Postnatal Brain Trajectories and Maternal Intelligence Predict Childhood Outcomes in Complex CHD

Highlights: Question: Do early infant brain trajectories in congenital heart disease (CHD) patients predict early childhood neurodevelopmental (ND) outcomes adjusted for known genetic abnormalities and maternal intelligence (IQ)? Findings: Reduced brain volumetric trajectories in infants with CHD predicted language outcomes at 5 years, adjusting for maternal IQ and genetic abnormalities. Maternal IQ substantially contributed to ND variance, nearly doubling from 1 year to 5 years. Meaning: Postnatal brain trajectories can predict early childhood ND in complex CHD. The influence of maternal IQ is cumulative and can exceed the influence of medical and genetic factors in CHD, underscoring the importance of not only heritable factors but also parent-based environmental factors. Objective: To determine whether early structural brain trajectories predict early childhood neurodevelopmental deficits in complex CHD patients and to assess relative cumulative risk profiles of clinical, genetic, and demographic risk factors across early development. Study Design: Term neonates with complex CHDs were recruited at Texas Children’s Hospital from 2005–2011. Ninety-five participants underwent three structural MRI scans and three neurodevelopmental assessments. Brain region volumes and white matter tract fractional anisotropy and radial diffusivity were used to calculate trajectories: perioperative, postsurgical, and overall. Gross cognitive, language, and visuo-motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development and with the Wechsler Preschool and Primary Scale of Intelligence and Beery–Buktenica Developmental Test of Visual–Motor Integration. Multi-variable models incorporated risk factors. Results: Reduced overall period volumetric trajectories predicted poor language outcomes: brainstem ((β, 95% CI) 0.0977, 0.0382–0.1571; p = 0.0022) and white matter (0.0023, 0.0001–0.0046; p = 0.0397) at 5 years; brainstem (0.0711, 0.0157–0.1265; p = 0.0134) and deep grey matter (0.0085, 0.0011–0.0160; p = 0.0258) at 3 years. Maternal IQ was the strongest contributor to language variance, increasing from 37% at 1 year, 62% at 3 years, and 81% at 5 years. Genetic abnormality’s contribution to variance decreased from 41% at 1 year to 25% at 3 years and was insignificant at 5 years. Conclusion: Reduced postnatal subcortical–cerebral white matter trajectories predicted poor early childhood neurodevelopmental outcomes, despite high contribution of maternal IQ. Maternal IQ was cumulative over time, exceeding the influence of known cardiac and genetic factors in complex CHD, underscoring the importance of heritable and parent-based environmental factors.