Hypoplastic left heart syndrome is associated with structural and vascular placental abnormalities and leptin dysregulation

Abstract

Introduction Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. Methods HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. Results HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 grams, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. Discussion Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases.

Characterization of the Placenta in the Newborn with Congenital Heart Disease: Distinctions Based on Type of Cardiac Malformation

“…Based on a large population-based study from Denmark, lower placental weight at birth is associated with tetralogy of Fallot, double-outlet right ventricle and “major” ventricular septal defects [22]. In a small series of 16 subjects with hypoplastic left heart syndrome, the placenta is reported smaller than normal in weight with a marked increased in fibrin deposition, decreased terminal villi and increased expression of leptin, an angiogenic and mitogenic hormone produced by the placenta, which may indicate an attempt to compensate for vascular abnormalities [23]. Placental dysfunction-related complications such as preeclampsia are associated with CHD [7, 8].…”

Neurodevelopmental Outcomes in Children With Congenital Heart Disease—What Can We Impact?

“…Complete mixing, as seen in those with functionally univentricular hearts, and limitations on compensatory lowering of cerebrovascular resistance, produce reduced fetal cerebral oxygen delivery. The contribution of the placenta adds complexity to the issue as it has been noted that placenta weights are much lower than normal and placental vascularity is abnormal (21). Furthermore, MRI measurements of umbilical vein oxygen saturations have been shown to be much lower than expected, suggesting placental dysfunction (17).…”

Transgenerational cardiology: One way to a baby's heart is through the mother

“…For example, aging could somehow disturb placental function, which would in turn increase the risk of cardiac malformation. Abnormalities of placental size and architecture have been reported in association with complex congenital heart defects, although the causal relationships are unknown (Jones et al, 2015; Andescavage et al, 2015). …”