Maternal caffeine intake and DNA methylation in newborn cord blood.

BACKGROUND: Epigenetic 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. OBJECTIVES: We examined preconception and pregnancy caffeine exposure with DNAm alterations in neonate cord blood (n = 378). METHODS: In 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 ß values using multivariable robust linear regression. A false discovery rate (FDR) correction was applied using the Benjamini-Hochberg method. RESULTS: In 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 (ß = 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 (ß = -0.013; SE = 0.002; FDR P = 0.036). No associations with self-reported intake during pregnancy were found. CONCLUSIONS: Few effects of maternal caffeine exposure on neonate methylation differences in leukocytes were identified in this population with relatively low caffeine consumption.