ORAL PLENARY SESSION II (Fellows Plenary) Friday, February 9, 2001, 8:00 am – 10:00 am

ORAL PLENARY S E S S I O N II (Fellows Plenary) Friday, February 9, 2001 7:45 a m - 10:00 am

Moderators:

Steven G. Gabbe, MD ThomasJ. Garite, MD

Judges:

Norman F. Gant, MD Valerie M. Parisi, MD Kathryn L. Reed, MD

Hilton Pavilion Abstract Numbers 27-34

$14 SMFM Abstracts 0027

,tan t m r y 2001 Am J Obstet Gynecol

OXYTOCIN REGIMENS FOR THE PREVENTION OF UTERINE ATONY AT CESAREAN DELIVERY Mary B. M u n n I, J o l m Owen'-', J o h n Hauth3; tUniversity of Alabama at Birmingham, Maternal Fetal Medicine, Birmingham. AL; 2University of Alabama at B i r m i n g h a m , Obstetrics a n d Gynecology, B i r m i n g h a m , AL; .~University of Alabama at B i r m i n g h a m , Maternal Fetal Medicine, Birmingham, AL OBJECTIVE: To d e t e r m i n e if third-stage oxytocin dosage affects the prescribed use of additional uterotonic agents at cesarean section. STUDY DESIGN: A r a n d o m i z e d , double-blind trial of 2 prophylactic oxytocin doses to prevent third-stage atony. Patients with a bleeding disorder or who had not labored were ineligible. The pharmacy prepared sequentially n u m b e r e d oxytocin solutions containing either 10 U / 5 0 0 mL or 80 U / 5 0 0 mL of Ringer's lactate, d e t e r m i n e d by a simple randomization scheme a n d stratified by intrapartum MgSO 4 therapy. After cord clamping, the oxytocin was infused over 30 minutes (333 m U / m i n vs 2667 m U / m i n ) . The need for additional oxytocin, m e t h e r g i n e , or 15 m-PGF~= was d e t e r m i n e d by the surgical team, a n d hypotension was d i a g n o s e d a n d treated by the anesthesiologist with additional crystalloid or a pressor agent. RESULTS: O n e h u n d r e d sixty-three women received 10 U a n d 158 received 80 U of oxytocin as assigned. The groups were similar with respect to maternal age, race, parity, a n d i n t r a p a r t u m MgSO 4, oxytocin, or chorioamnionitis. Rates of regional anesthesia were also comparable (92% vs 89%; P = .39). Women in the 10-U g r o u p received an additional uterotonic agent significantly more often than those in the 80-U g r o u p (39% vs 19%; RR 2.1, 95% CI 1.4 m 3.0). Moreover, women in the 10-L1 g r o n p received more methergine, 15 m-PGF2w or both (9.2% vs 1.9%; RR 4.8, 95% C1 1.4 to 16) after the additionally prescribed oxytocin (median 20 U) had been a d d e d to the study solution. The incidence of hypotension requiring either additional crystalloid (19% vs 16%; P = .55) or pressor treatment (25% vs. 24%; P = .82) was similar in both groups. C O N C L U S I O N : C o m p a r e d with an infusion rate of 333 m U / m i n , oxytocin infused at 2667 m U / m i n for the first 30 minutes of the third stage reduces the use of additional uterotonic agents at cesarean.

