![]() ![]() The most thoroughly studied epigenetic mechanism is DNA methylation (DNAm), particularly in the context of cytosine-phosphate-guanine (CpG) motifs and islands. Beyond the neurobehavioral and medical assessments, molecular biomarkers may provide insights into how the environment and experiences of the preterm newborn are internalized and may hold additional value as predictive tools useful in risk stratification.Įpigenetics refers to mitotically and meiotically heritable changes in gene expression potential that are not explained by changes in DNA sequence. Poorer performance on the NNNS has also been shown to be predictive of non-optimal developmental outcomes through early childhood 21. These neurobehavioral profiles in infants have been associated with prenatal exposures (prenatal drugs 21, 22 and perfluorooctanoic acid 23), birth outcomes (gestational age and birth weight 21), and with behavioral and cognitive outcomes in childhood 21, 22, 24. ![]() Latent profiles of NNNS summary scores have been used to classify infants into groups with similar responses across the overall NNNS assessment. There is growing evidence that neonatal neurobehavior (the relationships between the nervous system and behavior), as measured by the NICU Network Neurobehavioral Scale (NNNS) 16, predicts developmental deficits in infants born preterm and others at risk, beyond what can be predicted based on the assessment of medical risk factors throughout the newborn’s hospital stay 17, 18, 19, 20. As such, assessments prior to discharge from the neonatal intensive care unit (NICU) are needed to identify the earliest risks for adverse neurodevelopmental outcomes, and to maximize the potential benefits of interventions aimed at ameliorating long term deficits. In addition to immaturity, premature infants vary widely in the health complications they experience. These consequences of premature birth often require extensive healthcare, educational and psychosocial community resources, in addition to increased burden on the families and caregivers of these children, emotionally and financially. These youngest infants are more likely to suffer from chronic illnesses, potentially devastating brain injuries, and adverse neuromotor, cognitive, and behavioral outcomes that persist through adulthood 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15. Survival of infants born very preterm, prior to 30 weeks postmenstrual age (PMA), has improved due to technological and medical advancements 2, 3. In the United States one in eight children are born less than 37 weeks of gestation 1. Preterm birth is a significant global public health problem. These findings contribute to the existing evidence that neonatal epigenetic variations may be informative for infant neurobehavior. Some of the genes annotated to these CpGs included PLA2G4E, TRIM9, GRIK3, and MACROD2, which have previously been associated with neurological structure and function, or with neurobehavioral disorders. In contrast, infants with an atypical NNNS profile had differential methylation at 29 CpG sites (FDR < 10%). Infants with an optimally well-regulated NNNS profile had older epigenetic age compared to other NOVI infants (β 1 = 0.201, p-value = 0.026), but no significant difference in age acceleration. We adjusted for recruitment site, infant sex, PMA, and tissue heterogeneity. ![]() We tested whether epigenetic age, age acceleration, or DNAm levels at individual loci differed between infants based on their NICU Network Neurobehavioral Scale (NNNS) profile classifications. To this end, we examined whether variability in buccal cell DNA methylation (DNAm) associated with neurobehavioral profiles in a cohort of infants born less than 30 weeks postmenstrual age (PMA) and participating in the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) Study (N = 536). Neonatal molecular biomarkers of neurobehavioral responses (measures of brain-behavior relationships), when combined with neurobehavioral performance measures, could lead to better predictions of long-term developmental outcomes. ![]()
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