To assess the role of the maternal-fetal environment (MFE) on early neurodevelopmental and clinical outcomes in children with single ventricle heart disease (SVHD).

We performed a retrospective, single-center study of patients with a prenatal diagnosis of SVHD from 2011-2022. Impaired MFE was defined as exposure to diabetes, pre-eclampsia, tobacco, or chronic or gestational hypertension in utero. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development-III and 4 between 12 and 36 months of age.

Among 160 patients with SVHD (117 hypoplastic left heart and 43 hypoplastic right heart), 78 completed neurodevelopmental testing. Exposure to an impaired MFE was associated with lower cognitive scores ( P = .030), although this association became nonsignificant after adjustment for clinical covariates. Impaired MFE was also associated with lower language and receptive communication scores after clinical adjustment ( P = .023 and P = .040, respectively) but became nonsignificant after further adjustment for the Child Opportunity Index. No significant differences were observed in fine or gross motor scores, neonatal complications, hospital or intensive care unit stay, and 1-year mortality or transplantation between groups.

Among patients with SVHD, exposure to an impaired MFE was associated with lower cognitive and language outcomes, although these associations were attenuated after accounting for clinical and socioeconomic factors. These findings highlight the importance of early identification and monitoring of children with adverse prenatal exposures.