, MN, Dept. Pediatrics, Johns Hopkins, Baltimore, MD, Hormel Institute, Austin, MN. OBJECTIVES: The null hypothesis is that patterns of circulating serum phospholipid (PL) long chain essential fatty acids are unchanged by pregnancy. STUDY DESIGN: Serum was obtained from groups of normal pregnant women in each trimester of pregnancy (11-14 wks = 1st A [n=16], 26-30 wks = 2nd A [n=44], 34-39 wks = 3rd A [n=12]). Fatty acid (FA) analysis of serum PL was done by lipid extraction, TLC, methyl esterification, and capillary GLC. Mean + SEM results were compared using Student's t-test. RESULTS: Percent of total fatty acids in PL of serum in each trimester are given for each LCEFA: Fatty Acid First A Second A Third A Arachidonic acid 12.03 + 0.52 11.33 + 0 24 8.11 ..'t. 0.33** 22 4w6 0.81 + 0.07 0 62 + 0.02* 0.40 + 0.01"* 22:5w6 0 82 ..+_0.06 0 80 _+..0 03 0.79 + 0 05 EPA (20.5w3) 0 60 ..+_0 03 0.27 + 0 02* 0 22 + 0.02*** 22"5w3 0.92 .'t. 0.05 0 53 + 0 02* 0.37 + 0 02** 22:6w3 3.76 + 0 25 3 97 + 0.10 2.38 + 0 16"* (* = < .001, 1st A vs. 2rid A; ** = p < .001 2nd A vs. 3rd A,*** = p < 001 1st A vs. 3rd A) CONCLUSION: Patterns of circulating LCEFA in PL change as pregnancy progresses Significant decreases are see in most LCEFA of both omega-6 and omega-3 fatty acid families. These decreases support the concept that normal pregnancy transfers LCEFA to the fetus for growth and development leaving the mothers' fatty acid patterns consistent with essential fatty acid deficiency.

231

METABOLIC RESPONSE TO MEAL EATING AND EXTENDED O V E R N I G H T FAST IN TWIN GESTATION. H. Casele, S Dooley, B Metzger Dept. Ob/Gyn and Center for Endoermology, Metabolism and Nutrition, Northwestern Umverslty, Chicago, IL OBJECTIVE: To compare the metabohc response to normal meal eating and the vulnerability to starvation ketosis in twin versus smgleton gestauon STUDY DESIGN: 11 twin and 11 singleton non-diabetic gestations were enrolled into a 40-hour metabolic study Singletons were age (+_ 5 yrs) and prepragnancy weight (+ 10% Ideal Body Weight [IBW]) matched with the twins. The &et (35 kcal/kg IBW singletons; 40 kcal/kg IBW twins) was distributed as 1/5 0800 hr, 2/5 1300 br, 2/5 1800 br An overnight fast was extended until noon the following day Glucose and B-hydroxybutyrato (B-OHB) measurements were made hourly except at night when they were drawn every 2 hours Insulin values were obtained surroonding dinner and on the day when breakfast was delayed RESULTS: The glucose and insulin excursion m response to meal eating and fasting were similar in twins and singletons (ANOVA for repeated measures, p>.05) Dunng the day when the patients were fed, the ketone excursions are also smular. However, during fasting, the ketone excursions are significantly different (ANOVA for repeated m~s, 13= 0001 ) At 8"00 AM after a 14-hour fast, mean B-OHB vats 26 + .0g mmol/l for singletons and 28 + 12 mmol/l for twins (p> 05) By noon, mean B-OHB was 46 + 10 mmol/l for singletons and 76 + 36 retool/1 for twins (t=-2.52, p< 05) CONCLUSION: On the basis of these data, it appears that the metaboltc response to meal eating is strmlar m twins versus singletons despite the provision of additional calories to the twins. It also appears that twins are more vulnerable than singletons to accelerated starvation When an overnight fast was extended by delaying breakfast, ketone levels rapidly dewated. We speculate that tins observed difference may be due to the increased metabolic demands of twin gestation

232

OXYGEN TRANSPORT VARIABLES DURING NORMAL THIRD-TRIMESTER PREGNANCY C. Harveyx, G Hankms, S. Clark, E. U~kan x, D. Cotton. The Umversity of Texas Medical Branch at Galveston, TX. The Umversity of Utah, Salt Lake City, LIT.Wayne State Umverstty, Detroit, MI OBJECTIVE: To directly measure oxygen transport variables at moderate altitude in healthy normotensive pnmiparous patmnts at term STUDY DESIGN: Ten normotenslve pnrmparous patients between 36 and 38 weeks gestataon underwent pulmonary artery cathetenzatlon and radial artery canalization The study was approved by the hospital Institutional Review Board and an outside reviewer. Written informed consent was obtained. Basehne assessments were made in the left lateral recumbent position after a 30-mmutes stabilization period. Cardiac output was measured via thermechlutton. Simultaneously blood obtained from the pulmonary and radial arteries was analyzed for oxygen content on a blood gas analyzer (Cormng Model 168, Medfield, Mass.). All of the 10 subjects had complete oxygen transport profiles antepartum and seven subjects had complete data at 12 weeks postpartum. RESULTS: Individual oxygen delivery variables are listed in Table 1. TABLE 1

SaO2 SvO2 CaO2 CvO2 O2AV O2AVI V(Y2 VO21

OXYGENTRANSPORTVARIABLES ANTEPABTUM POSTPARTUM 0 96 0 722 1587 II 86 85481 482 51 214 94 121 45 0253

0 005 0 029 072 083 17773 95 04 41 77 23 52 0026

0 002 0011 028 032 6718 35 92 15 79 8 89

0 945 0 713 18 I 1358 81198 494 37 200 96 122 39 025

0 009 0 016 088 082 22259 116 76 50 37 25 25 0016

0 003 0 006 033 031 8413 44 13 19 04 9 54

p<0 05 NS p<005 p<005 NS NS NS NS NS

CONCLUSIONS: Ttus is the first report of darectly measured oxygen transport variables in the healthy pregnant patient. Although there were statistical differences in the antepartum (AP) and postpartum (PP) measurements, the difference is not chmcally sigmficant However, the difference in the APand PPCaO 2 and CvO2 are statistically significant and chmcally relevant, as a reduced CaO 2 and CvO2 in pregnancy must be addressed in medical management

375

376

],ln.,..y 199t,

SPO Abstracts

Am I ()bster (,xuc¢ol

233 ARTERIALBLOODGASANALYSISDURINGNORMALTHIRD-TRIMESTER PREGNANCY AND T H E EFFECT O F POSITION CHANGES. G. Hankins. S. Clark, E. Uqkan x, C. Harveyx, D Cotton. The Umverstty of Texas Medical Branch at Galveston, TX, The Umverslty of Utah, Salt Lake City, LIT,Wayne State Umversity, Detroit, MI. OBJECTIVE: To establish normative data and evaluate the effect of position change on arterial blood gas and acid base status of normotenstve primiparous patients. STUDY DESIGN: Ten normotemave pnnuparous patients between 36 and 38 weeks gestation volunteered to undergo radial artery canalization. The study was approved by the hospital Institutional Revaew Board and an outside reviewer. Written informed consent was obtained. Baseline assessments were made in the left lateral recumbent position after a 30-minute stabdlzaUon period. A 10 minute premeasurement stabihzation period was allowed between each position change. Measurements were obtained m the left lateral, right lateral, supme, sitting, standmg, and knee-chest positions. Blood samples were analyzed in duplicate for oxygen content on a blood gas analyzer (Cormng Model 168, Medfield, Mass.) Statistical analysis was ANOVA with srgmficance defined at p_<0.05. RESULTS: There was no srgmficant &florence in artenal blood gas variables between any positions in this antepartum population of term healthy women (Table 1).

[

TABLEI AR'I~RIALBLOODGASESANDBDSITIONCHANGE Position Leftlateral Rl,~htlateral Supine Slttln~ Standlnl~ Knee-chest Mean t,~I~ Mean ~D Mean :tSO ~Ul +XD Mean±SO M~an =SD pH pCO2 pO2 HCO3 SaO2

746:1:002 266 :t27 862 ±73 186 ± 19 096 ±001

746 274 877 183 096

:t006 :t20 :t45 ±14 ±00

745 267 867 188 096

:t002 ±21 ±72 ±14 ±00

7 4 6 ±003 2 6 4 :t22 911:1:73 184 :t08 0 9 6 :tOO

746 255 888 179 096

:t001 :t24 ±78 ±07 :t001

746 267 895 173 096

±002 ±12 ±5 9 :k16 ±0 0

CONCLUSIONS: Arterial blood gas variables were not altered after positron change of the subject. These results were obtained at moderate altitude; however, chmcally stgmficant changes in matemal oxygenation would have altered the hemoglobin saturation due to the low PaO 2 of the arterial samples. Contrary to prevaous reports of &fferences between arterial PaO 2 between slttmg and supine positions, we found no evidence of stgmficant arterial blood gas alteratlons

234 HUMAN

FETAL PULMONARY/SYSTEMIC VASCULAR RESISTANCE. J. Rasanen x, D. C. Wood x, A. Ludomirski*, J. C. Huhta x. Dept Ob/Gyn, Pennsylvania and *Temple Univ. Hospital, Philadelphia, PA. O B J E C T I V E : To establish the relation between human fetal weightindexed pulmonary (Rpi) and systemic (Rsi) vascular resistances and the changes during the second half of the gestation STUDY DESIGN: By using a cross-sectional study design 63 normal fetuses were examined between 19w and 39w (median 28w) by Doppler echocardiography. Heart rate (HR), diameters and time-velocity-integrals (TVI) at the aortic (AV) and pulmonary (PV) valve annuli, ductus arteriosus (DA), right (RPA) and left (LPA) pulmonary arteries were measured and weight-indexed blood flows (Qi) were calculated (TVI x area x HR/estimated fetal weight). The systemic blood flow (Qsi) was calculated by subtracting pulmonary blood flow (Qpi=QLPAi+QRPAi) from the fetal combined cardiac output ( Q A v i + Q P v i ) . Fetal mean transpulmonary pressure gradient (P) was assumed to be equal to fetal mean systemic pressure gradient, which was assumed from values m premature newborns at the same gestattonal ages. Weight-indexed vascular resistances were calculated: Ri(mmHg/ml/min/kg)=P(mmH g )/Qa (ml/min/kg) RESULTS: Meard:SD values at three gestational ages (comparison to 20w group: *p<0.05, **p<0.0001; comparison to 30w group: tip<0.005, Clip<0.001 ). P QPi Qsi Rpi RSi Rpi/Rsi 20w 30 91+33 496"k160 0.35+0.08 0.07:k0.03 5.952.5 30w 42 188+26"* 503:1=74 0.232-0.03* 0.08£-0.01 2.7:L-0.7' 38w 55 138+18 (l 470-k99 0.40-k0,05 ¢1<[ 0.12:~.02" 3.4~-0.3 CONCLUSIONS: The decrease in Rpi between 20w and 30w reflects lung growth and its increase later in gestation may be due to acquired vasoconstriction in the pulmonary circulation. The changes in Rpi/Rsi show the magnitude of the decrease m the Rpi and its importance in the regulation of the distribution of fetal cardiac output. We speculate that this regulation could be altered by therapeutic mampulation of fetal Rpi/Rsi.

235

DEVELOPMENT OF FETAL CARDIAC COMPLIANCE THROUGHOUT THE SECOND HALF OF PREGNANCY. Z__ WemeP:2., Z Efra¢'2, E Zimmer~'2, J Itskovltz~'2, MY Divon ~ Dept of Ob/Gyn, Albert Einstein College of Medicine ~, Bronx, N Y., and Rambam Methcal Centerz, Halfa, Israel. OBJECTIVE: To study the development of the human fetal cardiac comphance throughout the second half of pregnancy by measur:ng the 2 components of the ventncular filling, the rapid venmcular filling and the atrial systole STUDY DESIGN: A longitudinal study was performed on 25 low-risk pregnant women from 24 weeks' gestation until term. Doppler studies of the blood flow through the mltral and tricuspid valves were performed every 4 weeks using a pulsed wave Doppler ultrasound device (Acuson 128 XP10) The following indices were calculated from the flow velocity waveforms' 1) The ratio between peak-velocity during the rapid ventrlcular filling and the atrial systole (E/A rano), 2) The velocity time integral (VTI) of the amoventricular blood flow (this integral correlates with volume flow), 3) The ratio between VTI during the rapid ventncular filhng and the atrial systole (VTI ratio); 4) The FHR To improve the accuracy of these calculations we accepted only measurements obtained with a beam angle < 26° Pearson's correlanon was used to evaluate the effect of gestatlonal age on these indices. RESULTS: All patients dehvered at term and had an uncomphcated pregnancy. Each panant had 4-5 tests. Correlanons between the Doppler indices and gestatlonal age are presented. E/A ratio VTI VTI ratio Mltral r=0 75** r=0.49" r=0 56* * p < 0 01 Tncuspal r = 0 8** r=0.55" r=0 61"* **p<0 001 There was a slight but nonsigmficant decrease in FHR CONCLUSIONS: These results indicate that, m the human fetus, the relative contribution of the rapid ventricular filling to the total ventricular fillmg increases as gestatlonal age advances. These findings could be explained by an improvement in cardmc comphance and/or by a decrease m peripheral res:stance.

236 MYOGENIC ACTIVITY AND ENDOTHELIUM DEPENDENT DILATION

IN ISOLATED BLOOD VESSELS FROM PREGNANT WOMEN. H_..~. Nisell', K. Rasa-Kublickieu~, M.Y. Divon, B, Liudblom', N. Olov Lun©IP, M. Westgren. Department of OB/GYN, Huddinge University Hosp.; Uppsala University, Sweden & Albert Einstein College of Medicine, N.Y., U.S.A. OBJECTIVE: To evaluate changes in vessel diameter in response to constant and step-wise intralumiual pressure alterations under no-flow conditions in isolated resistance blood vessels from normal pregnant women. The vasoactive function of the endothelium was assessed by the response to acetyleholine(Aeh). STUDY DESIGN: lntramyometrial and omeatal arterioles were obtained during C/S and pressurized in a superinfused vessel chamber that allowed the internal diameter to be assessed continuously using video microscopic techniques. RESULTS: At a constant intraluminal pressure of 70 mmHg in calcium free solution with papaverine (104M), the passive diameter of omental and myomatrml arterioles did not differ significantly (311 +20 #m (moon +SEM) and 305±28, respectively). In Hopes-physiological saline (PSS) both omental and myometrial vessels developed spontaneous tone which reduced lumen diameter by 20+7 % and 34 +7 %, respectively, (p =NS) At an iatraluminal pressure of 70 mmHg, Ach (106M) induced relaxation & was significantly higher in myometrml (24+5%) compared with omental resistance vessels (9±2%), p < 0 05. In the absence of calcmm and presence of pnpaverine step-wise increment an perfnsion pressure from 20 to 120 mmHg evoked a continuous similar increase in diameter in both preparations. In Hepes-PSS change in intralummal pressure of myometrial anermles from 40 to 60 and 60 to 80 mmHg, caused an initial dilation, followed by myogenic constriction that returned the vessel diameter to the initial value over a period of several minutes. In omantal vessels, these changes in intraluminal pressure produced only a small passive dilation. CONCLUSIONS: Myogenic responses are more pronounced in myometrial arterioles as compared with omental vessels The results indicate an obligatory role for calcium m pressure-dependenttone development of resistance vessels in normal pregnancy. Ach receptor-mediated release of endothelial-derived vasedilators in the uterine vascular bed is significantly enhanced relative to omental vessels.

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SPO Abstracts

Effects of advancing Pregnancy on the Umbilical Artery (UA) Pulsitility Index (P1) after Strenuous Non-Weight Bearing (Bicycle) Exercise (Bex). J C Vellle, DR gatzmanx, K Ta~m x, K Stewart ~, P Mflsapsx Depts Obstet/Gynecol & Medacme (cardaology), Bowman Gray School of Me&cine, Winston-Salem, NC Introduction Prevmus studaes indacate that strenuous Bex does not slgnfficantly affect the UA Doppler waveforms (UADW) late in pregnancy The present study attempts to determine the effects of Bex longitudinally on the PI of the UA Study Desinn Fifteen conditioned subjects were studied 3 tunes during the course of the pregnancy. SubJects exerctsed on an electricallybraked bicycle (EBB) The reststance of the EBB was increased by 25 watts Q10 min untal the subject had reaohed an RQ of 1 1, thetr maximal heart rate or had stgmlicant leg fattgue. UADW were obtsmed pnor to the exerctse (Ex) and soon after the completion of the Ex. A minimum of three UADW were analysed and averaged. PI were compared pre and post Ex Results are reported as ~ + SEM Stattsttcal analyses were done using non parametric and ANOVA 17~ , putxtsnse Results: 1) PI decreased stgntficantly v mrtmeest oath advancing GA (p< 0 002); 2) There was no significant changes in the PI between pre and post Ex 3) Advancing GA did not affect UADW response to strenuous Bex Conclusion: Strenuous Bex does not seem to affect UADW at any of the GA periods studied

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238 Effect of Advancing Gestation on E/A Ratio of the Left and the Right Ventricle after Strenuous Bicycle Exercise. JC Vexlle. DR Katzrnanx, K TatumX,K StewaW, P Malsaps x Depts ObsteVGynecol & Medacine (CardMogy), Bowman Gray School of Medacine, WinstonSalem, NC Introduction Dtastohc venmcular filling (DVF) ts assessed by analysts of Early (E) to Atnal (A) ventncular inflow Doppler waveform The purpose of ttus study was to determine the effect of strenuous bmycle exercise (Bex) on the nght (RV) and the left (LV) ventrMe E/A raho with advancing pregnancy Material & Method Fifteen healthy subjects were studied three ttmes dunng thetr pregnancy Doppler waveforms (DW) were obtained from the RV and LV just below the A-V valves prior to and immediately after Bex A mmtrnum of 3-5 DW were traced and averaged Results are reported as ~ and ± SEM One way ANOVA rank test were done for slgndicance Results 1) There was a significant decrease m the E/A ratio of RV between rest and Bex only during the 1st study period (p<0 02) 2) There was a significant increase m the E/A ratm with advancing GA (p < 0 02) 3) Bex dad not slgntficantly affect tlus ratto dunng the other study periods Conclusion. Overall, strenuous Bex did not significantly affect the DVF in human fetuses

239

Longitudinal M-Mode echocardiography 0gc) of the End Diastolic (EDD) and End Systolic (ESD) dimension of the right (RV) and Left (LV) ventricles from early Fetal life to Year One. J C.Veille. K Tatumx, L Steele~, S MeNedX,Depts Obstet/Gyneeol&Pedtatnes (Cardiology),Bowman Gray School of Medmme,Winston-Salem,NC Objective: To evaluate RV and LV EDD and ESD using Ee m fetal, neonatal (Tranmtional)and infancy so as to understandhemodynarmeadapta~aondunng these penods Material & Methods: Ee were started at the 16th week of gestation m 52 normal fetusesand repeated every4- 6 weeks until term Two more Ee were done duringthe "Transitional"penod, and 3 more were done at 6 weeks, 6 months and at 12 months of age. The M-Mode cursor was placed so as to transect the A-V valves.All returning Ee were recorded on a strip chart at a preset speed of 50ram/see. EDD and ESD were measured accordingto published standards.Mean and SEM for each of the EDD (graph) and ESD were tabulated for each of the 11 study periods. Correlationeoeffiemntfor LV and RV were made and ANOVA for repeated measures were used for significance Results: l ) LV was highly correlated with o~ ~k advancing age {AG} (r2=O93, p<0 0001); 2) '' t AlthoughRV was eorrolatedto AG ,~ (r2=0 361 ;p<0.05), RVEDD had a slowerrate of growth after birth; 3) RVEDD was significantly rn~ larger m utero (p<0 01), and LVEDD was d significantlylarger after buth (p<0 0001) '¢ Conclusion: This is the first study to longitudinally , , . ,; followthe rate of growth of the RVEDD and n~ LVEDD dunng the fetal to the infant period. Changes m respeettve ventneular aflerloadmost hkely influence ventrieulardimensmns

240 Longitudinal Follow-up of the Descending Aorta (DA) Hemodynamics in Normally Grown and IUGR Fetuses From Early Intrauterine Life To Year One. J.C.Veille, K. Tatum x, L. SteeleX,C. Legaultx, Depts Obstet./Gynecol. & Public Health, Bowman Gray School of Medicine, Winston-Salem, NC Introduction: Studies have shown conflicting results regarding blood flow through the DA m IUGR human fetuses No longitudinal studies followed these fetuses into childhood to demonstrate residual effects from the poor in-utero environment. Materials & Methods: Sixty-six (66) Normally grown fetuses and thirteen (13) fetuses with IUGR were followed every 4 weeks with Doppler U/S from the 18th week until delivery. Two studies were done after delivery and one at w 6 wks, 6 months and 12 months. Results: There was no overall significant -. difference between the two groups during fetal, transitional and newborn period for the peak flow velocity (Top figm'e), for the time velocity integral (Lower figure)and for the AC/ET ratio (no figure shown) between the two populations. Conclusion: These prehminary results do not indicate major differences in the vascular hemodynamie of the DA between these two populations.

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s P a Abstracts

EVALUATION OF

iatmal 3 1996 Am ] ()l)~tet (,',he(o]

FETAL/MATERNAL PLASMA

LEUCINE

ENRICHMENTS IN NORMAL AND INTRAUTERINE GROWTH RETARDED PREGNANCIES. A.M.Marconi x, e.CetinX, E.Davolix, C.Paolini x, S.Ronzoni x, R.Fanelli x, M.Buscaglia x, G Pardi, F.C.Battaglia. Dept. of Ob/Gyn, Univ of Milano, Italy; M.Negri Inst. for Pharmacol. Res., Milana, Italy; Dept of Ped Univ of Co Sch of Med, Denver {USA) ORJECTIVE: To assess fetal maternal leucine relationships in AGA and IUGR fetuses at the time of fetal blood sampling. STUDY DESIGN: A maternal primed, constant infusion of L[1IsC]Leucine was given in 3 normal (AGA) and 6 intrauterine growth retarded (IUGR) pregnancies. IUGR pregnancies were divided according to velocimetry in the umbilical artery {PI) and to fetal heart rate (FHR) into: Group I, normal FHR and PI, 2 cases; Group 2, normal FHR, abnormal PI, 3 cases and Group 3, abnormal FHR and PI, I case. Maternal arterialized samples were taken at time 0 and every 15 minutes for 110.6 + 18 min. Umbilical venous samples were obtained after 94.2 + 18 rain from the start of the infusion. RESULTS:There was no difference in the fetal/maternal (F/M) leucine enrichment ratio between AGA and IUGR of Group I (0.79 vs 0.82). On the contrary, the F/M ratio decreased significantly (p<0.03) in IUGR of Groups 2 (0.72) and 3 (0.63). In all patients, there was a significant linear relationship between maternal leucine disposal rate (DR) and concentration (Leu DR i~mol/kg/min= 0.44+10.8 Leu conc p.mol/kg/min; r2= 0.67; p<0.01 ). CONCLUSIONS: This study shows lhat in IUGR pregnancies there is a progressive dilution of the fetal leucine enrichment, relative to the maternal plasma enrichment according to the severity of growth retardation. Since leucine is an essential amino acid, this dilution may reflect an increase of protein breakdown within the fetal and/or placental compartments and/or decreased transplacental leucine flux.

