Maternal and fetal adrenal function following single and repeat ...

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immune factors, race, and BV, elevated IL-1b levels in CV secretions are associated with increased risk for subsequent SPTB. *Supported by the March of Dimes ...

SMFM Abstracts S5 9

‘‘BETACODE TRIAL’’ANTENATAL BETAMETHASONE COMPARED TO DEXAMETHASONE: A RANDOMIZED CONTROLLED TRIAL ANDREW ELIMIAN1, DAVID GARRY1, REINALDO FIGUEROA1, ALAN R. SPITZER1, VANDY WIENCEK1, PAUL OGBURN1, J. GERALD OUIRK1, 1State University of New York at Stony Brook, Obstetrics, Gynecology and Reproductive Medicine, Stony Brook, New York OBJECTIVE: No human randomized study has formally compared betamethasone and dexamethasone, the preferred corticosteroids for antenatal therapy, with regards to their effectiveness in reducing neonatal morbidities and mortality. Our objective was to compare betamethasone with dexamethasone in terms of effectiveness in reducing perinatal morbidities and mortality among preterm infants. STUDY DESIGN: We enrolled 299 women at risk for preterm delivery in a double blind placebo-controlled randomized trial of antenatal betamethasone compared to dexamethasone 8/1/2002-7/31/2004. We excluded women with clinical chorioamnionitis, major fetal structural and chromosomal abnormalities, prior antenatal steroid exposure, and use of betamethasone or dexamethasone for other medical indications. Consenting women were randomly allocated to one of two groups by the Pharmacy using computer generated random numbers. The statistical analysis was performed in accordance of the intention-to-treat principle. Student t test, Chi square and Fisher exact test were used for analysis. A P value of ! .05 was considered statistically significant. RESULTS: There were no significant differences between the groups with regards to baseline characteristics including maternal age, gestational age (GA) at steroid administration, GA at delivery, birth weight, fetal gender, antibiotic exposure, surfactant therapy, mode of delivery, and histologic chorioamnionitis. The rate of respiratory distress syndrome, neonatal mortality, need for vasopressor, necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus and neonatal sepsis were not significant different between the groups. However the rate of intraventricular hemorrhage (IVH) was significantly lower in the dexamethasone group compared to the betamethasone group [6/105(5.7%) versus 16/98(16.3%), P=.027] CONCLUSION: Betamethasone and dexamethasone are comparable in reducing the rate of most major neonatal morbidities and mortality in preterm neonates. However dexamethasone appears to be more effective in reducing the rate of IVH.

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MATERNAL AND FETAL ADRENAL FUNCTION FOLLOWING SINGLE AND REPEAT COURSES OF ANTENATAL CORTICOSTEROIDS (ACS) RONALD J. WAPNER1, 1for the NICHD MFMU Network, Bethesda, Maryland OBJECTIVE: Repeat courses of ACS have been demonstrated to reduce specific fetal pulmonary and vascular complications compared to a single course. To determine the effect of repetitive courses of ACS on maternal and fetal adrenal function. STUDY DESIGN: Women presenting in preterm labor and pregnant one week after ACS were randomized to weekly courses of Betamethasone (Repeat) or placebo (Single). Maternal blood was drawn prior to the initial study course, at the fourth course, and delivery. Cord blood was obtained at delivery. Cortisol, dehydroepiandosterone sulfate (DHEAS) and estriol were evaluated by ELISA analysis. RESULTS: There were no differences in baseline maternal cortisol, DHEAS or estriol. Maternal cortisol, estriol, DHEAS and cord cortisol and DHEAS were reduced in the repeat group (Table & Figure). When 3 or more weeks elapsed from the last course to delivery, there was no difference in cord cortisol between single 7.8 (5.8) mg/dl and repeat 7.2 (5.3) mg/dl groups.

CONCLUSION: Repetitive courses of ACS significantly suppress maternal and fetal adrenal function.

