{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T13:39:08Z","timestamp":1791639548854,"version":"4.3.4"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T00:00:00Z","timestamp":1700179200000},"content-version":"vor","delay-in-days":16,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"United States National Institute of Health","award":["UR21HD109564"],"award-info":[{"award-number":["UR21HD109564"]}]},{"name":"Italian Ministry of Health Ricerca Corrente"},{"name":"Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death"},{"name":"PREDICT2"},{"name":"Australian Government\u2019s Medical Research Future Fund"},{"DOI":"10.13039\/501100001505","name":"Health Research Council of New Zealand","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001505","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"United States National Institutes of Health","doi-asserted-by":"publisher","award":["K01HL151754"],"award-info":[{"award-number":["K01HL151754"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) &amp;lt; 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal \u03b2-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR\/GA threshold for LQTS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal \u03b2-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7\u201342 weeks\u2019 GA from 267 pregnancies\/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or \u03b2-adrenergic response) had lower FHR. Maternal \u03b2-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR\/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Genotype, LQT1 variant, and maternal \u03b2-blocker therapy affect FHR. A predictive threshold of FHR\/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant\u2019s a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/europace\/euad319","type":"journal-article","created":{"date-parts":[[2023,11,17]],"date-time":"2023-11-17T08:33:03Z","timestamp":1700209983000},"source":"Crossref","is-referenced-by-count":16,"title":["Effects of cohort, genotype, variant, and maternal \u03b2-blocker treatment on foetal heart rate predictors of inherited long QT syndrome"],"prefix":"10.1093","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2334-5514","authenticated-orcid":false,"given":"Alexander M","family":"Kaizer","sequence":"first","affiliation":[{"name":"Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Anschutz Medical Campus , Aurora, CO , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9323-3166","authenticated-orcid":false,"given":"Annika","family":"Winbo","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Pediatrics, Ume\u00e5 University , Umea , Sweden"},{"name":"Department of Physiology, University of Auckland , Auckland , New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5276-1475","authenticated-orcid":false,"given":"Sally-Ann B","family":"Clur","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology, Emma Children\u2019s Hospital, Amsterdam University Medical Centers , Amsterdam , The Netherlands"},{"name":"Department of Cardiology, University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2492-422X","authenticated-orcid":false,"given":"Susan P","family":"Etheridge","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Cardiology, University of Utah School of Medicine , Salt Lake City, UT , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8011-3333","authenticated-orcid":false,"given":"Michael J","family":"Ackerman","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Mayo Clinic , Rochester, MN , USA"},{"name":"Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic , Rochester, MN , USA"},{"name":"Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic , Rochester, MN , USA"},{"name":"Windland Smith Rice Genetic Heart Rhythm Clinic and Windland Smith Rice Sudden Death Genomics Laboratory, Mayo Clinic , Rochester, MN , 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Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano , Via Pier Lombardo 22 , 2015 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1209-0157","authenticated-orcid":false,"given":"Carla","family":"Spazzolini","sequence":"additional","affiliation":[{"name":"Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano , Via Pier Lombardo 22 , 2015 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6458-3669","authenticated-orcid":false,"given":"Stacy A S","family":"Killen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Cardiology, Vanderbilt University Medical Center , Nashville, TN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5143-5029","authenticated-orcid":false,"given":"Annette","family":"Wacker-Gussmann","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease and Paediatric Cardiology, German Heart Center , Munich , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0528-0852","authenticated-orcid":false,"given":"Arthur A M","family":"Wilde","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center, Amsterdam, The Netherlands"},{"name":"Department of Cardiology, Amsterdam UMC Location University of Amsterdam , Amsterdam , The Netherlands"},{"name":"Department of Cardiology, Amseterdam University Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Sinkovskaya","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Eastern Virginia Medical School , Norfolk, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfred","family":"Abuhamad","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Eastern Virginia Medical School , Norfolk, VA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margherita","family":"Torchio","sequence":"additional","affiliation":[{"name":"Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano , Via Pier Lombardo 22 , 2015 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3120-5450","authenticated-orcid":false,"given":"Chai-Ann","family":"Ng","sequence":"additional","affiliation":[{"name":"Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, Victor Chang Cardiac Research Institute , Darlinghurst, New South Wales , Australia"},{"name":"The School of Clinical Medicine, UNSW Sydney , Darlinghurst, New South Wales , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9655-7783","authenticated-orcid":false,"given":"Annika","family":"Rydberg","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, Pediatrics, Ume\u00e5 University , Umea , Sweden"},{"name":"Department of Cardiology, University Medical Center, Amsterdam, The 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