Epigenetic Trajectories and Neurodevelopment among Infants Born Very Preterm

Primary Investigators: Barry Lester PhD, Todd Everson, PhD

Infants born very preterm are at increased risk of experiencing adverse developmental outcomes in childhood. Recent research in the field of behavioral epigenomics has indicated that preterm birth may have long term impacts on epigenetic regulation and that differential DNA methylation is linked to variability in cognitive and behavioral function. We aim to study how neonatal medical complications and neurobehavior influence trajectories of DNA methylation in early childhood, and whether these trajectories are associated with neurodevelopmental trajectories or are informative for predicting risk for poor developmental outcomes. We also aim to develop an algorithm that incorporates childhood epigenomic factors with other known risk factors to improve our ability to predict which infants born preterm are at highest risk of developmental impairments.

Epigenetics and Attention Problems in Children Born Very Preterm

Primary Investigator: Marie Camerota, PhD

Children born very preterm are at increased risk for developing attention problems in early childhood, including two- to four-times greater risk for attention-deficit/hyperactivity disorder (ADHD). Risk factors for attention problems include biological, cognitive, and caregiving factors, yet these have yet to be comprehensively studied in children born preterm. This study investigates the role of epigenetic regulation from birth through early childhood in the development of attention problems in a multi-site study of children born very preterm. We aim to test how changes in DNA methylation contribute to patterns of attention problems in this population and the relative contributions of epigenetics in addition to other risk factors such as maternal depressive symptoms and child executive function deficits. This project will improve understanding of the strongest individual or combined risk factors for attention problems in children born very preterm as well as identify sensitive periods at which biological, cognitive, and caregiving factors are most predictive of outcomes, providing critical information for the development of future interventions.

Epigenetic Pathways in Prenatal Opioid Exposure

Primary Investigator: Barry Lester PhD, Marie Camerota, PhD

Newborns exposed to opioids during pregnancy are risk for developing a drug withdrawal syndrome known as Neonatal Opioid Withdrawal Syndrome (NOWS). However, not all newborns are impacted and the symptoms and medical course for these infants can vary greatly. Epigenetic modifications in opioid- and stress-receptor genes have been shown to predict differences in NOWS severity and neurodevelopmental outcomes among infants exposed prenatally to opioids. Moreover, opioids act as an intrauterine stressor that alters the development of the stress response system. The goal of this project is to investigate whether prenatal exposure to opioids (including certain high-potency opioids such as fentanyl) and associated prenatal stress have impacts on the development of NOWS and neonatal neurobehavior and whether these effects are mediated by epigenetic and stress pathways. We hope to elucidate biological pathways that could be targets of future NOWS interventions and improve long-term outcomes for this vulnerable population of infants.