242 ANTEPARTUllMIDDLE HEAMCEREBRALSLOOBFLOWVELOCITYCOIIRELATloB

WITH MATERNALBENODYRAJIICS.Ketth Wltllsms, Susan Wilson, S,C.Women~s Hospital, Olv. of Maternal-Fetal Medicine, Van. D.C., Canada. V6H 3V5. OBJECTIVE: Ilean maternal cerebral blood floe velocity has been correlated in the Literature with cerebral vesospesm. No attempt has been made to correlate middle cerebral blood floe v e l o c i t y with other maternal hemodyrmmic factors. Me assessed middle cerebral blood floe velocity and correlated with other maternal

hemedynami¢ factors. STUDYOEEIOM: 5 normotensive patients Were assessed. Maternal

cerebral blood floe velocity was assessed using tranacranlaL Doppler. Cardiac output, stroke volume and other smterrmt hemedyrmmie factors uere assessed using a non-tnves|ve hemndynsmic monitor using thoracic electrical impedance. ALL hsmodyramie parameters ~ere sampled four times, assessing mean cerebral blood floe velocity, putsatility index, heart rate, simultaneousLy mean arterial pressure, cardiac output, stroke volume and Left

ventrteutar end diastolic volusm. Statistical analysis was than done using Pearson correlation coefficient and Logistic regression analysis utth stepaise regression. RESULTS: Mean vatuel for all of the persmeters were developed. Both p u t s a t | L | t y index and maen middle cerebral blood f l o e velocity correlated s i g n i f i c a n t l y utth mean arterial pressure (P<.05) but did not correlate with cardiac output, stroke volume or uith any other maternal hsmodynamtcparameters.

Cardiac Output (IPM) 8.6 + 2.6; Cardiac Index (iI~4/m2) 4.9 + 1.2; Stroke Volume O41) 103 .9-1 32.7; #aart Rate (b/sac) 8.3 :k 4.9; Mean Arterial Pressure (mi4g) 8.19 9.7; Mesn Middle Cerebral BLood FLOWVelocity (cat/see) 59.6 + II; Putaatltity Index .8.q ± .tS. CONCLUSIONS:H|ddte cerebral velocity correlates ulth moan arterial pressure but not wfth cardiac output or any other maternal hemedyrmmic parameter. In preecLamptlc pat|eats at risk for cerebral vesospasm, control of mean arterial pressure wilt result in improvement In mean cerebral blood floe velocity.

243

CEREBRAL METABOLISM IN THE OVINE FETUS DURING HEART RATE DECELERATIONS WITH UMBILICAL CORD COMPRESSION. B Richardson~, L. Carmichaelx, J. Haman ~, L

Johnstonx. Dept Ob\Gyn and Physiology, University of Western Ontario, London, Ontario, Canada. OBJECTIVE: We sought to determine the extent to which cerebral blood flow (CBF) is increased during variable-like fetal heart rate (FHR) decelerations with umbilical cord compression, and whether cerebral oxygen delivery (CDO2) and oxidative metabolism (CMRO2) are maintained. STUDY DESIGN: Nine near-term fetal sheep were studied immediately prior to, and again during the associated FHR deceleration with induced umbilical cord compression of -60 sec duration, and immediately afterwards. Cerebral arterial (a) venous iv) differences were analyzed for oxygen content, blood gases and pH. CBF was measured with the microsphera technique. RESULTS: Umbilical cord compression with associated FHR deceleration from 158±6 (SEM) to 67±4 bpm resulted in a drop in fetal PaO2, from 21 ±1 to 14±1 torr (p<0.01). CBF was variably changed, increasing from 184,17 to 220,24 mill 00gm/min iNS) during cord compression and to 227,12 ml/100gm/min (p<0.01) afterwards, with CDO 2 thus decreased during cord compression, from 618,48 to 470,30 /.~mol/100gm/min (p<0.02). CMRO 2 remained little changed as cerebral fractional O 2 extraction was increased from 0o28,0.01 to 0.35±0.03 (p<0.02) dunng umbilical cord compression, thereby contributing to the drop in sagittal sinus PvO 2 from 17,1 to 11 + 1 torr (p<0.01). CONCLUSIONS: The increase in CBF during moderate to severe variable-like FHR decelerations with umbilical cord compression is insufficient to maintain CDO 2 with a transient decrease in tissue oxygenation within the brain occurring.

244 THE EFFECT OF DURATION OF LABOR ON THE IMMUNOLOGICAL STATUS OF HEALTHY NEONATES. W. Sch611
$PO Abstracts

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BREATH PENTANE CONCENTRATIONS DURING LABOR AND THE EFFECT OF EPIDURAL ANALGESIA ON THE PENTANE CONCENTRATION. Y. Shin~, J. Collea, Y. Kim =, S. Kim x. Depts. Ob/Gyn/Anesthesia, Georgetown Univ., Washingto~ DC OBJECTIVE: Free radicals cause tissue damage by lipid peroxidafion of cell membrane lipids. Increased lipid peroxidation has been observed in pregnancy and particularly in preeclampsia. Physical stress is also known to increase the lipid peroxidadott Pentane, a product of lipid peroxidation, is a reliable index of lipid peroxidadon in vivo. We measured pentane in the breath of laboring women and the effect of epidural analgesia on the level. STUDY DESIGN: In thirty-six normotensive parturient women undergoing induction of lab~, the fu'st end-expired breath samples were collected into a bag (1 L) on admission. When epidural analgesia for relief of labor pain was requested, breath samplings were repeated before and after the epidural analgesia. The epidural analgesia was performed using bupivacaine and featanyl. Pentane was assayed by a digital gas chromatograph, and its concentration (ppb) was cxmverted to a molar c~acantration. Data were compared by aaslysis of variance. RF~ULTS: Pentane was detected from more than 95% of the breath samples. The mean concentration of pentane on admission was 0.126+_0.138 nmol/1 (mean_+SD), and the concentration was higher (0.201+_0.204 omol/l, p<0.01) during labor. After epidural analgesia, pentane levels decreased to 0.091_+0.106 nmol/1 (p<0.001 compared to the o0~centration before epidural analgesia). CONCLUSIONS: This study demonstrates that peutane can be measm'ed from single breath samples in parturient women. The increased breath pentan,¢ levels during labor suggest that labor may be accompanied by a rise in lipid peroxidation. Epidural analgesia may reverse the rise.

247

FETAL CARDIAC AND RENAL DOPPLER EVALUATION IN PREGNANCIES W I T H IDIOPATHIC POLYHYDRAMNIOS J Rosnes', M Penry x, JC Veille. Dept. of Ob/Gyn, Bowman Gray School of Medicine, Winston-Salem, NC OBJECTIVE: To compare fetal cardiac and renal blood flow in euhydramnic and idiopathic polyhydramnic fetuses, the null hypothesis is that fetal cardiac contribution to renal blood flow is increased in pregnancies complicated by idiopathic polyhydramnios. STUDY DESIGN: Five fetuses in pregnancies complicated by idiopathic polyhydramnios (IP), mean AFI=26.7, mean gestational age 28.4 weeks, were compared to 56 euhydramnic control fetuses, mean gestational age 30.7 weeks (P=NS). Doppler waveforms were recorded from the right and left ventricles just below the A-V annulus, and from the renal artery at the renal hilus. Waveforms of the right and left ventricles were analysed for time velocity integral (TVI) during diastole, and dimensions for the fetal arteries were obtained using the leading edge technique during systole. TVI and area were used to provide estimation of total cardiac output (TCO) and renal volume blood flow (RVBF). Mann-Whitney Rank Sum Test was used to significance at P<0.05. RESULTS: Fetuses with IP had significantly reduced TCO (P=0.035), RVBF (P<0.0001), % of TCO perfusing the kidneys (P=0.030) and renal artery diameter (P<0.001). CONCLUSION: This preliminary study suggests that fetuses with IP have a significantly decreased renal artery diameter, decreased TCO and % TCO perfusing the kidneys, when compared to control fetuses. This suggests that increased renal perfusion does not appear to be responsible for IP.

248

MANAGEMENT OF THE TWIN OLIGOHYDRAMNIOSPOLYHYDRAMNIOS SEQUENCE AND TWIN-TO-TWIN TRANSFUSION. J. Brunet. T. Andersonx. Dept. Ob/C-yn, Vanderbilt

University, Nsshvine, TN. OB3ECTWE: Evaluation of serial decompression amniocentesis in patientswilh the twin olignhydramnins-polyhydramniossequence (TOPS) and twin-to-twin transfusion (TTT). STUDY DESIGN: Women fulfilling the standard ultrasound criteria for the diagnosis of TOPS in the second trimester were assigned to TOPS or true TTT groups after performance of sequential cordocentesis to document presence absence or presence (respectively) of inter-twin transfusion. All pregnancies were managed by decompression amniocentesis to relieve signs or symptoms of polybydramnios. RESULTS. Of 8 women in this stody, true TTT was confirmed in 4. An average of 2.5 amniocanteses was performed (range 0-6), removing 2003000 ml of amniotic fluid per procedure (recent577 ml). Patients with provenTTT requiredmo¢ anmiocentcses(p=0.04), although less amniotic fluid was removed per procedure (p=0.005). All 8 suspected recipients were livcbom, compared with only 2 donors; both donors were documented TTT. Mean gestational age at delivery was 30 5/7 weeks (range26 0/7-38 0/7 weeks)with no significantdifference between groups. CONCLUSIONS: These data illustrate TTT as a subset of TOPS, both of which can be managed successfully by ~erial decompression of polyhydrammc (recipient) twins Suspected recipients benefit from ixobngat~mofp~nancy in the absence of more serious complications of fetal hypervolemia. Decompression amnincentesis does not appear to benefitolignhydramnic(donor) twins. Although pregnancy outcomewas simdarm both groups, the increased frequency of decompression required in documented TTT is likely relatedto patent anastomotic vessels, and suggeststhatmornaggressive surveillance or intervention may be required in these patients.

HUMAN AMNIOTIC FLUID DYNAMICS: MATHEMATICAL MODEL OF FETAL SWALLOWING AND INTRAMEMBRANOUS FLOW. S.Em Mann, MJM. N~jland~, MG. Ross. Dept. Ob/Gyn, Harbor-UCLA Med Ctr, Torrance, CA. OBJECTIVE: Amniotic fluid (AF) volume and composition is maintained by a balanceof felai fluid escretion (fetal urine, lung liquid) and resorption (fetal swallowing, intramembranous flow) Among the sites, only AF volume and fetal urine flow can be accurately quantified in human pregnancies. We sought to develop a mathemabcal model quantifying the relativecontribtddonsof fetal swallowing and intramembranoue flow to the maintenanceof AF volume and composition dudng human gestation STUDY.DESIGN: Published data of human AF and fatal urine compos~on and volume (11-42 wks), and extrapolated data from o~ne lung fluid production were utdtzed. Modelling assumptions included (1) dailychanges in AF volume result from a nat difference in AF production and resorption processes, (2) 50% of secreted lung fluid enters the amniotic cavity, (3) lung fluid is isotonic to fetal plasma, (4) wtth the excel~on of swallowed lung fluid, swallowed fluid is isotonic to AF, and (5) intramembranous flow is free water diffusion. RESULTS Calculated fetal swallowed volume (S) and intramembranous flow (I) !':l:j :"'" S are similar (7 to 230 ml/day) until 28-30 =' weeks Daily swallowed volume then i / exponentially increases to a maximum of ~ I 1320 ml/day at term, while intra' . r "~:''''''''" membranous flow continues on a hnear '* =~t 0,~h.) '= trend to reach 336 ml/day at term. CONCLUSIONS: The mathematical model indicates that the normal reduction in AF volume beginning at 34 wks results from the marked increasein swallowedvolume dunng the third tnmester. Modelling of AF dynamics can predict normal changes in fetal fluid exchange and may aid in understanding etiologies of AF imbalances

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249 THE EFFECTOF INTRAVENOUS FLUID LOAD ON AMNIOTI4C FLUID INDEX IN PATIENTS WITH OLIGOHYDRAMNIOS I. Bush.x H Mmkoff, S. McCalla S. Moy, H.Chung Dept. Ob/Gyn SUNY-HSCB Brooklyn,NY OBJECTIVE: To determine the effect of intravenous fluid load on the amniotic fluid index (AFI) of women with ohgohydramnios and to determine factors that predict response. MATERIALS & METHODS: A prospective cohort study of patients with oligohydramnios (AFI <5.0 cml admitted for induction of labor was performed at SUNY Brooklyn and Kings County Hospital Center. Patients with rupture of membranes, congenital anomalies, & contraindications to flutd challenge were excluded. Urine specfftc gravity and serum BUN and creatnme were performed. 500cc of normal saline or ringers lactate was infused over a thirty minute period. The infusion rate was then set at 125cc per hour. An AFI was performed prior to and, 30 minutes, I hour, and 2 hours after the initiation of the fluid load. To assess rehability and inter-observer variability, two examiners who were bhnded to each others finding measured the AFI m a subset of patients. The statistical design used was the student t test. RESULTS: Fourteen patients were included with an average gestational age of 39.3 weeks. Twelve patients had an increase in their AFI 2 hours after the initiatton of the fluid challenge. Seven had a 50% increase in their AFI. Three patients had a t00% increase in AFI. Four had an AFI > 5 after the fluid load. No correlation between percent increase in AFI and urine specific gravity was noted. CONCLUSIONS: 1. Intravenous fluid challenge is associated with an increase in AFI in a majority of patients with ohgohydramnios , m several cases resulting in normal values. 2. With this small sample size we were unable to establish a correlation between urine specific gravity and AFI increase 3. Further research is needed to determine if known risks of morbidity assocmted with oligohydrammos are less severe ff fluid level increases with fluid load.

250 THE EFFECTSOF DEVELOPINGAUTONOMOUSNERVOUSSYSTEMON

FHRVARIABILITIESDETERMINEDBYTHE POWERSPECTRALANALYSIS IN RHESUSMONKEYFETUSES M. Matsuura x, Y Murata, T. Hiranox, N. Nagatax, S. Deix, K Suda x Dept. of Ob/Gyn, Univ of California, Irvine, Orange, CA OBJECTIVE: The purpose of this study Is to evaluate the development of f~tal autonomous nervous system(ANS) and the effect of deve|opmg ANS on FHR variabihttes(LTV, ~ . S T U D Y D E S I G N : Eighteen chromcally mstrumented fetal rhesus monkeyswere used( ii 4-152 days gestatton(term=I6~i days)). R-R intervals of ECG were calculated(resolution of [ msec) and resampled at equal ttme mtervals of 350 msec. The power spectral analysts(PSA) by fast Fourier transform was performed. The frequency bands were diwded into low frequency (LF=o.os-o.2 Hz) and htgh frequency fftF=o.4-Lo ttz). Studies using autonomtc antagomsts have indicated that these were medtated by the sympathetle(SYM) and parasympathetic nervous systems(PSYM), respectwely(Akselrod S. AJ Phys. 249:H867J985). The power spectral density(PSD) of LF,HF and LF/HF ratto were then calculated. LTV and STV were defined as PSD of FHR fluctuations m o.os-oa Hz(eqmvalent to 3-6 cycles/rain) and as the total PSD of the difference of beat-to-beat variabdity, respectively.The data were dwided into two group.s according to fetal breathing movement(FBM) present or abscent. S-tattsttcal analysts was performed usmgliner regresston and ANOVA. RESULTS: 0 Both LF and HF showed sigmficant mcreases(pGA 0.8 term. z) LTV showed a significant increase (p0.8 term. 2) LTV and STV increased with the development of SYM and PSYM, respectively. 3) At a gwen GA, an mcrease m LTV or STV corresponded to a dominance of SYM or PSYM. 4) An increase m STV appeared responsible for an mcrease in vanabdity dunng FBM.

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251 EFFECTS OF FETAL SEIZURE ACTIVITIESON FETAL HEART RATE, BLOOD PRESSURE AND BREATHINGMOVEMENTSIN FETALLAMBS S. Doi x, y Murata, E.J. Quilligan, N. Nagatax, T Ikedax, S. Park.x Dept.OB/GYN, Univ of California,In~ne,Orange,CA. OBJECTIVE: To determine~e fetal biophyscal responsesto episodic Intrauterine seizuresafter recoveryfrom asphy'~cinsults. STUDY DESIGN:Fetalheadrate(FHR),breathingmovements(FBM), bloodpressure (FBP) wereobsen~d during 325 convulsiveepisodesin eightchronicallyIns~onted near-termfetal lambsequipped with ECG and ECOG electrodes, intratrachealand caro~l arterialcatheters.Fourfetusesshowedasphy'~cevidence(pH<7.0,BE<-16)at the end of surgery,but sundvud. The remainingfetusesundenNentthe surgerywithout stgntflcantchanges in add-base status and were subsequentlysut~ectedto severe asphy)da(pH<6.8, BE<-20) by umbilical cord occlusion for 60rain. All the fetuses showed complete recovery to normal acid-bsse status after the insults, but later developed in~autedne seizureactivities. Fetal seizurewas identified by a repeUtive and rhythmicdischargein ECoG, confirmedby jerky body and extremitymovements visualized using 2-dimensionalultraseundof the fetus. Fetal blood gas analyss was pedomledevery2 houraafterthe onseto~eachsezure. RESULTS: Fetal biophysicalchangesduring a seizureac~vity Nonanidemlc pHi7.20 AcidemlcpH<7.20 Numberofseizureepisodes 257 68 F'e~l BloodI ~ MAPelevated >10mmHg 220(85.6"/0) 57(83.8%) MAPdecareased >10mmHg 0 3(4.4%) No Changes 37(14.4%) 8(11.8%) FetalBreathingMovements Repe~tiverapidand deep FBMs* 160(62.2%) 10(14.7%) D ~ h ~R~ei / l nspiraS~n ° 43(16 7%) 53(77 9%) 54(21.0%) 5(7.4%) Deceleration>10bpm • Acceleration>10bpm " A c c e ~ followedbydecelera~'on*

33(12.8%) 68(26.5%) 146(56.8%)

59(86.8%) 0 0

NoChanges 10(3.9%) 9(13.2%) MAP:meanarenalpressure * p<0.001 .~ analysisor Fisher's exactprobability CONCLUSIONS: Fetal se=zureactivities produced elevated blood pressure and a ~ a l brea~lng movementsin both nonactdemtcand acldemicfetuses. The most common FHR pattern in nonaddernic fetuses was acceleration followed by decelera~on.FHR decalera~n was the mostcommonpaltem in acidemictetuse~

252 SPECTRAL ANALYSIS OF HEART RATE VARIABILITY GIVES NEW INSIGHT INTO FETAL AUTONOMIC RESPONSE TO V1BROACOUSTIC STIMULATION. R.M. Lewinsky', S. Degani'. Department of Obstetrics & Gynecology, Bnai Zion Medical Center, Haifa, Israel. OBJECTIVE: To characterize the fetal autonomic response to vibroacoustic stimulation (VAS) with and without prior exposure to narcotic analgesics. STUDY DESIGN: Fetal ECGs from 24 uncomplicated term pregnancies were analyzed. The power content of frequency bands representing sympathetic, parasympathetic and respiratory activity was determined. Measurements were taken during natural and narcotic-induced sleep, before and up to 1 hour after VAS. RESULTS: The immediate response to VAS was characterized by a significant increase in total power (p<0.01) and shift towards the very low frequency band (0-0.05 Hz) representing sympathetic activity (from 46 _+ 17% to 87 -+ 24%; p<0.001). This response was observed both during natural sleep or after narcotic-induced sleep. The decrease in power in the low (0.05-0.15 Hz) and high (0.5-0.9 Hz) frequency bands representing parasympathetic activity and respiratory sinus arrythmia respectively, were proportionally equal. While the increased sympathetic activity after VAS was sustained for up to 1 hour during natural sleep, after narcoticinduced sleep, a complete recovery to prestimulation values was observed after I0 minutes. CONCLUSIONS: Spectral analysis of FHR variability is effective in quantitating the fetal response to VAS. The change in fetal wake state, but not the immediate "startle response" is suppressed by narcotic analgesia.

Volume 174, N u m b e r I, Part 2 A m J ()b~tet Gvnecol

253

254

SPO Abstracts

QUANTITATIVE ASPECTS OF IN VIVO XH MR SPECTROSCOPY OF HUMAN FETAL BRAIN. Paul P. van den Berg', Arend Heerschap~, Departments of Obstetrics and Gynaecology and Diagnostic Radiology, Umversity Hospital Nijmegen, The Netherlands. OBJECTIVE: The principal possibility to use proton Magnetic Resonance Spectroscopy (~H MRS) as a new non-invasive tool to view a number of metabolites m the human fetal brain has been recently demonstrated [Heerschap A, van den Berg PP, Am J Obstet Gyn 1994;170.1150-1]. The purpose of this study is to quantify the levels of some of the metabohtes observed in the obtained spectra. STUDY DESIGN: Five healthy women with normally grown fetuses between 28 and 38 weeks of gestation were investigated after informed consent was obtained Examinations were performed on a Siemens MR system at 1.5 Tesla fieldstrength. A 10 cm diameter surface coil was used for MR signal reception ~H MR spectra were obtained from a box shaped volume, set at a location guided by MR images using a double spin-echo pulse sequence (T~ = 75-135 ms, T~ = 1.6 s, 384 scans, about 10 min scan time). The T~ relaxation time of the H~O spins were obtained from measurements at different echo times. RESULTS: Metabolite levels in a brain volume were estamated from its MR spectrum taking the signal of H~O of the same volume as a reference. Published data obtained from the preterm neonatal brain [Kreis R et al., MRM 1993;30:424-437] were used to correct for relaxation effects on the H~O and metabohte proton spins. Employing these relaxation data and a brain water content of 90%, we derived average concentration values (per kg brain Ussue) of 1.9_+0.4 mM for choline compounds, 4.1_+1 0 mM for creatine and 2.8+-0.9 mM for acetyl compounds. These values are in good agreement with previous data on brain metabolite contents of preterms. CONCLUSION: ~H MR spectroscopy is the first techmque that enables the acquisition of objective parameters about fetal brain metabolism during pregnancy. Apart from a possibility to characterize non-invasively certain metabohc aspects of the developing human fetal brain, a very important potential would be the detectton of signs of insufficient oxygen supply.

