The long-term effects of infant pain are complex, and vary depending on how early in life the exposure occurs, due to differences in developmental maturity of specific systems underway. Changes to later pain sensitivity reflect multiple factors such as age at pain stimulation, extent of tissue damage, type of noxious insult, intensity, and duration. In both full-term and preterm infants exposed to hospitalization, sequelae of early pain are confounded by parental separation and quality of pain treatment. Neonates born very preterm are outside the protective uterine environment, with repeated exposure to pain occurring during fetal life. Especially for infants born in the late second trimester, the cascade of autonomic, hormonal, and inflammatory responses to procedures may induce excitotoxicity with widespread effects on the brain. Quantitative advanced imaging techniques have revealed that neonatal pain in very preterm infants is associated with altered brain development during the neonatal period and beyond. Recent studies now provide evidence of pathways reflecting mechanisms that may underlie the emerging association between cumulative procedural pain exposure and neurodevelopment and behavior in children born very preterm. Owing to immaturity of the central nervous system, repetitive pain in very preterm neonates contributes to alterations in multiple aspects of development. Importantly, there is strong evidence that parental caregiving to reduce pain and stress in preterm infants in the Neonatal Intensive Care Unit (NICU) may prevent adverse effects, and sensitive parenting after NICU discharge may help ameliorate potential long-term effects.
Reply: “It is Time for a Universal Nutrition Policy in Very Preterm Neonates during the Neonatal Period? Comment on: Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm Infants Nutrients 2019, 11, 2772”