808: Improved respiratory compliance in preterm infants after a single rescue course of antenatal steroids: A randomized trial

SMFM Abstracts 806

IL-6 INDUCED GADD45A-P38 STRESS RESPONSE PATHWAY REGULATES SFLT-1 SECRETION IN HUVEC CELLS YALI XIONG1, DAN LIEBERMANN1, ELIEZER J HHOLTZMAN2, BARBARA HOFFMAN1, OSSIE GEIFMAN-HOLTZMAN3, 1Temple University, Philadelphia, Pennsylvania, 2Tel-Aviv University, Sheba Medical Center, Nephrology and Hypertension Institute, Ramat-Gan, Israel, 3Temple University, Wynnewood, Pennsylvania OBJECTIVE: To examine inflammation (IL-6) response activation of stress inducible Gadd45a protein and regulation of sFlt-1 secretion by stress response Gadd45a signaling pathway in preeclampsia. STUDY DESIGN: Human Umbilical Cord Vein Endothelial cells (HUVEC) were utilized as cell model to demonstrate the stress response signaling when treated with inflammatory cytokines-- IL-6. Cell protein and the supernatant of culture medium were collected 72h after incubation with (study) or without (control) 10ng/ml IL-6. Cell protein was subjected to western blot for quantification of Gadd45a and phospho-p38 protein levels. Cell culture supernatant was subjected to Elisa assay for the concentration of soluble Flt-1. Gadd45a knock-out model was included in this experiment to clarify the relationship between Gadd45a and sFlt-1 in response to inflammatory stress and P-38 inhibitor was also used to further examine the signaling pathway among Gadd45a, p-38 and sFlt-1. RESULTS: Gadd45a, together with its downstream stress element p-38 was induced by 10ng/ml IL-6 in HUVEC cell model. IL-6 also triggered the increase of sFlt-1 levels in supernatant. In the Gadd45a knockout model, sFlt-1 levels showed no change in response to IL-6. When p-38 inhibitor was applied in the cultured HUVEC cells, although Gadd45a was induced due to incubation with IL-6, increased level of sFlt-1 was not observed. CONCLUSION: Our study reveals IL-6, a cytokine which accumulates in maternal plasma of preeclamptic patients contributing to endothelial cell dysfunction, induces Gadd45a and the activation of the down stream p-38 pathway activation in HUVEC cells. This inflammatory response eventually regulates the secretion of sFlt-1. It provides novel evidence that links inflammatory stress to sFlt-1 secretion via the Gadd45-p38 stress response pathway.

www.AJOG.org 808

0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.837

807

PREDICTION OF VERY PRETERM BIRTH IN TRIPLET PREGNANCIES USING FETAL FIBRONECTIN AND CERVICAL LENGTH NATHAN FOX1, DANIEL SALTZMAN2, CHAD KLAUSER2, DANIELLE PERESS3, CHRISTINE GUTIERREZ4, ANDREI REBARBER2, 1Mount Sinai School of Medicine, New York, New York, 2Mount Sinai School of Medicine, Maternal Fetal Medicine, New York, 3Mount Sinai School of Medicine, New York, 4 New York Medical College, New York OBJECTIVE: To evaluate positive fetal fibronectin (FFN) and short cervical length (CL) as predictors of spontaneous preterm birth in asymptomatic triplet pregnancies STUDY DESIGN: Historical cohort of 14 asymptomatic triplet pregnancies managed from 2005-2008 in a maternal-fetal medicine practice with FFN and CL testing between 22 and 26 weeks gestation. A short CL was defined as ⬍20mm. Iatrogenic preterm births were not included in the analysis. Chi square test was used when appropriate. A p-value of ⬍0.05 was considered significant. RESULTS: Two patients had both a positive FFN and a CL ⬍20mm between 22 and 26 weeks. The other 12 patients had a negative FFN and a CL ⬎20mm. One of the two patients with positive tests delivered spontaneously at 23 1/7 weeks. The other patient spontaneously delivered triplet A at 25 1/7 weeks, and had a delayed delivery of triplets B and C at 26 1/7 weeks. One patient with negative tests had an intrauterine death of triplet A and delivered spontaneously at 31 3/7 weeks. No other patient with a negative test delivered ⬍34 weeks. A positive FFN or a CL ⬍20mm at 22-26 weeks was associated with a higher rate of delivery ⬍28 weeks (100% vs. 0%, p⫽.011) and delivery ⬍32 weeks (100% vs. 8.3%, p⫽.033). CONCLUSION: In asymptomatic triplet pregnancies, both positive FFN and a short CL at 22-26 weeks appear to have predictive value for very preterm birth. Consideration should be given to the routine use of these tests in asymptomatic triplet pregnancies. Large studies are warranted. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.828

