Abnormal fetal cerebral and vascular development in hypoplastic left heart syndrome

Prenat Diagn. 2019 Jan;39(1):38-44. doi: 10.1002/pd.5395. Epub 2018 Dec 27.


Objective: To assess the cerebral and vascular development in fetuses with hypoplastic left heart syndrome (HLHS).

Methods: Pregnant women carrying fetuses diagnosed with HLHS who decided to interrupt their pregnancies were included in our study. Aortic size and blood flow were assessed based from fetal echocardiography. Immunohistochemical staining was performed in brain sections obtained from pathology in fetuses with HLHS and control fetuses without heart disease.

Results: Twenty-seven midgestation fetal HLHS were included (gestational age, 23.3 ± 3.4 weeks). Head circumference z scores were lower in HLHS fetuses. Middle cerebral artery pulsatility index, a measure of cerebrovascular resistance, was inversely correlated with the ascending aortic z score (P < 0.05). Fetuses with HLHS had lower capillary density in the germinal matrix and their capillaries were larger compared with control fetuses with (P < 0.05). The expression of neuronal differentiation marker, FGFR1, and oligodendrocyte precursor, O4, were lower in HLHS brains compared with controls (P < 0.05).

Conclusion: Our study identified abnormalities of vascular flow and structural brain abnormalities in fetal HLHS associated with impaired neuronal and oligodendrocyte differentiation, as well as cerebral growth impairment, early in gestation. These findings may be related in part to early vascular abnormalities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Vessels / embryology*
  • Brain / abnormalities
  • Brain / embryology*
  • Brain / pathology
  • Capillaries / embryology
  • Echocardiography
  • Female
  • Fetal Diseases
  • Fetal Heart
  • Gestational Age
  • Humans
  • Hypoplastic Left Heart Syndrome / embryology*
  • Hypoplastic Left Heart Syndrome / physiopathology*
  • Immunohistochemistry
  • Middle Cerebral Artery / embryology
  • Pregnancy
  • Pulsatile Flow
  • Ultrasonography, Prenatal