Fetal MRI detects early alterations of brain development in Tetralogy of Fallot

Am J Obstet Gynecol. 2015 Sep;213(3):392.e1-7. doi: 10.1016/j.ajog.2015.05.046. Epub 2015 May 23.


Objective: Prenatal imaging has identified alterations of brain growth in fetuses with congenital heart disease. However, little is known about the timing of altered brain development and its occurrence in specific congenital heart disease subgroups. This magnetic resonance imaging study aimed to identify early (median, 25 gestational weeks [GW]) changes in fetal total brain (TBV), gray matter (GMV), and subcortical brain (SBV) volumes in Tetralogy of Fallot (TOF) cases in utero.

Study design: Fetal magnetic resonance imaging (1.5 Tesla) was performed in 24 fetuses who were diagnosed with TOF and 24 normal age-matched control fetuses (20-34 GW). TBV, GMV, SBV, intracranial cavity, cerebellar, ventricular, and external cerebrospinal fluid volumes were quantified by manual segmentation based on coronal T2-weighted sequences. Mixed model analyses of variance and t-tests were conducted to compare cases and control fetuses.

Results: TBV was significantly lower (P < .001) in early (<25 GW) and late TOF cases. Both GMV (P = .003) and SBV (P = .001) were affected. The GMV-to-SBV ratio declined in fetuses with TOF (P = .026). Compared with normal fetuses, ventricular volume was increased (P = .0048). External cerebrospinal fluid was enlarged in relation to head size (P < .001). Intracranial cavity volume (P = .314) and cerebellar volume (P = .074) were not significantly reduced in fetuses with TOF.

Conclusion: TOF is associated with smaller volumes of gray and white matter and enlarged cerebrospinal fluid spaces. These changes are present at ≤25 GW and indicate altered fetal brain growth in this pathophysiologic entity during early stages of human brain development.

Keywords: Tetralogy of Fallot; brain; development; fetal; imaging; magnetic resonance imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / embryology*
  • Brain / pathology
  • Case-Control Studies
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Models, Statistical
  • Pregnancy
  • Prenatal Diagnosis* / methods
  • Retrospective Studies
  • Tetralogy of Fallot / embryology*
  • Tetralogy of Fallot / pathology