{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T14:08:43Z","timestamp":1792159723851,"version":"4.4.0"},"reference-count":56,"publisher":"Wiley","issue":"6-7","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016337","name":"Department for the Economy","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016337","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019256","name":"NIHR Great Ormond Street Hospital Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100019256","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Prenatal Diagnosis"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>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\u2010cardiac malformations (ECMs) and CHA dependent upon anatomical subclassification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic review of the literature was performed using MEDLINE, EMBASE, Web of Science and grey literature January 2010\u2010February 2023. Studies were selected if they included greater than 20 cases of prenatally diagnosed CHA when standard testing (QF\u2010PCR\/chromosome microarray\/karyotype) was negative. Pooled incremental yield was determined. PROSPERO CRD 42022364747.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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%\u201321.6%), 9.3% (95% CI, 6.6%\u201312.3%) and 35.9% (95% CI, 21.0%\u201352.3%) 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%\u201365.3%). 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%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The likelihood of a monogenic aetiology in fetuses with multi\u2010system CHAs is high. Clinicians must consider the clinical utility of offering PES in selected isolated cardiac lesions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.6581","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T10:58:00Z","timestamp":1714993080000},"page":"821-831","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["The incremental yield of prenatal exome sequencing over chromosome microarray for congenital heart abnormalities: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"44","author":[{"given":"K.","family":"Reilly","sequence":"first","affiliation":[{"name":"Centre for Public Health Queens University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Sonner","sequence":"additional","affiliation":[{"name":"Centre for Public Health Queens University Belfast  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"McCay","sequence":"additional","affiliation":[{"name":"Department of Paediatric Cardiology Royal Belfast Hospital for Sick Children  Belfast UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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