Patterning in placental DNA methylation and infant neurodevelopment according to prenatal socioeconomic environment

Abstract

Background: Prenatal socioeconomic adversity (SA) is associated with poor infant neurodevelopment yet the mechanisms are not well understood. Fetal development can be shaped by the intrauterine environment through alterations in the function of the placenta. In the placenta, the HSD11B2 gene encodes the 11-beta hydroxysteroid dehydrogenase enzyme and the glucocorticoid receptor (NR3C1), both of which are key elements of the stress response, are regulated by DNA methylation and can be influenced by a variety of environmental stressors. However, the association of prenatal SA and placental methylation of HSD11B2 or NR3C1 has not been examined, and the impacts of such methylation on infant neurodevelopment are unknown. Aims: We examined whether prenatal SA would be associated with HSD11B2 and NR3C1 methylation and whether various levels of HSD11B2 and NR3C1 methylation in combination would be associated with different profiles of neurodevelopmental risk in infancy. Methods: We examined the association between DNA methylation of HSD11B2 and NR3C1 in the placenta of 445 healthy term newborn infants and several markers of prenatal SA. We also examined the association of HSD11B2 and NR3C1 methylation with classes of infant neurodevelopment as measured by the validated NICU Network Neurobehavioral Scales. Results: Infants with the greatest levels of prenatal SA had the lowest extent of placentalHSD11B2 andNR3C1methylation (p<0.05). Infants with lowNR3C1 methylation and also highHSD11B2 methylation were more likely to have a healthy neurodevelopmental profile (p<0.05) whereas infants with highHSD11B2and highNR3C1 methylation were more likely to have dysregulated neurodevelopment (p<0.05). Conclusions: Patterns of HSD11B2 and NR3C1 methylation suggest that environmental cues transmitted during gestation may program the developing fetus’s response to an adverse postnatal environment and may also influence neurodevelopmental risk and resilience.