255

P S Y C H O S O C I A L F A C T O R S AS P R E D I C T O R S O F L O W BIRTH WEIGHT AND PRETERM DELIVERY K.M. Paarlberg ~, A.J.J.M. V i n g e r h o e t s ~, J. PasschieP, G.A. D e k k e r ~, A.G.J.J. H e i n e n ~, H.P. v a n G e i j n ". D e p a r t m e n t of Obstetrics, F r e e U n i v e r s i t y H o s p i t a l A m s t e r d a m , T h e Netherlands. O B J E C T I V E : T o study t h e influence o f psychosocial factors on low birth weight ( L B W ) and p r e t e r m delivery (PD). S T U D Y D E S I G N : 396 nulliparous w o m e n c o m p l e t e d q u e s t i o n naires on: g e n e r a l characteristics, daily stressors, psychological and m e n t a l well-being, social s u p p o r t , a n d w o r k factors in e a c h gestational trimester. O u t c o m e m e a s u r e s were: L B W (birth weight _< 10th percentile; n = 4 0 ) versus n o r m a l birth weight, a n d P D (gestational age < 37 wk; nffi27) versus t e r m delivery. Results w e r e analysed by m u l t i v a r i a t e logistic r e g r e s s i o n a n d expressed in odds ratio's ( O R ) and their 9 5 % c o n f i d e n c e intervals (CI). R E S U L T S : I n d e p e n d e n t o f m a t e r n a l weight a n d height, educational level and smoking, the followin~ predictors w e r e found:

256

# hr hou~keepmg ~ r week in. # dady stre..~ors ,n depre~,on to: depress,on m an~aety m somatac ¢omplalnt~ in

trimeter 1 3 1 3 2 3

LaW 1.54 (1 04-2.29) 1 03 (1 00-I 06)

PD

1 06 (1.00-1 13) 1 13 (1.04-1.24) 1 28 (1.04-1 57) 0 76 (0 61-0 %)

C O N C L U S I O N S : N u m b e r of hours h o u s e k e e p i n g p e r w e e k in the first t r i m e s t e r d e m o n s t r a t e d to b e t h e m o s t p r o n o u n c e d predictor of low birth weight i n d e p e n d e n t o f b i o m e d i c a l risk. Psychological factors a p p e a r to have m o r e influence o n p r e t e r m delivery than on low birth weight.

A S S ~ I N G COGNITIVE PROCESSING IN THE HUMAN FETUS. LJ ...~9.m.~. DM Mooned, SB Holland~, LS Bantz~, JL AtZm'bmyX,RA Dykman~. Univm.sityof South Alalmm, Mobile, AL; Arkansas Childr~'s H o s p i ~ Little Ro~k; AR. OBJECTIVE: Studies in neomtm, in~nta, and adults provide couvin©ingevidence that • heart rate (HR) d~.e.lmtmy response to low-intensity stimuli is • physiological index of cognitive I m ~ m ~ g . Howard, • ©fitical feature of this rehtioaddp is that rehlively intanse sllmuli ~ o d d evoke • Hit a~,leratioa. The purpo~ of ~/~ Kudy w ~ th ~ e if human f ~ . lilm n ~ ' n infants, exhlbita decmue in HR whan slimuhted with low-internalW speech eounds and an inla'emlein HR whan Ioand intenldty ia i n ~ . Tbo finding tbot low- and highint~mity muod8 evoke d i f f m l typ~ of Hit mapom~ would help ~ the ~ th~ • HR d e , elation is a phyabdogicad eonehtte of mgnitive prec~sing in the human fetus. STUDY D ~ I G N : 18 low-rbk human f e t a ~ at 37-40 weeks were exposed to a 30-*mundummtingoftborepmti~. phonmm/ee/and/~h/ (500m./ecL500 m~/~/~ Tbe fml u~line d e ~ i ~ d .lgnal w ~ utptured t n m ~ b m l n a l l y at a rate of 1024 Hz and fetal R-wavu wece extracted using adaptive ~igmd pmcetung tw,baklu~. Fa~h fetua w ~ in quiet deep (QS) for 3-5 m befo~ belng ramtomiz~ ~ n g a w the stimuhmat an int~msityof citer g0 dB o¢ 90 dB. At 5-7 m following stimulu~oth~ _~h_,__,~_wbo bod ~ th~ 80-dB (90-dB) sound w~r~ ,timulat~ in QS a uamd llme at an intanmty of 90-rib (80-riB). R~pon~ magnitude and the effect of ~imuh~ iatzmity ~ ~ d u ~ e d by repeated ~ u r ~ ~ d y m of

linmr, quadmU~and ~u~..o~..oMl. ~

u~mdsw ~ o~mpuugl.

IP~g~JLT~: T l ~ w u a ~ y slnifigant d i f f ~ m ~ inthe mamaHR b~wom the gO-dBand 90-dB t ~ p o ~ e ¢utv~ F(I,17)-g.31, P~.011, m d trend mudy~s ahowod that the ~ ~ fix the 80-dB and 90-dB stlmuli wwe ~lauifieamtlydiffuenmtF (1,t7)-10.15, p<0.006. Follow-up t~m oftbo diffmm~ of mpomm Iremds from b u ~ n e revealod s aisni~amt d ~ n m p o ~ tu slimuJmionst an ~ ofS0 dB, qu~ba~ se~mds, F (1,17)-7.60, p<0.012, and eadle mined& F (1,17)-6.10, p<0.025; tad a , i ~ i ~ t a~.lemtuty ruponse to

, _ u . ' . ~ at ~ ~

of 99 d~. ~

~

F g,~7~..7~ p
Tlae imam'a~tionI~tw~m stimultm i n ~ ami HR w u ~dm . l l ~ t , F (39, 663)'~.67, p<&027. CONCLUSION: Low-6~ human fi~ums exhibited • mmU,im~d e m u ~ in HR to

~t~'tOa~.

.HRrm~o~'...tulo_w-m.Wty~f~ra~¢~abo~ltumdant~

LONGITUDINAL STUDY OF BEHAVIORAL STATE ORGANIZATION: CONTINUITY BETWEEN THE FETAL AND NEONATAL PERIODS. LI Groom~.MJ Sw'b~X JL A~d~ryX, LS Bantz ~, SB Holland ". Univevfity of South Alabama, Mobile, AL. OBJECTIVE: There is now a large body of data demonstrating that behavioral t~ oqlankaalm is a madaw of umtnd nervous system (CNS) development in both sell and neonatus. The purpo~ of this .~udy was to determine if fetal state organization was predi~ve of state organization m the neonatal period. STUDY DESIGN: 30 low-risk human subjects were examined u fg~us~ at 38 - 40 weeks gestation and again as n e o n . ~ at 2-w.eeh . p ~ . atal age. We were p e t ~ t d m t y . c ~ to £~.trd fix potmtml confoundinjl varinblgs: only non-smoking momars w~th no medical or obst~'icai ~omplicaao•s wore recruited; pt~nant fasted after midnight and were given the same standard meal on arrival to .the testing unit; behavioral states were assigned ,im!h~-Iyfor fetuses and neonates m terms of heart ratz (HR.) pattern and the ~ c e or absence of eye (EM) and eoay movemeata; and fetal and neonatal studies were conducted at the lame time of day m a quiet room. Data were analyzed using the Student t-test, Xa, and linear gggrc~ton. R F ~ . LTS: .The fr~fion of lime spent in quizt sleep (QS), active -loop (AS), and lamun~a perieds was vittua~y identical for fetuses and neonatce (QS: 33.3 + 7.9% vs 34.$ + 7.8%; AS: 56.3 + 9.3% vs 57.7 + 7.2%; TraM: 10.3 + 8.7% ~ 7 . g + 3.5%). No .r~ioa.ltip w ~ found betw~n the duration of AS qx~hs fix fetuses and the duration Of AS epochs for nooantes (r-0.174. p>0.05); but ~ u ~ who ~ in a ~ btmt OfQS f~¢, .c~tain lan[~h of~me bod QS bouts oftho same

,aL,~.w~.. ~

~

at 2-w~-~ postnatalqy.(r-0.500, p=O.O07).

F ~ made mgmficantly fewer QS-AS and AS-QS trama~ a pe¢ 100 minum of mloepthan neoan~ (2.9 + 0.9 w 3.6 + 0.6, p<9.001 ) but re sired more time to ~mpleteamt?dumse(Q$-AS: 2.7+3.4 minw2.1 _+1.9 mh p'0.064;AS~QS :.3.4+ 5.3 mm v* 1.7 + 2.1 nun. p-0.006). For both fetu~ a mad neonat~ a stgml~mt ddference w ~ found betwean QS*AS and AS-QS tmadtio~ in the ordmingof HR madEM:.'.'.for QS~AS tum.llimm, HR most •fl~m ©Imagedb¢fforeEM; and fix AS~QS tmas~Uona,Eld most oeam dmuged before HR (~tu~: Xa-50.9, .~.001; neonate: X'-91.3, p0.05);.~ o t d ~ . OfHR madEM f~. AS-QS transitions was -lgnifiumtly move mut~trm mr • e o n a ~ tlum fetm~ (X~ffiT.1,p-0.02g).

CONe.LUStON:Our r , ~ a ind~4a,t ~ whe,~ .CN.S~ r~¢ QS were fairlywelldevelopedby 3g.40 ~ of ~ ~ mgnifi~at nmuratio~ ~ty

of individual mlbje~;ato I'~guhtle~.

381

382 SPO Abstracts

la,ma, v 1996 Am [ ()bstet (,)ne¢ol

THE EFFECT OF ACIDEMIA ON FETAL HEART RATE VARIABILITY. D, ChaffinX,J. BamardX,T. Phemettonx, A. Newmanx, K. Reed. Departmentsof OB/GYN,Arizona Health Sciences Center, Tucson, AZ, Universityof Wisconsin, Madison,Wl, and Robert C. Byrd Health Sciences Canter/CharlestonDivision, Chaheston, WV. OBJECTIVE: To test the hypothesisthat acidemia with normoxia decreases heart rate variability. STUDY DESIGN: Seven time-bred ewes near term were surgically instrumented for FECG and fetal blood gas measurements.After a 5 day recovery period, baseline fetal ECG and blood gas tensions were measured. A 0.5M HCI solution was then infused at a rate of 0.764ml/min into a fetal vein. FECG recordings and blood gas measurementswere repeated at a letal pH 7.15, 7.05 and 6.95. The RR intervals were obtained from the FECGs using a computer. Long and short term variability (LTV and STV) were calculated using the algorithm el Huey et al. Results were compared using ANOVAwith repeated measures. RESULTS: The results are shown in the table. LTV and STV are reported as beats/100 beats. Fetal heart rate and long and short term variability increased with acidemia similar to the increase reported with acute hypoxia. CONCLUSIONS: These results suggest that the decreasein heart rate variability seen with chronic asphyxiais not the result el acidemia alone. Parameter Control pH 7.15 pH 7.05 pH 6.95 p Value [ Heart Rate (bpm) 1535:15 177+90 177+96 177:1:42 0.05 I LTV 285:16 625:20 9 5 + 4 0 6 7 + 2 5 0.0004 STV 935:37 202+85 2755:118 241+125 0.006 pCO2 (mmHg) 52.75:1.6 55.9-J:t.8 58.0+9.5 60.0-J:4.3 <0.001 I pO2 (mmHg) 20.9+1.6 24.6+3.0 26.3+9.1 26.8+_2.0 <0.001

257

EXPECTANT MANAGEMENT IN PREGNANCIES COMPLICATED BY GROWTH RETARDATION AND ACIDEMIA? SM Berry, SJ Field x, MP Dombrowskl, JM Lanouette*, CL Brown ~, DB Cotton. Dept. OB/Gyn, Wayne State Univ/Hutzel Hospital, Detro,t, MI. OBJECTIVE: Amdemia, a frequent find,rig in intrauterine growth retardation (lUGR), has been used as a justification for immedmte delivery. Our objective was to report our expenence w~th pregnancies complicated by lUGR and fetal acidemm. STUDY DESIGN: Rapid karyotype was the primary indication for venous cordocentesis among 10 IUGR fetuses at 23 to 37 weeks. Data were prospectwely collected over a 3 year period. RESULTS: All fetuses were karyotypically normal. Estimated fetal weights were <5th%tile in 9, and < lOth%tile in one fetus. Four had absent arterial end diastohc flow prior to cordocentesis. Nine fetuses had hemoglobin (Hub) values >95th%tile for gestational age (CA). All specimens had pH and oxygen content <5th%tile for CA. E=ght spec,mens had blood gas values consistent with a mixed ac=demia. Two fetuses with a metabolic acidemia were delivered > 2 days post procedure. S=x pregnancies continued > 2 days after cordocentesis (mean=24.3, range 2 to 1 12 days). The mean 5 m,nute Apgar score was 8.5, and 2 neonates had an umbihcal arterial pH <7.2 at delivery. There were 9 cesarean sections (CS), 8 for non-reassuring fetal heart rate tracings (one for a procedurerelated bradycardm), and one for a breech presentation. CONCLUSION: Fetal compensatory mechanisms for ac=demm appear to include an increase in Hub. In our experience, fetal acidemia =s not an intimation for immedmte dehvery in many cases. Nonetheless, ac=demia =s strongly associated w=th subsequent CS for non-reassuring fetal heart rate tracings.

259

258

PLACENTAL ARTERY NITRIC OXIDE SYNTHASE EXPRESSION INCREASES DURING THE THIRD TRIMESTER. C Sheppard, CE Shawx, IM Bird,, RR Magness~. Permatal Research Labs, Dept Obstetrics and Gynecology, U Wisconsin, Machson, WI. OBJECTIVE: To meet the metabolic demands of the growing fetus during the third trimester, placental and uterine blood flows increase dramatically. We hypothestzed that increased expressmn of endothelial mtnc oxide synthase (eNOS) contributes to this augmentation of perfuslon m both fetal-placental and uterine cwculations. DESIGN: Placental and uterine arteries (PA, UA) were collected from 20 ewes at 110, 120, 130, and 142 days' gestation (term=145+ 3d). Endothelittm was removed from the luminal surface and solubthzed. eNOS expression was measured by Western analysis and ECL detection. Densxtometry data were normahzed to human umbilical veto endothelial cell (HUVEC) signal and are reported as the mean percentage of HUVEC standard +_SE. Data were analyzed by ANOVA. RESULTS: eNOS expression was localized to the endothehum (and not the denuded vessel) by Western blot and confirmed by immunocytochemtstry. PA eNOS 400 expression at 130 d was 2.5-fold greater (*p=O.02) than at 110 d. At term, PA eNOS expression had 20O declined to levels similar to those observed at I10 and 120 d. In contrast, UA eNOS expression was 0 . . . . unaltered thro~ghont the third 110 120 130 142 trunester. Days

260 RELATIONSHIP OF ACID-BASE STATUS AND NEONATAL

CONCLUSION: Placental artery eNOS expression peaks at 130 d gestation, but no increase m UA eNOS occurs. This supports our hypothesis with respect to the fetal compartment, and suggests that the increases in placental and uterine blcod flows occur by mdependent, specific mechamsms. Supported by NIH HL 49210 and HD 33255.

MORBIDITY IN <1000 g INFANTS. D.F. Kimberlin. J.C. Hauth, R.L. Goldenberg, C. MacPherson x, E. Them x. S.F. Bottoms, D. McNellis. Dept. of OB/GYN, Univ. of Alabama at Birmingham, AL and the NICHD MFMU Network, Bethesda, MD. OBJECTIVE: To evaluate the relationship between acid-base status at birth and neonatal morbidity in _<1000 g infants. METHODS: In a one year (1992-1993) prospective, observational study, the NICHD MFMU Network collected outcome data for 799 infants _<1000 g. Only fetuses who were deemed potentially viable by the obstetrician and who would have received a cesarean section for fetal =ndicatlons were included in our analysis. We evaluated umbilical artery acid-base status and selected neonatal outcomes. Logistic regression was used to control for the effect of confounding variables (birthweight, race, gender, mode of delivery, chorioamnionitis, rcatemal MgSO, or cortlcosteroid therapy and neonatal surfactant therapy). RESULTS: Umbilical artery (UA) pH and base deficit results were available for 199 potentially viable infants. In this subgroup, the mean UA pH was 7.25 _+.11 (<7.00, n=5; 7.01-7.05, n=7; 7.06-7.10, n=lO; 7.11-7.20, n=27; >7.20, n=150). The mean UA base deficit was -6.51 _+ 4.38 (between 0 and -10, n=140; between -10 and -15, n=22; between -15 and -24, n=9). Univariate analyses did not reveal a statistically significant association between UA pH or base deficit and selected neonatal outcome variables: seizure act=vity (O=.211, p=.818), grade Ill/IV IVH (O=.568, p=.229), abnormal neurologic exam (O=.079, p=.550), and intact survival (o=.332, p=.233). As UA pH decreased, there was a significant increase in the frequency of prolonged (>35 d) mechanical ventilation (O= .009). Regression analysis controlling for multiple potential confounders confirmed the assoc=ation between UA pH and prolonged mechanical ventilation. When artenal, venous, and unlabeled specimens were grouped (n=363), similar univariate and regression analyses results were obtained. CONCLUSION: In this series of ~1000 g infants, decreases in UA pH were associated with an increased risk of prolonged mechanical ventilation. There was no association between UA pH or base deficit and grade Ill/IV IVH, seizure activity, abnormal neuroiogtc exam, or intact survival.

V o l u m e 174, N u m b e l A m I Obstet Oynecol

t, l'art 2

261 SKIN BLOOD FLOW RESPONSE TO STABLE ASPHYXIA IN THE

PREMATURE FETAL LAMB. P Bobby ~. MY Divon, E Yun~, A Santos ~ Depts of OB/GYN and Anesthesiology, Albert Einstein College of Medicine, Bronx, NY. OBJECTIVE: This study was designed to determine whether a prolonged period of stable asphyraa affects skin blood flow(SBF) m the premature fetal lamb METHODS: 9 chromeally instrumented pregnant ewes were studied at 118-119 days of 8estatmn ARer a control penod, fetal acid-base status was assessed and regional blood flows were determined with dye-labelled mlcrospheres Moderate fetal asphyma was then induced by partial umbilical cord occlusion and maintained over 90 minutes. Evaluation of cardiovascular and acid-base status was then repeated Regional blood flows(ml/mm*8) to areas of skin over the fetal vertex and breech were then compared. Data were evaluated by Student's t-test. RESULTS: mean±SD, *p<0.05 CONTROL ASPHYXIA pH 7 43±0 04 7 33±0 03* PC2 25±4 14±3" PCO2 41±4 48±2* SBF-VERTEX 0 48±0 24 1 75±0 79* SBF-BREECH 0 38±0 23 1 29± 1.23 CONCLUSIONS: Fetal skin Is accessible for mtrapartum evaluation. Previous investigators have shown that blood flow to the fetal carcass (bone, skin and muscle) increased in response to hypoxemla produced by umbdical cord occlusion of short (4-5 minute) duration I In this study, umblheal cord compression which produced a stable level of asphyxia over a 90 minute period resulted m a sJgmficant increase in SBF over the fetal vertex The increase m SBF to areas over the fetal breech approached significance in this small sample(p=0 07) These results must be considered when utlhzmg SBF or any method of mtrapartum fetal evaluation dependent upon SBF to demonstrate fetal well-being. lAmer[can Journal of Physiology(1987), v 257, H100

262 UMBILICAL CORD GAS ASSESSMENT IN HIGH RISK TWIN GESTATIONS. A F Bor~ida. F Eng*, JFX Egan, JF Rod[s, JS Smeltzer, G W Turner, and W A Campbell. University of Connecticut Health Center, Farmington, CT. OBJECTIVE: To compare the differences in umbilical cord blood g a s (CBG) values in h i g h risk twin gestations. S T U D Y D E S I G N : Twins h a d CBG obtained at the time of delivery. Arterial (Art) and v e n o u s (Ven) CBG w e r e analyzed for p H , p C 2 , pCO2, and HCO3. Birth order, p r e g n a n c y complications, delivery mode, and birth information w e r e r e c o r d e d for aIl twins. Data w e r e analyzed as m e a n values and m e a n difference b e t w e e n t w i n s A and B u s i n g p a i r e d t-test and A N O V A w i t h p<.05 significant. RESULTS: 110 sets of twins w e r e evaluated. The m e a n gestational age at birth was 31.7 weeks, and the mean birth weight was 1688 g r a m s . P r e g n a n c y complications included: p r e m a t u r e r u p t u r e d m e m b r a n e s - 3 0 % , p r e t e r m labor-45%, birth w e i g h t discordance-32%, preeclamp.sia-17%. Delivery w a s cesarean in 79%, v a g i n a l in 11%, and comlSmed m e t h o d s in 10%. There w e r e no differences in m e a n birth weights or median A p g a r scores. twin A twin B Art p H 7.30+.06 7.30+.07 Ven p H 7.34+.06 7.34+.06 Art p C 2 18.8+6.9 18.3+7 3 Ven p C 2 27.8+9.5 25.3+9.5* Art pCO2 47.8+7.5 48.0:1:9.6 VenpCO2 41.4+7.0 43.0+7.3 Art FICO3 23.5.-k2.6 23.1+3.5 Ven HCO3 22.2+2.5 22.8+2.7 (All data m e a n + SD) *p=.04 Analysis by m o d e of delivery s h o w e d the Ven p C 2 w a s significantly lower in t w i n B only w h e n delivery w a s c o m b i n e d (A=29.8+6.8, B=24.3.+.3.1, p=.01), and the Art H C O 3 w a s less in t w i n B w h e n both t w i n s h a d a v a g i n a l birth (A=23.0:k2.2, B=21.2+3.1, p=.04). N o differences w e r e related to d i s c o r d a n t g r o w t h or p r e g n a n c y complications. CONCLUSION: In this study, the largest of CBG m t w i n s to date, m a n y of the previously reported differences b e t w e e n twins A and B w e r e not c o n f i r m e d m o u r h i g h r i s k p o p u l a t i o n . The s m a l l differences found in this study were related to m o d e of delivery.

