In children with congenital heart disease (CHD), neurodevelopmental impairment is widespread, yet postnatal factors only account for 30% of the diversity in outcomes. For a study, researchers sought to determine whether prenatal brain volume predicted subsequent neurodevelopmental results in children with CHD to see if the antecedents for neurodevelopmental disorders could start in the womb.

Fetal brain magnetic resonance imaging and a 2-year neurodevelopmental evaluation were performed on fetuses with isolated CHD and sociodemographically equivalent healthy control fetuses (ABAS-3). In the CHD group, hierarchical regression looked at fetal total brain volume adjusted for gestational age and sex, sociodemographic factors, birth measurements, and medical history as possible predictors of Bayley-III and ABAS-3 outcomes.

The Bayley-III cognitive, language, and motor scores of the CHD group (n=52) were lower than those of the control group (n=26), while fetal brain sizes were identical. Larger fetal total brain volume was associated with better Bayley-III cognitive, language, and motor scores and ABAS-3 adaptive functioning scores in the CHD group (r=0.32–0.47; all P<0.05) but not in the control group. In univariate analysis, fetal brain volume predicted 10% to 21% of the variation in neurodevelopmental outcome markers. Depending on the developmental domain, multivariable models that incorporated social status and postnatal variables explained 18% to 45% of the variation in outcome. Furthermore, prenatal brain volume was the most consistent predictor of neurodevelopmental outcome across domains in final multivariable models. 

Small prenatal brain volume was a significant independent predictor of 2-year neurodevelopmental outcomes and might be a useful imaging biomarker of future neurodevelopmental risk in patients with CHD. The hypothesis required further research. Findings suggested that prenatal brain volume should be included in risk classification models and as a viable outcome in fetal neuroprotective intervention research.