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 MethylationEPIC BeadChip. We used robust linear regression to test the associations of FA concentration with methylation β-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 ω-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 × 10-8), LOXL1 (P = 5.5 × 10-8), SIK3 (P = 1.6 × 10-7), HTR1B (P = 1.9 × 10-7), and MCC (P = 2.1 × 10-7) 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.
Bibliographical noteFunding Information:
Supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, contract numbers HHSN267200603423, HHSN267200603424, HHSN267200603426, and HHSN275201300023I-HHSN2750008.
The authors’ contributions were as follows—SLM, EFS, and EHY: designed and conducted the research; WG: provided essential materials; XZ and SLR: performed the statistical analysis; SLR: wrote the manuscript; SLR and EHY: have primary responsibility for the final content; MT, KF, KK, and JGR: provided essential feedback in writing the manuscript; and all authors read and approved the final manuscript. JGR had been funded by the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and generous contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (Grant #2014194), Genentech, and alumni of student research programs and other individual supporters via contributions to the Foundation for the NIH. None of the other authors have any conflicts of interest related to this study. Data described in the manuscript, code book, and analytic code will be made available upon request.
© 2019 Published by Oxford University Press on behalf of the American Society for Nutrition 2019.
- DNA methylation
- mother-child dyads
- n-3 polyunsaturated fatty acids
- preconception nutrition
- saturated fatty acids
- trans fatty acids
PubMed: MeSH publication types
- Journal Article
- Multicenter Study
- Randomized Controlled Trial
- Research Support, N.I.H., Intramural