Effect of Fetal Brain Oxygenation and Volume on Brain Maturation and Neurodevelopmental Outcomes in Congenital Heart Disease.

Abstract

Background Neurodevelopmental delay is a cause of long-term morbidity in congenital heart disease (CHD). There are limited data on the effects of the fetal period on later neurodevelopment. Purpose To assess the effect of impaired fetal brain oxygenation and fetal brain volume on perinatal brain maturation and early neurodevelopmental outcomes. Materials and Methods In this secondary analysis of a single-center prospective study (April 2017 to November 2024), fetuses with CHD and normal fetuses underwent third-trimester fetal brain MRI with T2* mapping to assess oxygenation. Those with CHD underwent neonatal MRI, and neurodevelopmental testing at 30 months of age with the Bayley Scales of Infant and Toddler Development. T2* and brain volume were indexed by sex and gestational age to controls, to generate residuals. The associations of residual fetal T2* and residual fetal brain volume with brain volume growth rate from fetal to neonatal MRI, neonatal white matter (WM) apparent diffusion coefficient and fractional anisotropy, and neurodevelopment at 30 months were assessed using univariable and multivariable linear regression models. Results The study included 80 individuals (mean gestational age at fetal brain MRI, 34.0 weeks ± 0.9 [SD]; 52 male fetuses; 60 fetuses with CHD, 20 controls). There was no evidence of an association of residual fetal T2* with perinatal brain growth rate (β = 0.06 [95% CI: -0.00, 0.12]; P = .06), WM apparent diffusion coefficient (P = .11), WM fractional anisotropy (P = .21), or 30-month neurodevelopment (motor, P = .99; language, P = .89; cognition, P > .99). In multivariable analysis, single ventricle physiology was associated with worse motor scores than transposition of the great arteries (β = -19.87 [95% CI: -39.61, -0.13]; P = .049), while residual fetal brain volume was positively associated with language score (β = 0.79 [95% CI: 0.05, 1.54]; P = .04). Conclusion Fetal brain oxygenation was not associated with perinatal brain maturation or early neurodevelopmental outcomes, but fetal brain volume and lesion complexity (as represented by lesion type) were associated with improved language and worse motor outcomes, respectively. © RSNA, 2025 Supplemental material is available for this article.