Abstract

OBJECTIVES: Studies have demonstrated an association between congenital heart defects (CHD) and postnatal brain abnormalities and neurodevelopmental delay. Recent evidence suggests that some of these brain abnormalities are present even before birth. The primary aim of this study was to perform a systematic review to quantify the prevalence of prenatal brain abnormalities in fetuses with CHD. METHODS: MEDLINE, EMBASE and The Cochrane Library were searched. Reference lists within each article were hand-searched for additional reports. The outcomes included structural brain abnormalities (MRI), changes in brain volume (MRI, 3-D volumetric MRI, 3-D ultrasound and Phase Contrast Magnetic Resonance), metabolism or maturation (Magnetic Resonance Spectroscopy and Phase Contrast Magnetic Resonance) and blood flow (Doppler ultrasound, Phase Contrast Magnetic Resonance and 3D Power Doppler ultrasound) in fetuses with CHD. Cohort and case-control studies were included. Cases of chromosomal or genetic abnormalities, case reports and editorials were excluded. Proportion meta-analysis was used for analysis. Between-study heterogeneity was assessed using the I(2) test (Registration number: CRD42015025546). RESULTS: The search yielded 1,943 citations; and 20 studies were included in the review (n = 1175 cases, 221 in the meta-analysis). Three studies reported data on structural brain abnormalities, while data on altered brain volume, metabolism and blood flow were reported in 7, 3 and 14 studies, respectively. The three studies reporting data on structural brain abnormalities were suitable for inclusion in a meta-analysis (221 cases). The prevalence of prenatal structural brain abnormalities in fetuses with CHD was 28% (95% CI 18%-40%), similar prevalence in fetuses with tetralogy of Fallot of 25% (95% CI 14%-39). These abnormalities included ventriculomegaly (commonest), agenesis of the corpus callosum, ventricular bleeding, increased extra-axial space, vermian hypoplasia, white matter abnormalities and delayed brain development. Fetuses with CHD were more likely, than those without CHD, to have reduced brain volume, delay in brain maturation and altered brain circulation, most commonly in the form of reduced middle cerebral artery pulsatility index and cerebroplacental ratio. These changes are usually evident in the third trimester, but some studies have reported them as early as the second trimester. CONCLUSIONS: In the absence of known major aneuploidy or genetic syndromes, fetuses with CHD are at increased risk of brain abnormalities, which are present antenatally.