Effect of prenatal DHA supplementation on the infant epigenome: results from a randomized controlled trial

Abstract

BackgroundEvidence is accumulating that nutritional exposures in utero can influence health outcomes in later life. Animal studies and human epidemiological studies have implicated epigenetic modifications as playing a key role in this process, but there are limited data from large well-controlled human intervention trials.This study utilized a large double-blind randomized placebo-controlled trial to test whether a defined nutritional exposure in utero, in this case docosahexaenoic acid (DHA), could alter the infant epigenome. Pregnant mothers consumed DHA-rich fish oil (800 mg DHA/day) or placebo supplements from 20 weeks’ gestation to delivery. Blood spots were collected from the children at birth (n = 991) and blood leukocytes at 5 years (n = 667). Global DNA methylation was measured in all samples, and Illumina HumanMethylation450K BeadChip arrays were used for genome-wide methylation profiling in a subset of 369 children at birth and 65 children at 5 years.ResultsThere were no differences in global DNA methylation levels between the DHA and control group either at birth or at 5 years, but we identified 21 differentially methylated regions (DMRs) at birth, showing small DNA methylation differences (<5%) between the treatment groups, some of which seemed to persist until 5 years. The number of DMRs at birth was greater in males (127 DMRs) and in females (72 DMRs) separately, indicating a gender-specific effect.ConclusionMaternal DHA supplementation during the second half of pregnancy had small effects on DNA methylation of infants. While the potential functional significance of these changes remains to be determined, these findings further support the role of epigenetic modifications in developmental programming in humans and point the way for future studies.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12605000569606 and ACTRN12611001127998 Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0281-7) contains supplementary material, which is available to authorized users.

Nutritional Gaps and Supplementation in the First 1000 Days

“…The level of omega-3 fatty acids in the mother's bloodstream during pregnancy has been shown to correlate with insulin levels [46] and adiposity [47]. Newer lines of inquiry have indicated that prenatal DHA during the second half of pregnancy alters the infant epigenome (gene activity changes that do not affect the DNA sequence) and can alter developmental programming [48].…”

Impact of Micronutrient Status during Pregnancy on Early Nutrition Programming

“…A recent randomized controlled trial providing the omega-3 polyunsaturated fatty acid (n-3 PUFA) DHA to pregnant women reported differences in methylation in some DNA regions in their children relative to a control group [38].…”

The interaction between gut microbiome and nutrients on development of human disease through epigenetic mechanisms

“…BMI, body mass index. epigenetic mechanism, it was reported that maternal omega-3 PUFA induced changing of methylation level in differentially methylated regions [12] and the promoter methylation level of Interferon γ and IL13 [62]. Maternal omega-3 PUFAs regulated offspring obesity through recomposition of the gut microbiota, Epsilonproteobacteria, Bacteroides, Akkermansia, and Clostridia [63].…”

“…Non-coding RNA is an epigenetic mark that mediates epigenetic modification by environmental factors such as diet. Modification of chromatin architecture by epigenetic marks can be heritable and modify the risks of disease in later life (Table 1) [7][8][9][10][11][12][13][14][15][16][17].…”