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INFANT OUTCOMES AT 2 YEARS OF AGE WITH A SHORT LATENCY PERIOD AFTER PRETERM PREMATURE RUPTURE OF MEMBRANES IN A PROSPECTIVE REGIONAL COHORT STUDY (DOMINOS STUDY) JEAN-CHARLES PASQUIER1, EMMANUEL BUJOLD2, JEAN-CHARLES PICAUD3, MURIEL RABILLOUD4, OLIVIER CLARIS5, RENE ECOCHARD4, STEPHANIE MORET6, GEORGES MELLIER6, 1Universite de Sherbrooke, Obstetrics/Gynecology, Sherbrooke, Quebec, Canada, 2Universite´ de Montreal, Montreal, Quebec, Canada, 3Arnaud de Villeneuve Hospital and Montpellier University, Department of Neonatology, Montpellier, France, 4 Universite de Lyon, biostatistic, Lyon, France, 5Universite de Lyon, neonatology, Lyon, Rhone, France, 6Hospices civils de Lyon, Department of Obstetrics and Gynecology, Lyon, France OBJECTIVE: It remains unclear if a latency period longer than the 48 hours necessary to obtain the benefits of antenatal antibiotics and steroids is helpful after preterm premature rupture of the membranes (PPROM). We aimed to assess the impact of the latency period on infant outcomes after PPROM. STUDY DESIGN: A prospective cohort study of women with singleton gestation and no neonatal anomalies who experienced PPROM between 24 and 34 weeks gestation was performed in 81 hospitals over 2 years. Midwives were available in each centre to obtain consent and ensure data collection until maternal and neonatal discharge. Infants were followed at 2 years for survival, and a 2-year neurological questionnaire was implemented. Outcomes were compared according to the latency period: !48 hours and O48 hours. Multiple logistic regression adjusted for confounding factors, including gestational age, cerclage, maternal leucocytosis, oligohydramnios, antibiotics and antenatal steroids. RESULTS: 471 women were included (mean gestational age: 30.5G1.2 weeks). Among them, 170 (37%) presented a latency period !48 hours, and 301 (63%), a longer latency period. Prior to 30 weeks, the mortality rate was 16.3% in neonates with a short latency period compared to 7.3% for those with a long latency period (p!0.01), with pulmonary disease being the major cause of death. Conversely, after 30 weeks of gestation, a latency period O48 hours was associated with a higher mortality rate (0% vs. 3.7%, p=0.02), and infectious disease was the major cause of death. After adjustments, the latency period remained an independent factor associated with infant mortality. No differences were found in terms of 2-year neurological outcomes according to the latency period. CONCLUSION: For PPROM between 24 and 30 weeks of gestation, a latency period O48 hours is associated with a lower mortality rate whereas between 30 and 34 weeks of gestation, this long latency period is associated with a higher mortality rate.

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MEASURES OF VAGINAL INFLAMMATION AND SUBSEQUENT SPONTANEOUS PRETERM BIRTH (SPTB) ALICE GOEPFERT1, IDA VOGEL2, KRISTIN SKOGSTRAND3, PATRICK RAMSEY1, SUZANNE CLIVER1, WILLIAM ANDREWS1, ROBERT GOLDENBERG1, JOHN HAUTH1, 1University of Alabama at Birmingham, Obstetrics & Gynecology, Birmingham, Alabama, 2North Atlantic Neuro-epidemiology Alliances (NANEA), Department of Epidemiology, Aarhus C, Denmark, 3Statens Serum Institute, Department of Clinical Biochemistry, Cophenhagen S, Denmark OBJECTIVE: To evaluate the association between measures of inflammation in cervicovaginal (CV) secretions and SPTB. STUDY DESIGN: Asymptomatic pregnant women were prospectively evaluated in a nested case (CA)-control (CO) study: 119 women with SPTB !37 wks (CA) and 135 with birth R37 weeks (CO). CV swabs in fetal fibronectin buffer were obtained at 21-26 wks and stored at ÿ70(C. The following were measured in CV secretions: cytokines (IL-1b, IL-6, IL-8, IL-17, TNF-a) and soluble receptors (sTNFR1, sIL-6ra) by Luminex technology; defensins by ELISA, polymorphonuclear cell:epithelial cell (PMN:EPI) ratio and bacterial vaginosis (BV) by Gram stain. RESULTS: CA and CO were similar for maternal race, parity, and socioeconomic status. CA were younger (20.9G4 vs. 22.2G5 yrs, p=0.04) and had more prior SPTBs (12.6 vs. 3.7%, p=0.009). Of the immune factors tested, the following were signficantly assoicated with SPTB: IL-1b (Median; CA=1322.3 vs CO=635.1 pg/ml, p=0.004); sTNFR1 (Median; CA=296.4 vs CO=143.5 pg/ml, p=0.026), sIL-6ra (Median; CA 288.8 vs CO 175.5 pg/ml, p=0.012), PMN:EPI (!95% ile or 7; OR 3.6, 95% CI 1.4-9.5). In a stepwise logistic regression model, adjusting for each of the immune factors, race, and BV, only IL-1b was independently and significantly associated with SPTB (OR 2.8, 95% CI 1.6-5.1). When none of the 9 immune factors were in the highest quartile, the risk for SPTB was reduced (OR 0.5, 95% CI 0.3-0.8). CONCLUSION: When evaluated at 21-26 weeks’ GA in asymptomatic pregnant women, lack of inflammation in CV secretions as measured by a panel of proinflammatory and innate immune factors is associated with a reduced risk for SPTB at !37 weeks. When adjusting for the measured immune factors, race, and BV, elevated IL-1b levels in CV secretions are associated with increased risk for subsequent SPTB. *Supported by the March of Dimes 6-FY03-104 and the NICHD P01 HD33927, K12 HD01258 and K12 HD01402.

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