SPO Abstracts

263 INTRA

UTERINE FETAL ESSENTIAL FATTY ACID STATUS; COMPARISON WITH POSTNATAL VALUES OBTAINED AT COMPARABLE GESTATIONAL AGE ( G A ) .

Av Houwehueeu. M Foleman-v l)longelet~ M AI.'t; lhunshf, I I J'~lcohnl, K Nleolaldes Dept lhun Blol, [.llnbl.ug llulv, Maast, lt.ht, The Ncllclland,, OBJECTIVE Because a bettel knowledge ol file physloh~gy Id u'~atelnal-teta] eSSelltlal tatty acid trall~,[cl IS ICleVdll{ IIH Indlellhl] nutritional leCtHllnlelld,ttlIHlh, we Sltldletl the lelal csseUllal h.tty acid status dUllllg ongolug geMatl(ul hy ,Uhl]yMn.~ Ihe laity acid ~.tullpllMtll~ll ot pho,',phohplds tllun p]aslnd ohhuued by lclal bh~tfl s,unphng STYDY D E S I G N : The study tompllsed 86 lehd blood samples obhuned dmuig plegn,ln,.-y (18-37 weeks GA) and 26 mnbdJcd[ blood s,uuplc,,, hlken immediately ,dtel plelelIll hulh (28 5-37 weeks (;A) RESULTS: The total amouut ot phosphohlml-asst~th.lcd lally at. lds lU plasma did not change dnlmg gestallon The level el ]ultdClt ,tt_ld (18 2116) showed a slighl lllCledse (p=(} 015) dulJug gestation 'l'hu ~, the declcase lll fetal linolelc acid ob~elved behlle, dtlllUg tile [list tlUlleStel I)l plcgnancy does IIOl I-OllllUUC dUllUg file 2ud aud "~Id IlUllCbtcI The dlllt~lUll ot dlachldonlc acid (20 4n-6) decreased wllh local Inaluhdlou (p
264 MECONIUM HAS NO L OR S BUT AFFECTS THE L/S RATIO. S. Lonao. C. Towers, A. Strauss', T. Asrat, R. Freeman, OB/GYN, Long Beach Memorial Medical Center, Long Beach, CA and University of California, Irvine, Orange, CA. OBJIgCTIVZ: Although, there have been a few reports that

have evaluated the effect of meconiem on the US ratio for fetal lung maturity t~cd~. To date, these studies have only assessed the L ~ ratio of anmiotic fluid cont~mmmtedwith meconiem. The purpose of this study was to determine if meconium by itself 1) produces an L/S ratio, 2) contains Lecithin and Sphingomyelin, and 3) has values that are consent. STUDY DESIGN: A standard Thin Layer Chromatography (TLC) L/S ratiowas performed on the first meconium stoolof 19 neonates between 31 weeks and term. A quantitativeassay was perfonn~ on a sample from each gestationalage (7 samples, range 31 weeks to term) to confmn the presence of Lecithinand Sphingomyelin. RESULTS: The 19 samples gave atypical TIC migratory patterns that had dots similar to the zones for Lecithin and Sphingomyelin. The presumed L/S values ranged from I.I to 3.6 with no correlation to gestational age. However, the quantitative assay did not detect the presence of Lecithin or Spkingomyelin in any of the analyzed samples. CONCLUSIONS: Meconinm does not contain Lecithin or Sphingomyelin but has an unidentified material whose migratory pattern using a standard TLC qualitative assay is similar to that of Lecithin/Sphingomyelin. Therefore, the presence of meconinm in ~uninotic fluid may falsely raise or lower the L/S ratio and confuse fetal lung maturity interpretation.

383

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SPO Abstracts

CHRONIC ENDOTHELIN INFUSION IN THE RAT: EFFECTS ON R E G I O N A L PERFUSION AND PREGNANCY O U T C O M E . L_._GG

l a n u a D 1996 .Mn I Ob~tet (,vne~ol

267

Thaete,x M G Neerhof, g K. Sliver, "and M.S Caplua x ~ o n t s of Obstetrics and Gynecology and Pedmtrics, Northwestern Umversdy, Evanston Hospttal, Evanston, IL OBJECTIVE: To evaluate the effects of chronic endothelin (ET-1) infusion in the third-trimester on organ perfusion and pregnancy outcome m the rat. STUDY DESIGN: Venous and arterial catheters were placed on day 14 of gestation in Spragua-Dawley rats. Saline or ET-I (0 2 or 0.5 nmol/kg/lu-) was refused mtravanously vaa osmotic mmiponrp from days 15 to 21 of gestation (term=22 days). Mean arterial pressure (MAP) was recorded on days 15, 18, and 21. On day 21, radmlabeled nuerospheres were refused for evaluation of organ perfusion Anesthesm was then administered and a hysterotomy was performed Fetal and placental wetghts as well as the incidence of stillbirths were recorded Gamma counts were obtained from the following samples for evaluation of organ perfusion" reference blood, placenta, uterus, bdney, and brain. RESULTS: (Mama + SE) Saline# 0 2, nmol ET-I # 0.5 nmol ET-I # Organ Perfulion Placental perf (ml/min/g) 2 2 + 0 3 21+0.3 09+0.2* Uterine perf. (ml/mm/g) 0 5 + 0 . 1 0.5+0.2 04+0.1 gadney perf (ml/mm/g) 5 0 + 0 . 8 57+_06 3.5+_11 Bmin perf (ml/min/g) 08+02 1.0+-04 14+0.1 Pregnancy O u t c o m e MAP (day 18, mmHg) 114+-3 117+3 133+-6" Fetal weight (grams) 4.64+-0.06 429+-0.04* 397+-008* Pla¢ontal weight (grams) 053+_0.01 050+_001" 0.49+_0.01" Fetal death (#/litter) 060+_022 1.21+061 1.55+_0.65 #n=10 for each group *p
266

UTERINE AND PLACENTAL ENDOTIIELIN (EToI) RECEPTOR SUBTYPES IN THE RAT: RELATIONSHIP TO FETAL AND PLACENTAL GROWTH AND ORGAN PERFUSION. LG. Thaste, x S R Magnuson, x M.G. Nenrbof. Dept. of Obstetrics and Gynecology, Northwestern University, Evanston Hospital Evanston, IL and Abbott Labs, Abbott Park. IL. OBJECTIVE: To invest3gate the impact of chrome ET-I infusion on the expresston levels of ET-I receptor subtype (ETA & ET8) mRNAs in the uterus and placenta of the pregnant rat, and to evaluate the relationship between receptor mRNA status, uterine and placental perfusion, end fetal end pia~ntal growth. STUDY DESIGN: Chronic indwelling arterial and venous catheters were placed into 5 control and 5 expafimental Spragua-Dawley rats on (fay 14 of gestation Esther saline or ET-I (0.5 nmol/kg/hr) was infused intravenously vm osmotic mmipump from days 15-21 (tarm=22 days). On day 21, 57Co-labelad mlcreapheres were infused for evaluaUon of organ perfusion Anesthesaa was than administered and a hysterotomy was performed Gamma counts were obtained from samples of reference blood, placentas, end uterus. Uterine end placental samples from 3 control and 4 ET-l-treated rats were quick-frozen m liquid nitrogen for extraction of RNA. Total RNA was tsolated, a Northern gel eleetrophowsis and transfer were performed and 32P-labelad cDNA probes specific fur ETA or ETB mRNA were used to idantify and quantify these spacms. RESULTS: ETA mRNA ts 12 times more abundant m the uterus than in the placenta, and shows a slight (20%) decrease in response to ET-I infusion ETB mRNA levels are similar m the uterus and p ~ t a and are unaffected by ET-I infusion Perfasion and Grovah (Mean +_.SEM) Saline# 0.5 nmol ET-1# Placental perfusion (ml/min/g) 2 24 + 0.25 0.93 + 0.2 I* Utenne perfasion (ml/min/s) 0 50 + 0.12 0.40 +_.0.08 Fetal weight (grams) 4 64 + 0 06 3.97 + 0 08" Placental weight (grams) 0.53 +_.0 0 l 0 49 +_0 01" #n=5 for e~ch group *p<0 05 vs Saline CONCLUSIONS: The gravid rat uterus contains 12 Umes more ETA receptor than the placenta. Ere receptor concentrations m the uterus and placenta are slmdar Chronic infusion of ET-I has little effect on the relative coanentraUons of these receptors. Vasoconstriction of utenne arterioles, mediated at least in part by ET-1, hmits placental per~ston, and thereby placental and fetal growth

268

AGGRESSIVE UTILIZATION OF ANTENATAL STEROIDS IN VERY LOW BIRTH WEIGHT INFANTS Brian Sontad. Marion Stewart~, James Maher, Cindy MeEvoy~, Susan Bowling~,Gary Kleinmen, Dept. of Obstetrics & Gynecology, Dept of Pediatrics, Univ of Fl, Pensacola, FL OBJECTIVES - We compared the incidence of steroid utthzatton in our ~ent to the naUonalaveragefor steroid usage. We examined the dtfferenees between treated and untreated very low birth wstght (VLBW) infants for several outcome measures meluding hospital cost STUDY DESIGN - The subjects were 174 infants weighing between 500 and 1250 grams hospdahzed m our NICU from 1/92 to 12/94. Our department policy is to aggresstvely pursue corlacostero]dtherapy for lung maturatton m patients at risk for pretemadehvery including attempts to delay dalwery 48 hours whenever necessary Sixty infants were fully treated and 21 were partially treated prior to dehvery Contmcous variableswere compared wtth student's t-test, and categorical venables were compared by X2 analysis RESULTS - Our 35% rate of completed treatment with Betamethasone ts slgmficently}agberthen the pablishad national average of 15-20% (p<.001). Birth weight, geststtonalage, race and gender were sonilar between treated and untreated infants. Steroid therapy was associated with increased survwal compared to no treatment 88 3% vs 68 8%, p=.005. Although the length of stay for surviving infants was similar between treated and untreated mfants, the cost par day was sigedisanflylower in steroiduested infants, $1421/d vs $1985/d, p <0 01 Steroid treated infants had fewer severe (Grade 3 or 4) IVH 7.5% vs 21%, p< 05, higher systohc blood pressure 55 vs 46 mmhg, p<.001; less need for surfactant therapy 41% vs 67%, p<.01; less need for dopamme 2 1% vs 17.6°/6, p<.01, lower mean mrway pressure2 4 vs 4 9 cm H~O and a lower peak FrO2 24% vs 34% at 24 hours of age, p< 00l CONCLUSIONS - Although it is not possible to delay delivery in all preterm relents to acheve optimal antenatal steroid therapy, by making a concerted effort to trent whenevera patient is at risk for preterm dehvery, R is possible to improve on the htstonesl steand utiltzation rate. VLBW infants who receive the benefits of antenatal steroid therapy show an improved cardiovascular and pulmonary status. Overall these mfants have less morbtdity, lower mortality, and lower average health carecost

COMPARISON OF THE P A T H W A Y S OF A D E N Y L Y L CYCLASE S T I M U L A T I O N IN CULTURED H U M A N M Y O M E T R I U M A N D M O N O N U C L E A R LEUKOCYTES. Yu-Li Liux, Uchenna C. Nwosu, and Peter J. RiceL Departments of Pharmacology and Obstetrics & Gynecology, East Tennessee State University Quillen College of Medmine, Johnson City, TN. OBJECTIVE: This study compares activation of cAMP production in cultured human myometrium and peripheral blood mononuclear leukocytes, another model for the I$-adrenoceptor-cAMP system. METHODS: Human myometnum samples obtained at cesarean delivery or hysterectomy were cultured in DMEM/F12 with 10% FCS. Leukocytes from healthy males were studied fresh and maintained for 3 days in RPMI1640 with 20% FCS. cAMP production was measured by RIA under basal conditions and following stimulation by NaF/AICIs (lOmM/lOpM), Forskolin (24pM), or PGE1 (lOpM). RESULTS: cAMP production in leukocytes was =20-fold lower than in myometrial cells. In both tissues cAMP production was unaffected by G-protein stimulant NaF, but was maximally enhanced by PGEI. Forskolin, which directly activates adenylyl cyclase, enhanced cAMP production maximally in myometnum, but not in leukocytes maintained in culture. Stimulation of cAMP production was unaffected by 3-day exposure to a high climcal concentrations of tocolytic I~-agonist terbutaline (0.2gM). CONCLUSIONS: Leukocytes should be used cautiously as a model of the less accessible uterine f$-adrenoceptor-cAMP system. Exposure to high clinical concentrations of terbutaline does not affect the myometrium cAMP production system beyond the I&-adrenoceptor. (This study was supported in part by a grant from the ETSU Research Development Committee.)

Volume 174, Number l, Part 2 Am J Obster Gyne(ol

SPO Abstracts

269

ENDOTHELIN-1 INCREASES PRETERM OVINE FETAL URINE FLOW BY STIMULATION OF ATRIAL NATRIURETIC FACTOR (ANF) SECRETION. I~.K. Kqllam~=, M.E.G. Silva =, L.Day =, M.G. Ervinx, end M.G. Ross. Dept Ob/Gyn Harbor-UCLA Med Ctr, Torrance, CA. OBJECTIVE: Endothelin-1 (ET-1) is present in high concentrations in fetal plasma end ET-1 infusion (215 ng/kg/min) to nearterm (131 d) ovine fetuses increases arterial blood pressure, plasma ANFend urine flow. ET-1 induced increases in fetal urine flow have been primarily attributed to pressure diureeia. Aa ANF renal responsiveness is greater in preterm vs. nearterm fetuses, we hypothesized that preterm fetuses would exhibit ET-1 mediated diuresie primarily via ANF secretion. STUDY DESIGN: Six chronically catheterized preterm owns fetuses (t 16:1:1 d) were continuously monitored for arterial blood pressure end heart rate end fetal urine flow during sequential 60 man control, intravenous ET-1 infusion (25 ng/kg/min), and recovery periods. Five time-control animals received equivalent infusions of O. 1E M NeCI. RESULTS: In response to ET-1 infusmn, fetal plasma ET levels ( 109 + 16 to 204 + 35 pg/ml) significantly increased, though there was no change in fetal arterial blood pressure, heart rate, pH, pO2, or pCO2. There was • significant linear correlation between ET-t induced changes in fetal urine flow and plasma ANF levels (r =o.g2, p
271

ANGIOTENSIN II (All) INDUCED UTERINE VASODILATION IS MEDIATED BY AII TYPE 2 (AT-2) RECEPTORS VIA NITRIC OXIDE IN NONPREGNANT SHEEP D S. Lambers x, S.G. Greenbergx, K E Clark" Dept. Ob/Gyn. Umv of Cincinnati, Cmcmnah, OH OBJECTIVE To determine ff Angmtensm II-type 2 (AT-2) receptor shmulatmn causes vasoddatlon in the nonpregnant uterine vasculature STUDY DESIGN Uterine vasoconstrictor responses to AII are mediated through AT-l receptors m nonpregnant ewes (SGI 1995) and are slgmficantly blunted m the presence of AT-2 receptor shmulatmn possibly due to the release of a vasodflator To investigate this, mean arterml pressure (MAP), heart rate (HR), and uterine blood flow (UBF) were measured and uterine vascular resistance (UVR) was calculated m eight nonpregnant ewes Since no AT-2 agomst currently exists, we studied the effect of AT-2 stlmulatmn by AII in the presence of AT-I blockade (LI5gg09). Systemic and uterine hemodynamic responses to intrauterine artery (IUA) infusion of AII (0 03 ug/mm for 10 ram) were recorded before (baseline) and after IUA infusmns of L158809 (3 0 rag/ram for 5 min). To determine the mechanism of the observed vasoddatmn we tested mhibitors of prostaglandms (mdomethacm, 2 mg/kg ] v ), mtnc oxide synthetase (NOS, L-nitroargine methyl ester, LNAME, l0 mg ]UA) and AT-2 receptors (PD123319, 3 rag/ram for 5 m m ) RESULTS: As expected, IUA infusmn of AII (0 03ug/mm) decreased basehne UBF by 64+3% and increased UVR by 206+35% However, after AT-I receptor blockade with L158809, AII mfusmn increased UBF by 172+51% (p<0 007) and UVR actually decreased by 40+_7%(p<0.0001 ). A] Iinduced vasoddatlon was reversed by IUA PD123319 administration, and could be attenuated by pretreatment with PD123319 Indomethacm had no effect, whde L-NAME also reversed the vasoddatmn. No significant changes were observed m any systemic parameters. CONCLUSION: These data suggest that the vasoddation seen with AlI in the presence of AT-I blockade is medmted by the AT-2 receptor through stlmulatmn of NOS Since NOS Is elevated in pregnancy, stimulation of AT2 receptors in the pregnant owne uterus may in part explain the mechanism of uterine refractoriness to All Supported by HL-49901 and HL- 52280.

270

INCREASED FETAL COLONIC MUSCLE CONTRACTILITY FOLLOWING GLUCOCORTICOID AND THYROXINE (T4) THERAPY: IMPLICATIONS FOR MECONIUM PASSAGE. B. Ross, K. Bradley, L. Kullama x, M.J.M. Nijland x, M.G. Ross. Harbor-ULCA Med Ctr, Torrance, CA. OBJECTIVE: The incidence of meconium stained amniotic fluid increases with advanced gestational age and fetal stress, and meconium passage is likely dependent on fetal colonic muscle maturation. Antenatal steroid and/or T4 exposure improves fetal pulmonary and cardiovascular function. We hypothesize that in utero maturational agents effect an increase in fetal distal colonic muscle contractihty. STUDY DESIGN: In a randomized controlled study 126 d (term 145 d) ovine fetuses were treated with ultrasound gu=ded intramuscular rejections of 0.5 mg/kg betamethasone (n = 5), betamethasone plus 50 #g/kg thyroxine (n=5), or saline (n=7). After 48 h, fetuses (128 d) were delivered, distal colon segments were removed, and peak tens)on responses to bethanechol (10 e to 103M) characterized in in vitro organ baths. RESULTS: Peak muscle tensions were significantly greater zn combined betamethasone and thyroxine treated fetuses (989 + 190g/cm 2) than in betamethasone alone (559 + 75g/cm 2) or the saline treated animals (509 + 91g/cm2). The bethanechol EDso values (2,1 + 0 . 5 x 1 0 s M) were not different among the 3 groups. CONCLUSIONS: Antenatal fetal betamethasone and thyroid hormone treatment increases fetal colonic muscle contractility. We speculate that endogenous or exogenous fetal maturational agents may potentiate the passage of meconium.

272

EFFECTS OF ESTRADIOL.17J3 (Ez~) TREATMENT ON UTERINE ARTERY (UA) END0THELIAL NITRIC OXIDE SYNTHASE (NOS) EXPRESSION. RR Maenessx, CE Shawx, TM Phernettonx, IM Birdx Dept OblGyn Perinatal Research Labs, Univ of Wisconsin,MadisonWL OBJECTIVE: ExogenousEz~ treatment dramaticallyincreasesuterine bloodflow (UBF) and reproducesthe systemiccardiovascularadaptationsof normalpregnancy(Magnesset ai. 1993). SinceE2~ also increasesUA NOS specificactivity, we hypothesizethat Ez~ wdi locallyaugmentexpressionof constitutiveNOS,specificallyin UAendothelium. STUDY DESIGN: Nenpregnantewes{n- 14), receivedVehicle(16% EtDHin salineiv) or Ez~ (luglkg). Venousplasmawas obtainedat 0, 90, & 120 rain for measurementof cGMP,whichis producedin responseto NO; UA and ornental(systemic)arterieswerethen obtained.UsingWesternimmunoblotanalysislECLdetection,endothelialcell NOS(ecNOS) and neuronalNOS (nNOS)constitutiveisoformexpressionwere evaluatedin intact and denuded (vascularsmooth muscle; VSM] arteries, as well as in endotheliurn-enriched proteins.Thelatterwas obtainedby isolatingthe tunicaintirnainto "Westernlysisbuffer". RESULTS: UA expressecNOS,but not nNOS.ecNOSexpressionwas localizedonlyto the enduthelium, i.e. the intensityof the observedendothelium-enrichedecNOSproteinbands was as muchas 700-800foldgreaterthanthat observedin intactUA; expressionwas net observedin VSM. Cellularlocalizationand specificity of the ecNOSconstitutiveisoform expression also was confirmedby inun~necytochemistry.Ez~ given at a dose which induces maximal steady-staterises in UBF by 90-120rain, appeared to elevate ecNOS expressionin UA (48%), but not systemicarteryendothelium; VSM NOSexpressionwas unalteredby EzJ].PlasmacGMPlevels(11+ 1 pmel/ml)wereunalteredby Vehicle(-8 -+ 7%),but wereincreasedby 34 + 13% (p< 0.015) 90.120 min post-EzJ3injection.In other studies, unilateral injection of E2~ (3ug) directly into the uterine circulation locally increasedUBFandecNOSexpression,but onlyin the ipsilateraluterinehorn. CONCLUSIONS:1} Theconstitutiveisoformof NOSexpressedin UA endothehum,but not VSM, is ecNOS; nNOS was net detected.; 2) exogenousEs~ locally increasesecNOS expressmnin associationwith increasesin plasmacGMPlevels.Thesedata support the hypothesisthat endothelialocNOSproteinexpressionspecificallymediatesthe E)J].induced ~ncroasein UBF and possiblyother systemic cardiovascularadaptations of pregnancy. 3upportedby ~V/t~IlL 49210 andllD 33255.