0029

LEPTIN IN T H E OVINE FETUS CORRELATES WITH FETAL AND PLACENTAL SIZE Alan Buchbinder t, Uwe Lang 2, R. Scott Baker:~,Jeanne Hirth t, J a n e C. Khourv4, Kenneth Clark"; IUniversity 1)t Cincinnati, Obstetrics and Gynecology, (!incinnati, OH; '-'University of Giessen, Giessen, klessen; 3University o f Cincinnati, D e p a r t m e n t of Obstetrics a n d (;ynecolog% Cincinnati, OH: 4University uf Cincinnati, D e p a r t m e n t of Environmental Health, Cincim'tati, OH; :"University of Cincinnati. Mulectdar & Cethflar Physioloh,y, Cincinnati, O H OBJECTIVE: "It) determine the relationship between circulating leptin levels on (lay 138 of t r i n e p r e g n a n c y (term 145 days) a n d fetal body a n d placental weight. STUDY DESIGN: Pregnant sheep (n = 14) were instrumented to allow for chronic reduction of uterine blood flow (UBF) to produce intrauterine growth restriction (IUGR). Doppler flow probes were placed on both uterine arteries to measure total UBE Seven animals were used as control a n d 7 had UBF restricted to 700 + 25 m L / m i n from GD 115 to 138. Blood was obtained for leptin levels on GD 138; animals were sacriticed for m o r p h o r n e t r i c measurements. Fetal body weight (FBW), fetal length, and placental weight (PW) were determined a n d calctdated ponderal index. Spearman correlation and Wilcoxon rank sun1 were used for data analysis and expressed ,as median + 25th and 75th percentile values. RESULTS: UBF ~ras significantly lower in the restricted group, as was fetal weight, placental weight, and calctdated ponderal index (Table). Fetal leptins were significantly higher in the IUGR fetuses. Maternal plasma values were not significantly different in the 2 groups. Fetal leptin levels had at't inverse relationship with UBF (r = ~l.73, P= .01 ), FBW (r= --0.78, P = .01 ), and PW (r = -0.68, P = .001 ). CONCLUSIONS: In contrast to what has been reported in h u m a n beings, the circulating plasma leptin levels in growth-restricted ovine fetuses were significantly elewated, and these levels showed significant invex'se relationships with fetal weight and placental weight. CONTROL Fetal body weight (g) Fetal placental weight (g) Fetal leptin ( n g / m L ) Fetal ponderal index ( g / c m 3)

0028

GRAM-NEGATIVE SEPSIS AMONG LOW-BIRTH-WEIGHT INFANTS: INFECTION RATES BEFORE AND AFTER INITIATION OF GROUP B S T R E P T O C O C C U S PROPHYLAXIS Geralyn O'Reilly, MD I, J a n e Hitti I, Brigit Brock, MD 2, D. H e a t h e r Watts, MD 3, P r a b h c h a r a n Gill 4, T h o m a s Benedettil; IUniversity of Washington, Obstetrics and Gynecology, Seattle, WA; 2University of Washington, OB/GYN, Seattle, WA; -~National Institute of Child Health a n d Development, Bethesda, MD; 4Northeastern O h i o Universities College of Medicine, Obstetrics/Gynecology, Canton, O H OBJECTIVE: To d e t e r m i n e the impact of i n t r a p a r t u m antibiotic prophylaxis (IAP) on the rate of early-onset gram-negative sepsis (GNS) in lowbirth-weight (LBW) infants a n d organism resistance to ampicillin. STUDY DESIGN: We reviewed all positive blood/CSF cultures of infants <2500 g from the University of Washington L&D, postpartum, and NICU from J a n u a r y 1, 1983, to December 31, 1999. Cases were divided into 2 groups: those who delivered between 1983-1993, before the institution of GBS risk-based prophylaxis, a n d patients who delivered between 1994 a n d 1999. A positive b l o o d / C S F culture <7 days of age c o n f i r m e d the diagnosis of early-onset neonatal sepsis. We compared rates of GNS between groups a n d the rate of ampicillin resistance from isolates with sensitivities available. Z2 test was used to determine statistical significance. RESULTS: See Table. CONCLUSION: The rate of GNS in LBW infants has doubled since the introduction of lAP. Although not statistically significant, there appears to be a trend toward ampicillin-resistant gram-negative organisms. Although lAP has r e d u c e d the rate o f GBS sepsis, these data suggest a relationship between w o m e n treated for risk of p r e t e r m delivery a n d GNS in p r e t e r m infants. Further analysis of this relationship should be investigated.

Rate o f GNS in LBW hafants GNS GBS sepsis

Escherichia coli/all GNS Ampicillin-resistant GNR/all isolates with susceptibilities Ampicillin-resistant E coil~all E toll isolates GNR, Gram-negative rods.

