Poster Session V Prematurity, Physiology www.AJOG.org

STUDY DESIGN: Employing a robust population-based database withbiorepository, we selected for subjects with well documented pre-pregnancy or early pregnancy BMI. GWG was analyzed by validatedgestational age adjusted formulas. Random banked maternal serumspecimens (n¼120) from this nested cohort were analyzed for in-flammatory or oxidative pathway intermediates (12 analytes in total)using the Luminex xMap system.RESULTS: 731 subjects met strict study inclusion criteria. As shown inthe table, excess GWG was associated with gestational hypertensivedisorders (p¼.008), and unplanned CD for fetal indications or labordystocia (p¼.034). Conversely, obesity was associated with PTB(p¼.015) and GA adjusted birthweight >95th% (p¼.045). Whenadjusted for time to event (Poisson regression) incidence-rate ratioswere greater with GWG (Table). After controlling for confounders,obese gravidae with excess GWG had a 2.26-fold higher rate of PTB.Stratifying by BMI, Leptin and C-Peptide levels were noted to beconsistently elevated for excess GWG within each BMI cohort.CONCLUSION: In this cohort, independent of maternal BMI, excessweight gain was associated with hypertensive disorders and un-planned cesarean. GWG was similarly associated with increasedleptin and C-peptide levels at the time of delivery, consistent withexcess gain mediating the pro-inflammatory and insulin resistantstate previously attributed to obesity. Such aberrations in the in-flammatory cascade may contribute to adverse pregnancy outcomes,suggesting that the physiologic process of GWG can turn pathologicin excess.

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Vitamin D reduces TNF-a induced MMP-9 activity inhuman fetal airway smooth muscle cellsArij Faksh1, Rodney Britt3, Elizabeth Vogel3, Elizabeth Baldwin1,Mari Charisse Trinidad1, Wendy White1, Brian Brost1,Norman Davies1, Carl Rose1, Kristi Borowski1, Christina Pabelick2,Ys Prakash21Mayo Clinic College of Medicine, Maternal Fetal Medicine, Rochester, MN,2Mayo Clinic College of Medicine, Anesthesiology, Rochester, MN, 3MayoClinic College of Medicine, Physiology & Biomedical Engineering, Rochester,MN

OBJECTIVE: Premature infants are at risk of developing lung diseasesincluding asthma. There is a link between antenatal inflammationand airway remodeling that predisposes infants and children todevelopment of asthma and/or wheezing. Clinically, these airwaydiseases appear to be modified by maternal nutritional status, withstudies demonstrating inverse relationships between Vitamin Dlevels and prematurity, chronic lung disease, and childhood asthma.Using human fetal airway smooth muscle cells (fASMC) as an invitro model of the developing airway, we explored the hypothesisthat Vitamin D blunts the effects of inflammation in regard toextracellular matrix remodeling, thus alleviating structural airwaychanges that would contribute to asthma.

S340 American Journal of Obstetrics & Gynecology Supplement to JANUARY

STUDY DESIGN: Human fASMC were obtained from tracheobronchialtrees from the canalicular stage (18-20 weeks gestation). Cells weregrown to confluence, serum deprived for 24 hours, pre-treated withvehicle or 100 nM Vitamin D, and then treated with vehicle or 10 ng/mL TNF-a. Quantitative RT-PCR was used to examine componentsof the extracellular matrix including: matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9 (MMP-9) and collagen-I.Gelatinase zymography was performed to examine MMP-2 andMMP-9 activity. Extracellular deposition of collagen-I, collagen-IIIand fibronectin by cells across groups was determined.RESULTS: Vitamin D significantly reduced TNF-a induced MMP-9mRNA expression levels and activity, but did not significantly affectMMP-2. Vitamin D decreased MMP-9 expression, but did not affectMMP-2, collagen-I or collagen-III mRNA. Deposition of extracel-lular matrix proteins which was enhanced by TNF-a was substan-tially blunted by Vitamin D.CONCLUSION: Our findings demonstrate that Vitamin D can sub-stantially influence extracellular matrix composition in the setting ofairway inflammation. These in vitro studies suggest that Vitamin Dmay be a useful and safe therapeutic strategy for blunting thedetrimental effects of inflammation in the developing airway.

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Neonatal and childhood outcomes following early vslater preterm premature rupture of membranes (PPROM)Tracy Manuck1, Michael Varner11University of Utah, Obstetrics and Gynecology, Salt Lake City, UT

OBJECTIVE: Early PPROM (rupture <24.0 wks) has traditionally beenassociated with poor outcomes. Long term outcome data followingearly PPROM are limited. We hypothesized that babies deliveredafter early PPROM have higher rates of major childhood morbidityvs. those with later PPROM.STUDY DESIGN: Secondary analysis of a multicenter RCT of antenatalmagnesium sulfate (Mg) vs. placebo administered to women atimminent risk for early (<32 wk) PTB to prevent death and cerebralpalsy (CP) in their offspring. Women with non-anomalous single-tons and PPROM <32 wks were included. All women delivered�24.0 wks. Early PPROM (<24.0 wks) cases were compared to laterPPROM (24.0-31.9 wks) controls. Composite severe neonatalmorbidity (sepsis, grade III-IV IVH, PVL, severe NEC, BPD, and/ordeath) and composite severe childhood morbidity at age 2 [mod-erate/severe cerebral palsy (CP) and/or Bayley MDI or PDI scores >2SD below the mean] were compared.RESULTS: 1691 women with PPROM (133 early PPROM cases) wereincluded. Maternal age, race/ethnicity, and parity were similar be-tween groups. Cases delivered earlier (27.0 vs. 30.1 wks, p<0.001)but had a longer rupture-to-delivery interval (29.0 vs. 12.5 days,p<0.001). Case neonates had high rates of severe composite neonatalmorbidity (73.7% vs. 27.4% of controls, p<0.001). 33 (24.8%) diedby age 15 months (vs. 6.5% of controls, p<0.001). 100 early PPROMchildren survived; they had higher rates of composite severe child-hood morbidity at age 2 (46% vs. 21.4% for control children,p<0.001). Data were similar when those randomized to Mg wereanalyzed separately. Early PPROM remained associated with com-posite severe childhood morbidity/mortality in multivariable models(Table).CONCLUSION: Early PPROM is associated with high rates of neonatalmorbidity and early death. Early childhood outcomes remain poor;those surviving to age 2 after early PPROM had more than a 2.5-foldrisk of adverse childhood outcomes compared with children deliv-ered after later (24-31.9 wks) PPROM.

2014