Abstract
Background
The aim of this study was to investigate the influence of early-life pain/stress and medical characteristics on neurobehavioral outcomes in preterm infants.
Methods
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.
Results
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.
Conclusions
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.
Impact
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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.
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Gestational age remains one of the critical factors to predict neurobehavioral outcomes in preterm infants; older gestational age significantly predicted better neurobehavioral outcomes.
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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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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors thank medical and nursing staff in the NICUs of Connecticut Children’s Medical Center at Hartford and Farmington, CT for their support and assistance. We thank Victoria Vazquez, Shari Galvin, Megan Fitzsimons, and Dorothy Vittner for their assistance in recruiting subjects and data collection.
Funding
This study was supported by the NIH/NINR (grant numbers: K23NR014674 and NR016928; PI: X.C.; F31NR019940, PI: T.Z.).
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All authors met the Pediatric Research authorship requirements. Substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data: all authors. Drafting and revising the manuscript: T.Z., T.G., Y.Z., H.L., and X.C. Thoroughly reviewed and critiqued the manuscript for revision: B.L. and N.H. Final approval of the version to be published: all authors.
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Patient consent was required for our paper. Eligible infants were identified by the research study personnel after birth and/or admission to the NICU and consent from parents of the eligible infant was required and obtained for participating in our study.
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Zhao, T., Griffith, T., Zhang, Y. et al. Early-life factors associated with neurobehavioral outcomes in preterm infants during NICU hospitalization. Pediatr Res 92, 1695–1704 (2022). https://doi.org/10.1038/s41390-022-02021-y
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DOI: https://doi.org/10.1038/s41390-022-02021-y
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