IMPROVED RESPIRATORY COMPLIANCE IN PRETERM INFANTS AFTER A SINGLE RESCUE COURSE OF ANTENATAL STEROIDS: A RANDOMIZED TRIAL CYNTHIA MCEVOY1, DIANE SCHILLING1, SALLY SEGEL2, PATRICIA SPITALE1, LINDA WALLEN3, SUSAN BOWLING4, MANUEL DURAND5, MICHAEL GRAVETT6, 1Oregon Health & Science University, Pediatrics, Portland, Oregon, 2Oregon Health & Science University, Obstetrics & Gynecology, Portland, Oregon, 3Oregon Health & Science University, Portland, Oregon, 4Sacred Heart Hospital, Pensacola, Florida, 5University of Southern California, Pediatrics, Los Angeles, California, 6University of Washington, Obstetrics & Gynecology, Seattle, Washington OBJECTIVE: To compare pulmonary function in preterm infants randomized to a single rescue course of antenatal steroids (AS) vs placebo. STUDY DESIGN: Double-blind, randomized trial. Pregnant women ⬎ 14 days after initial course of AS and ⬍ 34 weeks were randomized to a rescue course of AS (two 12 mg doses of betamethasone) or placebo. The primary outcome was measurements of respiratory compliance (Crs) and functional residual capacity (FRC) within 72 hours. Crs was measured with the single breath occlusion and FRC with the nitrogen washout technique. Analysis was by intention-to-treat with planned subanalysis of patients delivering at ⬍/⫽ 34 weeks. Comparisons of the primary outcomes were done using linear mixed modeling to adjust for potential confounders while accounting for correlation between twins. RESULTS: A total of 85 randomized mothers delivered 113 babies. The primary results were presented (Pediatric Academic Societies, May 2008) showing signficantly improved Crs in the rescue group. 83 babies delivered at ⬍/⫽ 34 weeks: 44 received rescue AS and 39 placebo. The rescue AS group had a significantly higher Crs (adjusted 95% CI: 0.02-0.52; p⫽0.03), required less oxygen and surfactant than the placebo group (see Table; *p⬍0.05; mean values). There was no significant difference in birth weight (1467 vs 1541 g), gestational age (30.5 vs 30.8 wks), birth head circumference (27.8 vs 28.0 cm), % small for gestational age, or z scores for birth weight or head circumference between groups. CONCLUSION: Infants randomized to one rescue course of AS and delivering at ⬍/⫽ 34 weeks, have a significantly increased Crs vs those randomized to placebo. Our findings suggest that improved Crs translates into improved clinical respiratory outcomes. Long-term follow-up is needed. Outcomes of Randomized Patients

Crs (mL/cmH2O/kg) FRC (mL/kg) ⬎30% oxygen (%) Surfactant (%)

Placebo (n⫽39)

1.17 24.3 16 34

0.90* 21.1 41* 54

0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.839

809

EXPECTANT MANAGEMENT OF SUPERIMPOSED PREECLAMPSIA AMBER SAMUEL1, CAROL LIN1, ARUNDHATHI JEYABALAN1, 1University of Pittsburgh, Pittsburgh, Pennsylvania OBJECTIVE: Women with chronic hypertension have an increased risk of adverse pregnancy outcomes including preeclampsia. There is limited information regarding perinatal complications in women with superimposed preeclampsia diagnosed prior to term, particularly in those who are expectantly managed. The objective of this study was to review outcomes for expectantly managed women with preeclampsia superimposed on chronic hypertension prior to 37 weeks’. STUDY DESIGN: We retrospectively reviewed the charts of women admitted to our institution with the diagnosis of both chronic hypertension and preeclampsia prior to term. Superimposed preeclampsia was defined as worsening blood pressure with new onset or worsening of proteinuria, or, development of thrombocytopenia along with worsening blood pressure. We confirmed the diagnosis of chronic hypertension and superimposed preeclampsia and determined time to delivery, and maternal and fetal/neonatal outcomes. RESULTS: A total of 68 cases of women diagnosed with both chronic hypertension and preeclampsia prior to 37 weeks= were reviewed. Of these, 43 women were expectantly managed; 4 were excluded for multifetal gestation or pregestational diabetes. Of the remaining 39 women, the average gestational age at diagnosis was 31.3 weeks (range 23.6-36.4). The average time from diagnosis to delivery was 10.2 days (range 2-34 days). Adverse perinatal outcomes included 1 case of eclampsia, 2 cases of HELLP syndrome, 2 abruptions, 3 cases of pulmonary edema and 4 postpartum hemorrhages. There were no fetal/neonatal or maternal deaths. Median neonatal hospital stay was 14 days. CONCLUSION: Other than pulmonary edema, adverse pregnancy outcomes in this high risk cohort are comparable to historical controls of expectantly managed women with severe preeclampsia. This review adds to our limited understanding of outcomes for expectant management of chronically hypertensive women with superimposed preeclampsia prior to 37 weeks=. Prospective controlled studies are needed to more thoroughly determine the risks and benefits of approach. 0002-9378/$ - see front matter doi:10.1016/j.ajog.2008.09.840

S228

Rescue AS (n⫽44)

American Journal of Obstetrics & Gynecology Supplement to DECEMBER 2008