Preterm birth is associated with medical problems affecting the neuroendocrine system, altering cortisol levels resulting in negative effects on newborn neurobehavior. Newborn neurobehavior is regulated by DNA methylation of NR3C1 and HSD11B2. Aim: Determine if methylation of HSD11B2 and NR3C1 is associated with neurobehavioral profiles in preterm infants. Patients & methods: Neurobehavior was measured before discharge from the hospital in 67 preterm infants. Cheek swabs were collected for DNA extraction. Results: Infants with the high-risk neurobehavioral profile showed more methylation than infants with the low-risk neurobehavioral profile at CpG3 for NR3C1 and less methylation of CpG3 for HSD11B2. Infants with these profiles were more likely to have increased methylation of NR3C1 and decreased methylation of HSD11B2 at these CpG sites. Conclusion: Preterm birth is associated with epigenetic differences in genes that regulate cortisol levels related to high-risk neurobehavioral profiles.

Background:Although there are no accepted “normal” levels of circulating cortisol in preterm infants, critically ill preterm infants show lower cortisol levels than healthy preterm infants. The regulation of cortisol reactivity by epigenetic changes in glucocorticoid receptor gene (NR3C1) expression has been demonstrated. This study aims to examine the relationship between medical morbidities in preterm infants and DNA methylation of NR3C1.Methods:Pyrosequencing was used to determine DNA methylation in CpG sites 1-4 of promoter region 1F of NR3C1. Cluster analysis placed 67 preterm infants born <1,500 g into groups based on medical morbidities. The DNA methylation pattern was compared across groups.Results:Cluster analysis identified a high medical risk cluster and a low medical risk cluster. A Mann-Whitney U-test showed lower methylation at CpG1 for infants in the high-risk group (M = 0.336, SE = 0.084) than infants in the low-risk group (M = 0.617, SE = 0.109, P = 0.032). The false discovery rate was low (q = 0.025). Cohen's D effect size was moderate (0.525).Conclusion:Decreased DNA methylation of CpG1 of NR3C1 in high-risk infants may allow for increased binding of transcription factors involved in the stress response, repair and regulation of NR3C1. This may ensure healthy growth in high-risk preterm infants over increasing cortisol levels.