Analysis of Neonatal Neurobehavior and Developmental Outcomes Among Preterm Infants

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. N N NS 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 NN NS 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.