Abstract

The aim of this study was to investigate the influence of early-life pain/stress and medical characteristics on neurobehavioral outcomes in preterm infants. A prospective cohort study was conducted with 92 preterm infants (28-32 weeks gestational age [GA]). Early-life pain/stress was measured via the Neonatal Infant Stressor Scale (NISS) during the first 28 days of NICU hospitalization. Neurobehavioral outcomes were evaluated using the NICU Network Neurobehavioral Scale at 36-38 weeks post-menstrual age. Functional regression and machine learning models were performed to investigate the predictors of neurobehavioral outcomes. Infants experienced daily acute pain/stress (24.99 ± 7.13 frequencies) and chronic events (41.13 ± 17.81 h). Up to 12 days after birth, both higher acute and chronic NISS scores were associated with higher stress scores; and higher chronic NISS scores were also related to lower self-regulation and quality of movement. Younger GA predicted worse neurobehavioral outcomes; GA < 31.57 weeks predicted worse stress/abstinence, self-regulation, and excitability; GA < 30.57 weeks predicted poor quality of movement. A higher proportion of maternal breastmilk intake predicted better self-regulation, excitability, and quality of movement in older GA infants. Preterm infants are vulnerable to the impact of early-life pain/stress. Neurobehavioral outcomes are positively associated with increased GA and higher maternal breastmilk intake. During the first 12 days of life, preterm infant neurobehavioral outcomes were vulnerable to the negative impact of acute and chronic pain/stress. Future research is warranted to investigate the long-term effects of early-life pain/stress on neurobehavioral outcomes. Gestational age remains one of the critical factors to predict neurobehavioral outcomes in preterm infants; older gestational age significantly predicted better neurobehavioral outcomes. Feeding with a higher proportion of maternal breastmilk predicted better neurobehavioral outcomes. Future research is warranted to investigate how maternal breastmilk may buffer the negative effects of early-life pain/stress on neurobehavioral outcomes.

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