Early-to-mid pregnancy sleep and circadian markers in relation to birth outcomes: An epigenetics pilot study

Maternal sleep and circadian health during pregnancy are emerging as important predictors of pregnancy outcomes, but examination of potential epigenetic mechanisms is rare. We investigated links between maternal leukocyte DNA methylation of circadian genes and birth outcomes within a pregnancy cohort. Women (n = 96) completed a questionnaire and provided a blood sample at least once during early-to-mid pregnancy (average gestation weeks = 14.2). Leukocyte DNA was isolated and DNA methylation (average percent of methylation) at multiple CpG sites within BMAL1, PER1, and MTNR1B genes were quantified by pyrosequencing. Birth outcomes including gestational age at delivery, birthweight, and head circumference were abstracted from medical charts. Linear regression analyses were run between each CpG site with birth outcomes, adjusting for important confounders. Sleep duration and timing were assessed as secondary exposures. Higher methylation of a CpG site in PER1 was associated with smaller log-transformed head circumference (β=-0.02 with 95% CI -0.02 to 0.01; P, trend = 0.04). Higher methylation of MTNR1B (averaged across sites) was associated with lower log-transformed birthweight (-0.08 with 95% CI -0.16 to -0.01; P, trend = 0.0495). In addition, longer sleep duration was associated with higher birthweight (0.10 with 95% CI 0.02 to 0.18 comparing > 9 h to < 8 h; P, trend = 0.04). This pilot investigation revealed that higher methylation of PER1 and MTNR1B genes, and sleep duration measured in early-to-mid pregnancy were related to birth outcomes.