Adverse Maternal Exposures, Methylation of Glucocorticoid-Related Genes and Perinatal Outcomes: A Systematic Review

Abstract

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 HSD11β1/HSD11 β 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 β 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 β methylation. Conclusion:NR3C1 and HSD11 β methylation are useful biomarkers of specific environmental stressors associated with important perinatal outcomes that determine pediatric and adult disease risk.

Keywords::

• biomarker
• epigenetic
• hydroxysteroid 11-beta dehydrogenases
• infant
• glucocorticoid
• methylation
• pediatric
• perinatal
• smoking
• stress

Financial & competing interests disclosure

This study was supported by a grant received from the John Templeton Foundation (AE Shields). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported by a grant received from the John Templeton Foundation (AE Shields). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.