Predicting Neurodevelopmental Outcomes in Premature Infants with Multi-omic Measures (PRENOP)

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Abstract Each year, an estimated 15 million babies are born preterm (<37 weeks' gestational age [GA]) globally. These preterm infants are exposed to repeated stressful and often painful procedures or treatments as part of routine life-saving care within the neonatal intensive care unit (NICU). These stressful exposures result in altered methylation patterns and gene expression that have been associated with numerous negative sequelae for the infant and may be irreversible, including, blunted or exaggerated stress reactivity, increased risk for negative behavior patterns and alterations in brain microstructure. Understanding the epigenetic modifications that regulate persistent changes in gene expression may lead to interventions that would improve outcomes for these infants giving them the opportunity to enjoy a better life. The proposed application aims to rigorously examine: 1) genome- wide methylation longitudinally; 2) changes in gene expression longitudinally; 3) absolute telomere length, an innovative stress biomarker which has not, to our knowledge, been investigated serially post-NICU discharge will be measured at multiple time points from birth through 24-months- corrected-age during follow-up clinic visits; 4) associations between methylation, gene expression, telomere length and neurodevelopmental outcomes. This innovative combination of measurements has the potential to generate essential knowledge that may prove critical to improving neurodevelopmental outcomes for this vulnerable population.