Abstract 16244: Hypoplastic Left Heart Syndrome and Related Fetal Growth Abnormalities Are Associated With Placental Vascular Micropathology and Leptin Dysregulation
Introduction: Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation associated with fetal growth abnormalities, but the role of the placenta is unknown. We hypothesized that HLHS is characterized by placental vascular abnormalities and leptin dysregulation.
Methods: Maternal and neonatal clinical data were collected for term HLHS cases. Anthropometrics were obtained and gestational-age adjusted percentiles were assigned using the Olsen standard. Placental tissue was obtained from cases and controls to assess parenchymal morphology, and immunohistochemistry was performed to examine angiogenesis (VEGF-R2, ADAM-29) and leptin signaling (leptin, leptin-receptor).
Results: HLHS cases (n=19) and controls (n=8) were analyzed. Case demographics were representative, and the average birth weight was 2958 grams, including 26% SGA. A history of diabetes, preeclampsia, chorioamnionitis or previa was not associated with HLHS or SGA, and 8 cases of overweight (maternal pre-pregnancy BMI >25) were not associated with SGA. Among cases, mean placental weight was 447±103 grams (12±10 percentile) and the thickness dimension was disproportionately small. Umbilical cord anatomy was normal, but insertion was abnormally eccentric or marginal in 5 cases. Gross placental pathology was ostensibly normal, with non-specific excessive fibrin in 7 cases, but micropathology was abnormal in all cases as evidenced by decreased villous branching and vasculature, including decreased vessel density (p=0.001) and size (p<0.001). There was a trend toward smaller vessel density and size in the subset of cases with SGA. In HLHS placentas, compared to control, VEGF-R2 and ADAM-29 were increased in parenchymal perivasculature, and leptin and leptin-receptor were increased in the perivasculature and syncytium.
Conclusions: Placentas from HLHS pregnancies are characterized by vascular micropathology, and maladaptive angiogenic remodeling may trigger upregulation of leptin to compensate for reduced vasculature. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities.
- © 2013 by American Heart Association, Inc.