AUTHOR=Lucchini Maristella , Shuffrey Lauren C. , Nugent J. David , Pini Nicoló , Sania Ayesha , Shair Margaret , Brink Lucy , du Plessis Carlie , Odendaal Hein J. , Nelson Morgan E. , Friedrich Christa , Angal Jyoti , Elliott Amy J. , Groenewald Coen A. , Burd Larry T. , Myers Michael M. , Fifer William P. , Hankins Gary DV , Dukes Kimberly A , Sullivan Lisa M , Tripp Tara , Robinson Fay , Raffo Cheri , Petersen Julie M , Young Rebecca A , Mai Cindy , Grillo Elena , Baker Travis , Toland Gregory , Carmen Michael , Kinney Hannah C , Haynes Robin L , Folkerth Rebecca D , Holm Ingrid A , Boyd Theonia , Paterson David S , Steen Hanno , Markianos Kyriacos , Roberts Drucilla , Broadbelt Kevin G , Goldstein Richard G , Nelsen Laura L. , Cotton Jacob , Jacobs Perri , Elliott Amy J , Burd Larr , Angal Jyoti , Gromer Jessica , Hoyme H Eugene , Jackson Margaret , Mack Luke , Randall Bradley B , Sens Mary Ann , Tobacco Deborah , Eerden Peter Van , Odendaal Hendrik , Wright Colleen , Geerts Lut , Jong Greetje de , Schubert Pawel , Wadee Shabbir , Dempers Johan , Burger Elsie , Harbron Janetta , Groenewald Coen , Fifer William , Myers Michael , Isler Joseph , Sininger Yvonne , Nugent J David , Condon Carmen , Shair Margaret C , Thai Tracy , Willinger Marian , Hereld Dale , Hoffman Howard J , Li Chuan-Ming TITLE=Effects of Prenatal Exposure to Alcohol and Smoking on Fetal Heart Rate and Movement Regulation JOURNAL=Frontiers in Physiology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.594605 DOI=10.3389/fphys.2021.594605 ISSN=1664-042X ABSTRACT=

Negative associations of prenatal tobacco and alcohol exposure (PTE and PAE) on birth outcomes and childhood development have been well documented, but less is known about underlying mechanisms. A possible pathway for the adverse fetal outcomes associated with PTE and PAE is the alteration of fetal autonomic nervous system development. This study assessed PTE and PAE effects on measures of fetal autonomic regulation, as quantified by heart rate (HR), heart rate variability (SD-HR), movement, and HR-movement coupling in a population of fetuses at ≥ 34 weeks gestational age. Participants are a subset of the Safe Passage Study, a prospective cohort study that enrolled pregnant women from clinical sites in Cape Town, South Africa, and the Northern Plains region, United States. PAE was defined by six levels: no alcohol, low quit early, high quit early, low continuous, moderate continuous, and high continuous; while PTE by 4 levels: no smoking, quit early, low continuous, and moderate/high continuous. Linear regression analyses of autonomic measures were employed controlling for fetal sex, gestational age at assessment, site, maternal education, household crowding, and depression. Analyses were also stratified by sleep state (1F and 2F) and site (South Africa, N = 4025, Northern Plains, N = 2466). The final sample included 6491 maternal-fetal-dyad assessed in the third trimester [35.21 ± 1.26 (mean ± SD) weeks gestation]. PTE was associated with a decrease in mean HR in state 2F, in a dose dependent fashion, only for fetuses of mothers who continued smoking after the first trimester. In state 1F, there was a significant increase in mean HR in fetuses whose mother quit during the first trimester. This effect was driven by the Norther Plains cohort. PTE was also associated with a significant reduction in fetal movement in the most highly exposed group. In South Africa a significant increase in mean HR both for the high quit early and the high continuous group was observed. In conclusion, this investigation addresses a critical knowledge gap regarding the relationship between PTE and PAE and fetal autonomic regulation. We believe these results can contribute to elucidating mechanisms underlying risk for adverse outcomes.