The variation in childhood social-emotional development within at-risk populations may be attributed in part to epigenetic mechanisms such as DNA methylation (DNAm) that respond to environmental stressors. These mechanisms may partially underlie the degree of vulnerability (and resilience) to negative social-emotional development within adverse psychosocial environments. Extensive research supports an association between maternal adversity and offspring DNAm of the NR3C1 gene, which encodes the glucocorticoid receptor (GR). A gap in knowledge remains regarding the relationship between NR3C1 DNAm, measured in neonatal (1-month of age) buccal cells, and subsequent social-emotional development during infancy and early childhood. We conducted a longitudinal cohort study of n = 53 mother-child dyads (n = 30 with developmental outcomes formed the basis of current study) who were enrolled in a home visiting (HV) program. Higher mean DNAm of the NR3C1 exon 1_F promoter was significantly associated with lower 6-month Ages and Stages Questionnaire: Social-Emotional (ASQ:SE) scores-more positive infant social-emotional functioning. A similar trend was observed at 18-months of age in a smaller sample (n = 12). The findings of this pilot study indicate that in a diverse and disadvantaged population, the level of neonatal NR3C1 DNAm is related to later social-emotional development. Limitations and implications for future research are discussed.

(1) Introduction: Epigenetic changes have been proposed as a biologic link between in-utero exposure to maternal smoking and health outcomes. Therefore, we examined if in-utero exposure to maternal smoking was associated with infant DNA methylation (DNAm) of cytosine-phosphate-guanine dinucleotides (CpG sites) in the arginine vasopressin receptor 1A AVPR1a gene. The AVPR1a gene encodes a receptor that interacts with the arginine vasopressin hormone and may influence physiological stress regulation, blood pressure, and child development. (2) Methods: Fifty-two infants were included in this cohort study. Multivariable linear models were used to examine the effect of in-utero exposure to maternal smoking on the mean DNAm of CpG sites located at AVPR1a. (3) Results: After adjusting the model for substance use, infants with in-utero exposure to maternal smoking had a reduction in DNAm at AVPR1a CpG sites by -0.02 (95% CI -0.03, -0.01) at one month of age. In conclusion, in-utero exposure to tobacco smoke can lead to differential patterns of DNAm of AVPR1a among infants. Conclusions: Future studies are needed to identify how gene expression in response to early environmental exposures contributes to health outcomes.