DNA Methylation in Former Extremely Low Birth Weight Newborns: Association with Cardiovascular and Endocrine Function

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-beta hydroxysteroid dehydrogenase type 2 (11BHSD2), leptin, and the LINE1 repetitive DNA element. RESULTS: We observed a modest correlation between logAUC for salivary cortisol and methylation of leptin in preterm infants and a negative correlation between methylation of region 1 of the glucocorticoid receptor 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.