Adverse maternal exposures, methylation of glucocorticoid-related genes and perinatal outcomes: a systematic review

Aim: Maternal environmental exposures affect perinatal outcomes through epigenetic placental changes. We examine the literature addressing associations between adverse maternal exposures, perinatal outcomes and methylation of key genes regulating placental cortisol metabolism. Methods: We searched three databases for studies that examined NR3C1 and HSD11 beta 1/HSD11 beta 2 methylation with maternal exposures or perinatal outcomes. Nineteen studies remained after screening. We followed Cochrane's PRISMA reporting guidelines (2009). Results: NR3C1 and HSD11 beta methylation were associated with adverse infant neurobehavior, stress response, blood pressure and physical development. In utero exposure to maternal stress, nutrition, preeclampsia, smoking and diabetes were associated with altered NR3C1 and HSD11 beta methylation. Conclusion: NR3C1 and HSD11 beta methylation are useful biomarkers of specific environmental stressors associated with important perinatal outcomes that determine pediatric and adult disease risk.