385

386

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REPEATED USE OF BETAMETHASONE: EFFECTS ON ADRENAL FUNCTION AND BIRTH WEIGHT IN THE RABBIT L Pratt, RR Magnesw, SK Hendrcks, DH Abbott,.T Phernetton,,,lM Bird, Dept OB/GYN, Univ. of Wtsconsin, Mad=san,WI

lanualy 1996 Am J Obstet Gynecol

275 CHRONIC ENDOTIIELIN INFUSION IN TIlE PREGNANT RAT:

HEMODYNAMIC, BIOCHEMICAL, AND PLACENTAL HISTOLOGIC EFFECTS. L.G. Thaete,x M.G. Neesho£ R.K Sdver, M.S Caplan,x and A.G. Bredin.x Departments of Obstetrics and Gynecology, Pediatrics, and Pathology, Northwestern Umversity,Evanston Hospital, Evanston, IL. O.~dECTIVE: To determine if chronic endothelin (ET-I) mfuslon produces any of the heraodyuannc,hieehemtesl, or placental histolo~c clmmctenstics described m HELLP syndrome in the human or with nitric omde synthase antagonism m the rat. STUDY DESIGN: Chronic mdwelling arterial and venous catheters were placed on day 14 of gestation in Sprague-Dawley rats. Saline or ET-I (0.2 or 0 5 nmol/kg/hr) was mfnsed intravenous~ via osmotic monpump from days 15 to 21 of gestanon (term=22 days). On days 14, 18, and 21 of gestation, mean arterial pressure (MAP) was measured On day 21, arterial blood was obtained ibr a CBC, liver funcaon tests, and blood gas analysis and a hysterotomy was performed In 4 rats treated with 0.5 nmol ET-I and in 3 controls, a uterine horn was removedand fixed en block for histohigicevaluation. RESULTS: (Mean + SE) Saline# 0.2 nmol ET-I # 0.5 nmol ET-1# MAP (day 18, mm Hg) 114_+3 117_+3 133+6" Hematocrit(%) 27.6 _+1 1 31.1 +0.8 30 5+_0.9 Platelet Count (103/cc) 828 _+36 728 _+57 789 +-40 SGOT (rd/lilgt) 145 +_20 9t + 16 98 + 25 SGPT (IU/liter) 59 +_.15 54 + 10 49 + 8 Attend pO2 (mm Hg) 905+35 922+_3.7 862+_.8.6 Arterial pH 742+0.03 7.41_+0.01 7.41_+0.02 #n=10 for esch group *p<0.05 vs Saline by ANOVA Placental histology of mrs treated chronically wah ET-I exhibited penvusculur mflammahon, but these was no evidence of neoresls or infarction CONCLUSIONS: Clwonic ET-I infusion does not produce the biochemical charactefisn©sof HELLP syndrome. Maternal hypertension ts observed only wtth high.doce infusion. ET-I infusion does not produce the placental necrosis and mfaretion described with chronic mtn¢ oxide mhihition in the rat.

OBJECTIVE: To determtne whether repeated maternal frea~nent with betamethasone (BETA) for fetal lung maturity suppresses fetal or maternal adrenal funcbon or affects birth wetght (BW) in rabbits RESEARCH DESIGN: 35 time-lzed rabbtts (tann=31d) were assigned to five groups, no b'eafrnent; saltne (0 2ml IM); or 1, 2, or 3 courses of BETA A BETA course = 0.1mg/kg IM q24h x2. BETA injecbons began on d19&20 (1.2, and 3 coursea) and were repeafed on d21&22 (2&3 courses) and d25&26 (3 courses) At sacrifice (d27) sera for cortisol levels (EIA) and adrenals for 17~t.hydroxylase (17OH) mRNA expression (Northern analysis) were collected Data were analyzed by ANOVA (cor~sal, BW) and t-test (17OH). RESULTS: Are expressed as % of maternal sahne confrol (~ISD). :ontrol I sahne I1 course I 2 courses 13 courses 'nat cortlsol 166 9(42 8)+ 100+ 93 4(93 7)+ 55 2(84 31# 1 1(0 8} ^ etsl cortlsot28.0(7 0)4 30 4(19 5}+ 26 9 24 8 4 -~3.9 2 0)+ 0(098)# nat 17OH 1175(477)+1004 79 6(4 4)+# ~.3 4(19 0)#j 120(203)" eta] 17OH 57.1(47 7)4 50 5(27 6)+ 50 4(15 9)+ 2S.0(24 6}# 2 1(3 2)" 3W(grns) 314(30)+ 318(42}4 306(28)+ Z66(38)# 196(34)"Means wdh the same symbol ere not significantly afferent from one another within the same row Symbols whch dtffer wlthtn the same row denote stgnlfieance at p<0 05 Maternal cerbsol levels were unaffected by 1 course of BETA, declined 50% with 2 courses and were suppresaed by 3 courses Fetal cortisel levels were suppressed alter 3 courses. Expression of the mRNA encoding 17OH, the rata hmttmg erL~me ~ cortisol syntheats, paralled these results BW was adversety affected following 2 and 3 courses. CONCLUSION: Whereas a stngle course of BETA does not affect fetal growth or suppress adrenal funcbon, repeated use of thts drug results in complete suppre~on of maternal and fetal adrenal function and k'npactsfetal stze We ere now explerlng fr~ possible relattonship between timing of repeated BETA usa relatrve to negabve feedoack Lnducedadrenal suppression

274 Inhibition of lnterleukin-10 During Pregnancy Results in Neonatal

Growth Retardation. p, ~ihsin~,hani, S. Bhatlaz, K. Thompsonx, L. Tygrettx and T. Waldschmidtx. Depta of Ob/Gyn and Pathology, Univ. of lowa, Iowa City, IA. OBJECTIVE: IL-10 is a major immuno-reguhtory ¢ytokine secreted at the maternal-fetal interface. Preliminary studies suggest it may play an important role in reproductive fitness. We hypothesized that neutralizing IL-10 with an lgG antibody would lead to pregnancy losses and alter Tcell immunity. STUDY DESIGN: Pregnant Balb/c mice were randomized to receive either anti-IL-10 antibodies or saline every other day starting day 10 of gestation. Six liners were studied for fetal outcome. A litter of eight neonates exposed to anti-lL-10 in utero was compared to four liners of untreated control mice. T-cell development was studied in the anti-IL-10 treated mothers by examining the major T-cell subsets based on CD4 and CD8 and the early precursors based on CD44 and CD25. RESULTS: Prolonged deprivation of IL-10 did not alter intrauterine growth or pregnancy outcome. However, all neonates born to mothers given anti-IL-10 during pregnancy showed evidence of growth retardation by weaning. Fefus/Neonate Anti-IL-10 Rx CpnCr01 P v~lu¢ 18 d fetus wt. (g) 0.98±0.3 0.84±0.2 NS CRL (cm) 2.03 :l: 0.27 1.96 :l: 0.2 NS Litter size (n) 6.8 + 2.3 6.4 + 1.9 NS 4wksneonatewt. (g) 7.3 +0.9 9.4 4- 1.4 <0.0001 5wksneonatewt. (g) 11.0 + l . 1 14.0 4"1.0 <0.0001 6 wks neonate wt. (g) 14.7 5:1.4 16.8 4- 0.8 0.01 No significant differences were observed in maternal thymic involution and T cell subsets between anti-IL-10 treated and control pregnant mic©. CONCLUSIONS: There is a significant correlation between deprivation of IL-I0 in utem and neonatal growth and development.

276

PROPRANOLOL INHIBITS PHOSPHATIDYLCHOLINE (PC) SYNTHESIS BY ALVEOLAR TYPE-II CELLS J.L. Kim x. F.H.C. Tsao x and C.B.Martin, Jr. Depts. of Ob-Gyn and Pediatrics, University of Wisconsin, Madison, WI. O B J E C T I V E : 6-adrenergic antagonists inhibit the secretion of pulmonary surfactant, but an effect on surfactant synthesis has not been clearly demonstrated. Therefore, we investigated the effect of 6-adrenergic blockade with propranolol on surfactant synthesis by alveolar type-II epithelial cells. STUDY DESIGN: In vitro study using isolated adult rat alveolar type-lI epithelial cells in culture. In short incubation experiments, 3H-choline (a PC precursor) and test drug were added to the culture after an 18-h preincubation, and the cultures incubated a further 2 h. In other experiments the test drugs were added during the primary incubation (18 h). After the cells were washed, 3Hcholine was added for an additional 2 h incubation period. PC synthesis was determined by quantification of 3H-PC. R E S U L T S : Propranolol (50 p.M) decreased PC synthesis to 75% of control after 2 h (P=0.01), and to 50% of control after the longer incubation (P=0.0048). The depression of PC synthesis was also dose-dependent over the range 1 to 50 p.M. Addition of dexamethasone (0.1 p/el) to cultures with 50 p.M propranolol restored PC synthesis to control levels. CONCLUSIONS: These data demonstrate that propranolol inhibits PC synthesis by alveolar type-II epithelial cells at a cellular level in a time- and dose-dependent manner. This inhibition is reversed by dexamethasone. These observations may have clinical relevance in the m a n a g e m e n t of pregnancies complicated by maternal hypertension, when preterm delivery is contemplated.

SPO Abstracts 387

Volume 174, N u m b e r 1, Part '2 Am.] Obstet Gynecol

EFFECT AGAINST NMETHYLoD-ASPARTATE-INDUCED SEIZURES IN RATS. CA SIandlev ", DB Cotton. Department of Ob/Gyn, Wayne State University/Hutzel Hospital, Detroit, MI O B J E C T I V E : There eyasts a paucity of data regarding the effects of pregnancy on seizure potential. We examined seizure a c t m t y using the convulsant N-methyl-D-aspartate (NMDA) in pregnant versus nonpregnant rats. S T U D Y D E S I G N " 74 Long-Evans rats were anesthetized with pentobarbital sodium and a bipolar recording electrode was implanted into the dorsal hippocampus, while a carmula was set into the lateral cerebral veaatncle. One week later, rats were mated, while others served as nonpregnant controls. Nonpregnant and pregnant rats (GA=20 days) were rsn&xnized to receive no drug or a single injection of N M D A (5, 10 or 20 lag) through their indwelling eannulae (9-12 rats/group). Seizures were thereafter assessed for 20 minutes. Pups were counted and wetghed following delivery. Adult brains were processed for histology. Data were analyzed with A N O V A and Student's t-test. R E S U L T S : Total seizure duration and total number of seizures were sagnifieantly reduced in pregnant versus nonpregnant rats, espeetally at the 10 and 20 lag doses of N M D A (p<9 05, respectwely) Onset to seizure activity was not significantly affected by pregnancy. The number of healthy pups at postnatal day 3 tended to be reduced in mothers injected with higher doses of N M D A . C O N C L U S I O N S : These data demonstrate that seizure actwity m v o l v i n g N M D A receptors is reduced in pregnant rats compared to nonpregnant rats. Using autoradiography, we have previously shown that N M D A receptors are altered during pregnancy. We therefore suggest that pregnancy affords some protectaon against seizures reduced by an activation of N M D A receptors in the brain.

279

FETAL GROWTH RESTRICTION: REVERSAL BY DIETARY LARGININE IN A RAT MODEL. KB Harvey-Wilkesx, ILl Vosatka. Division of Newborn Medicine, New England Medical Center/Tufts University School of Medicine, Boston, MA. OBJECTIVE: Nitric oxide, a potent vasod:lator, has been proposed to have a role m regulating the uteroplacental circulation. Nitric oxide is synthesized from L-arginine. We have studied the effect nf increasing the dietary supply of L-arginine on fetal weight in a rat model nf fetal growth restriction. We hypothesized that increased dietary L-arginine would lead to increased synthesis of nitric oxide. N:tric oxide could then increase uteroplacental blood flow, thereby improving oxygen and nutrient delivery to the fetus and improving fetal growth. STUDY DESIGN: 31 pregnant rats were exposed to hypobanc atmosphere (380 tort) between fetal day 9 and 21 (term=22 days). 13 of the hypoxic rats had 2% L-arginine added to their drinking water (HYP-LARG). 3 had 2% D-arginine added (HYP-DARG). 15 were not supplemented (HYP-H20) l I pregnant rats served as room air controls (RA). Fetuses were delivered by hysterotomy on day 21. RESULTS: HYP-H20 fetuses were smaller than RA fetuses (HYPH20): 3.38+0.70g, n=101 fetuses, RA:5.11+0.75g, n=65 fetuses, p<0.01). HYP-LARG fetuses 94.78+0.56g, n=52 fetuses) were larger than HYP-H20 fetuses (p<0.05) and nnt different from RA fetuses. There was no difference in protein intake between HYP-ARG mothers and HYP-H20 mothers (HYP-ARG 9.49+0.92g, HYP-H20 9.55+0.92g). The influence of arginine on fetal weight was stereospecific. HYPDARG fetuses were smaller than RA fetuses (HYP-DARG:4.32+0.83g, n=31 fetuses, p<0.05 vs. RA). CONCLUSIONS: L-arginine is a specific regulator of fetal growth, possthly as a precursor of nitric oxide.

THE EFFECT OF MAGNESIUM SULFATE INFUSION ON THE ECG IN PREGNANT WOMEN. M.E. Caine, R.L. Thomas, D.H. MacKayx, K. Comportx, Department of Obstetrics and Gynecology. The Western Pennsylvania Hospital, Pittsburgh, PA. OBJECTIVE: Magnesium sulfate (MgSO4) is infused intravenously (IV) to treat preterm labor and as seizure prophylaxis for prcoclarnpsla. MgSO, acts by slowing or blocking neuromuscular and cardiovascular conducting system transmission. Past studies in animals have shown prolongation of the QT interval with MgSO, administration. Prolongation of rate corrected QT interval (QT,) has been associated with malignant veotricular errhythmias in humans. ECG (electrocardiogram) effects of MgSO4 in pregnancy have never been reported. This study was designed to evaluate ECG changes in pregnant women undergoing IV infusion of MgSO4. STUDY DESIGN: Sixty-one ECG rhythm strips were evaluated in ten pregnant women undergoing MgSO4 infusion for complications of pregnancy. Baseline ECGs were performed prior to MgSO4 infusion and then hourly. PR, QT, and QRS intervals, serum electrolytes, MgSO4 levels, maternal heart rate, and maternal arrhythmia were recorded. QT was corrected for maternal heart rato (QT.). Statistical anidysis was per formed using repeuted measures analysis of verianco. (P < .05 was considered statistically significant). RESULTS: Mean MgSO4 levels obtained after one hour reflected a steady state. A significant increase was note,d from baseline (1.72 meq/L vs 6.35 meq/L, P < .001). A significant prolongation of the QTo interval from baseline during IV MgSO, was noted. Baseline QT, = .4471s, steady state QTo = .4845s (P < .001). No significant difference in other parameters was noted. Two arrhythmias were identified during IV MgSO,, premature atrial contractions and trigominy. Neither was considered dangerous. CONCLUSIONS: The QTo interval during administration of therapeutic doses oflVMgSO 4 is significautly prnlonged from baseline, prolongation of the QT, interval did not result in a dangerous arrhythmin in this pilot study. ECG monitoring during IV MgSO, infusion is probably unnecessary.

280

A PROSPECTIVELY RANDOMIZED TRIAL OF TWO SOLUTIONS FOR INTRAPARTUM AMNIOINFUSION: EFFECTS ON FETAL ELECTROLYTES, OSMOLALITY AND ACID-BAS~ STATUS. E. Pressmanx K. Blakemore. Dept. of Gyn/Ob, The Johns H u p k m Univ. Sc~. of Med. l~'Itimore,Md. OBJECTIVE: To compare the effects of intrapertum anmiolnftadon with normal saline (NS) vs. lactatedRinger's solutionplus physiologicglucose (LR+DmW) on neonatal electrolytes, glucose, omnolality, lactic acid concentration, and acid-base balance. STUDY DESIGN: Patients undergoing amnioinfimion for variable fetal heart rate decelerations, oligohydrnnmios or thick uteoonium gaining of the smaiotlc fluid were randomized to receive N$ or LR+DmW at mmaderdized amnioinfusion rates. Data were collected proepectivdy on maternal demographics, course of labor and maternal snd neonatal outcomes. Arterial cord blood wag obtained for analysis of electrolyte, glucose, omnoinlity, hu:tic acid and blood gases. Laboratory permanal were blinded to the mlution used for anmioinfusion. Control subjects with normal fetal heart rate pmterns, clear amnioti¢ fluid and not receiving anmioinftmion were studied com~urrnutly. Statistical analysis was performed using an analysis ofverianco, t test, Fisobe¢'s exact test or Pearson's correlation where appropriate. RESULTS: Data were collected on 59 patients (21 NS, 1| LR+DIoW and 20 controls). No significant differences were noted in ~ demogrsphi~ or neonatal outcome. The indications for amnloinfuaion, duration of labor and volume of anmioinfusate were similar in the NS and LR+D,eW groups. Cemream sections were performed morn often in the umininfualon groups (33.3~ for NS, 38.9~ for LR+DIoW) than in the control group (5.0~), p < 0.05. Cord arterial alectrolytes, glucoso, nmolality, lactlc acid and blood lpmas were not altered by anmioinfimion with either solution. CONCLUSION: Intrapartum anmioin fusion with either NS or LR+ DleW lure no effect on neonatal electrolytes, glucose, olmolality, lactic acid or acid-lume balance.

277 P R E G N A N C Y HAS A PROTECTIVE

278

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J a n u a r y 1996 A m J Obstet (,ynecol

MATERNAL MORTALITY AT A TERTIARY CENTER WITH CRITICAL CARE OBSTETRICS. S BlackwnlP, MW Tomhnson, B Gomk, BA Mason, JE Wh~tty, DB Cotton Dept OblGyn, Hutzel HospNVayne State Umv, Detroit, MI OBJECTIVE: In contrast to nahonally reported data, anecdotal expenence suggests that maternal mortahty (MM) ehologms may differ in an tuner city tertmry care center w=th an indigent population. This study rewews a single institution's 5 yr experience to better define thls msue Maternal deaths from 1990-94 were identified from an estabhshed pennatal data base Charts were rewewed for demographics, prenatal care, and underlying med=cal condJtlons When autopsy data was unavailable, cause of death was asslgned chn=cslly 17 deaths occurred m 43,083 births (MM rate SO 39 5/100,000 btrths) Causes of death are shown Mean age was 31 yrs, 88% were African American, and 24% had insurance. 88% had some prenatal care Underlying medical condihons were present in 65%. 59% presented Ct~lae Faebelle bt~tkt NI~ Other antenataUy, and 35% exptred within 24 hrs of admiss=on Adult resptratory distress syndrome was the proximate cause of death in all sepsis cases CONCLUSIONS: Cardiac dtsease accounts for a disproportionate number of maternal deaths m th=s setting Underlying disease is a sigmficant contnhuhng factor Tradlhonal etiologies such as hemorrhage, hypertension (HTN), and septic shock have a lesser =mpact

283

GRADED-COMPRESSION ULTRASOUND(GCUS) FOR EARLY RECOGNITION OF APPENDICITIS IN PREGNANCY. JB Landwehr ~ MR Leonardt*, DR Bryant x, SC Johnson X, an~d SF Bottoms Wayne State Unwersity, Hutzel Hospital, Detrott, MI, OBJECTIVE: To determine the utility of the GCUS of the appendix as an adjunct m the early recognition of acute appendicitis m pregnancy STUDY DESIGN: Retrospec'ove chart analysis was performed on all pregnant patmnts hawng a GCUS of the appendtx at our institutmn between the years 1991-95 All patients had vague abdominal pain with a low to moderate chnical suspicion for appendicitis Dmcnmmant function analysts (DFA) was used to delineate the most useful predtctors for acute appendmflJs RESULTS: Mean gestsfional age at the time of graded-compression U/S was 20 1 :t: 8.2 weeks Graded-compression U/S successfully predicted appendmttis in 4 of 5 patients (80%) The sensitiwty, specificity, and negative predictwe value were 80%, 97%, and 97%, respectively The results of the DFA were as follows

284

STUDYDESIGN: RESULTS:

--7]

282

Mean values Value appendicitis (n=5) no appendtcfl~s (n=43) p GCUS(+) 80% 2 6% <0 001 Temperature 37 3 37 5 NS VVBC 17 9 13 2 NS Constipation 0 0% 30% <0 01 Nausea/vomiting 100% 65% NS Diarrhea 67% 30% NS Anorexia 100% 33% NS Abdominal pain 80% 98% NS Fever/chills 100% 45% NS CONCLUSION: Graded-comprassmn ultrasound is a useful adjunct in the early recognJtion of acute appendmttis m pregnancy, perhaps allowing for earlier surgtcal intervention m patients with a low to moderate suspmlon for appendtelUs GCUS proved to be far superior than any of the other chnlcal s=gns or symptoms m predicting appendtcltls m th=s selected group of patients

EXCESS RISK OF F E T A L D E A T H IN BLACKS VARIES BY G E S T A T I O N A L AGE. SN Wall~and JC Collin~ Dept. of Pediatrics, Northwestern Univ Med School, Chicago, IL. OBJECTIVE--Fetal deaths, as well as other adverse perinatal outcomes, are more common in pregnancies of black women compared to white women. While socioeconomic disadvantage is associated with adverse perinetal outcomes in blacks, the etiology of the racial disparity in fetal mortality is not well understood. To determine if the excess risk of fetal death in blacks varies over the course of gestation, we analyzed national databases of live births and fetal deaths. METHODS--Using 1986 live birth and fetal death data from the National Center for Health Statistics, the fetal mortality rate (FMR), calculated as fetal deaths per 1000 live births (LB), was determined for black and white women. At each gestatioual age (GA) between 20 and 42 weeks, FMR was calculated as the number of fetal deaths divided by all live births at the same or later gestational ages. RESULTS.-There were 3,309,818 singleton live births and 21,829 singleton fetal deaths to black or white women between 20 and 42 weeks' gestation. Overall FMR for blacks and whites respectively was 11 and 5.7 deaths per 1(300 live births. The black and white FMR at each GA (Fig. 1) and the relative risk (RR) of fetal death in blacks (black FMR divided by white FMR) at each GA (Fig. 2) are shown below. Conclusions--The increased fetal death risk in black women is highest in the second trimester and decreases as pregnancy approaches term. Figure I Figure

2 ' ~ I"~1"[. 2 ~.~....--Black ~..,.,.~. ....4, i~je3 ,i,i,~;~|~,~],i~i.=~l,|~;g|] 0 ........ ~:::: 22222 2222 20 "2~ -24 "2~ -18 30 32 34 36 38 40 42

Gestational Age (weeks)

20 22 24 26 2S 30 3234 36 38 40 42

Crestational Age (weeks)

SIMl~tlqll~ AODIE ~ SOORE (SAPS ID A C C U R A T E L Y PREDICTS M O R T A L I T Y IN AN OBSTETRIC ICU POPULATION. D- Beazlev x, BM. Sibal. and WC Mabie. Department of Obstetrics and Gynecology, University of Tennessee, Memphis, TN. O B J E C T I V E : Severity of illness classification systems have been validated in multidiscipiinary intensive care units(ICUs) and in various disease states. Little is known regarding their applicability in an obstetric ICU. SAPS H represents the easiest of all ICU severity systems to use for obtaining the probability of hospital mortality. Our objective was to determine the applicability of SAPS II in predicting maternal outcome in a critically ill obstetric population. STUDY DESIGN: We evaluated the validity of SAPS II scores in 251 patients with various complications managed in our obstetric ICU. SAPS II scores ware calculated using the 17 variable SAPS H scoring sheet which includes 12 physiologic variables in addition to age, type of admission (scheduled surgical, unscheduled surgical or medical complication) and three underlying disease variables (AIDS, metastatic cancer, and hematologic malignancy). The worst values within the first 24 hour observation period in the ICU were recorded. This score was then converted to the probability of hospital mortality and compared with the actual mortality yielding a mortality ratio. A Receiver Operating Charsctea'istic (ROC) curve was used to define the SAPS II score that was best predictive of outcome. RESULTS: ROC analysis reveals that a SAPS H score of 38 or greater has a sensitivity of 86% and a specificity of 97.% The positive predictive value of this score is 63% and the negative predictive value is 99%. In addition, when a SAPS II score of 38 is used, the mortality ratio (actual/predicted mortality) is 1.01" which is not statistically different from the expected mortlditv ratio of 1. Predicted I m ~ ' u ' u % l [ M°rtafity OB vatients [ N ° ] SAPS ~:0reH [ In3ltditv~ ratio TOTAL 251 16.83 5.52 5.58 Survivors 237 14.97 3.21 0 Non sm-vivors 14 48.43 44.70 100 1.01" *p=0.962 CONCLUSION: SAPS R accurately predicts the probability of hospital mortality in an obstetric ICU population.

