Association of prenatal alcohol exposure with offspring DNA methylation in mammals: a systematic review of the evidence

Mitchell Bestry; Martyn Symons; Alexander Larcombe; Evelyne Muggli; Jeffrey M Craig; Delyse Hutchinson; Jane Halliday; David Martino

doi:10.1186/s13148-022-01231-9

Association of prenatal alcohol exposure with offspring DNA methylation in mammals: a systematic review of the evidence

Clin Epigenetics. 2022 Jan 21;14(1):12. doi: 10.1186/s13148-022-01231-9.

Authors

Mitchell Bestry¹, Martyn Symons^{1

2}, Alexander Larcombe^{3

4}, Evelyne Muggli^{5

6}, Jeffrey M Craig^{6

7

8}, Delyse Hutchinson^{6

7

9

10

11}, Jane Halliday^{6

12}, David Martino^{13

14}

Affiliations

¹ Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.
² National Drug Research Institute, Faculty of Health Sciences, Curtin University, Perth, Australia.
³ Wal-yan Respiratory Research Centre, Telethon Kids Institute, Perth, Australia.
⁴ School of Population Health, Curtin University, Perth, Australia.
⁵ Victorian Infant Brain Studies, Murdoch Children's Research Institute, Parkville, VIC, Australia.
⁶ Department of Paediatrics, The University of Melbourne, Parkville, VIC, Australia.
⁷ Murdoch Children's Research Institute, Parkville, VIC, Australia.
⁸ IMPACT - the Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, Geelong, Australia.
⁹ Centre for Social and Early Emotional Development and Centre for Drug, Alcohol and Addiction Research, School of Psychology, Faculty of Health, Deakin University, Geelong, Australia.
¹⁰ Centre for Adolescent Health, Royal Children's Hospital, Melbourne, Australia.
¹¹ National Drug and Alcohol Research Centre, University of New South Wales, Sydney, Australia.
¹² Public Health Genetics, Murdoch Children's Research Institute, Parkville, VIC, Australia.
¹³ Wal-yan Respiratory Research Centre, Telethon Kids Institute, Perth, Australia. david.martino@telethonkids.org.au.
¹⁴ Murdoch Children's Research Institute, Parkville, VIC, Australia. david.martino@telethonkids.org.au.

Abstract

Background: Prenatal alcohol exposure (PAE) is associated with a range of adverse offspring neurodevelopmental outcomes. Several studies suggest that PAE modifies DNA methylation in offspring cells and tissues, providing evidence for a potential mechanistic link to Fetal Alcohol Spectrum Disorder (FASD). We systematically reviewed existing evidence on the extent to which maternal alcohol use during pregnancy is associated with offspring DNA methylation.

Methods: A systematic literature search was conducted across five online databases according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Web of Science, EMBASE, Google Scholar and CINAHL Databases were searched for articles relating to PAE in placental mammals. Data were extracted from each study and the Risk of Bias in Non-Randomized Studies of Interventions (ROBINS-I) was used to assess the potential for bias in human studies.

Results: Forty-three articles were identified for inclusion. Twenty-six animal studies and 16 human studies measured offspring DNA methylation in various tissues using candidate gene analysis, methylome-wide association studies (MWAS), or total nuclear DNA methylation content. PAE dose and timing varied between studies. Risk of bias was deemed high in nearly all human studies. There was insufficient evidence in human and animal studies to support global disruption of DNA methylation from PAE. Inconclusive evidence was found for hypomethylation at IGF2/H19 regions within somatic tissues. MWAS assessing PAE effects on offspring DNA methylation showed inconsistent evidence. There was some consistency in the relatively small number of MWAS conducted in populations with FASD. Meta-analyses could not be conducted due to significant heterogeneity between studies.

Conclusion: Considering heterogeneity in study design and potential for bias, evidence for an association between PAE and offspring DNA methylation was inconclusive. Some reproducible associations were observed in populations with FASD although the limited number of these studies warrants further research. Trail Registration: This review is registered with PROSPERO (registration number: CRD42020167686).

Keywords: DNA methylation; Epigenetics; Fetal alcohol spectrum disorder; Pregnancy; Prenatal alcohol exposure.

Publication types

Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Alcohol Drinking / adverse effects*
Alcohol Drinking / physiopathology
Animals
DNA Methylation / genetics*
DNA Methylation / physiology
Female
Mammals / genetics*
Mammals / physiology
Pregnancy
Prenatal Exposure Delayed Effects / diagnosis*
Prenatal Exposure Delayed Effects / epidemiology
Prenatal Exposure Delayed Effects / physiopathology

Abstract

Publication types

MeSH terms

Grants and funding