Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease


Regional Brain Growth Trajectories in Fetuses with Congenital Heart Disease

Caitlin K Rollins 1 2Cynthia M Ortinau 3Christian Stopp 4Kevin G Friedman 4 5 6Wayne Tworetzky 4 5 6Borjan Gagoski 7 8Clemente Velasco-Annis 7Onur Afacan 7 8Lana Vasung 7 8Jeanette I Beaute 1Valerie Rofeberg 4Judy A Estroff 3 5 7 8P Ellen Grant 7 8Janet S Soul 1 2 5Edward Yang 7 8David Wypij 4 6 9Ali Gholipour 7 8Simon K Warfield 7 8Jane W Newburger 4 6

Ann Neurol. 2021 Jan;89(1):143-157.  doi: 10.1002/ana.25940. Epub 2020 Nov 4. PMID: 33084086 DOI: 10.1002/ana.25940


Take Home Points:

  • This novel study suggests that fetuses with congenital heart disease (CHD) especially those with lowest cerebral substrate delivery, show a region-specific pattern of small brain volumes and impaired brain growth before 32 weeks gestation.
  • The brains of fetuses with CHD were more similar to those of CHD-related than optimal controls, suggesting genetic or environmental factors also contribute.


Manoj Gupta


Commentary from Dr. Manoj Gupta (New York, USA), section editor of Pediatric & Fetal Cardiology Journal Watch: In this interesting study the authors investigated the abnormal brain development in utero in association with congenital heart disease, with fetal magnetic resonance imaging (MRI). From 2014 to 2018, the authors enrolled 179 pregnant women into 4 groups: 1. “HLHS/TGA” fetuses with hypoplastic left heart syndrome (HLHS) or transposition of the great arteries (TGA) – diagnoses with lowest fetal cerebral substrate delivery; 2. “CHD-other,” with other CHD diagnoses; 3. “CHD-related,” healthy with a CHD family history; and 4. “optimal control,” healthy without a family history.


Two MRIs were obtained between 18 and 40 weeks gestation. Random effect regression models assessed group differences in brain volumes and relationships to hemodynamic variables.


HLHS/TGA (n = 24), CHD-other (50), and CHD-related (34) groups each had generally smaller brain volumes than the optimal controls (71). Compared with CHD-related, the HLHS/TGA group had smaller subplate (−13.3% [standard error = 4.3%], p < 0.01) and intermediate (−13.7% [4.3%], p < 0.01) zones. These volumetric reductions were associated with lower cerebral substrate delivery.