Time- and Sex-Dependent Associations Between Prenatal Alcohol Exposure and Placental Global DNA Methylation

Abstract

Aim: Epigenetic changes, in particular in the placenta, may mediate the effects of prenatal alcohol exposure (PAE) on children’s health. We examined the relationship between PAE patterns, based on dose and timing, and placental global DNA methylation. Methods: Using linear regression analysis, we examined the association between different PAE categories and placental global DNA methylation (n = 187), using the proxy measure of Alu-interspersed repeats. Results: Following adjustment for important covariates, we found no evidence of an association between PAE and placental global DNA methylation overall. However, when stratifying by newborn sex, PAE throughout pregnancy was associated with higher placental global DNA methylation (1.5%; p = 0.01) of male newborns. Conclusion: PAE may have sex-specific effects on placental global DNA methylation if alcohol is consumed throughout pregnancy.

Keywords::

• global DNA methylation
• placenta
• prenatal alcohol exposure

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2017-0147

Authors contribution

J Halliday, JM Craig, E Muggli and R Saffery conceived and designed the study. E Muggli, J Halliday and E Elliott were involved in the design, recruitment and sample collection of Asking QUestions about Alcohol in pregnancy cohort. L Nguyen performed the lab work and generated DNA methylation data. YJ Loke analyzed the data under the supervision of J Ryan and E Muggli. YJ Loke, J Ryan, E Muggli, JM Craig, E Elliott and J Halliday wrote the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The authors are extremely grateful to all the women and their children who are taking part in this study and wish to thank the researchers who were involved in sample collection. Special mention to S Lewis who provided the Asking QUestions about Alcohol in pregnancy co-variates for analysis.

Financial & competing interests disclosure

This work was supported by the Australian National Health and Medical Research Council Grant #1011070; senior research fellowship #1021252 (J Halliday) and #1045161 (R Saffery), and practitioner fellowship #1021480 (E Elliott) and the Victorian State Government’s Operational Infrastructure Support Program. The study has also received funding from the McCusker Charitable Trust to assist with the biospecimen collection at birth. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

Informed and signed consent were obtained from all the participants involved. The Asking QUestions about Alcohol in pregnancy project was approved by the Eastern Health Research and Ethics Committee (E54/1011) and the Human Research Ethics Committees of Mercy Health (R11/14), Monash Health (11071B), the Royal Women’s Hospital (11/20) and the Royal Children’s Hospital (31055A).

Additional information

Funding

This work was supported by the Australian National Health and Medical Research Council Grant #1011070; senior research fellowship #1021252 (J Halliday) and #1045161 (R Saffery), and practitioner fellowship #1021480 (E Elliott) and the Victorian State Government’s Operational Infrastructure Support Program. The study has also received funding from the McCusker Charitable Trust to assist with the biospecimen collection at birth. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.