New Study – Prenatal supplementation with marine omega-3 DHA results in epigenetic changes in the resulting infants

By Rob Winwood

A new, large study from Australia (1) has demonstrated that maternal supplementation with DHA in the second half of pregnancy was associated with epigenetic changes, through DNA methylation, of a small subset of genomic regions in the infants. The relevant genes are involved in a diverse range of biological processes including immune function and neurodevelopment.

The exposure of the human fetus to adverse environments, e.g., malnutrition, micronutrient deficiency and smoking are known to affect the infant epigenome. These epigenetic changes occur mainly through methylation of DNA at specific sites. An increased prenatal supply of the marine omega-3 fatty acid DHA (docosahexaenoic acid) has been associated with improved metabolic health and reduced risk of allergy in the infant (2,3). In one study, DHA and EPA have been shown to alter the methylation of specific single-strand DNA in adult humans at specific CpG (5-Cytosine-Phosphate–Guanine-3) regions (4).

A new study utilized blood samples taken at birth and at five years of age from a large randomized trial in Australia (4) called DOMInO (DHA to Optimise Mother Infant Outcome) where the mothers were given a daily supplement of 800mg DHA and 100mg EPA (eicosapentaenoic acid) during the second half of pregnancy. A total of 669 mother/child blood samples were analyzed for any changes in methylation of DNA.

When compared with the placebo arm, the infants whose mothers received prenatal DHA supplementation showed no differences in the overall degree of methylation of DNA either at birth or five years of age. However, 21 differentially methylated regions (DMR) of DNA were found, some of which were still apparent at five years of age, indicating that permanent epigenetic change had occurred. Curiously, there were 77% more of these DMR in male infants compared with females. It is likely that specific genetic sub-groups are more likely to benefit from these DMR than the population as a whole.

The authors (1) summarized their findings as follows: “In this large, well-characterised study population, we showed that maternal DHA supplementation across the second half of pregnancy was associated with modest alterations in DNA methylation in a small subset of genomic regions with genes involved in diverse biological processes.”

1. Van Dijk SJ, Zhou J, Peters TJ et al.; “Effect of prenatal DHA supplementation on the infant epigenome: results from a randomized controlled trial”; Clinical Epigenetics 2016, 8(1), 114. http://doi.org/10.1186/s13148-016-0281-7
2. De Giuseppe R, Roggi C& Cena H ; “n-3 LC-PUFA supplementation: effects on infant and maternal outcomes”; Eur J Nutr 2014; 53(5):1147–54.
3. Hauner H, Brunner S & Amann-Gassner U; “The role of dietary fatty acids for early human adipose tissue growth.”; Am J Clin Nutr  2013; 98(2):549S–55.
4. Hoile SP, Clarke-Harris R, Huang R-C et al.; “Supplementation with N-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells”; PLoS One. 2014; 9(10):e109896.
5. Makrides M, Gibson RA, McPhee AJ et al.; “Effect of DHA supplementation during pregnancy on maternal depression and neurodevelopment of young children: a randomized controlled trial”; JAMA 2010; 304(15):1675–83.