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

• Type of Material: Article
• Authors: James F. Padbury, Brown University; Barbara T. Do, RTI International; Carla M. Bann, RTI International; Carmen Marsit, Emory University; Susan R. Hintz, Stanford University; Betty R. Vohr, Brown University; Jean Lowe, University of New Mexico; Jamie E. Newman, RTI International; Douglas A. Granger, University of California Irvine; Allison Payne, Case Western Reserve University; Kristi Watterberg, University of New Mexico; Anthony Piazza, Emory University; Brenda Poindexter, Emory University
• Language: English
• Date: 2021-05-05
• Publisher: SPRINGERNATURE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use
• Final Published Version (URL): http://dx.doi.org/10.1038/s41390-021-01531-5
• Title of Journal or Parent Work: PEDIATRIC RESEARCH
• Volume: 91
• Issue: 6
• Start Page: 1469
• End Page: 1477
• Grant/Funding Information: The National Institutes of Health, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Heart, Lung, and Blood Institute (NHLBI) provided grant support for the Neonatal Research Network’s Extended Follow-up at School Age for the SUPPORT Neuroimaging and Neurodevelopmental Outcomes (NEURO) Cohort through cooperative agreements. NHLBI provided support for this study (R01HL117764). Analytical work on pyrosequencing was carried out in the core research facilities supported by awards from the National Institutes of Health Institute for General Medical Sciences awards P30GM114750, P20RR18728 and P30GM103410. While NICHD staff had input into the study design, conduct, analysis, and manuscript drafting, the comments and views of the authors do not necessarily represent the views of the NICHD.
• Keywords: Science & Technology; LONG-TERM CONSEQUENCES; NR3C1; Life Sciences & Biomedicine; Pediatrics; MATERNAL DEPRESSION; INFANT GROWTH; PLACENTA; FETAL
• Research Categories: Health Sciences, Obstetrics and Gynecology; Health Sciences, Medicine and Surgery; Psychology, Developmental

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Impact: 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.