1983-1993

1994-1999

P

26/5265 (4.9/1000) 39/5,265 (%4) 21/26 8/19

20/1973 (10.1/1000) 1/ 1973 (0.5) 15/20 10/16

.01

7/16

8/12

<.001 .73 .23 .22

0030

IUGR

P

4486 (4235, 4915) 425 (369,629) 4.6 (4.3, 5.9)

2616 (2275. 3334) 266 (223, 310) 6.7 (6.5.7.9)

.002 .006 .01

3.50 (3.19, 3.59)

2.4(I (2.34, 2.63)

.0(12

EFFECTIVENESS OF A RESCUE DOSE OF ANTENATAL BETAMETHASONE AFTER AN INITIAL SINGLE COURSE Stephen Vermillion t, Mark Bland, MD 2, David Soper, MD'2; tMedical University of South Carolina, Obstetrics a n d Gynecology a n d Maternal-Fetal Medicine, Charleston, SC; 2Medical University of SC, OB/GYN, Charleston, SC OBJECTIVE: To evaluate the effects of a single rescue dose of antenatal betamethasone after an initial single course on the frequency of" neonatal respiratory distress syndrome (RDS) a n d perinatal infectious morbidity in pregnancies complicated with preterm labor a n d delivery. STUDY DESIGN: We performed a prospective observational analysis of singleton pregnancies delivering between 28 and 34 weeks' gestation after a completed single course of betamethasorle administered belore 28 weeks. Patients were then segregated into the following 2 g r o u p s based on betamethasone exposure immediately preceding delivery: (1) a single 12-rag injection (rescue dose), a n d (2) observation only. Patients delivering within 24 h o u r s of the rescue dose were excluded as were those with r u p t u r e d membranes for >24 hours before delivery, preeclam~sia, or instdin-requiring diabetes. Data were analyzed using the paired t test, Z', and Fisher's exact tests. Multiple logistic regression was p e r f o r m e d to examine the effect of each steroid dosing regimen on RDS. Two-tailed P values <.05 were considered significant. RESULTS: A total of 152 patients were included with 89 in the rescue dose g r o u p a n d 63 in the observation group. Both groups were similar with respect to maternal demographics, mean gestational age at the initial single course a n d at delivery, m o d e of delivery, a n d mean birth weights. Rescue dosing was significantly associated with a reduction in the frequency of RDS (odds ratio 0.44, 95% CI 0.2 to 0.9) and mean ventilator days (odds ratio 0.42, 95% CI 0.2 to 0.8) compared with observation alone. The frequencies of the other studied perinatal outcomes analyzed were similar between the groups. Multiple Iogisdc regression confirmed an i n d e p e n d e n t association between a single rescue dose a n d a reduction in the frequency of RDS (odds ratio 0.40, 95% CI 0.2 to 0.9). CONCLUSIONS: A single rescue dose o f b e t a m e t h a s o n e is associated with a reduction in the frequency of RDS without an apparent increase in perinatal infectious morbidity.

SMFM Abstracts $15

Voltlme 184, N u m b e r 1 Am J Obstet Gynecol 0031

THERE IS N O ASSOCIATION BETWEEN MATERNAL T H R O M B O P H I L I A AND RECURRENT FIRST-TRIMESTER LOSS H a n k Roque 1, Michael Paidas'-', Andre: Rebarber '2, Sarla Khan 3, Edward Kuczynski4, Charles Lockwood'-'; INew York University Obsetrics and Gynecology, New York, NY; '-'New York University, Obstetrics and Gynecology, New York, I~'; SNYU Medical Center, O h / G y n ; 4NYU medical center, O b / G y n , NewYork, NY OBJECTIVE: There has beeu increasiug use of anticoagnlant therapy iu patients with acquired or inherited thrombophilia experiencing r e c u r r e n t first-trimester loss. Therefore, we sought to determine if there is, in fact, an association between maternal thrombophilia a n d recurrent first-trimester loss. MATERIALS AND METHODS: Three h u n d r e d seventy-seven patients with a history of adverse p r e g n a n c y outcomes were tested for antiphospholipid antibodies, the factor V Leiden a n d p r o t h r o m b i n G20210A ntutations, hyperhomocysteiuemia, as well as protein C, protein S, anti antithrombin III deficiencies. Patients were further stratified as having recurrent euploid or aneuploid aborters on tile basis of serial abortus karyotypes. RESULTS: There was no increase in tile prevalence of thrombophilia with increasing numbers of first-trimester spontaneous abortions (SABs) up to 8 (r = -0.26; P = .5). T h e r e were also no differeuces in tire prevalence of thrombophilia a m o n g patients with recurrent euploid losses (18.2%; n = 44) compared with recurrent aneuploitl losses (22.9%; n = 48) (P= .5). Moreover, there was no association between individual thrombophilias and first-trimester losses. The prevalence of thrombnphilia was significantly lower in the g r o u p with <3 first-trimester losses a n d no living offspring compared to the g r o u p with <3 first-trimester losses and living offspring (12% vs 28.3%, P = .03). There was no differettce in the grottp with >3 losses with no living versus living offspring (28.6% vs 20.5%, P = .7). X2 analysis revealed an odds ratio of 0.82 (0.5 to 1.3) for the association of thrombophilia and first-trimester loss. This study had >90% power to detect a 20% difference between groups. CONCLUSIONS: There is no association between recurrent first-trimester loss a n d maternal thrombophilia, suggestiug such patients do not require thrombophilia evaluation or anticoagulant therapy.

