Poster Session IV ajog.org

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Prenatal nicotine exposure is associated withalterations of the postnatal offspring epigenomeMelissa Suter1, Adi Abramovici2, Emily Griffin1, D. Ware Branch4,Robert Lane5, Joan Mastrobattista1, Virender Rehan3,Kjersti Aagaard11Baylor College of Medicine, Houston, TX, 2University of Texas HealthScience Center of Houston, Houston, TX, 3Los Angeles Biomedical ResearchInstitute at Harbor-UCLA Medical Center, Torrance, CA, 4University of Utah,Salt Lake City, UT, 5Medical College of Wisconsin, Milwaukee, WIOBJECTIVE: How the fetus responds to and adapts to nicotineexposure is a major public health issue. Fetal exposure to nicotineis not limited to maternal tobacco smoke: pregnant women whoutilize nicotine replacement therapy or electronic cigarettessimilarly expose their fetus. Primate studies have shown thatnicotine exposure in utero renders offspring susceptible to asthmaas well as learning and memory deficits later in life, and nicotineexposure in adult mice potentitates cocaine addiction. The mo-lecular mechanisms underlying these observations are poorlyunderstood. We hypothesized that nicotine exposure would beassociated with epigenetic changes in the offspring lung and brainwhich may contribute to a molecular memory of this in uteroexposure and render suspetibility to later in life disease and riskof addiction.STUDY DESIGN: Timed mated Sprague-Dawley rat dams receivedeither saline or 2mg/kg of nicotine by intraperitoneal injection in100ul volumes once daily from embryonic day 6 (e6) to e22. Pupswere sacrificed on day 1 of life following spontaneous term delivery,and tissue was harvested (N¼3 per group). Histones were isolatedfrom offspring lung and whole brain tissue by acid extraction andused for Western blotting. Histone deacetylase (HDAC) assays wereperformed on nuclear extracts.RESULTS: Nicotine exposed offspring have altered histone modifi-cations in the brain. Dimethylation of lysine 9 of histone H3 isdecreased (0.43-fold, p¼0.03) while acetylation is significantlyincreased (1.79-fold, p¼0.031). HDAC activity is significantlydecreased with nicotine exposure in both brain and lung (0.11-fold,p<0.001; 0.12-fold, p<0.001, respectively).CONCLUSION: In utero nicotine exposure is associated with anepigenetic reprogramming of the offspring brain, as well asdecreased HDAC activity in the brian and lung. This exposure maybe priming the fetal brain for later in life addiction. These resultsfurther demonstrate that no amount of nicotine is known to be safein pregancy.

Prenatal nicotine exposure alters the brain epigeneome in postnataloffspring. In the brain, levels of H3K4me2 are decreased whileH3K9ac levels are increased with nicotine exposure compared withcontrol. Neither modifications significantly differ in offspring lungtissue.

S334 American Journal of Obstetrics & Gynecology Supplement to JANUARY

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Fetal heart rate baseline in labor: is change normal?Michael Yang1, Molly Stout1, Ryan Colvin1, George Macones1,Alison Cahill11Washington University in St. Louis School of Medicine, Saint Louis, MOOBJECTIVE: Changes in normal baseline are observed daily during themanagement of labor with electronic fetal monitoring (EFM), butthe expected physiologic baseline change has never been defined ininfants with normal outcomes. We aimed to describe the incidenceand characteristics of baseline change among normal term neonatesin labor.STUDY DESIGN: Within an ongoing prospective cohort study of allconsecutive singleton, nonanomalous, term pregnancies, weincluded women with continuous EFM in the last 2 hours of labor.To describe normal, physiologic baseline change, we excluded infantsadmitted to the NICU or with acidemia (umbilical cord arterial pH<7.10), 5 minute Apgar score <4, or any bradycardia or tachycardia.EFM was extracted by trained obstetric research nurses blind toclinical information or outcomes, using the NICHD criteria. Wedivided the trace into 10 minute epochs, determined baseline foreach, and evaluated change between any 2 epochs meeting theNICHD defined �15 bpm and �10 minutes. We defined changeamplitude as maximum baseline minus minimum and trajectory asthe final baseline minus initial from a regression line of baseline FHRover the 2 hours. Each 10 minute period was classified as greaterthan, less than, or equal to the final 10 minutes. Incidence of baselinechange was estimated, and univariable and multivariable analyseswere performed.RESULTS:Of 2,983 women who gave birth to a normal, term neonate,264 (8.9%) had a baseline change of �30 bpm, and 1,240 (41.6%)had a baseline change of �20 bpm. The average trajectory was0.12�0.93 bpm. Across the final 2 hours of labor for all women(n¼32,813 epochs), 15,713 (47.9%) epochs were equal in baseline tothe final 10 minutes; 8,130 (24.8%) were higher, and 8,970 (27.3%)were lower.CONCLUSION: In labor of healthy term infants, baseline changeswithin the normal range are common, often with 20 or 30 bpmmagnitudes, and occur equally in the increasing or decreasing di-rection. Observation of these normal physiologic changes should beexpected during term labor management.

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Assessing the impact of smoke-free legislation onperinatal health in the netherlandsMyrthe Peelen1, Aziz Sheikh2, Marjolein Kok1, Luc Zimmerman3,Boris Kramer3, Ben Mol4, Jasper Been51Academic Medical Center, Amsterdam, Netherlands, 2The University ofEdinburgh, Centre for Population Health Sciences, Edinburgh, UnitedKingdom, 3Maastricht University Medical Center, Department of Paediatrics,Maastricht, Netherlands, 4University of Adelaide, The Robinson Institute,School of Paediatrics and Reproductive Health, Adelaide, SA, Australia,5Maastricht University Medical Center, School for Public Health and PrimaryCare (CAPHRI), Maastricht, NetherlandsOBJECTIVE: To study the association between the introduction ofsmoke-free legislation in The Netherlands and perinatal outcome.STUDY DESIGN: We performed a national quasi-experimental studyusing data from the Netherlands Perinatal Registry between 2000

2015