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nary Survanta was visualized with indigo carmine (panel A, red arrow)and neonatal survival and feeding by milk spot (black arrow). In situquantitation of gene expression (mRNA) and protein (IHC) was per-formed on lung sections harvested at 3h, 6h, and 24h postnatally.RESULTS: Antenatal dex accelerated CRH downregulation in bothErk3�/� (p0.05). However, neonatal Survanta with antenatal dexresulted in enhanced survival of the KO pups from a median of 2h to6h of life, with �50% of neonates surviving 24h without signs ofrespiratory distress syndrome (RDS; A). This neonatal RDS free sur-vival with dex�Survanta in Erk3-/- pups rescued SPB productionrelative 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 Sur-vanta with antenatal glucocorticoids enhanced neonatal RDS-freesurvival, decreased pulmonary CRH expression, and rescued SPBproduction to partially restore functional fetal lung maturation. Thesefindings emphasize the power of animal models and robust discovery-based platforms in applied perinatal translational research.
514 Do oxygen tension and carbon monoxideregulate bacteria-stimulated cytokineproduction by fetal membranes?Morgan Peltier1, Natalia Klimova2, Nazeeh Hanna2
1Winthrop University Hospital, Department of Obstetricsand Gynecology, Mineola, NY, 2Winthrop UniversityHospital, Department of Pediatrics, Mineola, NYOBJECTIVE: Preterm birth (PTB) is often caused by infections thatstimulate an inflammatory response by the placenta and fetal mem-branes. Animal studies indicate that IL-1� and TNF-� mediate theeffects of infection to cause PTB and that the anti-inflammatory cy-tokine, IL-10, inhibits infection-mediated PTB. In recent studies, wefound that oxygen (O2) tensions that are hyperoxic (pO2 �140 mmHg) for the maternal-fetal interface (normal pO2 �40 mm Hg) re-duce IL-1� and promote IL-10 production by placental explants. Wehave also shown that carbon monoxide (CO) at low, sub-toxic, levelscan prevent bacteria-stimulated IL-1� production by the placenta. Inthis study, we tested whether O2-tension and CO, alone or in combi-nation, have similar anti-inflammatory properties on extra-placentalfetal membranes.STUDY DESIGN: Cultures of fetal membranes from normal, term deliv-eries (n�7) were treated with 0, 10^5,10^6,10^7 or 10^8 CFU/mlheat-killed Escherichia coli (EC) and incubated for 24 h under 21%O2 (hyperoxic conditions) or 5% O2 (normoxic conditions) in thepresence and absence of 250 ppm CO. IL-1�, TNF-�, and IL-10 levelsin the conditioned medium were quantified by ELISA. Viability of thecultures 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 andEC-stimulated IL-10 production was enhanced by culture under 21%O2 compared with 5% O2. Basal, but not EC-stimulated, TNF-� pro-
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 pro-duction under either O2 tension. TNF-� production by cultures stim-ulated with 10^8 CFU/ml EC was reduced by CO under both O2tensions. No effect of EC, CO or O2 on viability of the cultures wasdetected.CONCLUSION: Hyperoxia reduces the inflammatory response of fetalmembranes to EC by inhibiting IL-1� and enhancing IL-10 produc-tion. Supplemental CO may also reduce inflammation in the mem-branes by inhibiting EC-stimulated TNF-� production.
515 Prediction of spontaneous preterm birth inasymptomatic triplet pregnancies using combinedfetal fibronectin and cervical lengthNathan Fox1, Daniel Saltzman2, AshleyRoman2, Chad Klauser3, Andrei Rebarber2
1Mount Sinai School of Medicine, Obstetrics and Gynecology,New York, NY, 2Carnegie Imaging for Women, Obstetrics andGynecology, New York, NY, 3Maternal Fetal Medicine Associates,PLLC, Obstetrics and Gynecology, New York, NYOBJECTIVE: To report the prediction of spontaneous preterm birth inasymptomatic women with triplet pregnancies using combined fetalfibronectin (fFN) and cervical length (CL).STUDY DESIGN: A cohort of 39 consecutive women with asymptomatictriplet pregnancies managed in one Maternal-Fetal medicine practicefrom 2005-2011 was analyzed. Combined fFN and CL testing wasperformed every 2 weeks from 22-32 weeks. A short CL was defined as�20mm. Fishers exact test, Students t-test, one-way ANOVA, andchi-square testing were used, where appropriate.RESULTS: A positive fFN was significantly associated with spontane-ous preterm birth �28 weeks, �30 weeks, �32 weeks, and �34 weeks.A short CL was significantly associated with spontaneous pretermbirth �32 weeks. On combined testing, having both tests positive wasassociated with the highest likelihood of spontaneous preterm birth atall gestational ages (Table). As a screening test for spontaneous pre-term birth �32 weeks, having both a positive fFN and a short CL hada sensitivity of 62.5%, specificity of 90%, positive predictive value of62.5%, negative predictive value of 90%, positive likelihood ration of2.98 and negative likelihood ratio of 0.88. Combined fFN and CLoutperformed fFN alone, CL alone, or either test being positive alone.CONCLUSION: In asymptomatic women with triplet pregnancies, fFNand CL are each significantly associated with spontaneous pretermbirth. For the prediction of spontaneous preterm birth, combined fFNand CL testing outperforms either test alone.
Risk of spontaneous preterm birth in asymptomatic women with tripletpregnancies, based on the combined results of fetal fibronectin(fFN) and cervical length (CL) testing from 22-32 weeks
Mean GA atdelivery(weeks)
Risk for spontaneous preterm birth*
<28weeks
<30weeks
<32weeks
<34weeks
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 reducesvasoconstriction in the placentaNathaniel Miller1, Brad Dolinsky1, Peter G. Napolitano2
1Madigan Healthcare System, Obstetrics and Gynecology,Tacoma, WA, 2Madigan Healthcare System, Departmentof Obstetrics and Gynecology, Tacoma, WAOBJECTIVE: Current clinical guidelines recommend the use of proges-terone therapy for reduction of preterm birth in high risk patients.
www.AJOG.org Doppler Assessment, Fetus, Prematurity Poster Session III
Supplement to JANUARY 2012 American Journal of Obstetrics & Gynecology S233