Neurobehavior related to epigenetic differences in preterm infants

Abstract

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.

Keywords: DNA methylation; NICU Network Neurobehavioral Scale; cortisol; epigenetics; high-risk infants; prematurity; programming.

Conflict of interest statement

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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

Figures

Figure 1.. Neonatal Intensive Care Unit Network Neurobehavioral Scale profiles for high- and low-risk infants.

Figure 2.. Percentage methylation of NR3C1 by CpG site.

NNNS: Neonatal Intensive Care Unit Network Neurobehavioral Scale.

Figure 3.. Percentage methylation of HSD11B2 by CpG site.

NNNS: Neonatal Intensive Care Unit Network Neurobehavioral Scale.

Figure 4.. Proposed pathways leading to low-risk and high-risk and neurobehavioral profiles based on Neonatal Intensive Care Unit Network Neurobehavioral Scale summary scores.

The solid arrows in infants with the low-risk profile (A) indicate normal developmental processes and appropriate levels of cortisol. The dashed lines in infants with the high-risk profile (B) indicate disrupted processes including transcription factors and thick arrows for increased levels of cortisol.