0033

OPTIMAL PENICILLIN D O S I N G F O R G R O U P B S T R E P T O C O C C U S PROPHYLAXIS Jeffrey J o h n s o n I, David Colombo -'2,Debra Gardner, PharD s, Eunsun Cho, PharD 3, Patricia Fan-Havard, PharD -s, Cynthia Shellhaas4; IOhio State University, Maternal-Fetal Medicine, Columbus, OH; 2Ohio State University, Maternal Medicine, Columbus, OH; 3Ohio State University, Maternal-Fetal Medicine, Columbus, OH; 4Ohio State University, Obstetrics a n d Gynecolog3,, Columbus, O H OBJECTIVE: To determine the optimal dose of intravenous penicillin in the third trimester of pregnancy for the prophylaxis of g r o u p B streptocoecns (GBS). STUDY DESIGN: Healthy women in low-risk prenatal clinics in the third trimester with a singleton pregnancy were recruited. Eligibility included no previous penicillin or cephalosporin allergy, and no history of renal disease. A baseline 24-hour urine for total protein and creatinine clearance was obtained. Two intravenous catheters were placed, and 1 million units of penicillin G sodium was infused thruugh 1 catheter. Serial blood samples were obtained through the second catheter at 1, 5, 15, 30, 60, 90, 120. 150, 180, 210, a n d 240 minutes. Serum was stored at -.80°C until assays were performed. Reversephase high-performance liquid chromatography determined serum concentrations, and pharmacokinetic curves were obtained. RESULTS: Fifteen patients met eligibility. The average 24-hour total protein i~ras 187 m g / d L (range 11 to 478) and creadnine clearance was 190.5 m L / m i n (range 117 to 304). Average maximum serum concentration (Cm~) was 67.8 ~tg/mL (range 33.8 to 181.8) a n d took 5 minutes to reach. Average half-life was 1.4 hours (range 1.0 to 3.0). The averaged pharmacokinetic curve is shown in the figure. CONCLUSION: ; ~ f ~ ~ The Minimal Inhibitor 3, Concentration (MIC) for penicillin in GBS proph)~ I O ~ laxis has previously been 8~lb established at 0.1 lag/mL, and serum anti-GBS conI • • • O • • centration is 0.1 to 1.0 g g / m L . The Cnu~xs~-as67 ~ g / m L (670 times MIC). Penicillin pK Curve One million units of intravenous penicillin G sodium exceeds MIC in the treatment of GBS. The dosing interval should be every 6 hours to ensure anti-GBS activity in all patients. More frequent dosing does not increase activity. Current recommendations for GIgS prophylaxis using penicillin G should be modified pending future studies of neonatal penicillin concentrations.

