515: Prediction of spontaneous preterm birth in asymptomatic triplet pregnancies using combined fetal fibronectin and cervical length

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Doppler Assessment, Fetus, Prematurity

nary Survanta was visualized with indigo carmine (panel A, red arrow) and neonatal survival and feeding by milk spot (black arrow). In situ quantitation of gene expression (mRNA) and protein (IHC) was performed on lung sections harvested at 3h, 6h, and 24h postnatally. RESULTS: Antenatal dex accelerated CRH downregulation in both Erk3⫹/⫹ (p0.05). However, neonatal Survanta with antenatal dex resulted in enhanced survival of the KO pups from a median of 2h to 6h of life, with ⬎50% of neonates surviving 24h without signs of respiratory distress syndrome (RDS; A). This neonatal RDS free survival with dex⫹Survanta in Erk3-/- pups rescued SPB production relative antenatal dex alone (p⬍0.001) or saline (p⫽0.025; panel B), as well as SPA (p⫽0.004) and SPC (p⫽0.002). CONCLUSION: As predicted by our discovery platform, neonatal Survanta with antenatal glucocorticoids enhanced neonatal RDS-free survival, decreased pulmonary CRH expression, and rescued SPB production to partially restore functional fetal lung maturation. These findings emphasize the power of animal models and robust discoverybased platforms in applied perinatal translational research.

514 Do oxygen tension and carbon monoxide regulate bacteria-stimulated cytokine production by fetal membranes? Morgan Peltier1, Natalia Klimova2, Nazeeh Hanna2 1 Winthrop University Hospital, Department of Obstetrics and Gynecology, Mineola, NY, 2Winthrop University Hospital, Department of Pediatrics, Mineola, NY

OBJECTIVE: Preterm birth (PTB) is often caused by infections that stimulate an inflammatory response by the placenta and fetal membranes. Animal studies indicate that IL-1␤ and TNF-␣ mediate the effects of infection to cause PTB and that the anti-inflammatory cytokine, IL-10, inhibits infection-mediated PTB. In recent studies, we found that oxygen (O2) tensions that are hyperoxic (pO2 ⬃140 mm Hg) for the maternal-fetal interface (normal pO2 ⬃40 mm Hg) reduce IL-1␤ and promote IL-10 production by placental explants. We have also shown that carbon monoxide (CO) at low, sub-toxic, levels can prevent bacteria-stimulated IL-1␤ production by the placenta. In this study, we tested whether O2-tension and CO, alone or in combination, have similar anti-inflammatory properties on extra-placental fetal membranes. STUDY DESIGN: Cultures of fetal membranes from normal, term deliveries (n⫽7) were treated with 0, 10^5,10^6,10^7 or 10^8 CFU/ml heat-killed Escherichia coli (EC) and incubated for 24 h under 21% O2 (hyperoxic conditions) or 5% O2 (normoxic conditions) in the presence and absence of 250 ppm CO. IL-1␤, TNF-␣, and IL-10 levels in the conditioned medium were quantified by ELISA. Viability of the cultures was ascertained by the MTT assay. RESULTS: Membranes cultured under 21% O2 produced less IL-1␤ than those under 5% O2 for all concentrations of EC tested. Basal and EC-stimulated IL-10 production was enhanced by culture under 21% O2 compared with 5% O2. Basal, but not EC-stimulated, TNF-␣ pro-

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duction was less for cultures under 21% O2 than those under 5% O2. CO had no effect on basal or bacteria-stimulated IL-1␤ or IL-10 production under either O2 tension. TNF-␣ production by cultures stimulated with 10^8 CFU/ml EC was reduced by CO under both O2 tensions. No effect of EC, CO or O2 on viability of the cultures was detected. CONCLUSION: Hyperoxia reduces the inflammatory response of fetal membranes to EC by inhibiting IL-1␤ and enhancing IL-10 production. Supplemental CO may also reduce inflammation in the membranes by inhibiting EC-stimulated TNF-␣ production.

515 Prediction of spontaneous preterm birth in asymptomatic triplet pregnancies using combined fetal fibronectin and cervical length Nathan Fox1, Daniel Saltzman2, Ashley Roman2, Chad Klauser3, Andrei Rebarber2 1 Mount Sinai School of Medicine, Obstetrics and Gynecology, New York, NY, 2Carnegie Imaging for Women, Obstetrics and Gynecology, New York, NY, 3Maternal Fetal Medicine Associates, PLLC, Obstetrics and Gynecology, New York, NY

OBJECTIVE: To report the prediction of spontaneous preterm birth in asymptomatic women with triplet pregnancies using combined fetal fibronectin (fFN) and cervical length (CL). STUDY DESIGN: A cohort of 39 consecutive women with asymptomatic triplet pregnancies managed in one Maternal-Fetal medicine practice from 2005-2011 was analyzed. Combined fFN and CL testing was performed every 2 weeks from 22-32 weeks. A short CL was defined as ⱕ20mm. Fishers exact test, Students t-test, one-way ANOVA, and chi-square testing were used, where appropriate. RESULTS: A positive fFN was significantly associated with spontaneous preterm birth ⬍28 weeks, ⬍30 weeks, ⬍32 weeks, and ⬍34 weeks. A short CL was significantly associated with spontaneous preterm birth ⬍32 weeks. On combined testing, having both tests positive was associated with the highest likelihood of spontaneous preterm birth at all gestational ages (Table). As a screening test for spontaneous preterm birth ⬍32 weeks, having both a positive fFN and a short CL had a sensitivity of 62.5%, specificity of 90%, positive predictive value of 62.5%, negative predictive value of 90%, positive likelihood ration of 2.98 and negative likelihood ratio of 0.88. Combined fFN and CL outperformed fFN alone, CL alone, or either test being positive alone. CONCLUSION: In asymptomatic women with triplet pregnancies, fFN and CL are each significantly associated with spontaneous preterm birth. For the prediction of spontaneous preterm birth, combined fFN and CL testing outperforms either test alone. Risk of spontaneous preterm birth in asymptomatic women with triplet pregnancies, based on the combined results of fetal fibronectin (fFN) and cervical length (CL) testing from 22-32 weeks Mean GA at delivery (weeks)

Risk for spontaneous preterm birth* <28 weeks

<30 weeks

<32 weeks

<34 weeks

All negative 34.38 ⫾ 2.02 0% 4.5% 5.9% 6.2% .......................................................................................................................................................................................... One Positive 34.45 ⫾ 1.80 0% 0% 15.4% 23.1% .......................................................................................................................................................................................... Both Positive 30.43 ⫾ 4.47 33.3% 42.9% 62.5% 62.5% .......................................................................................................................................................................................... P* 0.002 0.004 0.017 0.003 0.004 .......................................................................................................................................................................................... * One-way ANOVA or chi-square for trend

516 Micronized progesterone reduces vasoconstriction in the placenta Nathaniel Miller1, Brad Dolinsky1, Peter G. Napolitano2 1 Madigan Healthcare System, Obstetrics and Gynecology, Tacoma, WA, 2Madigan Healthcare System, Department of Obstetrics and Gynecology, Tacoma, WA

OBJECTIVE: Current clinical guidelines recommend the use of progesterone therapy for reduction of preterm birth in high risk patients.

Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology

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