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Objectives: To determine the incremental yield of prenatal exome sequencing (PES) over standard testing in fetuses with an isolated congenital heart abnormality (CHA), CHA associated with extra‐cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification. Methods: A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010‐February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF‐PCR/chromosome microarray/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747. Results: Overall, 21 studies, incorporating 1957 cases were included. The incremental yield of PES (causative pathogenic and likely pathogenic variants) over standard testing was 17.4% (95% CI, 13.5%–21.6%), 9.3% (95% CI, 6.6%–12.3%) and 35.9% (95% CI, 21.0%–52.3%) for all CHAs, isolated CHAs and CHAs associated with ECMs. The subgroup with the greatest yield was complex lesions/heterotaxy; 35.2% (95% CI 9.7%–65.3%). The most common syndrome was Kabuki syndrome (31/256, 12.1%) and most pathogenic variants occurred de novo and in autosomal dominant (monoallelic) disease causing genes (114/224, 50.9%). Conclusion: The likelihood of a monogenic aetiology in fetuses with multi‐system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions. Key points: What is already known? Congenital heart abnormalities are the most commonly occurring congenital anomalies and can be associated with chromosomal or monogenic conditions.With the increasing use of fetal sequencing, there is a need to define the association between monogenic conditions and specific cardiac abnormalities, particularly when isolated to facilitate triaging for prenatal sequencing. What does this study add? The incremental yield of prenatal exome sequencing over and above chromosome microarray for congenital heart abnormalities is 9.3% in isolated lesions and 35.2% in the presence of complex lesions/heterotaxy.Clinicians should consider the clinical utility of offering prenatal exome sequencing in selected isolated cardiac lesions dependent on resources available. [ABSTRACT FROM AUTHOR]

Objective: Non-invasive prenatal testing (NIPT) investigates placental DNA and may detect confined placental mosaicism (CPM). The aim of this study was to confirm CPM in the term placenta in cases with abnormal NIPT but normal follow-up cytogenetic studies of fetus and mother. Additionally we examined the distribution of abnormal cells over the placenta., Methods: Four chorionic villus (CV) biopsies from four placental quadrants were requested in cases where CPM was assumed. Both cell lineages of the CV, cytotrophoblast (CTB) and mesenchymal core (MC), were analyzed separately with SNP array., Results: The chromosome aberration was confirmed in 67 % of the placentas. Three quarters of the CTB and MC biopsies from these mosaic placentas were uniformly normal (57 %) or abnormal (20 %), and a minority showed mosaicism. Among 16 cases of CPM where first trimester CV were examined as well, 11 had chromosomally normal results during pregnancy., Discussion: Cytogenetic investigations of term placental biopsies suspected to be affected with CPM did not reveal the chromosome aberration in one third of the placentas. This is caused by the patchy pattern in which chromosomally abnormal cells are distributed over the placenta with the majority of the biopsies being uniformly normal. Further CPM research, including its clinical impact, requires the analysis of more than four biopsies to get insight into the extent of the affected part. Moreover, a subset of CPM type 1 and 3 seems to be only detectable with NIPT and not with first trimester CVS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)