Examining the Link Between an Impaired MFE, Children with SVHD and Neurodevelopment

Research study background

Children with complex congenital heart disease (CHD), including single ventricle heart disease (SVHD), face significant neurodevelopmental challenges that can profoundly affect their quality of life. Major advances in surgical techniques and therapies have greatly improved life expectancy for these patients, and this progress has brought with it a growing focus on improving quality of life. While neurodevelopmental outcomes in this population are likely multifactorial, the role of the fetal environment is an increasingly important area of discussion.

“As a fetal cardiologist, I am particularly interested in how the maternal-fetal environment shapes outcomes like neurodevelopment in patients with complex congenital heart disease,” says Sam Holmes, MD, first author of the study. “This understanding allows us to identify at-risk patients earlier and explore interventions that begin before birth to support long-term outcomes.”

In the retrospective single-center study, researchers looked at patients with a prenatal SVHD diagnosis between 2011 and 2022 to determine if an impaired maternal-fetal environment (MFE) affected early neurodevelopmental and clinical outcomes. Impaired MFE was defined as exposure to diabetes, pre-eclampsia, tobacco, or chronic or gestational hypertension in utero.

Among the 160 patients with SVHD, 117 had hypoplastic left heart syndrome and 43 had hypoplastic right heart syndrome. Of those, 78 completed neurodevelopmental testing. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant and Toddler Development-III and 4 between 12 and 36 months of age.

“Other centers have demonstrated that an impaired maternal-fetal environment is associated with higher rates of mortality, transplant and longer hospital stays in patients with congenital heart disease,” Dr. Holmes says, “but its impact on neurodevelopmental outcomes had not been studied.”

The study’s authors say this research is particularly relevant given that children with congenital heart disease are known to have structural brain differences, which have been associated with worse neurodevelopmental outcomes. Prior research found associations between the maternal-fetal environment and preoperative white matter injury, and there is growing evidence that placental dysfunction can adversely affect brain development. However, this study is the first to examine how the maternal-fetal environment influences functional neurodevelopmental outcomes in this patient population.

Study results

The results of the study showed that exposure to an impaired MFE was associated with lower cognitive scores (P = .030), although this association became less significant 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 less significant 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 stays, and one-year mortality or transplantation between groups.

Clinical implications

When taking into account clinical and socioeconomic factors, the association between an impaired MFE and early neurodevelopmental and clinical outcomes was attenuated given the small sample size. Nonetheless, researchers conclude that these findings still highlight the importance of early identification and monitoring of children with adverse prenatal exposures.

“Outcomes in children with congenital heart disease are multifactorial and complex,” says Emily Bucholz, MD, senior author of the study. “Understanding how the prenatal environment shapes neurodevelopmental outcomes is essential to identifying the best ways to support these patients and their families. Recognizing risk factors during the prenatal period gives us an opportunity to intervene early. The earlier we identify high-risk patients, the better positioned we are to make a meaningful difference in their long-term outcomes.”

Drs. Holmes and Bucholz emphasize the importance of collaboration when caring for this high-risk population. While the study focuses on the maternal-fetal environment, they say the care these patients receive is never the work of a single team. To achieve the best possible outcomes for these children requires many disciplines working together, particularly between maternal-fetal medicine, neonatology and pediatric cardiology, which makes optimizing care before birth possible. They say there is much we can learn about the effects of prenatal exposures on postnatal development and outcomes in this patient population, and continued cross-disciplinary collaboration will be crucial.