Maternal mental well-being during pregnancy and glucocorticoid receptor gene promoter methylation in the neonate

Abstract

Maternal mental health during pregnancy has been linked to health outcomes in progeny. Mounting evidence implicates fetal "programming" in this process, possibly via epigenetic disruption. Maternal mental health has been associated with glucocorticoid receptor methylation (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) in the neonate; however, most studies have been small (n < 100) and have failed to control for multiple testing in the statistical analysis. The Barwon Infant Study is a population-derived birth cohort with antenatal recruitment. Maternal depression and anxiety were assessed using the Edinburgh Postnatal Depression Scale and psychological distress using the Perceived Stress Scale. NR3C1 cord blood methylation levels were determined using Sequenom MassArray for 481 participants. Maternal psychological distress and anxiety were associated with a small increase in neonate NR3C1 methylation at specific CpG sites, thus replicating some previous findings. However, associations were only nominally significant and did not remain after correction for the number of CpG sites and exposures investigated. As the largest study to explore the relationship between maternal well-being and offspring NR3C1 cord blood methylation, our results highlight the need for caution when interpreting previous findings in this area. Future studies must ensure they are adequately powered to detect the likely small effect sizes while controlling for multiple testing.

Sex Differences in Vulnerability to Prenatal Stress: a Review of the Recent Literature

“…Mina et al found sex-specific associations suggesting that infant girls might be particularly susceptible to the effects of prenatal maternal distress on placental mRNA levels of genes regulating fetal glucocorticoid exposure and placental growth [68]. Finally, data from the Barwon Infant Study ( N = 481) showed no evidence of sex dependence in associations between PNMS and cord blood NR3C1 glucocorticoid receptor gene methylation [25]. …”

Maternal prenatal stress and infant DNA methylation: A systematic review

“…The twelve studies assessing NR3C1 methylation all examined exon 1 F ; one study also examined exons 1 B and 1 D (Hompes et al, ). The number of CpG sites analyzed ranged from 2 (Murgatroyd, Quinn, Sharp, Pickles, & Hill, ) to 47 sites (Mansell et al, ). Three studies used identical data on mother‐infant dyads from the Democratic Republic of Congo (Kertes et al, ; Mulligan, D'Errico, Stees, & Hughes, ; Rodney & Mulligan, ).…”

The impact of psychological distress during pregnancy on the developing fetus: biological mechanisms and the potential benefits of mindfulness interventions

“…Its expression levels can decrease in chronically stressed individuals, leading to desensitization to cortisol's regulatory effect on the HPA axis [43], and thus perpetuating the physiological response to chronic stress. Studies have found that maternal prenatal perceived stress [42], depression [40] and anxiety [44] were all associated with higher levels of methylation of the NR3C1 promoter in the infants. These epigenetic changes have been associated with low birth weight [42], lethargy and hypertonia [40], respectively.…”