{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:18:21Z","timestamp":1787897901213,"version":"build-2784847793"},"reference-count":61,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indiana University School of Medicine Strategic Research Initiative (SRI)"},{"name":"Physician Scientist Initiative (PSI)"},{"name":"American Heart Association Transformational Project Award AHA 19TPA34850054"},{"name":"National Institute of Health P01 HL 1345599 (SMW)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Extracardiac anomalies (ECAs) are strong predictors of genetic disorders in infants with congenital heart disease (CHD), but there are no prior studies assessing performance of ECA status as a screen for genetic diagnoses in CHD patients. This retrospective cohort study assessed this in our comprehensive inpatient CHD genetics service focusing on neonates and infants admitted to the intensive care unit (ICU). The performance and diagnostic utility of using ECA status to screen for genetic disorders was assessed using decision curve analysis, a statistical tool to assess clinical utility, determining the threshold of phenotypic screening by ECA versus a Test-All approach. Over 24% of infants had genetic diagnoses identified (n = 244\/1013), and ECA-positive status indicated a 4-fold increased risk of having a genetic disorder. However, ECA status had low\u2013moderate screening performance based on predictive summary index, a compositive measure of positive and negative predictive values. For those with genetic diagnoses, nearly one-third (32%, 78\/244) were ECA-negative but had cytogenetic and\/or monogenic disorders identified by genetic testing. Thus, if the presence of multiple congenital anomalies is the phenotypic driver to initiate genetic testing, 13.4% (78\/580) of infants with isolated CHD with identifiable genetic causes will be missed. Given the prevalence of genetic disorders and limited screening performance of ECA status, this analysis supports genetic testing in all CHD infants in intensive care settings rather than screening based on ECA.<\/jats:p>","DOI":"10.3390\/genes15040505","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T07:55:54Z","timestamp":1713426954000},"page":"505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Clinical Decision Analysis of Genetic Evaluation and Testing in 1013 Intensive Care Unit Infants with Congenital Heart Defects Supports Universal Genetic Testing"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5597-0202","authenticated-orcid":false,"given":"Benjamin M.","family":"Helm","sequence":"first","affiliation":[{"name":"Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Epidemiology, Indiana University Fairbanks School of Public Health, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Ware","sequence":"additional","affiliation":[{"name":"Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"},{"name":"Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.clp.2015.02.009","article-title":"Genetics and genetic testing in congenital heart disease","volume":"42","author":"Cowan","year":"2015","journal-title":"Clin. 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