0032

CAN PRENATAL ULTRASOUND FINDINGS PREDICT AMBULATORY STATUS IN FETUSES WITH O P E N SPINA BIFIDA (OSB)? Joseph R. Biggio, Jr. I, J o h n Owen I, Katharine Wenstrom '2, WaherJerry Oakes3; IUniversity of Alabama at Birmingham, Obstetrics a n d Gynecology, Birmingham, AL; 2University of Alabama at Birmingham, OB/GYN, Birmingham, AL; -SUniversity of Alabama at Birmingham, Pediatric Neurosnrgery, Birmingham, AL OBJECTIVE: To determine whether sonographic findings in fetuses with OSB can identify g o o d prenatal surgery candidates tie, those who would ultimately be nonambttlatory or require a shunt). STUDY DESIGN: All o n g o i n g pregnancies complicated by OSB from January 1996 to March 2000 at our referral center were assessed (n = 33). Serial static images a n d reports generated every 3 to 4 weeks until delivery were reviewed for lesion level a n d type, ventriculomegaly (VM, atrium > 10 ram), m a x i m u m atrial width (MaxA), a n d club foot (CF). Pediatric charts were reviewed. Ambulatory was defined as sufficient leg function to permit unassisted or supported ambulation. RESULTS: In univariate analyses, lesion level ( P < .001) and MaxA before delivery (P = .003) were independently associated with ambulatory status. No infant with a Tg-T12 lesion (n = 11) was ambulatory, all had VM (mean MaxA 30 mm ± l0 mm) a n d required a shunt, a n d 45% h a d CE In contrast, all infants with L4-$3 lesions (n = 10) were ambulatory a n d 70% had VM (mean MaxA 14 ± 5 mm). Only 1 had CF, a n d all but 1 required a shunt. O f fetuses with L1-L3 lesions (n = 12), 50% were ambulatory; however, neither the presence of VM, nor the presence of CF, n o r MaxA was able to discriminate ambulatory versus n o n a m b u l a t o r y status. All fetuses in this g r o u p required shunts. In the entire cohort, only 2 of 8 infants with CF a n d 0 of 7 with myeloschises were ambulatory. CONCLUSIONS: All fetuses with L4-$3 lesions were ambulatory. Because fetuses with T9-TI2 lesions were n o n a m b u l a t o r y a n d h a d worse VM, these fetuses may be good candidates for fetal surgery. The inability to distinguish ambulatory versus nonambnlatory status sonographically a m o n g those with L1L3 lesions makes the selection of surgical candidates difificult. Ultrasound does not predict the need for shunting because nearly all fetttses with OSB require it.

0034

IS NORMAL PREGNANCY CHARACTEBIZlgD BY A STATE O F LEUKOCYTE ACTIVATION AKIN T O SEPSIS? Nihal Naccasha, MD I, Maria-Teresa Gervasi, MD 2, T i n n a k o r n Chaiworapongsa, MD 2, Susan Berman, MD s, Bo Hyun Yoon, MD 4, Eli Maymon, MD x. Roberto Romero, MD2; IWayne State University, Obstetrics a n d Gynecology, Detroit, MI; 2Perinatology Research Branch, NICHD, Bethesda, MD, Detroit, MI; SWayne State University, Obstetrics a n d Gynecology, Detroit, MI; 4Seoul National University, Obstetrics and Gynecology, Seoul, Korea OBJECTIVE: Normal pregnancy has been characterized as a state of physiologic activation of the innate limb of the immune response. Recent studies have concluded that "Normal pregnancy produces inflammatory changes in peripheral blood leukocytes akin to those of sepsis" (AmJ Obstet Gynecol 1998). This unexpected observation has implications critical for understanding the susceptibility of pregnant women to sepsis a n d preeclampsia a n d for understanding the biology of normal pregnancy. This study was designed to examine the magnitude of in vivo granulocyte a n d monocyte activation in normal pregnancy and in pregnant patients with systemic infection (SI). STUDY DESIGN: A prospective study was c o n d u c t e d including normal pregnant women (n = 14) a n d pregnant patients with positive blood cultures a n d / o r pyelonephritis (n = 11). The magnitude of intravascular inflammation was studied using flow cytometry a n d m o n o c l o n a l antibodies to detect granulocyte a n d monocyte activation (CD1 lb, CD49ti, CD62L, CD64, CD66b, a n d HLA-DR). RESULTS: The percentage of granulocytes a n d monocytes expressing activation of surface markers was significantly higher in patients with SI than in normal p r e g n a n c y (Table). The mean channel brightness was significantly h i g h e r in granulocytes a n d monocytes for C D l l b , CD64, a n d CD66b in patients with Sl than normal pregnancy (P< .05 for all). C O N C L U S I O N : T h e m a g n i t u d e of in vivo leukocyte activation is profoundly greater in p r e g n a n t women with SI than in normal pregnancy. These quantitative differences indicate that the innate limb of the i m m u n e response is not maximally activated during normal pregnancy. NORMAL PREGNANCY GRANULOC'X~g (%) CDI Ib CD49d CD64 CD66b

73.8 3.9 16.0 72.7

Values expressed as medians. *P< .05; Mann-Whitney UtesL

MONOCYTE (%) 57.5 28.6 88.9 2.3

SYSTEMIC I N F E C T I O N GRANULO- M O N O C Y T E C t q ~ (%) (%) 97.8* 2.9 98.3* 97.5*

89.6* 70.2* 98.1" 6.0