Relationships between the maternal prenatal diet and epigenetic state in infants: a systematic review of human studies

Abstract Most human studies investigating the relationship between maternal diet in pregnancy and infant epigenetic state have focused on macro- and micro-nutrient intake, rather than the whole diet. This makes it difficult to translate the evidence into practical prenatal dietary recommendations. To review the evidence on how the prenatal diet relates to the epigenetic state of infants measured in the first year of life via candidate gene or genome-wide approaches. Following the PRISMA guidelines, this systematic literature search was completed in August 2020, and updated in August 2021 and April 2022. Studies investigating dietary supplementation were excluded. Risk of bias was assessed, and the certainty of results was analysed with consideration of study quality and validity. Seven studies were included, encompassing 6852 mother-infant dyads. One study was a randomised controlled trial and the remaining six were observational studies. There was heterogeneity in dietary exposure measures. Three studies used an epigenome-wide association study (EWAS) design and four focused on candidate genes from cord blood samples. All studies showed inconsistent associations between maternal dietary measures and DNA methylation in infants. Effect sizes of maternal diet on DNA methylation ranged from very low (< 1%) to high (> 10%). All studies had limitations and were assessed as having moderate to high risk of bias. The evidence presented here provides very low certainty that dietary patterns in pregnancy relate to epigenetic state in infants. We recommend that future studies maximise sample sizes and optimise and harmonise methods of dietary measurement and pipelines of epigenetic analysis.