Contrasting neonatal brain morphometry and its impact on neurodevelopmental outcome between preterm birth and congenital heart disease.

Congenital heart disease (CHD) and prematurity are leading causes of infant mortality and morbidity. Both groups of infants share certain common neurological sequalae, such as increased risk of neonatal brain injury and neurodevelopmental impairments later in life, leading to hypotheses that there may be shared underlying structural differences in the infant brain. However, there is no empirical evidence to support this, and our objective with this study was to compare and contrast neonatal brain structure between at-risk infant groups, then analyse their relationship with neurodevelopmental outcome. We carried out a retrospective, longitudinal, case-control analysis of 602 T2-weighted infant brain MRIs, acquired between 37 and 44 weeks postmenstrual age (PMA). The cohort comprised early preterm (n = 60), late preterm (n = 67), infants with congenital heart disease (CHD; n = 116), and term-born controls from the Developing Human Connectome Project (n = 360). We analyse structural covariance networks, a data-driven extraction of co-maturing neuroanatomical structures, capturing the variation in brain morphometry for each infant. We found distinct structural profiles in CHD and preterm infants, with minimal overlap observed between groups. A subset (n = 428) returned for neurodevelopmental follow-up at 18-24 months, and we explored the association with Bayley-III cognitive and motor scores. We found that variation in neonatal brain morphology is a significant predictor of toddler neurodevelopment in preterm infants and controls, but this association is absent in CHD. These findings suggest divergent neurobiological pathways may underlie adverse outcomes in these high-risk infants.