Alcohol is a teratogen that disrupts fetal brain development via neural and glial mechanisms including proliferation, migration, synaptogenesis, and myelination [1]. This can lead to a variety of long-lasting physical, behavioral, and neurological deficits in children. Most large health organizations recommend abstaining from alcohol during pregnancy, yet prenatal health care providers do not always convey this advice [2], and nearly 10% of pregnant individuals report consuming alcohol [3].
A growing literature has used magnetic resonance imaging (MRI) to highlight widespread structural and functional brain differences associated with prenatal alcohol exposure (PAE) [4]. However, most human studies have focused on heavy PAE (≥4 drinks/week) and/or a diagnosis of fetal alcohol spectrum disorder (which requires heavy PAE or the sentinel facial features associated with heavy PAE). Furthermore, most human studies struggle to obtain accurate exposure information, and have been unable to separate the effects of PAE from other factors such as socioeconomic status and prenatal exposure to other substances. These factors affect brain development and confound interpretation in many existing studies. Thus, there is little robust evidence for brain changes associated with low PAE, which is one reason why some pregnant individuals and prenatal health care providers perceive small amounts of alcohol as ‘safe’ during pregnancy [2].
New, emerging evidence has challenged these assumptions. One MRI study showed altered brain volumes in occipital, temporal, and parietal areas in a large sample of children (mean age = 9.9 years) with low PAE (average < 1 drink/week) [5]. In a recent study, we described weaker structural brain connectivity in 9–10 year old children with low PAE (1 drink/week) compared to unexposed controls matched on child age, sex, family income, maternal education, and caregiver status; neither group had other prenatal substance exposures. Children with PAE had lower fractional anisotropy, measured by diffusion MRI, in left postcentral, parietal, temporal and bilateral occipital white matter (Fig. 1) [6]. These human studies provide clearer evidence of brain alterations associated with low PAE, and more robustly show that brain alterations are associated with alcohol specifically, compared to previous studies with sociodemographic and other exposure mismatches between exposed and control groups.
Fig. 1. Low levels of PAE are associated with brain fractional anisotropy (FA) in children.
A recent study of children with low levels of PAE (average = 1 drink/week) found lower FA in 5 subcortical white matter brain regions.
Together, these new studies highlight the importance of considering any amount of PAE, both in clinical practice and research studies. From a policy perspective, these findings provide strong evidence to support recommendations against any alcohol consumption during pregnancy and should be highlighted in policy documents. For research, these results emphasize the need to consider PAE as a potential confound in studies of brain development, developmental disorders, diseases, or brain injuries.
Future studies should endeavour to carefully and prospectively quantify PAE, including via biosamples, to systematically investigate the effects of timing and amount of exposure, especially at the lower end of the spectrum. Longitudinal studies of low levels of PAE are also essential to understand patterns of brain growth. With careful and deliberate data collection across a variety of settings, the coming years will help provide further understanding of the effects of PAE on the developing brain and will ultimately support better policies and practices to improve child outcomes.
Author contributions
CL and XL conceptualized this work, drafted the manuscript, and critically revised the manuscript.
Funding
Salary support was provided by the Canada Research Chair program (CL).
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Goodlett CR, Horn KH, Zhou FC. Alcohol teratogenesis: mechanisms of damage and strategies for intervention. Exp Biol Med. 2005;230:394–406. doi: 10.1177/15353702-0323006-07. [DOI] [PubMed] [Google Scholar]
- 2.Coons KD, et al. “No Alcohol Is Recommended, But…”: health care students’ attitudes about alcohol consumption during pregnancy. Glob Qual Nurs Res. 2017;4:1–18. doi: 10.1177/2333393617707663. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Popova S, et al. Estimation of national, regional, and global prevalence of alcohol use during pregnancy and fetal alcohol syndrome: a systematic review and meta-analysis. Lancet Glob Health. 2017;5:e290–e299. doi: 10.1016/S2214-109X(17)30021-9. [DOI] [PubMed] [Google Scholar]
- 4.Donald KA, et al. Neuroimaging effects of prenatal alcohol exposure on the developing human brain: a magnetic resonance imaging review. Acta Neuropsychiatr. 2015;27:251–69. doi: 10.1017/neu.2015.12. [DOI] [PubMed] [Google Scholar]
- 5.Lees B, et al. Association of prenatal alcohol exposure with psychological, behavioral, and neurodevelopmental outcomes in children from the adolescent brain cognitive development study. Am J Psychiatry. 2020;177:1060–72. doi: 10.1176/appi.ajp.2020.20010086. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Long X, Lebel C. Evaluation of brain alterations and behavior in children with low levels of prenatal alcohol exposure. JAMA Netw Open. 2022;5:e225972. doi: 10.1001/jamanetworkopen.2022.5972. [DOI] [PMC free article] [PubMed] [Google Scholar]