TY - JOUR
T1 - Prenatal to postnatal trajectory of brain growth in complex congenital heart disease
AU - Ortinau, Cynthia M.
AU - Mangin-Heimos, Kathryn
AU - Moen, Joseph
AU - Alexopoulos, Dimitrios
AU - Inder, Terrie E.
AU - Gholipour, Ali
AU - Shimony, Joshua S.
AU - Eghtesady, Pirooz
AU - Schlaggar, Bradley L.
AU - Smyser, Christopher D.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH) Institute of Clinical and Translational Sciences ( UL1 TR000448 and KL2 TR 000450 ) (C.O.), National Institute of Neurological Disorders and Stroke ( K02 NS089852 ) (C.S.), National Institute of Biomedical Imaging and Bioengineering ( R01EB018988) (A.G.), and the Eunice Kennedy Shriver National Institute Of Child Health & Human Development under Award Number U54 HD087011 to the Intellectual and Developmental Disabilities Research Center at Washington University (B.L.S.) ; the Children's Discovery Institute of Washington University and St. Louis Children's Hospital (C.O. and C.S) ; the McKnight Foundation Technological Innovations in Neuroscience Award (A.G.) ; and a Career Development Award from the Office of Faculty Development at Boston Children's Hospital (A.G.) . The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors would like to thank Jennifer Brockmeyer and Reginald Lee for their assistance with recruitment and MRI analysis.
Publisher Copyright:
© 2018 The Authors
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Altered brain development is a common feature of the neurological sequelae of complex congenital heart disease (CHD). These alterations include abnormalities in brain size and growth that begin prenatally and persist postnatally. However, the longitudinal trajectory of changes in brain volume from the prenatal to postnatal environment have not been investigated. We aimed to evaluate the trajectory of brain growth in a cohort of patients with complex CHD (n = 16) and healthy controls (n = 15) to test the hypothesis that patients with complex CHD would have smaller total brain volume (TBV) prenatally, which would become increasingly prominent by three months of age. Participants underwent fetal magnetic resonance imaging (MRI) at a mean of 32 weeks gestation, a preoperative/neonatal MRI shortly after birth, a postoperative MRI (CHD only), and a 3-month MRI to evaluate the trajectory of brain growth. Three-dimensional volumetric analysis was applied to the MRI data to measure TBV, as well as tissue-specific volumes of the cortical gray matter (CGM), white matter (WM), subcortical (deep nuclear) gray matter (SCGM), cerebellum, and cerebrospinal fluid (CSF). A random coefficients model was used to investigate longitudinal changes in TBV and demonstrated an altered trajectory of brain growth in the CHD population. The estimated slope for TBV from fetal to 3-month MRI was 11.5 cm3 per week for CHD infants compared to 16.7 cm3 per week for controls (p = 0.0002). Brain growth followed a similar trajectory for the CGM (p < 0.0001), SCGM (p = 0.002), and cerebellum (p = 0.005). There was no difference in growth of the WM (p = 0.30) or CSF (p = 0.085). Brain injury was associated with reduced TBV at 3-month MRI (p = 0.02). After removing infants with brain injury from the model, an altered trajectory of brain growth persisted in CHD infants (p = 0.006). These findings extend the existing literature by demonstrating longitudinal impairments in brain development in the CHD population and emphasize the global nature of disrupted brain growth from the prenatal environment through early infancy.
AB - Altered brain development is a common feature of the neurological sequelae of complex congenital heart disease (CHD). These alterations include abnormalities in brain size and growth that begin prenatally and persist postnatally. However, the longitudinal trajectory of changes in brain volume from the prenatal to postnatal environment have not been investigated. We aimed to evaluate the trajectory of brain growth in a cohort of patients with complex CHD (n = 16) and healthy controls (n = 15) to test the hypothesis that patients with complex CHD would have smaller total brain volume (TBV) prenatally, which would become increasingly prominent by three months of age. Participants underwent fetal magnetic resonance imaging (MRI) at a mean of 32 weeks gestation, a preoperative/neonatal MRI shortly after birth, a postoperative MRI (CHD only), and a 3-month MRI to evaluate the trajectory of brain growth. Three-dimensional volumetric analysis was applied to the MRI data to measure TBV, as well as tissue-specific volumes of the cortical gray matter (CGM), white matter (WM), subcortical (deep nuclear) gray matter (SCGM), cerebellum, and cerebrospinal fluid (CSF). A random coefficients model was used to investigate longitudinal changes in TBV and demonstrated an altered trajectory of brain growth in the CHD population. The estimated slope for TBV from fetal to 3-month MRI was 11.5 cm3 per week for CHD infants compared to 16.7 cm3 per week for controls (p = 0.0002). Brain growth followed a similar trajectory for the CGM (p < 0.0001), SCGM (p = 0.002), and cerebellum (p = 0.005). There was no difference in growth of the WM (p = 0.30) or CSF (p = 0.085). Brain injury was associated with reduced TBV at 3-month MRI (p = 0.02). After removing infants with brain injury from the model, an altered trajectory of brain growth persisted in CHD infants (p = 0.006). These findings extend the existing literature by demonstrating longitudinal impairments in brain development in the CHD population and emphasize the global nature of disrupted brain growth from the prenatal environment through early infancy.
KW - Brain volume
KW - Congenital heart disease
KW - Fetal
KW - Magnetic resonance imaging
UR - http://www.scopus.com/inward/record.url?scp=85054423077&partnerID=8YFLogxK
U2 - 10.1016/j.nicl.2018.09.029
DO - 10.1016/j.nicl.2018.09.029
M3 - Article
C2 - 30308377
AN - SCOPUS:85054423077
SN - 2213-1582
VL - 20
SP - 913
EP - 922
JO - NeuroImage: Clinical
JF - NeuroImage: Clinical
ER -