Allostatic Load and Biomarkers of Stress in the Preterm Infant: An Integrative Review

Every year, an estimated 15 million babies are born preterm (<37 weeks’ gestational age) 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). Low thresholds for tactile and nociceptive input make it more difficult for neonates to discriminate between noxious and nonnoxious stimuli, which can result in continuous activation of stress responses in an attempt to achieve stability through adaptation, or allostasis. Rapidly reoccurring stressors can render stress-response systems over- or underactive, creating wear and tear, or allostatic load. A better understanding of biomarkers related to allostatic load might aid in early detection and prevention/alleviation of allostatic load in this population. To identify stress biomarkers that have been studied in preterm infants at different time points in the NICU and as long-term outcome measures. Systematic searches were conducted of PubMed, CINAHL, SCOPUS, and PsychInfo databases. Twenty-one studies met inclusion criteria for this review. Several putative biomarkers were identified, including cortisol levels, epigenetic markers, brain microstructure, markers of oxidative stress, and the brain–gut–microbiome axis. The interaction of disease with therapeutic interventions may inadvertently increase infant allostatic load. In addition to human studies, future research should leverage newly available large data sets to conduct additional analyses