Effects of Prenatal Exposure to Alcohol and Smoking on Fetal Heart Rate and Movement Regulation.

Maristella Lucchini,Lauren C Shuffrey,William P Fifer,Ayesha Sania,Christa Friedrich,Michael M Myers,Nicoló Pini,Hein J Odendaal,Lucy Brink,Amy J Elliott,Coen A Groenewald,Larry T Burd,Morgan E Nelson,J David Nugent,Jyoti Angal,Margaret Shair,Carlie Du Plessis

doi:10.3389/fphys.2021.594605

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.

Highlights

Many deleterious effects of alcohol consumption during pregnancy on fetal development, birth outcomes, and subsequent childhood development are well-documented (Popova et al, 2016)
We found a significant association between smoking and mean heart rate (HR) in state 1F, but only for women who quit before the end of the first trimester
Several studies have reported associations of smoking and drinking during pregnancy with negative gestational outcomes and health in offspring (Schoendorf and Kiely, 1992; Scragg et al, 1993; Cnattingius, 2004; Mamluk et al, 2017; Shuffrey et al, 2020). These reports clearly demonstrate there are adverse effects of Prenatal alcohol exposure (PAE) and Prenatal tobacco exposure (PTE), they do not provide information about the contributions of timing and amount of exposure on fetal autonomic nervous system (ANS) function. This current study addresses that shortcoming by focusing on assessments of fetal HR, HRSD, and movement during weeks 34 to 38 of pregnancy

Summary

Introduction

Many deleterious effects of alcohol consumption during pregnancy on fetal development, birth outcomes, and subsequent childhood development are well-documented (Popova et al, 2016). Prenatal tobacco exposure (PTE) has been associated with higher risk of negative outcomes including preterm birth and stillbirth as well as sudden infant death syndrome (SIDS), attention deficit hyperactivity disorder (ADHD) (Huang et al, 2018), and conduct disorder in offspring (Klonoff-Cohen and Lam-Kruglick, 2001; Cnattingius, 2004; Vardavas et al, 2010). A possible marker of effects of alcohol and smoking on fetal development is autonomic nervous system (ANS) activity as assessed through measures of fetal heart rate (HR) and heart rate variability (HRV). With increasing gestational age (GA), fetal HR tends to decrease while HRV increases, due to increased parasympathetic activity, maturation of central mechanisms, and more frequent occurrence of breathing movements (Cnattingius, 2004)

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