Impact of catch-up growth on brain structures involved in emotional regulation in preterm children at 2 years of age

BACKGROUND: Extrauterine growth restriction (EUGR) is common in very preterm infants and has been associated with adverse neurodevelopmental outcomes. Early postnatal catch-up growth may mitigate the effects of prematurity on brain development; however, its long-term impact on brain regions involved in emotional regulation has not been well defined. OBJECTIVE: To determine whether weight catch-up by 2 years of age in very low birth weight preterm infants with EUGR is associated with structural brain differences at school age, particularly in regions related to emotional processing. METHODS: We conducted an observational cohort study of very low birth weight preterm children (<1500 g, <32 weeks' gestation) admitted between 2008 and 2017. Children with fetal growth restriction, major neurological disorders, or moderate-to-severe cognitive impairment were excluded. At school age, participants underwent awake structural brain MRI (3 T) and cognitive assessment using the WISC-V. Brain morphometry was analyzed using FreeSurfer, focusing on prefrontal, cingulate, temporal, insular, and subcortical regions implicated in emotional regulation. Children with EUGR were classified according to achievement of weight catch-up (≥10th percentile) by 2 years of age. RESULTS: Of 115 children included, 44 had EUGR; 26 achieved weight catch-up by 2 years and 18 did not. Children without catch-up showed significantly smaller volumes in several prefrontal regions (including bilateral superior frontal gyrus and orbitofrontal cortex), bilateral superior and middle temporal gyri, the left posterior cingulate cortex, and the left thalamus (all p < 0.05). No significant differences were observed in global cognitive performance between groups. CONCLUSIONS: In preterm children with EUGR, failure to achieve weight catch-up by 2 years of age is associated with persistent structural alterations in brain regions involved in executive and emotional regulation at school age, despite preserved global cognitive performance. These findings highlight early postnatal growth as a critical modifiable factor for long-term brain development.