Abstract 4552: Abnormal Cerebrovascular Development in Hypoplastic Left Heart Syndrome During Fetal Life
Background: Microcephaly is common in newborns with hypoplastic left heart syndrome (HLHS) possibly related to altered cerebral blood flow during fetal life and may lead to neurocognitive deficits. We assessed cerebrovascular growth in fetuses with HLHS.
Methods: 27 mid-trimester fetuses with autopsy-confirmed HLHS (gestational age, 23±3 weeks; 11 males) without known chromosomal malformations (2002– 07) were included. Body weight (BW) and head circumference (HC) z scores were calculated. Fetal brain sections were studied in 6 HLHS and 5 normal controls. Brain capillary density (von Willebrand factor, vWf), vascular endothelial growth factor (VEGF), and CD133 (stem cell marker) was measured in germinal matrix, intermediate, subcortical and cortical layers.
Results: Mean BW z score was −0.1±1; HC z score was −0.6±1.4. Capillary density (/hpf) was lower in HLHS vs controls in the germinal matrix (4.1±1.4 vs 7.8 ±1.7; p=0.002) (Fig 1⇓) and cortex (0.9±0.7 vs 3.5±3.2, p=0.09). Capillaries were larger in the HLHS vs controls (vessel area: 0.059±0.019 vs 0.042±0.016 mm2, p=0.005) suggesting reactive dilation to maintain cerebral blood flow. Although VEGF expression was not different between HLHS and controls, the stem cell marker, CD133, was reduced in HLHS (Fig 1⇓).
Conclusion: This study demonstrates early onset cerebral growth impairment in fetuses with HLHS. This may be related to reduced stem cells and reduced brain capillary density. Whether antenatal interventions that augment antegrade aortic blood flow can improve vascular development and cerebral growth requires further investigation.