Altered placental development is present in all types of fetal congenital heart disease

BACKGROUND: Fetal congenital heart defects (CHD) are related to fetal growth restriction, pregnancy complications and placental abnormalities. We hypothesize that abnormal placental development in fetal CHD is not solely associated to the altered fetal circulation, but is also related to abnormalities in developmental pathways. OBJECTIVES: To assess placenta and umbilical cord histology in pregnancies with fetal CHD and relate this to cardiac development and fetal oxygenation and flow. STUDY DESIGN: Placental tissue from pregnancies with fetal CHD (n = 111) and healthy controls (n = 80) was obtained from a Dutch academic biobank. CHD cases were categorized based on fetal hemodynamics, embryological development and cardiac morphology. Placental histology and a placental severity scores were compared between CHD groups and controls. Pregnancies with genetic abnormalities, multiple gestations, fetal demise, or termination were excluded. RESULTS: CHD placentas showed significantly lower placental weight (<10th percentile), increased delayed villous maturation, fetal vascular malperfusion, nucleated red blood cells, and inflammatory lesions compared with controls. In addition, magistral vascular chorionic vasculature and hypercoiling in the umbilical cord, were more frequent in CHD. The placental severity score was significantly higher in CHD cases compared to controls (median 13 vs. 7, p < 0.001). Although differences in placental abnormalities were observed between CHD subgroups, these could not be linked to fetal aortic flow, oxygenation, or cardiac classification. CONCLUSIONS: Placental and umbilical cord abnormalities in fetal CHD could not be related to fetal hemodynamics or cardiac anatomy, suggesting a primary defect in placental development. Impaired placentation may contribute to the pathogenesis of fetal CHD in some cases.