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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. 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. 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. 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. Histological outcomes were related to fetal Dopplers and biometry. A placenta severity score was used to assess the severity of placental abnormalities per case. 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. 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. • Placental features in fetal CHD could not be related to aortic flow and oxygenation. • Next to hemodynamic alterations, alternative contributing factors might play a role. • Abnormal placental development might influence neurodevelopment in these cases. [ABSTRACT FROM AUTHOR]

Background: Birthweight (BW) is an important prognostic factor in newborns with congenital heart defects (CHD)., Objectives: To give an overview of the literature on BW z-score in children with isolated CHD., Search Strategy: A systematic search was performed on isolated CHD and BW in PubMed, Embase, Web of Science, COCHRANE Library and Emcare., Selection Criteria: Neonates with isolated CHD were included if a BW percentile, BW z-score or % small-or-gestational age (SGA) was reported., Data Collection and Analysis: BW z-score and percentage SGA were pooled with random-effect meta-analysis. Quality and risk of bias were assessed using the modified Newcastle Ottawa Scale., Main Results: Twenty-three articles (27 893 cases) were included. BW z-scores were retrieved from 11 articles, resulting in a pooled z-score of -0.20 (95% CI -0.50 to 0.11). The overall pooled prevalence of SGA <10th percentile was 16.0% (95% CI 11.4-20.5; 14 studies). Subgroup analysis of major CHD showed similar results (BW z-score -0.23 and percentage SGA 16.2%)., Conclusions: Overall BW in isolated CHD is within range of normality but impaired, with a 1.6-fold higher risk of SGA, irrespective of the type of CHD (major CHD vs all CHD combined). Our findings underline the association between CHD and BW. The use of BW z-scores provides insight into growth of all fetuses with CHD., Tweetable Abstract: Infants with a congenital heart defect (CHD) have a lower birthweight z-score and a higher incidence of small-for-gestational age (<10th percentile). This was encountered both in the major CHD-group as well as in all-CHD combined group analysis. Future research on the association between birthweight and CHD should include all types of CHDs (including mild cardiac defects) and placental-related disease, such as pre-eclampsia. We advocate the use of international standardised fetal growth and birthweight charts in CHD research., (© 2022 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd.)