DNA Methylation, Environmental Adversities and Attention Problems in Children Born Very Preterm

Children born preterm are at higher risk of attention problems compared to children born at term, yet not all preterm children are affected. The purpose of this study was to identify epigenetic predictors of early childhood attention problems among children born very preterm and to examine the joint role of epigenetic and environmental factors in predicting attention problems in this population. We studied 242 participants from a multi-site study of infants born less than 30 weeks gestational age. Neonatal buccal swabs were assayed for DNA methylation levels at over 450,000 CpG sites and age acceleration metrics were calculated using existing epigenetic clocks. A composite of postnatal environmental adversity was calculated using maternal reported risk factors. Attention problems were assessed in early childhood (mean age 6.58 years) using the Conner’s Kiddie Continuous Performance Test 2nd Edition. After adjustment for multiple testing, we found that DNA methylation of 9 CpG sites was associated with childhood attention problems. Several CpGs were located in genes previously linked to neurodevelopmental traits and inflammation in prior epigenome-wide and genome-wide association studies. Greater environmental adversity was also associated with increased attention problems. When tested together, DNA methylation and environmental adversity independently predicted attention problems. This study is the first to show associations between DNA methylation, environmental adversity, and objectively measured attention problems in school-age children born very preterm. These results could shed light on the etiology of attention problems in this population and may help us identify at birth preterm children at highest risk for later ADHD diagnosis.