Maternal fatty acid concentrations and newborn DNA methylation.

Background: Preconception nutrition sets the stage for a healthy pregnancy. Maternal fatty acids (FAs) are related to beneficial neonatal outcomes with DNA methylation proposed as a mechanism; however, few studies have investigated this association and none with preconception FAs. Objectives: We examined the relations of maternal plasma FA concentrations at preconception (n = 346) and 8 weeks of gestation (n = 374) with newborn DNA methylation. Methods: The Effects of Aspirin in Gestation and Reproduction Trial (2006-2012) randomly assigned women with previous pregnancy loss to low dose aspirin or placebo prior to conception. We measured maternal plasma phospholipid FA concentration at preconception (on average 4 mo before pregnancy) and 8 weeks of gestation. Cord blood DNA from singletons was measured using the Methylation EPIC BeadChip. We used robust linear regression to test the associations of FA concentration with methylation beta-values of each CpG site, adjusting for estimated cell count using a cord blood reference, sample plate, maternal sociodemographic characteristics, cholesterol, infant sex, and epigenetic-derived ancestry. False discovery rate correction was used for multiple testing. Results: Mean +/- SD concentrations of preconception marine (20:5n-3+22:6n-3+22:5n-3) and omega-6 PUFAs, SFAs, MUFAs, and trans FAs were 4.7 +/- 1.2, 38.0 +/- 2.0, 39.4 +/- 1.8, 11.6 +/- 1.1, and 1.0 +/- 0.4 % of total FA, respectively; concentrations at 8 weeks of gestation were similar. Preconception marine PUFA concentration was associated with higher methylation at GRAMD2 (P = 1.1 x 10(-8)), LOXL1 (P = 5.5 x 10(-8)), SIK3 (P = 1.6 x 10(-7)), HTR1B (P= 1.9x10(-7)), and MCC (P= 2.1x10(-7)) genes. Preconception SFA concentration was associated with higher methylation at KIF25-AS1 and lower methylation at SLC39A14; other associations exhibited sensitivity to outliers. The trans FA concentration was related to lower methylation at 3 sites and higher methylation at 1 site. FAs at 8 weeks of gestation were largely unrelated to DNA methylation. Conclusions: Maternal preconception FAs are related to newborn DNA methylation of specific CpG sites, highlighting the importance of examining nutritional exposures preconceptionally. This trial was registered at clinicaltrials.gov as NCT00467363.