Associations between preterm infant stress, epigenetic alteration, telomere length and neurodevelopmental outcomes: A systematic review

Background: Every 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 as part of routine life-saving care within the neonatal intensive care unit (NICU). Preterm birth continues to be a major health issue associated with increased risk of neurodevelopmental and behavioral disorders such as cerebral palsy, cognitive impairment, autism spectrum disorders and psychiatric disease. Objective: This paper identifies epigenetic alterations and incidence of telomere erosion that have been studied in preterm infants while in the NICU and as a long-term outcome measure. Better understanding of epigenetic alterations and telomere erosion might aid in early detection and prevention/alleviation of the negative effects of cumulative painful/stressful experiences in this population. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were used to guide this review. Systematic searches of databases included PubMed, CINAHL, SCOPUS and PsychInfo. Results: Twenty-one studies were included, appraised and then synthesized into a narrative summary. Discussion: Several putative epigenetic markers were identified although there was a paucity of studies related to telomere length. The interaction of disease entity combined with therapeutic interventions intended to treat may inadvertently increase infant allostatic load or ability to adapt to stress. Future research should include not only human studies but leverage newly available large data sets to conduct additional analysis.