Dataset Information

Maternal fatty acid concentrations and newborn DNA methylation.

ABSTRACT:

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 ?-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 ?-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.

SUBMITTER: Robinson SL

PROVIDER: S-EPMC7049533 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Maternal fatty acid concentrations and newborn DNA methylation.

Robinson Sonia L SL Mumford Sunni L SL Guan Weihua W Zeng Xuehuo X Kim Keewan K Radoc Jeannie G JG Trinh Mai-Han MH Flannagan Kerry K Schisterman Enrique F EF Yeung Edwina E

The American journal of clinical nutrition 20200301 3

<h4>Background</h4>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.<h4>Objectives</h4>We examined the relations of maternal plasma FA concentrations at preconception (n = 346) and 8 weeks of gestation (n = 374) with newborn DNA methylation.<h4>Methods</h4>The Effects of Aspirin ...[more]

PMID: 31858113

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Project description:BackgroundEpigenetic mechanisms may underlie associations between maternal caffeine consumption and adverse childhood metabolic outcomes. However, limited studies have examined neonate DNA methylation (DNAm) patterns in the context of preconception or prenatal exposure to caffeine metabolites.ObjectivesWe examined preconception and pregnancy caffeine exposure with DNAm alterations in neonate cord blood (n = 378).MethodsIn a secondary analysis of the Effects of Aspirin in Gestation and Reproduction Trial (EAGeR), we measured maternal caffeine, paraxanthine, and theobromine concentrations from stored serum collected preconception (on average 2 months before pregnancy) and at 8 weeks of gestation. In parallel, self-reported caffeinated beverage intake was captured via administration of questionnaires and daily diaries. We profiled DNAm from the cord blood buffy coat of singletons using the MethylationEPIC BeadChip. We assessed associations of maternal caffeine exposure and methylation β values using multivariable robust linear regression. A false discovery rate (FDR) correction was applied using the Benjamini-Hochberg method.ResultsIn preconception, the majority of women reported consuming 1 or fewer servings/day of caffeine on average, and caffeine and paraxanthine metabolite levels were 88 and 36 µmol/L, respectively. Preconception serum caffeine metabolites were not associated with individual cytosine-guanine (CpG) sites (FDR >5%), though pregnancy theobromine was associated with DNAm at cg09460369 near RAB2A (β = 0.028; SE = 0.005; FDR P = 0.012). Preconception self-reported caffeinated beverage intake compared to no intake was associated with DNAm at cg09002832 near GLIS3 (β = -0.013; SE = 0.002; FDR P = 0.036). No associations with self-reported intake during pregnancy were found.ConclusionsFew effects of maternal caffeine exposure on neonate methylation differences in leukocytes were identified in this population with relatively low caffeine consumption.

Project description:BACKGROUND:Prenatal maternal plasma persistent organic pollutant (POP) concentrations have been associated with neonatal outcomes. However, the underlying mechanisms remain unknown. Placental epigenetic mechanisms may be involved, but no prior epigenome-wide studies have investigated the impact of maternal POPs on placental DNA methylation. We studied the association between maternal plasma POP concentration in early pregnancy and epigenome-wide placental DNA methylation among 260 pregnant women from the NICHD Fetal Growth Studies. RESULTS:Our analysis focused on POPs with more than 80% plasma concentrations above the limit of quantification, including 3 organochlorine pesticides (hexachlorobenzene, trans-nonachlor, p,p'-dichlorodiphenyldichloroethylene), 1 polybrominated diphenyl ether (PBDE 47), 3 polychlorinated biphenyls (138/158, 153, 180), and 6 poly- and perfluorinated alkyl substances (PFASs) (perfluorodecanoic acid, perfluorohexanesulfonic acid, perfluorononanoic acid, perfluorooctanesulfonic acid, perfluoroundecanoic acid (PFUnDA)). Using 5% false discovery rate, POPs were associated with a total of 214 differentially methylated CpG sites (nominal p values ranging from 2.61 × 10-21 to 2.11 × 10-7). Out of the 214 CpG sites, 24 (11%) were significantly correlated with placental expression of 21 genes. Notably, higher PFUnDA was associated with increased methylation at 3 CpG sites (cg13996963, cg12089439, cg18145877) annotated to TUSC3, and increased methylation at those 3 CpG sites was correlated with decreased expression of TUSC3 in the placenta. Increased methylation at cg18145877 (TUSC3) and decreased expression of TUSC3 were correlated with shorter birth length. Out of the 214 CpG sites, methylation at 44 CpG sites was correlated (p value < 0.10) with at least one neonatal anthropometry measure (i.e., birth weight, birth length, and head circumference). Seven CpG sites mediated (p value < 0.05) the association between PBDE 47 and neonatal anthropometry measures. Genes annotating the top differentially methylated CpG sites were enriched in pathways related to differentiation of embryonic cells (PBDE 47) and in pathways related to brain size and brain morphology (PFASs). CONCLUSIONS:DNA methylation changes in the placenta were significantly associated with maternal plasma POPs concentration. The findings suggest that placental DNA methylation and gene expression mechanism may be involved in the prenatal toxicity of POPs and their association with neonatal anthropometry measures.

Dataset Information

Maternal fatty acid concentrations and newborn DNA methylation.

Background

Objectives

Methods

Results

Conclusions

Publications

Maternal fatty acid concentrations and newborn DNA methylation.

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