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.
Babies born prematurely are exposed to repeated painful/stressful procedures as part of routine care and/or treatment within the neonatal intensive care unit, and cumulative pain/stress in these neonates has been associated with altered methylation patterns and poor neurodevelopmental outcomes. The proposed application is exploratory in nature and will provide the groundwork to begin the development of mechanistically-targeted interventions with implications for public health by: 1) characterizing methylation and gene expression patterns in multiple stress-related genes and absolute telomere length longitudinally through hospital discharge and ensuing follow-up clinic visits; and, 2) assess associations between methylation patterns, gene expression and telomere length with neurodevelopmental outcomes. This innovative combination of measurements has the potential to generate essential knowledge that may lead to the development of novel interventions to improve long-term outcomes in this vulnerable population.
