TY - JOUR
T1 - Fetal Brain Volume Predicts Neurodevelopment in Congenital Heart Disease
AU - Sadhwani, Anjali
AU - Wypij, David
AU - Rofeberg, Valerie
AU - Gholipour, Ali
AU - Mittleman, Maggie
AU - Rohde, Julia
AU - Velasco-Annis, Clemente
AU - Calderon, Johanna
AU - Friedman, Kevin G.
AU - Tworetzky, Wayne
AU - Grant, P. Ellen
AU - Soul, Janet S.
AU - Warfield, Simon K.
AU - Newburger, Jane W.
AU - Ortinau, Cynthia M.
AU - Rollins, Caitlin K.
N1 - Funding Information:
Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke (grant K23NS101120 to Dr Rollins); the National Heart, Lung, and Blood Institute (grant K23HL141602 to Dr Ortinau); the National Institute of Biomedical Imaging and Bioengineering (grant R01EB013248 to Dr Warfield and grants R01EB018988, R01NS106030, and R01EB031849 to Dr Gholipour); a National Heart, Lung, and Blood Institute Pediatric Heart Network Scholar Award (Dr Rollins); the American Academy of Neurology Clinical Research Training Fellowship (Dr Rollins); the Brain and Behavior Research Foundation NARSAD (National Alliance for Research in Schizophrenia and Depression) Young Investigator (Dr Rollins) and Distinguished Investigator (Dr Warfield) Awards; the McKnight Foundation Technological Innovations in Neuroscience Award (Dr Gholipour); the Office of Faculty Development at Boston Children’s Hospital Career Development Awards (Drs Gholipour and Rollins); the Mend A Heart Foundation (Dr Ortinau); and the Farb Family Fund (Dr Newburger). The content does not necessarily represent the official views of the National Institutes of Health or other funding agencies.
Publisher Copyright:
© 2022 Lippincott Williams and Wilkins. All rights reserved.
PY - 2022/4/12
Y1 - 2022/4/12
N2 - 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.
AB - 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.
KW - brain
KW - heart defects, congenital
KW - magnetic resonance imaging
UR - http://www.scopus.com/inward/record.url?scp=85128223409&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.121.056305
DO - 10.1161/CIRCULATIONAHA.121.056305
M3 - Article
C2 - 35143287
AN - SCOPUS:85128223409
VL - 145
SP - 1108
EP - 1119
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 15
ER -