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
Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, United States.
Division of Developmental Neuroscience, New York State Psychiatric Institute, New York, NY, United States.
Front Physiol. 2021 Jul 30;12:594605. doi: 10.3389/fphys.2021.594605. eCollection 2021.
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, = 4025, Northern Plains, = 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.
产前烟草和酒精暴露（PTE和PAE）与出生结局及儿童发育之间的负相关关系已有充分记录，但对其潜在机制的了解较少。与PTE和PAE相关的不良胎儿结局的一个可能途径是胎儿自主神经系统发育的改变。本研究评估了PTE和PAE对胎儿自主调节指标的影响，这些指标通过心率（HR）、心率变异性（SD-HR）、胎动以及孕龄≥34周胎儿群体中的心率-胎动耦合来量化。参与者是安全通道研究的一个子集，这是一项前瞻性队列研究，招募了来自南非开普敦临床地点和美国北部平原地区的孕妇。PAE分为六个等级：不饮酒、早期低量戒酒、早期高量戒酒、持续低量饮酒、持续中等量饮酒和持续高量饮酒；而PTE分为四个等级：不吸烟、早期戒烟、持续低量吸烟和中等量/高量持续吸烟。采用自主测量指标的线性回归分析，并对胎儿性别、评估时的孕龄、地点、母亲教育程度、家庭拥挤程度和抑郁情况进行控制。分析还按睡眠状态（1F和2F）和地点（南非，n = 4025；北部平原，n = 2466）进行分层。最终样本包括在孕晚期评估的6491对母婴二元组[平均孕周35.21 ± 1.26（均值 ± 标准差）周]。仅对于孕早期后继续吸烟母亲的胎儿，PTE与2F状态下平均心率的降低呈剂量依赖性相关。在1F状态下，母亲在孕早期戒烟的胎儿平均心率显著增加。这种效应由北部平原队列驱动。PTE还与暴露程度最高组的胎儿胎动显著减少相关。在南非，早期高量戒酒组和持续高量饮酒组的平均心率均显著增加。总之，本研究填补了关于PTE和PAE与胎儿自主调节之间关系的关键知识空白。我们相信这些结果有助于阐明不良结局风险的潜在机制。
