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Effects of cohort, genotype, variant, and maternal β-blocker treatment on foetal heart rate predictors of inherited long QT syndrome
Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Anschutz Medical Campus, CO, Aurora, United States.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Physiology, University of Auckland, Auckland, New Zealand.ORCID iD: 0000-0002-9323-3166
Department of Pediatric Cardiology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, Netherlands; Department of Cardiology, University Medical Center, Amsterdam, Netherlands.
Department of Pediatrics, Division of Cardiology, University of Utah School of Medicine, UT, Salt Lake City, United States.
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2023 (English)In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 25, no 11, article id euad319Article in journal (Refereed) Published
Abstract [en]

AIMS: 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) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-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.

METHODS AND RESULTS: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-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 7-42 weeks' 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 β-adrenergic response) had lower FHR. Maternal β-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.

CONCLUSION: Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.

Place, publisher, year, edition, pages
Oxford University Press, 2023. Vol. 25, no 11, article id euad319
Keywords [en]
Bradycardia, Channelopathy, Foetal arrhythmia, Foetus, Inherited arrhythmias, Long QT syndrome, Potassium currents, Stillbirth, Sudden death
National Category
Obstetrics, Gynecology and Reproductive Medicine Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:umu:diva-217540DOI: 10.1093/europace/euad319ISI: 001107634900003PubMedID: 37975542Scopus ID: 2-s2.0-85177987474OAI: oai:DiVA.org:umu-217540DiVA, id: diva2:1819309
Available from: 2023-12-13 Created: 2023-12-13 Last updated: 2023-12-15Bibliographically approved

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Winbo, AnnikaRydberg, Annika

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