NR3C1 and IGF2/H19 methylation patterns predict infant and preschooler temperament: Links to maternal stress in pregnancy

Abstract

Background: Maternal distress has been associated with many offspring behavioural developmental outcomes, potentially through epigenetic modification of the glucocorticoid receptor NR3C1 or the imprinting control region between insulin-like growth factor 2 and H19 (IGF2/H19). Methods: 148 mother-infant pairs from the Prenatal Early Life Stress (PELS) cohort participated in this study. Maternal self-reported psychosocial and work-related factors were determined during pregnancy. NR3C1 and IGF2/H19 methylation levels were measured by bisulfite-pyrosequencing in the buccal cells of the infant (3-5 months). Infant and preschooler (4 years) temperament were assessed by the Infant-and Children's Behavior Questionnaire (IBQ-R-vsf and CBQ-R-vsf, respectively). Linear mixed effect models, linear regression models and mediation analyses were used to test associations. Findings: Maternal work-related physical and emotional demands were predictive of infant NR3C1 and IGF2/H19 methylation on several cytosine-phosphate-guanine sites. NR3C1 and IGF2/H19 methylation were associated with infant surgency. NR3C1 was found to mediate the association between maternal work-related physical demands and surgency in infancy. Conclusions: Occupational stressors during pregnancy were shown to associate with NR3C1 and IGF2/H19 methylation in the infant, which may be linked with temperament.