Association Between Prenatal Exposure to Alcohol and Tobacco and Neonatal Brain Activity

Lauren C Shuffrey,Maristella Lucchini,Larry Burd,Morgan E Nelson,Amy J Elliott,Timothy N Ochoa ,Joseph R Isler,Hein J Odendaal,Nicolò Pini,J David Nugent,Carlie Du Plessis,Jyoti Angal,Michael Myers ,Lucy Brink,Ayesha Sania,Christa Friedrich,Coen Groenewald,Carmen Condon,William P Fifer

doi:10.1001/jamanetworkopen.2020.4714

Abstract

Research to date has not determined a safe level of alcohol or tobacco use during pregnancy. Electroencephalography (EEG) is a noninvasive measure of cortical function that has previously been used to examine effects of in utero exposures and associations with neurodevelopment. To examine the association of prenatal exposure to alcohol (PAE) and tobacco smoking (PTE) with brain activity in newborns. This prospective cohort study enrolled mother-newborn dyads from December 2011 through August 2015, with data analyzed from June 2018 through June 2019. Pregnant women were recruited from clinical sites in Cape Town, South Africa, and the Northern Plains region of the US. Participants were a subset of newborns enrolled in the Safe Passage Study. Exclusions included birth at less than 37 or more than 41 weeks' gestation, multiple birth, or maternal use of psychiatric medication during pregnancy. PAE and PTE groups were determined by cluster analysis. Analyses of covariance were run on EEG spectral power at 12 scalp locations across the frequency spectrum from 1 to 45 Hz in 3-Hz bins by sleep state. The final sample consisted of 1739 newborns (median [interquartile range] gestational age at birth, 39.29 [1.57] weeks; 886 [50.9%] were female; median [interquartile range] newborn age at assessment, 48.53 [44.96] hours). Newborns whose mothers were in the low continuous (95% CI, -0.379 to -0.031; P < .05; 95% CI, -0.379 to -0.045; P < .05), quit (95% CI, -0.419 to -0.127; P < .001; 95% CI, -0.398 to -0.106; P < .005), and moderate or high continuous (95% CI, -0.430 to -0.124; P < .001; 95% CI, -0.420 to -0.119; P < .005) PAE clusters had increased 4- to 6-Hz and 7- to 9-Hz left-temporal EEG power. Newborns with moderate or high continuous PTE had decreased 19- to 21-Hz (95% CI, 0.034 to 0.327; P < .05) and 22- to 24-Hz (95% CI, 0.022 to 0.316; P < .05) right-central EEG compared with newborns with no PTE. Newborns with moderate or high continuous PTE had significantly decreased 22- to 36-Hz right-central EEG power compared with the quit smoking group (22-24 Hz, 95% CI, 0.001 to 0.579; P < .05; 25-27 Hz, 95% CI, 0.008 to 0.586; P < .05; 28-30 Hz, 95% CI, 0.028 to 0.607; P < .05; 31-33 Hz, 95% CI, 0.038 to 0.617; P < .05; 34-36 Hz, 95% CI, 0.057 to 0.636; P < .05). These findings suggest that even low levels of PAE or PTE are associated with changes in offspring brain development.

Highlights

Negative long-term effects of excessive prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) on risk for multiple adverse outcomes have been well established
Newborns with moderate or high continuous PTE had decreased 19- to 21-Hz and 22- to 24-Hz right-central EEG compared with newborns with no PTE
Newborns with moderate or high continuous PTE had significantly decreased 22- to 36-Hz right-central EEG power compared with the quit smoking group (22-24 Hz, 95% CI, 0.001 to 0.579; P < .05; 25-27 Hz, 95% CI, 0.008 to 0.586; P < .05; 28-30 Hz, 95% CI, 0.028 to 0.607; P < .05; 31-33 Hz, 95% CI, 0.038 to 0.617; P < .05; 34-36 Hz, 95% CI, 0.057 to 0.636; P < .05)

Summary

Introduction

Negative long-term effects of excessive prenatal alcohol exposure (PAE) and prenatal tobacco exposure (PTE) on risk for multiple adverse outcomes have been well established. PAE is the leading cause of preventable intellectual disability, and smoking during pregnancy is one of the most modifiable causes of perinatal morbidity and mortality.[1,2] Understanding the associations of quantity, timing, and various combinations of in utero alcohol and smoking exposures with early brain function could help identify mechanisms that underlie adverse long-term neurobehavioral outcomes. Assessing neonatal brain activity through electroencephalography (EEG) provides a means of examining potential associations of PAE and PTE with brain activity in the immediate postnatal period. Less is known regarding the development of EEG power during the neonatal period, developmental changes in oscillatory activity are postulated to reflect decreases in synaptic density that underlie neural pruning to increase functional specialization.[7,8] EEG power in newborns has been shown to predict developmental outcomes at later ages when controlling for gestational age at birth and sleep state.[9,10,11,12,13] there is significant heterogeneity in prior studies, relative to neurotypical populations, infants at risk for developmental disorders often exhibit atypical developmental trajectories in neural oscillations, such as increased delta and theta or decreased beta or gamma power.[14,15,16,17,18,19,20,21,22]

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