Volume 174, N u m b e r 1, Part 2 A m J Obstet Gynecol

SPO Abstracts

285

P R E G N A N C Y C O M P L I C A T I O N RATES IN AN I N N E R - C I T Y P R E N A T A L DRUG T R E A T M E N T P R O G R A M . l~ C ardonickx, M Comfortx, K Kaltenbachx, N Silverman. Depts of Ob/Gyn and Pediatrics, Jefferson Medical CoUege of Thomas Jefferson Univ. Hosp, Phila, PA O B J E C T I V E : To evaluate pregnancy complication rates over a 6-year period in a single-institution cohort of substance-dependent women enrolled in a mulladlsclplinary prenatal treatment program. STUDY DESIGN: Retrospective analysis of prospechvely recorded pregnancy outcome data for 182 women delivered from 1988-1994 All self-reported drug use was confirmed by routine unne toxtcology testing For analysis, subjects were grouped as (1) Methadone-treated, + any dlicit substances other than cocaine; (2) Cocaine use, + other substances, including methadone, and (3) Currently drug-free Comparisons used either X 2 or Fisher's exact test, where appropnate R E S U L T S : In the overall group, premature rupture of membranes (PROM) occurred in 20% of palaents, 70% of whom delivered preterm Clinical abruption occurred m 8% of pregnancies, 62% of which were preterm, while meconium-stained fluid was seen at 21% of deliveries. The overall cesarean section (C/S) rate was 21%. Pregnanc]es complicated by preterm dehvery (28% overall) had significantly htgher rates of both PROM (47% vs 9%, p < 0.001) and abruption (17% vs 4%, p = 004) than those delivered at term. When the rates of these comphcatmns were examined by drug-use groups, the higher rates for both PROM and abmption seen in preterm deliveries persisted only in the cocaine-using group. In addition, trends toward lower rates for CIS (15% vs 23%), small-for-gestailon newborns (13% vs 22%) and abruptaon (3% vs 11%) were seen among women either drug-free or using methadone only, compared to those who used any illicit substances ~ Q N C L U S I O N S : High rates of pregnancy comphcatlons were seen m this cohort of substance-addicted women, with most assoc]ated with the group that used cocaine. Preterm pregnancies in these women were associated with higher rates of abruption and PROM than those delivered at term Women who remained free of dlic]t drug use during pregnancy trended toward lower rates of the complications studied

287 CCMMUNITY-ACQJIRED PNEUMONIA IN PREGNANCY. RG Briaas. WC Mabie, BM Sibai. Department of Obst..~c.s andGyr,~cology, Uni'v. of Tennessee, Memp.his uujct./ivc: lO oetermlne the eti~ogy as Well as the maternal and perinatal outcome of community-acquired pneumonia (CAP) C~Tq01icating pregnancy_. STUDY DESIGN: Hospital records of 34 antepartum patients diagnosed with CAP between January 1, 1988 and January 1, 1995 were reviewed. Fever exceeding 37.5"C cough, and infiltrate on chest x-ray were nc usion cr teria. RESULTS: Coexisting illness (asthma, sickle cell anemia HIV infection, and epilepsy) was present in 10 patients (29%); 11 (,32%) had predisposing factors such as smoking >10 cigarettes/day and/or cocaine use. Diagnosis frequently required multiple laboratory procedures including sputum gram stain blood and/or sputum culture, arterial blood gas analysis, and chest x-ray. Invasive procedures sucfi as thoracentesis and bronchoscopy were also performed. The etiology was established in only 12 (35%), with varicella-(42%) .and Streptococcuspneumoniae(25%), diagnosed most frequently. Nine patients developed acute respiratory failure; 7 (78%) of these required intubation and mechanical ventilation, the other 2 (22%) required continuous positive airway pressure ventilation (CPAP) by fa.ce mask. Five of these 9 developed acute res~ratory distress syndrome (ARDS) with 2 (22%) resultant maternal deaths. In addition, there were 2 perinatal deaths (1 stillbirth at 2.2 weeks and 1 neonatal death at 28 weeks gestation). CONCLUSION: The mortality and morbidity for CAP in pregnancy remain high. Coexisting illness or predisposing factors were not prerecjulsites for the develoPment of CAP. Since the etiology is frequently not established, empidc antibiotic therapy is appropdate.

286

E F F E C T OF C O C A I N E ON N I T R I C OXIDE P R O D U C T I O N BY CULTURED HUMAN UMBILICAL VEIN E N D O T H E L I A L CELLS (HUVEC) IN V I T R O C.D. Hsu. Y.K. Chung x, J.A. Copel. Department of Ob/Gyn, Yale University School of Medicine, New Haven, CT. O B J E C T I V E : Cocaine can induce vasoconstriction. Nitric oxide (NO) is a potent vasodilator. We studied the effect of cocaine on nitric oxide production using the in vitro model of cultured HUVEC. S T U D Y D E S I G N : HUVEC were incubated with different concentrations of cocaine hydrochloride at 0, 10 "6, 10-5,10 -4 M (N=4 each). After 24 hours of incubation, the media was changed to Hank's balanced salt solution supplemented with CaCI 2 (l.3mM), MgSO 4 (0.6 raM), and arginine (100mM). Histamine (201.tM) was added as stimulator to test the release of NO by the cultured HUVEC with or without exposure of cocaine. After 60 minutes of stimulation, the supernatant was collected for analysis of NO. NO was measured by monitoring the formation of total NO x (NO+nitrite+nitrate) by a chemiluminescence detector after reduction of NO x to NO by acidic vanadium (II1), and quantified using an integrator by reference to NaNO 3 standard. Results were adjusted by the cellular protein in each well. Kruskal-Wallis test and Mann-Whitney rank sum test were used for statistical analysis. Results are given as mean+ SEM. RESULTS" Cocaine NO 0 10"6M 10"5M 10"4 M P

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Hist(+) 102+1.7 9.05:1.2 8.7+ 1.7 9.3+ 1.7 P=NS Baseline 5.4 +1.7 6.2+1.4 5.05:2.0 5.7+ 1.8 P=NS Hist(+):Histamine-stimulated,NO:pmol/lagprotein,NS:not-significant C O N C L U S I O N S : Cocaine does not alter NO production by cultured HUVEC after 24 hours of exposure. Although NO is a potent vasodilator, our data sugeest that cocaine-induced vasoconstriction may not be mediated through the pathway of an inhibition of NO production.

BACTEREMIA IN OBSTETRICS: THE EMORY UNiVERSITWGRADY MEMORIAL HOSPITAL EXPERIENCE. L. Nathan. B. Dozier, M. Sprauve, Dept. of Gynecology end Obstetrics, Emory University School of Medicine, Atlanta, GA. OBJECTIVE: Since the early 1970s, little attention has bean pald to becteremla In obstatrlca. New practice patterns and the widespread use of broad-spectrum antibiotics has stlmulsted a renewed Interest In infections complicating pregnancy. This study was dealgned to charscterizo the mlct'oblology of infections complicated by bactaramis on an urban obstetric service in the 1990,. STUDY DESIGN: From pregnenclea delivering between 10/I/91 and 9/30/93, those complicated by bacteremis were Identlfied retrcepeatJvaly. These charts were reviewed and a descriptive snelysls of outcomes compiled. RESULTS: Becteremia was diagnosed in 116 obstetric patients durlng this period, during which 10,695 women were delivered. Pyelonephritis (36%), choricemnionitie (35%), end endomyomstritis (19%) were the most frequent diagnoses. Eecherichla coll, Streptococcus egelectiea and Staphylococcus euraua were the most frequently recovered aerobes, whereas anaerobes were leolsted from only 11 (9%) patients. There were no deaths among these patients. Antibiotic Sensitivities Amp Gent Pcn Met Eryth Venc Cefaz Cafel E coli (n=47) 40% 100% 100% 100% S egelectlea (n=23) 100% Saureus (n=7) 0%100% S7% 100% CONCLUSION: Knowledge of the most common microorganleala responsible for becteramia in obstetrics and their usual antibiotic eaneitivitiee should assist in planning entimicrobial therapy.

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January 1996 Am J Obstet Gynecol

289 ALVEOLAR-ARTERIAL OXYGEN G R A D I E N T IN ACUTE

PULMONARY EMBOLISM IN PREGNANCY. R. Powriex L. Larson×, K. Rosene Montella. Dept of Med & O b / G y n , Women & Infants' Hospital, Brown Univ., Providence, RI. OBJECTIVE: To determine the incidence of normal alveolararterial (A-a) gradients in pregnant patients with documented pulmonary embolism (PE). gTUDY OESIGN. A retrospective chart review was performed on all pregnant women without complicating cardiopulmonary disease wlio had a documented PE at our institution between 1987 apd 1995. Patients with high probability ventilation-perfusion (VQ) scans,opositive p u l m o n a r y angiograms, or intermediate probability VQ scans associated with documented deep venous thrombosis were included in the study. Room air blood gases (ABG) atpresentation were used to calculate A-a gradient by the formula A-a gradient = 150 - (1.25 PaC02) - Pa02. This calculated value was compared to established normals as defined by: 1) values < 20 mfiaHg; 2) values < age in years/4+4, 3) Pa02 > 80 RErr~sLTS: Eleven patients with PE were identified who had room air ABGs drawn. Four of 11 (36%) had A-a gradients < 20, 6'11(55%1 patients had room air P02> 80 mmHg, and 2"11 (18%) had normal A-a gradients as predicted for age by the formula age/4+4. This varies from publlshed data on nonpre/~nant patients with PE where the range of normal A-a gradients vanes from t.9% -20%. CONCLUSIONS: In this study, a higher percentage of pregnant patients with PE had normal A-a gradients and Pa02 on room air than in m a n y previous studies investigating A-a gradients in nonpregnant patients with PE. This suggests that a normal A-a gradient as calculated from room air ABE; m a y not be adequate alone to rule out PE in the pregnant woman.

290 APPLICABILITY OF

A THIRD GENERATION THYROID STIMULATING HORMONE (TSH) ASSAY IN PREGNANCY. R Bobrewski, P Strelcherx, J Dzieczkowskix, M Dombrowski, K Puder, B Gonik, Depts. of Ob/Gyn and Path, Wayne State Univ., Detroit, MI. OBJECTIVE: A new third generation TSH assay is now available, but its use in gravid patients has not been validated. We sought to determine the applicability of this ultresensitive assay in pregnancy. STUDY DESIGN: We obtained serum from 93 grevidas with a smgleton gestation Women with symptoms or history of thyroid disease were excluded. TSH was determined by a two-site immunoenzymatic ("sandwich") assay with a reportable range of 0.006-I00.0 /AU/mL (Sanofi Diagnostics, Chaska, MN). Standard enzyme immunoassays were employed for total T4 (tT4), free 14 (fl4) and T3 levels. Reference ranges (RR) established by the kit manufacturer were used for comparision. Analysis was by MANOVA. RESULTS: Mean and range values for pregnant subjects were: MEAN RANGE RR TSH (plU/mL) 1.2 0 1-3.4 0.5-5.6 tT4 (pg/dL) 7.9 2.3-11.6 5.0-12.0 if4 (ng/dL) 1.1 0.7-1.8 1.0-2 5 T3 (ng/dL) 221 144-312 80-200 There were no d=fferences in mean values between trimesters for TSH, tT4, fT4, and T3 Thirteen of the 93 women (14%) had a TSH value below the lower limtt of the RR, though none had clinical evidence of hyperthyroid=sm or an elevated fT4. CONCLUSIONS: Currently available RRs for a third generation TSH assay may not be applicable to pregnant women. Until additional data become avadable, isolated TSH measurements for screening or monitonng hyperthyroidism during pregnancy should be discouraged.

291 DIFFERENCES

IN THE CONCENTRATION OF A N ENDOTOXIN BINDING PROTEIN HELP EXPLAIN SENSITIVITY TO SEPTIC COMPLICATIONS IN PREGNANCY. BK Irive. PI Rumney~, D AdhooP, T Asrat, CV Towers, SF Carroll', Mli Cart, JA Adashek, M White z. Long Beach Memorial Medical Center, Long Beach, CA, and University of California, at Irvine, Orange, CA. OBJECTIVE - Endotoxin, through the activation of cellular and humoral cascades, initiates the inflammatory response and multisystem organ changes associated with sepsis. Two recently described binding proteins, bacteriaeidal permeability-increasing protein (BPI) and lipopolysaccharide binding protein (LBP), both link with endotoxin but result in markedly different actions. LBP, which is made by the liver, binds endotoxin and delivers it to the maerophage thus stimulating cytokine production and a cascade of other inflammatory changes involved in the complications of sepsis. In contrast, BPI is produced by neutrophils and competltwely brads endotoxm and plevents LBPinduced signalling. Thus, BPI acts as an antagonist to the actions of LBP. Due to effects of pregnancy on the sites of production of each protein, we hypothesized levels of these proteins would be changed in the gravid patient and thus increase sensitivity to endotoxin (by leading to increased LBP, decreased BPI. or increased LBP/BPI) BPI results will be presented at a future date. STUDY DESIGN- 18 pregnant pahents in their 3rd trimester of gestation were matched by age and race to 18 non-pregnant controls. Patients were excluded for evidence of active infection. Plasma was obtained and the level of LBP was assayed. RESULTS Pregnant Non-pregnant p (N=18)

(N=I8)

Age (yrs) 32 (18-42) 31.5 (21-45) 0.80 AST (IU/L) 16 (7-33) 15.5 (8-28) 0.77 LBP (mcg/ml) 105 (4.6-22.7) 3.8 (1.7-7.7) <0.0001 CONCLUSIONS - These data display that levels of LBP are markedly increased, with pregnancy possibly leading to enhanced cytokine release and detrimental inflammatory responses. This finding supports the theory that LBP may be an etiologic agent behind the enhanced sensitivity of the pregnant patient to sepsis and its complications.

292 THE LACK OF ASSOCIATION BETWEEN

SELECTED HEMATOLOGIC PARAMATERS AND FREQUENCY OF PAINFUL SICKLE CELL CRISIS DURING PREGNANCY. A. Anyaegbunam, MD, M.S. Mikhail, MD', D. Jadali, MD' and H. Blllett,MD'. Albert Einstein College of Medicine, Bronx, New York. OBJECTIVE: Painful vasooclusive crists Is the most common cause of morbidity in sickle cell(ss) disease and pregnancy has been associated with an increase in the frequency of painful crises. The present study evaluates the association between prepregnancy hematuloglc parameters and the frequency of crisis during pregnancy m women with sickle cell disease. STUDY DESIGN: The study population consisted of 37 homozygous sickle cell disease women recruited from our non-pregnancy sickle cell thsease program. All patients were followed from the first trunester of pregnancy until delivery. RESULTS: The rate of painful crisis was 2.88 + 3.23 per pregnancy. Selected hcmatulogic tests and their average pregravid values viere; hemoglobin level (8.51 + 1.35) g/dl, hemoglobin F concentration (6.13 +4.22)%, percentage of dense cells (13.43 +9.717% and the reticulocytv count (13.08 + 5.32)%. There was no relauonshlp between frequency of sickle cell crisis during pregnancy and hemoglobin level (r=-.05; p=0.81); hemoglobin F concentration (r=0.12,p=0.56), percentage of dense cells (r=0.06;p=0.67), or the rettculocyte count (r=0.08;p=0.67). CONCLUSIONS: The studled prepregnancyhematologic parameters are not predictwe of the frequency of painful sickle cell crisis during pregnancy. Further search is needed to detect marker(s) that may identify paueets at risk for frequent sickle cell crisis during pregnancy. Such markers would be useful m prepregnancy counseling and prenatal management of patients with sickle cell disease.

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Volume 174, N u m b e r 1, Part 2 A m J Obstet Gynecol

293

MATERNAL OUTCOME ASSOCIATED WITH ADULT RESPIRATORY D1STRESS SYNDROME. K.G. Perry, Jr., R.W. Martin, P.G. BlakC, W.E. l~berts, J.N. Martin, Jr. Dept. Ob/Gyn, Univ. of Mississippi, Jackson, MS. OBJECTIVE: The purpose of our study was to characterize pregnancy-related adult respiratory distress syndrome (ARDS) in a single tertiary care center, and identify any factors that might be predictive of maternal outcome. STUDY DESIGN: Records of all pregnant patients diagnosed with ARDS and admitted to Intensive Care at a single tertiary care center over a 14-year period were reviewed. Data collected on each patient included demographic characteristics, precipitating factors, coexisting diseases, obstetric and nonobstetric complications, days in the ICU, and outcome. The cases were stratified into survivors and non-survivors in order to analyze any factors that might be predictive of outcome. RESULTS: Port}, one easas of pregnancy-related ARDS were identified with an incidence of 0.7 per 1000 llve births. Thirty one patients survived for e maternal mortality rate of 24.4%. ARDS was diagnosed in the antepartum period in 23 (56. 1%) patients, most in the third trimester (73.9%). There was no statistically significant difference in demographic characteristics between the survivor and non-survivor groups (p > 0.05). Coexisting diseases were divided

295

oomumption occur m pr~chmpsia and placental insufficiency. Small vessd pathology exists in both the uteroplacental bed and fetal placental vdli. Our objective was to investigate whether activation of circulating platelets ts present in both the fetal and maternal systems in these cases STUDY DESIGN: We stu&ed 6 normal pmgnancias and 20 mother-fetus pairs with an abnormal ~ Doppler study in "dacating ~ pathology. At eleclave Caesarean delivery blood was collected in s o d m m alrate, diluted with Tyrodes buffer, u x ' u ~ e d with monodonal antibodies and fixed. A flow c y t o m e t ~ technique was used. The platelot population w a s specified w a h a monodonal anta glycoprotein 111a ( C I ~ I ) whilst monodonal anti - P selectm ((2[362) ldenttfied activated platelets, Using LYSIS II software a chscrimination gate was placed around the platelet population to molate them from red/white cells and dd~is, Platelet rt~xnxse to

similarly between survivors (S) and non-survivors (Non-S). Precipitating Factors

S (n = 31)

Non-S(n ffi tO)

Infection/sepsis 12 08.7%) 3 (30%) Preeclampsia/HELLP 10 02.3%) 3 (30%) Preterm labor/tocolysis 4 (12.9%) 2 (20%) Aspiration 3 (9.7%) 1 00%) Obstetric hemorrhage 2 (6.5%) 1 (10%) The cause of death among the non-survivors included multisystem organ failure (5 patients), sepsis (4 patients), and disseminated intravascalar coagulation (1 patient). CONCLUSION: Pregnancy-related ARDS continues to be associated with a high maternal mortality rate although this appears to be lower than previously reported. The etiology for ARDS during pregnancy is most often due to an obstetric condition or complication which is not predictive of maternal outcome.

294

MASSIVE F E T O M A T E R N A L H E M O R R H A G E AND F E T A L D E A T H : IS I T P R E D I C T A B L E ? R Samadt MD.x D Mdler MD, R Setllage MD,x I Gvmzda,x R Paul MD, and T M Goodwin MD Unwersity of Southern Cahforma School of Medicine, Los Angeles. CA O B J E C T I V E : To report the incidence of massive fetomatemal hemorrhage (FIvlH) in fetal death and to test the hypothesis that tfus finding is less hkely to be present m cases of fetal death with nsk factors for FMH than in those without risk factors. S T U D Y D E S I G N : All cases of spontaneous fetal death greater than 500g were reviewed retrospectively from 1/1/90 to 12/31/94 Kleihauer-Betke (K-B) testing was ordered upon admission at the discretion of the attending physician Massive FMH was defined as greater than 1% fetal cells in the maternal circulation Risk factors for FIvlH included abruption, hypertensive disorders of pregnancy, trauma, uterine rupture and selected fetal/placental anomalies Women with risk factors were compared to those without risk factors m regard to the occurrence of massive FMH R E S U L T S : During the study period, 645 cases of spontaneous fetal death above 500 grams were identified The K-B test was performed in 319 (,49 5%) patients Massive FMH was identified m 15/319 (4 7%) eases It was present m 6/110 (5 5%) patients with risk factors for FMH and in 9/209 (4 3%) patients with no risk factors (P=0 86) C O N C L U S I O N : Masswe FMH Is an uncommon but not a rare finding m cases of fetal death, and its presence is not reliably predicted by clinical risk factors To our knowledge, our data represents the largest series of fetal deaths systematically stu&ed for FIvIH. Based on these findings, we recommend that K-B testm 8 be perfom~cd in all cases of fetal death regardless of supposed risk factors for FMH

PLACENTAL INSUTFICIENCY IS CHARAutI~c, IZED BY PLATELET A C T I V A T I O N I N $ E ' I ~ S A N D MOTHER. B.I. Trudinger, 7_ Wu*, ]. Song,* SAtowlandg'. The University of Sydney at Wasm~ead H m p i t a l - W e s t m e a d N S W 2145 AUSTRALIA OB~CI'IVE: Maternal endothehal cell injury and platelet

thrombim (0.~ to 0.25 ug/ml) was ~------"'~ RESUL~$c In the normal patients there w a s no evidence of platelet act~vatmn (<1% platelet population). In the study group platelet activation was present in mother ( 5.7 + Z9%) and fetus (5.0 + 2.9%) and an exaggerated response to thrombin ~ No diffe~nce w a s noted m the subgroup of mothers with I:a'eechmpsia (8 cases) in maternal (6.0%) or fetal (4.8%) results, and with fetal IUGR C O N C L L ~ I O N S : In placental i n s u f f i ~ platelet activation is present in both fetus and mother and ~ of the ~ syndrome of ~ l a m p s i a . T h r o n ~ n sermitivity is enhanced m both. It was present to the same extont in eerly and advanced dtsease suggesting a w a s an oarly fmture of the dismse t n ~ r .

