506: Impairment of the placental barrier in response to activation of HIF-1α hypoxia-related...

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Page 1: 506: Impairment of the placental barrier in response to activation of HIF-1α hypoxia-related signaling

Poster Session III ajog.org

significantly higher risk of sPTB compared to women with a vaginaldelivery after a SS �2 hours. Future studies should investigate theetiology of this increased risk.

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The impact of labor length on adverse maternaloutcomes in women with severe preeclampsiaLisa Levine1, Meghana Limaye1, Mary Sammel2, Sindhu Srinivas11University of Pennsylvania Perelman School of Medicine, Maternal andChild Health Research Program Dept of Obstetrics and Gynecology,Philadelphia, PA, 2University of Pennsylvania Perelman School of Medicine,Department of Biostatics and Epidemiology, Center for ClinicalEpidemiology and Biostatistics, Philadelphia, PAOBJECTIVE: Expert opinion recommends an induction (IOL) forsevere preeclampsia (SPEC) be “carried out aggressively” and suggesta 24 hour time point for delivery. The effect that length of labor hason adverse maternal outcomes (AMO) in women with SPEC isunknown.STUDY DESIGN: Retrospective cohort study of women with SPEC whodelivered 7/2011-2/2013. Women were included if they had the SPECdiagnosis at the start of their planned cesarean (CD), IOL, oraugmentation of latent labor (AoLL) and were �34 wks. Womendiagnosed with SPEC in active labor were excluded. Our compositeAMO was defined as the presence of �1 of the following prior todischarge: liver/renal failure, thrombocytopenia, abruption, trans-fusion, pulmonary edema, DIC, stroke, eclampsia, ICU admission,death. Chi square analysis compared categorical data and logisticregression calculated odds and controlled for confounders (BMI,age, mode of delivery).RESULTS: 202 women were included. The overall AMO prevalencewas 14.8%. 22 women (11%) had a planned CD, and 180 (89%)labored (167 with IOL; 13 with AoLL). While not statistically sig-nificant, women that labored (n¼180), had a higher AMO comparedto those with a planned CD (n¼22), 15.6 vs. 9.1%, p¼0.4. Amongthose that labored, there was a significantly higher AMO rate inwomen delivered via CD compared to vaginal delivery (25.5 vs.12.3%, p¼0.03). When evaluating the effect that length of labor hason AMO, we found a 6% increase in the rate of AMO with eachadditional hour of labor after adjusting for confounder (aOR 1.06[1.01-1.11], p¼0.02). Women that labored for �24 hours had a 5.6fold higher odds of AMO compared to those that labored for <24hours after adjusting for confounders (aOR 5.61 [1.85-17.02],p¼0.002). Both prolonged labor (�24 hours) and mode of deliverycontribute to an increased risk of AMO (table).CONCLUSION: Length of labor and CD in labor are associatedwith AMO related to SPEC. Future studies should evaluate theoptimal length of labor and mode of delivery on AMO in womenwith SPEC.

S254 American Journal of Obstetrics & Gynecology Supplement to JANUARY

Reported as percentage AMO (number of patients)

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Impairment of the placental barrier in response toactivation of HIF-1a hypoxia-related signalingLissa Francois1, Kristin Bircsak2, Lauren Aleksunes21Robert Wood Johnson - Rutgers, Obstetrics, Gynecology and ReproductiveSciences, Nanuet, NY, 2Rutgers University, Ernest Mario School of Pharmacy,Department of Pharmacology and Toxicology, Piscataway, NJOBJECTIVE: The BCRP/ABCG2 transporter is expressed on syncy-tiotrophoblasts and removes chemicals from the placenta back to thematernal circulation. The purpose of this project was to determinewhether activation of signaling by the hypoxia inducible factor 1a(HIF-1a) using hypoxia mimetics alters the expression and functionof the BCRP efflux transporter.STUDY DESIGN: We hypothesize that treatment of BeWo placenta cellswith hypoxia mimetics activates HIF-1a-mediated transcription anddecreases BCRP protein expression and function. For this purpose,human choriocarcinoma BeWo cells were treated with vehicle, cobaltchloride (200 mM) or deferoxamine (200 mM) for 24 and 48 h. Cellswere collected for western blot and ELISA as well as assessment oftransport function and cell viability.RESULTS: In response to treatment with hypoxia mimetics, HIF-1aprotein levels increased by 5-fold as compared to controls. Theglucose transporter 1, a known hypoxia responsive protein, was up-regulated 2-fold at 24 and 48 h confirming the functional activationof the HIF-1a transcriptional pathway. Hypoxia mimetics decreasedBCRP protein expression by 50% at 48 h without reducing cellviability. Moreover, cobalt chloride increased the accumulation ofthe BCRP substrate, Hoechst 33342 in BeWo cells consistent withreduced efflux activity. In addition, treatment of naïve cells with theHIF-1a protein inhibitor, KC7F2, increased BCRP protein levels by2-fold.CONCLUSION: Low oxygen tension is part of the physiologic devel-opment of the placenta and is a feature of pathologic disorderssuch as IUGR. Our findings that HIF-1a activation decreases BCRPtransporter expression and function aligns with prior resultsdemonstrating reduced BCRP levels in first trimester trophoblastsexposed to hypoxic conditions (5% O2) as well as placentas fromIUGR babies. Taken together, these findings highlight potential pe-riods of pregnancy during which the placental barrier may becompromised.

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Use of allostatic load scoring to predict adversepregnancy outcomesM. Camille Hoffman1, Sara Mazzoni1, Amanda A. Allshouse2,Jennifer Hyer1, Nanette Santoro11University of Colorado/Denver Health Medical Center, Obstetrics &Gynecology, Denver, CO, 2University of Colorado Anschutz Medical Campus,Biostatistics, Aurora, COOBJECTIVE: Allostatic load (AL) is a term for the accumulation of“wear and tear” to the human body in response to chronic stress.Excess AL is a potential biologic pathway for adverse perinataloutcomes (APOs) in the presence of socioeconomic and de-mographic disparities. The objective of this study was to determinevariables for an AL scoring system predictive of APOs.STUDY DESIGN: This was a secondary analysis of data from theMaternal-Fetal Medicine Unit Network Preterm Prediction Study. Acomposite APO was defined as fetal, neonatal or maternal adverseevents and was compared with pregnancies resulting in uncompli-cated term deliveries. Over 40 demographic, co-morbidity, mooddisorder, stress and biomarker variables were compared betweenrecords by composite APO category (t-tests for continuous, X2 for

2015