JAMA Pediatr. 2026 Jan 20. doi: 10.1001/jamapediatrics.2025.5866. Online ahead of print.
ABSTRACT
IMPORTANCE: Children born very preterm or with very low birth weight are at higher risk for executive function deficits, affecting attention, self-regulation, and problem-solving. Early developmental interventions have shown potential benefits, but their long-term effect on executive functioning remains uncertain.
OBJECTIVE: To evaluate whether an enhanced developmental intervention (EDI) initiated in the neonatal intensive care unit (NICU) and continued at home through the first 2 years improves executive function at school age in very preterm children.
DESIGN, SETTING, AND PARTICIPANTS: This secondary analysis assessed school-aged outcomes from a randomized clinical trial of infants born with fewer than 32 weeks of gestation or with birth weight less than 1500 g from January 2016 to February 2019. Follow-up assessments were conducted from July 7, 2023, to August 16, 2024, at a single center in Porto Alegre, Brazil. Data analyses were completed from August to December 2024.
INTERVENTION: EDI compared with usual care.
MAIN OUTCOMES AND MEASURES: The primary outcomes were the scaled scores of Developmental Neuropsychological Assessment, Second Edition, subtests, which measures auditory attention, inhibition, design fluency, and motor persistence. The examiner was masked to group allocation. Medical records identified children with neurodevelopmental conditions that precluded formal assessment. The effect size for the Mann-Whitney U test comparisons was calculated using the rank-biserial correlation. Binary logistic regression was used to compare performance in the primary outcomes. Sensitivity analyses were used for those lost to follow-up.
RESULTS: Of the original randomized clinical trial, 80 children (96% of those eligible) were assessed at a mean (SD) age of 7 (1) years; 34 children (43%) were female. Baseline characteristics were similar between groups. In the primary analysis of median scaled scores, children who received EDI demonstrated significantly better performance across all 4 executive function domains compared to usual care (median scores, 12-14 vs 2-9; r = 0.44-0.77; all P < .001). All results remained significant after Bonferroni correction (P < .0125), indicating medium to large effect sizes. In the secondary analysis of performance classification, EDI was associated with higher odds of expected performance in design fluency (odds ratio, 11.3; 95% CI, 4.08-31.7; P < .001). No statistically significant differences were observed for the remaining 3 domains.
CONCLUSIONS AND RELEVANCE: In this secondary analysis of a randomized clinical trial, early EDI, beginning in the NICU and extending through the first 2 years, contributed to sustained improvements in executive function in very preterm children. These findings support the long-term neurodevelopmental benefits of early intervention, with potential implications for academic and socioemotional outcomes in children from low- and middle-income settings.
TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02835612.
PMID:41557341 | DOI:10.1001/jamapediatrics.2025.5866
