Fetal Brain Volume Predicts Neurodevelopment in Congenital Heart Disease

Author:

Sadhwani Anjali12ORCID,Wypij David345,Rofeberg Valerie3,Gholipour Ali67ORCID,Mittleman Maggie8,Rohde Julia8,Velasco-Annis Clemente6,Calderon Johanna12ORCID,Friedman Kevin G.34,Tworetzky Wayne34,Grant P. Ellen67ORCID,Soul Janet S.89ORCID,Warfield Simon K.67ORCID,Newburger Jane W.34ORCID,Ortinau Cynthia M.10,Rollins Caitlin K.89ORCID

Affiliation:

1. Department of Psychiatry and Behavioral Sciences (A.S., J.C.), Boston Children’s Hospital, MA.

2. Department of Psychiatry (A.S., J.C.), Harvard Medical School, Boston, MA.

3. Department of Cardiology (D.W., V.R., K.G.F., W.T., J.W.N.), Boston Children’s Hospital, MA.

4. Department of Pediatrics (D.W., K.G.F., W.T., J.W.N.), Harvard Medical School, Boston, MA.

5. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (D.W.).

6. Department of Radiology (A.G., C.V.-A., P.E.G., S.K.W.), Boston Children’s Hospital, MA.

7. Department of Radiology (A.G., P.E.G., S.K.W.), Harvard Medical School, Boston, MA.

8. Department of Neurology (M.M., J.R., J.S.S., C.K.R.), Boston Children’s Hospital, MA.

9. Department of Neurology (J.S.S., C.K.R.), Harvard Medical School, Boston, MA.

10. Department of Pediatrics, Washington University in St Louis, MO (C.M.O.).

Abstract

Background: Neurodevelopmental impairment is common in children with congenital heart disease (CHD), but postnatal variables explain only 30% of the variance in outcomes. To explore whether the antecedents for neurodevelopmental disabilities might begin in utero, we analyzed whether fetal brain volume predicted subsequent neurodevelopmental outcome in children with CHD. Methods: Fetuses with isolated CHD and sociodemographically comparable healthy control fetuses underwent fetal brain magnetic resonance imaging and 2-year neurodevelopmental evaluation 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 evaluated potential predictors of Bayley-III and ABAS-3 outcomes in the CHD group, including fetal total brain volume adjusted for gestational age and sex, sociodemographic characteristics, birth measures, and medical history. Results: The CHD group (n=52) had lower Bayley-III cognitive, language, and motor scores than the control group (n=26), but fetal brain volumes were similar. Within the CHD group, larger fetal total brain volume correlated with higher Bayley-III cognitive, language, and motor scores and ABAS-3 adaptive functioning scores ( r =0.32–0.47; all P <0.05), but this was not noted in the control group. Fetal brain volume predicted 10% to 21% of the variance in neurodevelopmental outcome measures in univariate analyses. Multivariable models that also included social class and postnatal factors explained 18% to 45% of the variance in outcome, depending on developmental domain. Moreover, in final multivariable models, fetal brain volume was the most consistent predictor of neurodevelopmental outcome across domains. Conclusions: Small fetal brain volume is a strong independent predictor of 2-year neurodevelopmental outcomes and may be an important imaging biomarker of future neurodevelopmental risk in CHD. Future studies are needed to support this hypothesis. Our findings support inclusion of fetal brain volume in risk stratification models and as a possible outcome in fetal neuroprotective intervention studies.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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