Placenta histology related to flow and oxygenation in fetal congenital heart disease

Background: Fetuses with congenital heart defects (CHD) show delayed neurodevelopment, fetal growth restriction (FGR) and placenta related complications. The neurodevelopmental delay may be, partly, attributed to placental factors. Aim: As both placental development and fetal aortic flow/oxygenation influence neurodevelopment, placentas were compared within fetal CHD groups based on aortic oxygenation and flow, aiming to unravel the true effects in the developmental processes. Study design: Placental tissues of pregnancies with fetal CHD and healthy controls were selected from biobanks of two Dutch academic hospitals (LUMC, UMCU). Additionally, biometry and Dopplers were assessed. Subjects: CHD cases with reduced oxygenation (RO) towards the fetal brain were compared to cases with reduced flow (RF) in the aortic arch and healthy controls. Genetic abnormalities, termination of pregnancy, fetal demise and/or multiple pregnancies were excluded. Outcome measures: Histological outcomes were related to fetal Dopplers and biometry. A placenta severity score was used to assess the severity of placental abnormalities per case. Results: In CHD, significantly more delayed maturation, maternal vascular malperfusion, fetal hypoxia and higher placenta severity scores (median 14 in RO, 14 in RF, 5 in controls, p < 0.001) were observed. Doppler abnormalities (PI UA > p90, PI MCA < p10, CPR < p10) and FGR were more often found in CHD. There were no differences in placental abnormalities, fetal growth and fetal Dopplers between cases with RO and RF. Conclusion: Fetal hemodynamics in the ascending aorta could not be related to placenta characteristics. We hypothesize that placental development influences neurodevelopment in excess of hemodynamics in CHD cases.