296

IS THERE AN ANTIPHOSPHOLIPID ANTIBODY NEGATIVE ANTIPHOSPHOLIPID-LIKE SYNDROME? JR. ScotP, RNI. Sliver, DW. Branch. Dept OB/GYN, U of Utah, SLC, UT. OBJECTIVE: To ldenufy women who fulfill chmcal criteria for the antlphosphohptd syndrome (APS) but lack anticartholipin antibodies (aCL) and lupus anticoagulant (LA) and to characterize their medical and obstetrical outcomes STUDY DESIGN: The study group consisted of 12 patients who had experienced a thrombotic episode and at least one fetal death. All women tested negative for IgG and IgM aCL antibothes and LA. RESULTS: These patients had 19 separate thrombouc episodes including 11 DVTs, 6 pulmonary emboh, l CVA and 1 arterial thrombosis. 26% of these thrombotic episodes occurred during pregnancy. One woman also had autoimmune thrombocytopema, and several had severe preeclampsla or a growth retarded fetus in a prior pregnancy. Of 56 pregnancies, 16 (29%) were first trimester losses, 19 (34%) were fetal deaths, and 21 (37%) were hve births. Pregnancy outcomes and complications were similar to those of patients with APS and antlphosphohpld antthodles. CONCLUSIONS: This case series emphasizes that some patients with clinical features strongly suggestive of APS are negatwe for LA and aCL. These patients may have an as yet uncharacterized autmmmune syndrome and pose a difficult clinical dilemma. Their apparently high risk for thrombosis, as well as their fustory of poor fetal outcome, call for a prospective evaluation of anticoagulant therapy m these women.

391

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297 HEPARIN T H E R A P Y R E D U C E S T H E RISK O F F E T A L D E A T H AND IUGR AND IS E F F E C T I V E IN T H E T R E A T M E N T O F T H E ANTIPHOSPHOLIPID ANTIBODY S Y N D R O M E AND O F R E P E A T E D P R E G N A N C Y LOSSES. ~ , J. Hirshberg~, M.C Leiva x, R. Librizzi, J.E. Tolosa. Department of OB/GYN, Peunsylvama Hospital/Thomas Jefferson University, Philadelphia, PA and the Perinatology Research Branch, NICHD, Bethesda, MD. OB3ECTIVE: To determine the safety and efficacy of heparin treatment m paUents with antiphosphohpid antibody syndrome (APAS). STUDY DESIGN: A case-control design was used to study 134 pregnancies in 72 women diagnosed with APAS and repeated pregnancy losses Three groups were defined and each woman served as her historic control 1) Systemic Lupus Erythematosus and + antibodies (Anticardiolipin antibody, Lupus anticoagulant, Antinuclear antibodies) 6/72; 2) Poor obstetric history ( > 3 first trimester losses and/or abruptio placentae, IUGR, ohgohydrammos, placental mfarctious, IUFD) and + antibodies, 50/72, 3) Poor obstetric history alone, 16/72 IUFD was defined as intrauterine death after 12 weeks gestaUonal age (GA) Heparm wan started at 12,500 units by subcutaneous injection twice daily, adjusting the dose through a trough PTT > 40. 75 pregnancies were treated and 59 were not Concomitant use of asptrin occurred in 24% and of prednisone m 12% of the pregnancies Odds ratios (OR) and 95% confidence intervals (Cl) were calculated for pregnanctes progressing beyond 12 weeks GA RESULTS: Heparm treatment reduced the rate of fetal demise, IUGR and plaeontal infarction, OR and 95% CI' 0.02 (0.01, 0.09), p < 0.0001, 0.31 (.10, 94), p = O 0 1 9 and 38 (.16, 89), p = O 0 1 4 , respectively Stratified analysis indicated that neither aspirin nor prednisone treatment conferred any adthtional benefit. Thrombocytopema ( < 100,000) occurred in 8% of treated pregnanctes; one patient had an abdominal wall hematoma which required operatave drainage CONCLUSIONS: 1) Hepann treatment of the APAS and of women with repeated fetal losses ts effectwe by reducing fetal mortality and morbidity 2) This therapeutic modality appears to be safe during pregnancy

298

VERTEBRAL COMPRESSION FRACTURES IN PREGNANCIES COMPLICATED BY PROLONGED HEPARIN AND C O R T I C O S T E R O I D THERAPY. N. Shilletto S Granovsky-Cmsaru, T G Tenh, K Spttzer, D. Farine, C Laskin Dept OB/GYN, Mt Sinai Hosp, Dept of Med, The Toronto Hosp., Univ of Toronto, ON, CANADA. OBJECTIVE: To ussess the impact of a Instory of heparin, predmsone and aspn-m therapy, alone or in combination, on the incidence of osteoporotlc vertebral compression fractures in women with recurrent p r e ~ a n c y loss (RPL). STUDY DESIGN: In a retrospective analysis of 150 women evaluated at Mount Sinai Hospital for RPL, 101 patients wtth documented autoantibodles or pre-existing auto-unmune disease were placed on one of a variety of treatment protocols using low dose aspinn (ASA) 80 mg/day, predmsone 0 5 mg/kg/day and/or heparm 20,000 units s.q./day The patient records of those undergoing therapy were reviewed for obstetric outcome and for the Incidence of ostenporotic vertebral fractures RESULTS: In 101 patients undergoing therapy, 96 pregnancies reached the third trunestor. O f these, 2 (2 0%) were placed on heparm only, 2 (2 0%) on predmsone only, 18 (18.7°,6) on ASA alone, 13 (13.5%) on heparin and ASA, 53 (55.2%) on predmsone and ASA and 8 (8 3%) on all three agents Of these, 3 patients suffered vea~obral compression fractures, two of whom had prolonged therapy with one agent prior to wegmmcy ( one

prcdmsone, one hcparin ). The third had a 20 pack year smoking lustory. Seven of eight patients with triple agent therapy begun dmang pregnancy had neither fractures nor symptomatic ostenlx~otic disease. C O N C L U S I O N : Patients with longterm smgle agent heparin or comcesteroid therapy predating pregnancy are at markedly increased risk of vertebral fractures if heparin or corticusteroid thompy is added to their treatment regimen.

J a n u a D' 1996 A m J Obstet Gvneco]

299 MANAGEMENT OF IMMUNE THROMBOCYTOPENIA DURING PREGNANCY, BY MEANS OF FOETAL BLOOD SAMPLING. Barlot P__H.~, H Reman O, Arrazola J, Levaltier X, Herhcoviez M, Leporrier M, Muller G, Levy G, Umverslty Hospital Center, Caen, France OBJECTIVE: Obstetric management of Immune Thrombocytopenla (ITP) during pregnancy and its influence on neonatal outcome is controversial Our goal was to determine the form of dehvery for thrombocytopenlc women using a foetal blood sampling (FBS) technique. STUDY DESIGN: This is a prospective study approved by an ethical commntee, undertaken from May 1993 to May 1995 All women attempting delivery at the matermty chnlc of the University Hospital Center (C H.R U ) of Caen (6300 patients) had a platelet count of 36 weeks of gestaUon After exclusion of all other thrombocytopemc mechanisms (allo-lmmunologlc, infectious disease, Anttphosphohptdlc syndrome, preeclampsla, thrombocytopathic thrombocytopenla), we included in a FBS protocol, 20 patients featunng platetet counts Inferior to 100 Giga/I, including all cases of previously treated ITP, even with normal platelet counts Therapy of these patients included cortlcostermds and/or intravenous immunoglobulins FBS was performed between 38-40 weeks gestation and delivery induced wlthm 1 week RESULTS Of the 20 cases in this study, 8 cases were known as to be previously affected by the illness. AVERAGE PLATELET COUNT BEFORE DELIVERY AFTER DELIVERY Patlent~ 85 Giga/l (range 44-225) 202 Giga/l (range 74-2"6) Pattentr 90 Glga/l (range 56-150) 225 Gigrdl (range 20-313) No maternal or foetal comphcattons after FBS were evidenced

CONCLUSIONS: Current pregnancy care involves increasing diagnosis of maternal thrombocytopenia through systematic prenatal hsematologlc examinations Our knowledge of an increased Incidence of cerebral lesions In * vaginal deliveries of infants presenting a thrombocytopenla, has shown the preventive importance of a Cesarean Section, when plateiet counts are inferior to 50 Gtga/l Cordocentesis in high risk patients can be performed vathout any bleeding comphcattons. Further studies will be needed to establish the actual value, risks, and limRatmns of this approach in foetal medicine

300

~LITIC UR~H¢ 5T~ROJ~,ff]FIROJBOFI¢ THROJBOCITOPlffVI¢ P g ~ P ~ 1N PRB~/A¥CE.. J~W'/LNgOF ~ ~ , RS Eperman and BM Sibai. Department of Olztetric* and Cqnerology, Universityof Tennessee, Memphis. O~I~EF/;'~ Little information etim regarding hemdytic uremic syndrome (HUb')and thrombotic thrombecytopenic purpura (TIP) during pregnancy. Few cases of antepartum HUS have been published. We report the largest series of HUS/VrP, with emphasis on diagnoatc and management dilemmas dthis rare condition. S F t ~ F DEIICOI: Between 1988 and 1995, 9 women with either TIP (n =6) or HUS (n = 3) were evaluated. Clinical and laboratory findings, as well as maternal and neonatal outcomes, were studied. The patients were further categorized into two groups: Group I developed the syndrome mound delivery or immediately postpartum (n =5); Group II were known to have the syndrome before pregnancy (n = 4). ih=-,M.gT$.• In Group I, 4 patients were delivered at 27-39 weeks with a diagnosis of severe preeclampsia. Subsequently, they had worsening clinical and laboratory findings that were consistent with TIP postpartum (day 1-11); the remaining patient had an elective termination of pregnancy at 13 weeks, was subsequently madmitted on postoperative day 1 for endometrith, and found to have severe renal failure. She had clinical and laboratory findings comistent with HUS on postoperative day 2; the diagn~is was confirmed by renal biopsy. Among the 4 ongoing pregnandes, them were 3 hve births (27, 33, and 37 weeks) and 1 stillbirth (39 weeks). All 5 women required repeated courses of fresh frozen plasma (FFP), and 3 required plasmapheresis (PHR).All 4 patients in Group II were in remission prior to pregnancy. The 2 pattents with pre-existing HUS required delivery at 15 and 27 weeks' gestation because of severe deterioration in their dinical condition. The 2 remaining patients with pre.existing TIP had exacerbation of their disease requiring delivery at 17 weeks because of fetal demise and at 33 weeks because of recurrent hte decelerations. All 4 women required repeated courses of FFP, and 3 required PHIL Mortality or major morbidity was signilicandy higher in Group I than in Group II (5/5 ¢s. I/4, p = 0.048). GROUPI GRO~ Platelet nadir x 103//~L(range) 28.8 (2--88) 22 (13--42) Mean LDH (IU./L)(range) 2433 (1455--4195) 1189 (396-1800) Renal iusuf/iciency 5/5 3/4 Mean creatinine (tag/d0 (range) 6.88 (1.8-13.9) 4.3 (1.9-8.5) Residual neurologic deficit 1/5 0/4 Chronic dialysis 2/5 1/4 Death 215 014 CONCLUSION: Hus/rTP that develops de novo in pregnancy is associated with high maternal and fetal morbidity and mortality. Despite intensive monitoring in those with pre-existing disease, renal complications during pregnancy nevertheless occurred and fetal outcome was poor; long-term maternal sequelae, however, were less severe.

Volume 174, N u m b e r 1, Part 2 Am.l Obstet Gynecol

SPO Abstracts

301 CHOLESTASIS OF PREGNANCY: PERINATAL OUTCOME

303 PROSPECTIVE LONGITUDINAL STUDY USING STABLE

302 OUTCOMES IN PREGNANCIES COMPLICATED BY DIABETES

304 INCREASED INCIDENCE OF LARGE FOR GESTATIONAL AGE

ASSOCIATED WITH EXPECTANT MANAGEMENT O Alsulvman. J Ouzounian, M A Castro, R Paul, T M Goodwm Univ. of Southem California School of Medicine, Los Angeles, CA OBJECTIVE: To compare the pregnancy outcome of pottents with cholestasis of pregnancy managed expectantly with antepartum tostmg to other patients followad with a similar testing scheme. STUDY DESIGN: All cases of cholestasis of pregnancy followed with antepartum testing at our institutton from 1988-1994 were reviewed. Their pregnancy outcomes were compared to controls (matched for age and parity) followed with the same testing scheme for a history of prior stdlbirth. Both groups had a weekly nonstress test and amniotic fired assessment untd spontaneous labor or dehvery for standard obstetrical indications. R E S U L T S : The two groups did not differ with respect to mean gestational age at delivery (38.5 vs. 38.8 weeks) or mean birth wmght /3239 vs. 3256 ~ms). Other results are summartzad below. Cholestasis Control P ~n=74) (n=74 / Spontaneous preterm 12 (16%) 7 (9.5%) 0 2 birth (< 37 weeks) Meconium stained 31 (42%) 8 (11%) <0.001 amniotic fluid Mecomum aspiration 3 (4%) 0 0.08 Fetal death 2 (2.7%) 0 0.15 The two cases of fetal death occurred at 36-37 weeks of gastatmn within 5 days of normal antepartum testing in the absence of other pregnancy complications. Thick meconium and appropriate birth weight were noted in both cases. C O N C L U S I O N : Cholestasis of pregnancy is associated with increased incidence of meconium passage at delivery and mecomum aspiratmn syndrome. There is a trend toward increased mcidance of fetal death not predicted by conventional fetal surveillance.

(CLASS B TO FR) VERSUS NON-DIABETIC CONTROLS. E. Sivan=, C. Homl~, E.A. Reece, Department of OB/GYN & RS, Temple Univ Sch of Med, Philadelphia, PA. OBJECTIVE: The ~ of the current study was to evaluate the impact of contemporary diabetes m.n%oement on the outcome of pregnancies complicated by insulin-dependent diabetes meilitus (IDDM). STUDY DESIGN: The study population consisted of two hundred and eighty-eight (288) women with IDDM and one hundred and fifty (150) healthy controls (Group 1). Diabetic womm were grouped according to the presence (Group 2; n-103) or abseage (Group 3; n-185) of diabetic vaseulopathy. Data were collected regarding diabetes mauagemeait, level of glycomic control, and fetal and maternal outcomes. RESULTS: A significant difference was found betwom the combined diabetes groups (Group 2 and 3) and healthy controls in all materual-fetal outcomes examined, except SGA and stillbirth. However, there was no significant differe=~cebetwom the two diabetes groups in terms of preterm labor, polyhych-amnios, welonephritis, or growth aberrations. Acute hyper'ten~ve complications and the rate of malformations were significantly higher in women with vssculupathy: 51.6% vs 32.9 (p <0.05), and 6.8% vs 1.6% (p <0.05), respectively. A number of peripartum complicatious were significantly higher in IDDM women who were poorly exmtrolled vs. ~ controlled during the third trimester: preterm labor - 30.8% vs 11.4%; polyhy&anmios - 17.3 vs 5.1%; and macrosomia - 51.9 vs 33.0%, respectively; p <0.05. CONCLUSIONS: Women with diabetes can be counseled to expect favorable pregnancy outcomes, although the Incldence of maternal and fetal complications are Increased above the general population. Furthermore, with the exception of hypertemive disorders and malformatinns, outcomes In IDDMs with vmm]olmthy are comparable to diabetic women withmtI mlerovaseular diseMe.

393

ISOTOPES IN PREGNANCY TO ASSESS CHANGES IN INSULIN SENSITIVITY IN OBESE INSULIN REQUIRING DIABETIC WOMEN. E. Sivan', C. Hcmkoz, X. ~ = , G. Boden=, E.A. Reece. Depts. of OB/GYN & GCRC, Temple Univ Sch of Med, Phils., PA. OBJECTIVE: The purpose of the current study was to longitudinally quantify for the first time, insulin sensitivity In obese pregnant women with diabetes mellitus as competed to non-diabetic controls. STUDY DESIGN: Pregnant women (n=10) were evaluated using 4-hour hyperinsulinemic-euglycemic clamp studies at 16-27 and 32-38 weeks' gestation. Body comtx~tiou was estimated by s]dnfold anthropometw and dilution deuterium methoeL Basal endogenous glucose production was estimated with a primed constant infu~on of 6,6-2 l-l=glucose. Insulin sensitivity was determined by the glucose infusiou rate needed to maintain plasma glucose constant at a level of 85 mg/dL RESULTS: Blood glucose levels wete m ~ at 83.3,3.51 mg/dL for the eoutrol group and 85.4±2.8 mg/dL for the diabetic group during the 4-hour clamp study. The glucose infusion rate (GIR) required to maintain englycemia was significantly lower In the diabetes group in coml~'isou to healthy controls during both the second (2.59~0.59 vs. 5.46~ 1.8 mg/Kg/min; p <0.05) and third (2.45i0.54 vs. 4.95±1.69 mg/Kg/min; p <0.05) trimesters. However, the GIR did not decrease between the second and third trimesters in either the diabetic or control groups. The mean body mass index for the study group was 34.1 i 8.9 kg/m2 and mean percentage body fat was 39.9 ± 6.2%. CONCLUSIONS: Although insulin sensitivity is reduced In obese IDDM women during pregnancy, we observed minimul change In GIR between the second and third trimesters In o u r study population. We postulate that insulin re.~wance is already well estaly lisbed in obese women by the second trimester, and therefore little change in insulin sensitivity was observed with advancing gestation.

INFANTS NOT ATTRIBUTABLE TO GESTATIONAL DIABETES. M._RR Leonardl x, SF Bottoms Department of Obstetrics & Gynecology, Wayne State University, Hutzel Hospital, Detroit, Michigan OBJECTIVE: To determine the If maternal obesity or gestational diabetes is responmble for increased frequencies of large for gestatlonal age (LGA) and macrosomic infants STUDY DESIGN: Gestatlonal diabetes was diagnosed by National Diabetes Data Group criteria In 117 gravld women. They were compared to 3090 control patients without gestational diabetes Women with pregestatlonal diabetes and multiple gestations were excluded LGA and macresomJa were defined as dependant variables Macrosomla was defined as a birthwelght > 4000g. Prepregnancy body mass index (BMI) was used as a measure of maternal obesity Stepwise logistic regression was used to identify the influence of multiple antenatal variables as predictors of LGA and macrosomla. RESULTS: Women with gestatlonal diabetes tended to be older, heavier, and more parous. Whde GDM was predictive for LGA (p=0.001), the best predictor of an LGA infant in the total population was BMI (p< 0001) Once maternal obesity was accounted for (p < 0 0001 ), GDM did not significantly affect the incidence of macrosomla In gravidas whose prepregnancy weight was less than 140 pounds (n=1596), neither BMI or GDM predicted LGA as an outcome (p >0.4) CONCLUSIONS: It appears that maternal obesity, rather than GDM itself, is responsible for the increased frequencies of LGA and macrocomlc infants =n pregnancies complicated by GDM. When interpreting these results, it is important to consider that most patients with GDM received treatment, potentially altering outcome. Further study Is needed to determine if untreated GDM alters the frequencies of these outcomes.

394

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J a n u a r y 1996 Am J Obstet Gynecol

PREGNANCY OUTCOME IN WOMEN WITH TYPE II DIABETES MELLITUS. BM. Rosenn, M. Miodovnik, J.C. Khoury ", T.A. Siddiqi. Dept. Ob/Gyn, Univ. of Cinti., Cincinnati OH OBJECTIVE: There is a paucity of data on outcome of pregnancy in women with Type II diabetes (NIDDM). In these pregnant women, duration and severity of disease is generally assumed to be less than in women with Type I dtabetes (IDDM). The purpose of this study was to test the hypothesis that women with NIDDM have a better outcome of pregnancy than women with IDDM. STUDY DESIGN: Women with diabetes were enrolled in our Diabetes in Pregnancy Program between 1978-1995, and all data were compiled in a computerized database Classification of diabetes was based on clinical and laboratory characteristics Chi-square and t test were used as appropriate to analyze outcomes of interest, p<.05 was considered significant. RESULTS: There were 450 pregnancies in IDDM women and 84 pregnancies in NIDDM women Characteristics of subjects were as follows

Age Race (White-Black) Years of diabetes Age of disease onset Microvascular disease Prepregnancy wt (Lbs)

IDDM(n=450)

NIDDM(n=84)

256_5 1 84%-15% 12.8-6.6 12.7-6.5 27% 135±24

29.1__.55 66%-34% 5.1 .*.4.8 23.4__.6.4 7% 204±52

307

PATIENTSWITH ELEVATEDGLUCOSESCREENINGTESTS ARE AT HIGHER RISK FOR CESAREAN SECTION, MACROSOMIAAND BIRTH TRAUMA DESPITEA NORMAL3 HOURGLUCOSETOLERANCETEST. Carol A. Malor. MD. Bruce F. Cohen, MD and Tricia Reimbold, RNx. Department of Obstetrics and Gynecology. University of California, Irvine Medical Center, Orange, CA. OBJECTIVE: Patients with an elevated 1 hour glucose screening test (GST) followed by a normal 3 hour glucose tolerance tests (Gl-r) are usually managed as if they had normal glucose tolerance. The purpose of this study is to compare the birthweights, incidence of macrosomla, rates of cesarean section (C/S) for cephalopelvic disproportion (CPD) and rates of shoulder dystcoia in patients with elevated GST and normal GTT to normal controls (normal GST). STUDY DESIGN: All patients with an elevated GST and a normal GTT (n=130) were identified by reviewing laboratory records. A control group of patients with normal glucose screening (n=130) was selected from patients delivering during the same t~me period. Charts were reviewed for demographic data and outcome variables including birthweight, route of delivery and birth trauma. The glucose screening test (GST) consisted of a 50 gm oral glucose load followed by a 1 hour plasma glucose determination. A value of > 140 rag/all was considered abnormal and indicated the need for a 3 hour 100 gm oral glucose tolerance test (GTr). An abnormal GTI required that two or more of the tollow=ng glucose values be met or exceeded: fashng 105 mg/dl; 1 hour 190 mg/dl; 2 hour 165 mg/dl; 3 hour 146 rag/all. Macrosomia was defined as a birthwelght > 4000gin. RESULTS:Those patients with an elevated GST and normal GI-F, when compared to those with normal glucose screen=ng, had a higher birthweight (3692+ 537gm vs 3273:t502gm, p = 0 001), a higher rate of macrosomia (28/130 vs. 11/130; OR 2.97 CI 1.34-6.71; p = 0.005), a higher rate of C/S for CPD (18/130 vs. 8/130; OR 2.65 CI 1 03-6.96; p= 0.030), and a higher rate of shoulder dystocia (9/130 vs. 2/130; OR 4.76 CI 0.93-32 6; p= 0 04 ) There were no differences between the groups with regards to maternal age, parity, race, or gestational age at delivery CONCLUSION: Patients with elevated 1 hour glucose screening tests are at higher risk than controls for C/S for CPD, macrosomia, and shoulder dystocia despite normal 3 hour glucose tolerance testing.

