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DOI: 10.1001/jamanetworkopen.2022.22249


Importance: The ability to identify poor outcomes and treatable risk factors among very preterm infants remains challenging; improving early risk detection and intervention targets to potentially address developmental and behavioral delays is needed.

Objective: To determine associations between neonatal neurobehavior using the Neonatal Intensive Care Unit (NICU) Network Neurobehavioral Scale (NNNS), neonatal medical risk, and 2-year outcomes.

Design, Setting, and Participants: This multicenter cohort enrolled infants born at less than 30 weeks' gestation at 9 US university-affiliated NICUs. Enrollment was conducted from April 2014 to June 2016 with 2-year adjusted age follow-up assessment. Data were analyzed from December 2019 to January 2022.

Exposures: Adverse medical and psychosocial conditions; neurobehavior.

Main Outcomes and Measures: Bayley Scales of Infant and Toddler Development, third edition (Bayley-III), cognitive, language, and motor scores of less than 85 and Child Behavior Checklist (CBCL) T scores greater than 63. NNNS examinations were completed the week of NICU discharge, and 6 profiles of neurobehavior were identified by latent profile analysis. Generalized estimating equations tested associations among NNNS profiles, neonatal medical risk, and 2-year outcomes while adjusting for site, maternal socioeconomic and demographic factors, maternal psychopathology, and infant sex.

Results: A total of 679 enrolled infants had medical and NNNS data; 2-year follow-up data were available for 479 mothers and 556 infants (mean [SD] postmenstrual age at birth, 27.0 [1.9] weeks; 255 [45.9%] female). Overall, 268 mothers (55.9%) were of minority race and ethnicity, and 127 (26.6%) lived in single-parent households. The most common neonatal medical morbidity was BPD (287 [51.7%]). Two NNNS behavior profiles, including 157 infants, were considered high behavioral risk. Infants with at least 2 medical morbidities (n = 123) were considered high medical risk. Infants with high behavioral and high medical risk were 4 times more likely to have Bayley-III motor scores less than 85 compared with those with low behavioral and low medical risk (adjusted relative risk [aRR], 4.1; 95% CI, 2.9-5.1). Infants with high behavioral and high medical risk also had increased risk for cognitive scores less than 85 (aRR, 2.7; 95% CI, 1.8-3.4). Only infants with high behavioral and low medical risk were in the clinical range for CBCL internalizing and total problem scores (internalizing: aRR, 2.3; 95% CI, 1.1-4.5; total: aRR, 2.5; 95% CI, 1.2-4.4).

Conclusions and Relevance: In this study, high-risk neonatal neurobehavioral patterns at NICU discharge were associated with adverse cognitive, motor, and behavioral outcomes at 2 years. Used in conjunction with medical risk, neonatal neurobehavioral assessments could enhance identification of infants at highest risk for delay and offer opportunities to provide early, targeted therapies.

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JAMA Netw Open





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MeSH Keywords

Child Development; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Infant, Very Low Birth Weight; Intensive Care Units, Neonatal; Male


Child Development; Premature Infant Diseases; Very Low Birth Weight Infant; Neonatal Intensive Care Units


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