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DNA methylation in former extremely low birth weight newborns: association with cardiovascular and endocrine function
Journal article   Open access   Peer reviewed

DNA methylation in former extremely low birth weight newborns: association with cardiovascular and endocrine function

James F Padbury, Barbara T Do, Carla M Bann, Carmen Marsit, Susan R Hintz, Betty R Vohr, Jean Lowe, Jamie E Newman, Douglas A Granger, Allison Payne, …
Pediatric research, Vol.91(6), pp.1469-1477
05/2022
DOI: 10.1038/s41390-021-01531-5
PMCID: PMC8568736
PMID: 33953357
url
https://www.ncbi.nlm.nih.gov/pmc/articles/8568736View
Open Access

Abstract

There is increased risk of cardiovascular, metabolic, and hypertensive disorders in later life in the preterm population. We studied school-age children who had been born extremely premature who had undergone endocrine, cardiovascular, and anthropometric evaluations. School age measurements of salivary cortisol, adrenal androgens, blood pressure, and anthropometric markers were correlated with DNA methylation of 11-betahydroxysteroid dehydrogenase type 2 (11BHSD2), leptin, and the LINE1 repetitive DNA element. We observed a modest correlation between log AUC for salivary cortisol and methylation of leptin in preterm infants and a negative correlation between methylation of region 1 of the glucocorticoid receptor (GR in term-born infants. There was an association between LINE1 methylation and cortisol response to awakening and a negative correlation between LINE1 and systolic blood pressure at 6-7 years. Methylation of the GR promoter region showed a positive association with systolic blood pressure at 6-7 years of age. These results show that extremely preterm birth, followed by complex patterns of endocrine, cardiovascular, and metabolic exposures during early postnatal life, is associated with lasting changes in DNA methylation patterns in genes involved in hypothalamic pituitary adrenal axis function, adrenal hormonal regulation, and cardiometabolic risk. Preterm infants have significant environmental and physiological exposures during early life that may have lasting impact on later function. Alterations in hypothalamic pituitary adrenal axis (HPA) function have been associated with these exposures. We examined the associated changes in DNA methylation of important genes involved in HPA function, metabolism, and global DNA methylation. The changes we saw in DNA methylation may help to explain associated cardiovascular, metabolic, and growth disturbance in these children in later life.
Child DNA Methylation Female Humans Hydrocortisone Hypothalamo-Hypophyseal System - metabolism Infant Infant, Extremely Low Birth Weight Infant, Newborn Infant, Premature Leptin Pituitary-Adrenal System - metabolism Premature Birth

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