308

EARLYSCREENINGFOR GESTATIONALDIABETES:IS THERE A ROLE? Michele A. Gerber, MDx MPH, Carol A. Maior. MD and Bruce F. Cohen, MD. Dept. of Obstetrics and Gynecology, University of California, Irvine Medical Center, Orange, CA. OBJECTIVE:The timing of diabetic screening during pregnancy in patients at high risk for development of gestational diabetes (GDM) is controversial. Many practitioners routinely screen patients with a previous history of GDM, fetal macrosomia, an unexplained stillbirth or glycosuria at the first prenatal visit. The objective of this study is to determine if there is benefit to early diabetic screening in these patients at high nsk for gestational diabetes. STUDY DESIGN: We reviewed the medical records of women receiving prenatal care at our Public Health Department over a 1 year period. Inclusion criteria for the study included: 1) First prenatal vtsit pnor to 20 weeks, 2) Participation in the Health Department's protocol of glucose screening at the first prenatal visit and again at 2428 weeks, 3) a history of prior GDM, fetal macrosomia, previous stillbirth or persistent glycosuna. The glucose screening test (GST) consisted of a 50 grn' oral glucose load followed by a 1 hour plasma glucose determination. A value of -> 140 mg/dl was considered abnormal and indicated the need for a 3 hour 100 gm oral glucose tolerance test (GTT). An abnormal GTI or a dehn=tive dtagnosis of GDM required that two or more of the following glucose values be met or exceeded: fasting 105 mg/d[; 1 hour 190 mg/dl; 2 hour 165 mg/dl, 3 hour 145 mg/dl. RESULTS: 149 patients satisfied the inclusion cnteria for the study. 14/149 (9.4%) had an abnormal GST prior to 20 weeks and only 1 of these 14 patients (7.1%) had an abnormal GTr and was subsequently treated for GDM. At 24-28 weeks, repeat screening revealed that 21 out of 149 (14%) patients had an abnormal GST and that 5 of these 21 patients had an abnormal GTT. Early glucose screening detected 1 out of 5 of these cases for a sensitivity of 20%. The total cost of the eady diabetic screening protocol was $9428. The cost of performing traditional glucose screen=ng at 24-28 weeks would have been $5274. Therefore, the cost of early identification of 1 case of GDM was $4154. CONCLUSION: Even in this population who was at high risk for developing GDM, the incidence of GDM was extremely low and the sensitivity of early screening was poor. Early GDM screening was not cost effective Lnour population

p <.0001 < 0001 <.0001 <.0001 <.0001 < 0001

Glucose control was slightly better in women with NIDDM. However, there were no dLfferences between groups with respect to rates of preeclampsia, preterm labor or delivery, weight gain, cesarean delivery, LGA, macrosomia, or newborn hyperbilirubmemia, but infants of IDDM women had a higher rate of hypoglycemia and RDS. CONCLUSIONS: Although diabetic disease appears to be less severe in pregnant women with NIDDM, most comphcations of pregnancy are as common as tn women wLth IDDM.

306

PLATELET ACTIVATION IN DIABETIC PREGNANCY J Star. K Rosane, M W Carpenter, J Ferland', V Ray', G DiLeone x, L Larson', A Kestin '. Brown University, Depts of Ob/Gyn & Medicine, Women and Infants/Rhode Island Hospital, Providence, Rhode Island OBJECTIVE: To determine ffthe observed third trimester decrease in platelet activation, as measured by platelet glycoprotem (GP) membrane receptor binding, is amplified by maternal dmbetes STUDY DESIGN. Fwe cc of whole blood were obtained by atraumaUc venipuncture from 20 third trimester pregnant subjects (8 with diabetes without evidence of vascular disease (4 Type I, 4 Type II), and 12 with normal glncose tolerance) and 13 nonpregnantcontrols The platelets ware exposed to thrombm at maximal and minimal doses in whole blood, in parallel with a buffer control. The samples were fixed and incubated with an indicator antibody (Ab) and three test antibodies: $12 (= granule/P-selectin), 7E3 (fibrinogerdGPllb/IIIa) and 6Dl (yon Wfllebrand factor/GPIb). Using a flow cytometric technique, mean fluorescence intensity was determined for 5000 platelets per sample. RESULTS Diabetic subjects showed significantly increased actwatlon by S 12 binding prmr to stimulation, followed by decreased activation at minimal thrombin doses, compared with nondmbetic subjects (p<.05). 7E3 binding was significantly decreased in all pregnant subjects tested at maximal thrombm doses compared to nonpregnant controls, as previously reported (data not shown) No significant differences were noted with 6DI. Mean fluorescence intensity with S12 (± SD) Thrombin(U/ml/ Diabetic subjects Nondiabetlc subiccts 0 3.9 (±6.4) -1.4 (±3) 0 08 35 4 (±24.4) 65.8 (±3 l) CONCLUSIONS' Third trimester subjects with diabetes show evidence of increased acttvation m resting platelets, with subsequently decreased sensitw~ty to agomst stimulation Fthrinogen receptor binding is decreased in diabetic and nondmbetlc subjects compared with nonpregnant controls. These findings suggest a chronic activation state in platelets during late pregnancy, which is accelerated by maternal diabetes

SPO Abstracts

Volume 174, N u m b e l 1, Part 2 A m J Obstet Gynecol

309

LOWERING THE THRESHOLD FOR THE DIAGNOSIS OF GESTATIONAL DIABETES. O.A. Rust, J.A. Bofill, M. Andrewx, T. Kincadex, T. Stubbs, E. Millerx, J .C. Morrisen. Depts. Ob/Gyn and Preventive Mud., Univ. of Mississippi, Jackson, MS and Dept. Ob/Gyn Carolinas Mud. Ctr., Charlotte, NC. OBJECTIVE: To determine if lowering the threshold for the diagnosis of gnstatioual diabetes mellitus (GDM) will select a population at higher risk for adverse perinatel outcome. STUDY DESIGN: In this retrospective study, 434 patients with an abnormal 50-gin glucose screen underwent n standardized 3-hour oral glucose tolerance test (GTT) and were stratified into 4 groups: group 1 (n = 102) had the diagnosis of GDM by standard criteria, group 2 (n ffi 71 ) would have had GDM if the threshold had been lowered (fasting > 95, l-hour > 172, 2-hr > 151, 3-hr > 130). Group 3 (n ffi 78) had one abnormal value on GTr. Group 4 (n = 183) had a normal G"IW. Multiple variables assessing periantal outcome were analyzed. RESULTS: Demographics, risk factors for abnormal testing, route of delivery, and antenatal complications were similar for all groups except for age. Additional findings included:

311

CAN WE IMPROVE SCREENING FOR GESTATIONAL DIABETES? M. SermeP, D. NayloP, D. Farine, K. Ritchie, D. Gara~, H. Cohen. Univ. of Toronto, ON, Canada Objective: To compare screening strategies for detection of gestational diabetes (GDM). Study Design: In a prospective analytic cohort study 3,836 patients were each assessed with random plasma glucose, a 50 8m Glucose Challenge Test (GCT), and a 100 gm Oral Glucose Tolerance Test (OGTI). Clinical and historical risk factore were recorded. Results: In a multivariate analysis, age, race, body mass index, and an abnormal obstetrical history were all significantly and independently associated with altered risk of GDM. For example, the odds ratio (OR) were: 1.0, 1.4 and 7.4 for ages _<30,31-34, and >35 respectively. The OR for BMI of > 25.1 was 3 overall with blacks (ORffil.8) and orientals (ORffi5.8) at increased risk. Receiver operating characteristic (ROC) curve analysis showed random plasma glucose was unhelpful, but screening efficiency was optimized by combmiog the above risk factors with the GCT. Areas under the ROC curve are as follows: standard GCT, 0.791; GCT adjusted for time since last meal as previously reported from this cohort, 0.804; and risk factors plus adjusted GCT, 0.873. A scoring system was derived based on the clinical risk factors. Rising scores led to higher incidences of GDM (p < 0.0001 for trend): among patients scoring 0-2, 1.6% had GDM versus 12.8% among those scoring 7. Conclusions: Screening for GDM can be improved by assessing risk factors thus providing a rationale for altering screening strategies ie no testing,GCT or OGTr without GCT. Furthermore, combining risk factors with the GCT results will improve the risk assessment for individual patients.

312

CESAREAN DELIVERY IN RELATION TO BIRTHWEIGHT AND GESTATIONAL GLUCOSETOLERANCE: PATHOPHYSIOLOGYOR LABELING BIAS? M. SermeP, D. Naylo~, D. Farine, K. Ritchie, D. Gate~, H. Cohen. Dept. Ob/Gyn and ICES, Univ. of Toronto, Toronto Ont, Canada Objective: To compare the birth outcomes of women with unrecognized gestatloual diabetes (GDM), treated GDM, and normoglycemia, with particular reference to birthweight and cesarean section. Study Design: A prospective analytic cohort study of 3,778 gravides aged 24 years and over, with post hoc case-control comparisons. Subjects underwent a 3-hour 100 8m oral glucose tolerance test at 28 weeks gestation, regmdlass of screening test results. Those meeting the National Diabetes Data Group (NDDG) criteria for GDM (n - 143) received the usual care, consisting of plasma glucose monitoring, dietary modtficatlon, and insulin where indicated. Physicians and patients were blinded to glucose results for all other subjects, including 115 women wtth unrecognized GDM by the broader Caq~nter and Coustan criteria. Crude and adjusted rates of cesarean section and neonatal macrosomia (4,000 gins) formed the main outcomes of interest. Results: Compared to normoglycemic controls, patients with unrecognized GDM had increased rates of macrosomm (28.7% vs 13.7"/,, p < 0.001) and cesarean section (29.6'/, vs 20.2%, p ffi 0.016). Usual care of NDDG diabetes normahzed b~rthweights, but the mcraased rate of cesarean section among treated patients compared to controls permsted despite adjustment for maternal age, race, parity, body mass index, pre-eclampaia, and gestational age (adjusted odds ratio: 2.1, 95% confidence interval: 1.39-3.22). Other maternal-fetal outcomes were similar between treated and untreated diabetic gravides. Conclusion: Untreated GDM women (based on the broader Carpenter and Coustan criteria) had an increased risk of ~ i a and surgical delivery. Detection and treatmentofgestatlonal diabetes normalized birthweights, but did not otherwise improve maternal-fetal outcomes compared to women with unrecognized diabetes. Specifically, rates of cesarean section remained inexplicably high. Recognition of GDM may lead to n lower threshold for surgical delivery that mittgates the potential benefits of ~atment.

Group (mean) Variable

I

2

3

4

P

Age (yr) 25.1 25.7 23.7 22.7 0.0001 Prepreg BMI 26.6 26.6 25.5 24.8 0.011" 0cg/m2) Pr©g wt gain (Ib) 36.8 36.4 37.9 35.4 NS Birth wt (gin) 3277.3 3284.1 3345.4 3314.1 NS Nee hypogly (%) 27.5 5.6 10.6 10.9 0.0009 *NS after Bonferroni correction All other maternal and neonatal outcome variables were similar for the 4 groups, CONCLUSIONS: Our results indicate that lowering the absolute GTT threshold or using one abnormal value of GTT would over-diagnose GDM without improving perinatal outcome.

310

H O W PREDICTIVE IS THE DEGREE OF ABNORMALITY OF THE G L U C O L A TEST FOR G E S T A T I O N A L DIABETES ? T SvendsenX, A Abuhamad, M de Vecmna, J Morgan x, A. T Evans Dept Ob/Gyn, Eastern Virgima Medical School, Norfolk, VA OBJECTIVE: To determine how well the degree of abnonnahty on a 1 hour glucola test predicts the dmgnosis of Gestatmnal Dmbetes [GDM] STUDY DESIGN: Over a 7 year permd [1987-93], 2611 pregnant pahents were screened for GDM using a 1 hour [50gin] glucola test. Patients were usually screened at 24-29 weeks Those with risk factors for GDM were screened at their ftrst prenatal vlstt Pahents wRh a I hour plasma glucose (1 hr PG) > 140 mg/dl had 3 hours [100gm] OGTTs GDM was diagnosed ff >_ 2 OGTT values w e r e . abnormal (>105/190/165/145 mg/dl) Senstttvtty, specificity and predictive values at vanous lhr PG value cutoffs were calculated RESULTS: Mean maternal age was 27 2 + 5 8 yrs [range 14-44] and gestatmnal age at screemng was 24 3 + 7 0 wks [range 5-37] 389/2611 had an abnormal lhr PG [15%] 45/389 were lost to followup, 344/389 [88%] had 3hr OGTFs Stahstlcal parameters for varmus 1 hr PG cutoffs are presented below. 17/344 [5%] had at least one value > 250 on their 3hr OGTT, of these, 8/17 [47%] had a lhr PG > 220 mg/dl and 6/17 [35%] had a normal FBS No slgmficunt antepastum comphcatmns occurred m pattents w~th at least one value >250 on OGTT l h r P G mg/dl [ Sensitivity Specificity Pns P Val Neg P Vnl I >140 [ 99 3 0 39 0 0 >180 [ 37 0 90.0 70 4 69 0 >190 I 27 4 95 7 80 4 67 2 >200 20 7 97 6 84 8 65 7 >220 96 99 5 92 9 63 1 CONCLUSIONS: A I hr PG > 190 mg/dl is commonly considered dmgnostic of GDM In our populatmn, 20 % ofpattents wath l hr PG > 190 mg/dl had a normal OGT1~ A lhr PG cut off>220 mg/dl appears to be more predtcttve of GDM in our population

395

396

313

SPO A b s t r a c t s

lanuary 1996 Am J Obstet Gynecol

DELAYED PULMONARY MATURATION IS ASSOCIATED WITH POOR GLUCOSECONTROL IN DIABETIC PREGNANCIES. J Piper, O. Langer, Dept Ob/Gyn, UTHSC, San Antomo, TX OBJECTIVE: Pregnancies complicated by diabetes have been shown to have delayed fetal pulmonary maturation as measured by both the delayed appearance of biochemical indicators of pulmonary matunty (phosphahdyl glycerol [PG] and lecithin/sphingomyehn ratio [US]) and the occurrence of hyahne membrane disease (HMD) even m term gestat;ons We sought to test the hypothesis that maternal glucose control influences the occurrence rate of delayed fetal pulmonary maturation METHODS: ConsecuUve dmbetlc pregnancies with documentation of maternal glycemic control and ammottc fluid analysis for PG and L/S were analyzed Maternal glycemTccontrol was defined as good if the mean blood glucose (MBG) was 5105 mg/dL and poor if >105 mg/dL Amnlotlc fluid PG was considered mature if present HMD was defined by well established criteria. RESULTS: 621 diabetic pregnancies were analyzed (261 good control, 360 poor control ) Overall PG was absent m 21% of good control vs. 31% of poor control pregnancies (o<0.005) When stratified by gestahonal age, the nsk of an immature PG was significantly higher in the poor control group % Immature PG Overall O.R. 1 <34

34-36 9

37-379

38-389

~39 Wks

Poor Ctrl

92%

58%

34%

18%

17%

Good Ctrl

92%

36%

23%

13%

8%

n 24 90 172 213 122 At 36-37 9 weeks, the control pregnancies had s~gnificantlyh=gherrates of immature PG [37% vs 22%, O R 2 04 (1 1-3 9)] All cases of HMD were m poor control pregnancies <37 weeks (3/69, 4 3%) There were no cases of HMD beyond 37 weeks gestation CONCLUSION: Abnormal maternal glucose levels are associated wdh delayed appearance of PG m dtabetlc pregnancies, however, beyond 37 weeks gestat=on no significant neonatal pulmonary d=sease occurred.

314 GLYCEMIC

CONTROL 1N PREGESTATIONAL DIABETICS INFLUENCES THE INCIDENCE OF PREECLAMPSIA A Mentskis', J. Kuboshige*,C. R. Brink.manllI'. MT Cabalum, Dept ofOb/Gyn, Harbor-UCLA Medical Center, Torrance, CA. OBJECTIVE: To assess whether glycemic control in the second and third trimesters of preganncy influences the incidence of preeclamsia. STUDY DESIGN Medical records of 108 pregestational diabetics (PGDM) seen from 1982-1994 were reviewed Second and third trimester fasting (FBS) and two hour postprandial (2pp) blood sugars were evaluated The diagnosis of preeclampsia (P/E) was made after 20 weeks based on blood pressures (BP) >140/90 and urine protein >1+ on a catheterized specimen Good glycemic control was presumed to be present if the FBS <105 mg/dl and the 2pp<120 mg/dl Renal/vascalardisease was defined as the presence of >300 mg of protein in a 24hour urine specimen, or crentinine clearance <120 ml/min, or evidence of diabetic retlnopathy, or history of chronic hypertension based on BP>140/90 before 20 weeks The association between glycemic control and preeclampsia was evaluated by chi-square and Fisher's exact analysts. RESULTS" The incidence of P/E m the 108 patients with PGDM was 20.6% Giycemic control during the second (23 9% vs 21 1%, p=0.45) or third trimester (18 1% vs 37 5°/*, p=0.33) did not influence the incidence of P/E These patients were stratified in two groups: (1) Group A (N=58) with evidence of renal/vascular disease, and (2) Group B (N=50) without evidence of renal/vascular involvement In Group A, 81ycemlccontrol m either the second(42.1% vs 23 3 %, p=0 33) or third tnmestem (42.8% vs 24 A%, 13=015) did not influence the incidence of P/E In Group B, 81ucosecontrol m either the second (12.5% vs 10.5%,p=0 99) or third trimesters (23.3% vs 10 l%,p=0 09) was not associated with an increase in the incidence of P/E However. when the FBS and 2pp were analysed independently, patients in Group A had a significantly higher incidence of P/E if the third trimester 2pp>120 mg/dl (53 3% vs 22 2.p<0 05) Addltlonallly, patients in Group B with FBS>105 mg/dl during the third tnmester had a slgmficantly higher incidenceof preeclampsla. (50% vs 4 4%,p<0.005). CONCLUSION' (1) Glycemlc control during the second and third trimesters does not influence the incidence of P/E in PGDM with and without evidence of vasculopathy (2) There is an association between third tnmester mean FBS and the occurrenceof P/E in PGDM without vascular disease, and third trimester mean 2pp sugars m PGDM patients with vaseulopathy.

315 3-YEAR E X P E R I E N C E W I T H INSULIN P U M P T H E R A P Y DURING P R E G N A N C Y . R. Silverman R. Artal. Dwision of Maternal-Fetal Medicine, SUNY Health Science Center, Syracuse, NY O B J E C T I V E : To determine whether therapy with constant subcutaneous insulin infusion pump throughout pregnancy results in less daily capillary glucose variability. STUDY DESIGN: Eighteen pregnant patients (White's Classification Class B through R) that were placed on insulin pumps during their three trimesters of pregnancy were compared to 18 diabetic controls matched for age, race, gravida, duration of diabetes and compliance to care. Premeal and hs capillary glucose were averaged per week of gestation and compared across both groups. RESULTS: In the first trimester, predinner/hs glucose were lower for pump versus control patients (118 versus 154 mg/dl, 113 versus 146 mg/dl, p <0.05). In the second trimester, fasting and hs capillary glucose were lower for pump versus control patients (110 versus 143 mg/dl and 125 versus 152 mg/dl, p <0 05). In the third trimester, fasting capillary glucose were lower in pump versus control patients (109 versus 125 mg/dl, p <0.05). Averaging all trimesters, the fasting, predinner and hs capillary glucose were lower for the pump versus control patients (120 versus 132, 124 versus 135 and 121 versus 144 mg/dl, p <0.05). All other values were nonsignificant between insulin pump and control patients. The mean HbAIC, was lower in the second and third trimesters for pump patients (5.0 versus 6.6, and 4.6 versus 6.0, p <0.05). CONCLUSION: Use of constant subcutaneous insulin infusion pumps results in lower capillary daily glucose variability as reflected by: (1) Lower mean capillary glucose (2) Lower mean HbA1C during the second and third trimesters.

316 RECURRENCE OF GESTATIONAL DIABETES MELLITUS: IDENTIFICATION OF RISK FACTORS. CY Strong, L. Guinermo',J. Kuboshign~, T. Cabalum. Dept ofOb/Gyn. Harbor-UCLAMedical Center, Torrance, CA Objective: To evaluate the influence of certain maternal and neonatal factors on the recurrence of gnatatioual diabetes (GDM). Study Design: A study was conducted on 164 predominantly Hispanic patients whose index pregnancy was complicated by GDM and whose subsequent consecutive pregnancy was nmnaged at our institution between January 1988 and December 1992. The diagnosis of GDM was based on the criteria recommended by the National Diabetes Data Group using a 100 g oral glucose tolerance test. R~ults: One hundred eleven (68%) of the 164 women had recurrence of GDM. Fifty-threo (32%) did not demonstrate recurrence in their subsequent pregnancy. Patients with recurrence had GDM diagnosed earlier (30.3 vs 32.5 wenks, p=0.03)), frequently required insulin (25% vs 8%, p = <0.05) and had more hospital admissions (32% vs 10%, p<0.05) in their index pregnancy compared to women who did not have recurrence of GDM. Women who had recurrence had elevated mean third trimester plasma glucose values: fasting 87.6 vs 83 mg/dl, (p=O.O09) and 2-hour postprandial 109.7 vs 102.2 mg/dl, (p=O.008). Neonates of patients with recurrence were heavier (3656 vs 3373 gin, p=0.004) and had increased incidence of macrosomia (26% vs 10%, p<0.05). No significant differences were observed in maternal age, prepregnancy body mass index, Hgb AI C, second trimester plasma glucose levels, incidence of shoulder dystocia, and apgar scores between the two groups of women. Conclusion: Patients with history of GDM have significant risk of recurrence in their subsequent pregnancy. The risk for recurrence in women is increased if GDM is diagnosed earlier, they require insulin, have elevated third trimester plasma glucose level, and deliver macrosomlc infants in their index pregnancy.