Summary: Smaller fetal brain volume measured by prenatal MRI predicts later neurodevelopmental outcomes in children with congenital heart disease across cognitive, language, motor, and adaptive domains.
Source: Boston Children’s Hospital
Children born with congenital heart disease (CHD) frequently experience neurodevelopmental difficulties. Historically these problems were attributed largely to surgical complications or reduced oxygen delivery after birth, but recent evidence shows that brain development can be affected before birth.
Fetal brain development in pregnancies affected by CHD may be altered by reduced oxygen delivery to the developing brain or by the same genetic factors that cause the heart defect. Because many forms of CHD are now diagnosed prenatally, researchers at Boston Children’s Hospital investigated whether fetal brain imaging—specifically fetal MRI—could predict later neurodevelopmental risk. If prenatal imaging can identify infants at higher risk, it could support earlier, more targeted interventions.
“A great deal of critical brain development happens during the fetal period and can shape a child’s developmental trajectory,” says study leader Caitlin Rollins, MD, of the Department of Neurology and the Cardiac Neurodevelopmental Program at Boston Children’s Hospital. “Prenatal MRI may help identify infants who would benefit from early, intensive support.”
Fetal MRI brain volumes linked to neurodevelopmental outcomes
Beginning in 2014, Rollins and colleagues across Cardiology, Radiology, and Psychiatry enrolled pregnant women whose fetuses were diagnosed with CHD. An earlier report in Annals of Neurology showed that fetuses with CHD—especially those with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA)—often have smaller brain volumes than fetuses without CHD.
A follow-up study published in Circulation examined whether these smaller fetal brain volumes were associated with developmental outcomes at 18 to 24 months. The team compared 56 pregnant women carrying fetuses with severe CHD to 26 control women with family histories of CHD but whose fetuses were healthy. Fetuses with known genetic syndromes or major noncardiac anomalies were excluded.
All participants underwent at least one interpretable fetal brain MRI. When the children reached 18 to 24 months, researchers assessed neurodevelopment using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and adaptive functioning using the Adaptive Behavior Assessment System, Third Edition (ABAS-3).
Among children with CHD, smaller total fetal brain volume on MRI correlated with lower cognitive, language, and motor scores on the Bayley-III, and with lower adaptive functioning on the ABAS-3. These correlations were not observed in the healthy control group. In analyses that considered other factors—birth weight, caregiver education, complications such as seizure or stroke, and neonatal surgeries—total fetal brain volume remained the most consistent predictor of later neurodevelopment and the only variable that reliably forecast adaptive functioning, which reflects everyday practical skills.
“To our knowledge, this is the first study linking fetal brain development with subsequent neurodevelopmental outcomes in children with CHD,” says coauthor Jane Newburger, MD, MPH, associate cardiologist-in-chief and founder of the Cardiac Neurodevelopmental Program. “These findings suggest fetal brain size could help trigger early postnatal interventions and serve as an outcome measure in trials of fetal therapies.”
Implications for prenatal and postnatal intervention
Rollins emphasizes that while fetal brain volume predicted outcomes at the group level, it may not be accurate for every individual infant. Still, the research supports using prenatal MRI to stratify risk and guide more intensive care when appropriate. Interventions might include enhanced early intervention services and therapies that target adaptive skills, communication, and motor development.
The Cardiac Neurodevelopmental Program already offers a Prenatal Stress Reduction Program—using mindfulness and cognitive-behavioral strategies—to pregnant people carrying fetuses with CHD, because maternal stress can influence fetal brain development. Rollins plans to test this and similar prenatal interventions in clinical trials, using fetal brain imaging as a biomarker to measure effects.
Other proposed neuroprotective approaches include supplemental maternal oxygen and pharmacologic therapies, though these strategies remain investigational and controversial. Rollins notes that future trials may test agents or interventions—particularly for high-risk diagnoses such as HLHS and TGA—using prenatal MRI metrics as outcome measures.
Next steps and longer-term follow-up
Researchers at Boston Children’s and collaborating centers are developing infrastructure for multicenter studies to evaluate fetal brain MRI across diverse types of CHD, which will require larger samples to define the value of prenatal imaging in different diagnostic groups.
Meanwhile, the original cohort is reaching school age (6 to 8 years), and the team is beginning longer-term follow-up to determine whether smaller fetal brain volumes have lasting effects on cognition, adaptive functioning, attention, executive skills, and social cognition—areas that often become more apparent as children enter school.
“We want to know whether early differences in brain size translate into sustained developmental effects,” Rollins says. “Many higher-order deficits in attention, executive functioning, and social cognition emerge at school age, so long-term follow-up is critical.”
About this fetal development and neuroimaging research news
Author: Nancy Fliesler
Source: Boston Children’s Hospital
Contact: Nancy Fliesler – Boston Children’s Hospital
Image: The image is in the public domain
Original Research: Open access. “Fetal Brain Volume Predicts Neurodevelopment in Congenital Heart Disease” by Anjali Sadhwani et al., Circulation.
Abstract
Fetal Brain Volume Predicts Neurodevelopment in Congenital Heart Disease
Background:
Neurodevelopmental impairments are common in children with congenital heart disease (CHD), yet postnatal factors account for only about 30% of outcome variance. To evaluate whether antecedents of neurodevelopmental disability begin before birth, the study tested whether fetal brain volume measured by MRI predicts later neurodevelopmental outcomes in children with CHD.
Methods:
Fetuses with isolated CHD and sociodemographically matched healthy control fetuses underwent fetal brain MRI and were later evaluated at 2 years with the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), and the Adaptive Behavior Assessment System, Third Edition (ABAS-3). Hierarchical regression assessed predictors of Bayley-III and ABAS-3 outcomes in the CHD group, including fetal total brain volume (adjusted for gestational age and sex), sociodemographic factors, birth measures, and medical history.
Results:
In this cohort the CHD group (n=52) scored lower on Bayley-III cognitive, language, and motor measures than controls (n=26), although mean fetal brain volumes did not differ between groups. Within the CHD group, larger fetal total brain volume correlated with higher Bayley-III cognitive, language, and motor scores and with higher ABAS-3 adaptive functioning scores (r=0.32–0.47; all P<0.05). Fetal brain volume alone accounted for 10%–21% of outcome variance in univariate analyses. Multivariable models that incorporated social factors and postnatal variables explained 18%–45% of variance depending on the domain; fetal brain volume remained the most consistent predictor across domains.
Conclusions:
Small fetal brain volume is a robust independent predictor of 2-year neurodevelopmental outcomes and may serve as an important prenatal imaging biomarker of neurodevelopmental risk in CHD. These findings support including fetal brain volume in risk stratification and as a potential outcome measure for fetal neuroprotective intervention trials. Further studies are needed to validate and expand these observations.