Insufficient gestational weight gain associated with higher DNA methylation in cord blood cells

Abstract Background Gestational weight gain (GWG) is one of the crucial factors affecting fetal growth as well as the in utero environment, influencing fetal cell programming during development. We reported previously that GWG affected the occurrence of outlying CpG methylation values of placental DNA in a U-shaped manner, with the occurrence of outlying values from adequate GWG subjects positioned at the bottom of the curve. In the present study, we aimed to elucidate the effects of GWG on the infant epigenome by the view that the influence of insufficient GWG on infant DNA methylation may turn in some other direction at the borderline of the optimal weight gain. Method We collected cord blood from 60 subjects with uncomplicated term delivery whose mean pre-pregnancy body mass index and mean GWG was 19.8 ± 1.9 and 8.1 ± 4.3 kg, respectively. Cord blood DNA was underwent analysis using the Infinium MethylationEPIC BeadChip to profile genome-wide methylation status. Results GWG was continuously associated with cord blood DNA methylation at five CpG loci significantly (multiple test corrected p -value, 0.043) in the lower than upper limit of the recommended GWG group (n = 51). The significant association between DNA methylation levels and GWG was disappeared when added 9 subjects who gained weight more than upper limit of recommendation during pregnancy. The methylation plot of the five loci plateaued or traced a U-curve near the border of the upper limit of the GWG recommendation. Cord blood DNA methylation of these five still tended to be associated with GWG after considering gestational age as covariate with involving the other eleven CpG sites with the same p -value (multiple test corrected p -value, 0.056). The fifteen out of the identified 16 CpG sites showed negative association between GWG and DNA methylation levels and five of them colocalized at inferred enhancer region. Conclusions It is known that demethylation at enhancer region in genome is one of the features during late fetal development. We found that insufficient GWG showed higher methylation status in some enhancer-candidate loci in cord blood cells, which may indicate incomplete demethylation during in utero development.