Cognition, internalizing symptoms and neonatal cingulate-amygdala interaction in children born very low birth weight

Children born with very low birth weight are at increased risk of cognitive difficulties and internalizing symptoms, including anxiety, withdrawal, and depressive features. However, the early neurodevelopmental pathways that connect neonatal brain maturation with emotional outcomes remain incompletely understood. This study examined whether internalizing symptoms at preschool age are associated with cognitive performance in children born with very low birth weight, and whether the interaction between cingulate and amygdala volumes is related to these symptoms directly or through cognition.

This longitudinal cohort included infants born with very low birth weight who were admitted to a neonatal intensive care unit between 2018 and 2021. Participants underwent brain magnetic resonance imaging at term-equivalent age and follow-up assessment at 4 to 6 years. Cognitive performance was evaluated with the Wechsler Preschool and Primary Scale of Intelligence, and internalizing symptoms were assessed with the Child Behavior Checklist. Adjusted linear regression models examined associations between cognition, neonatal regional brain volumes, and internalizing symptom scores. An observed-variable path model tested direct and indirect associations involving cingulate-amygdala interaction and cognition, and receiver operating characteristic analysis evaluated discrimination for clinically relevant internalizing symptoms.

Ninety-five children were included; mean gestational age was 29.4 ± 2.1 weeks and mean birth weight 1191.6 ± 350.8 g. Clinically relevant internalizing symptoms were present in 24/95 children (25.3%). Lower internalizing T-scores were associated with Higher IQ after adjustment (B = -0.282; P = 0.020). The cingulate-amygdala interaction was associated with internalizing symptoms (B = -60.377; P = 0.009). In path analysis, IQ was inversely associated with internalizing symptoms (B = -0.315; P < 0.001), and the indirect effect through IQ was significant (B = -19.449; P = 0.003). The MRI-based logistic model showed acceptable discrimination (area under the curve, 0.75).

Among children born VLBW, preschool internalizing symptoms were associated with poor cognitive performance and neonatal cingulate-amygdala interaction. These findings support interconnected brain-cognition-behavior pathways after preterm birth and underscore the value of integrated neurodevelopmental follow-up.