Change search
ReferencesLink to record
Permanent link

Direct link
Third Trimester Fetal Heart Rate Predicts Phenotype and Mutation Burden in the Type 1 Long QT Syndrome
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
Show others and affiliations
2015 (English)In: Circulation: Arrhythmia and Electrophysiology, ISSN 1941-3149, E-ISSN 1941-3084, Vol. 8, no 4, 806-814 p.Article in journal (Refereed) Published
Abstract [en]

Background—Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype.

Methods and Results—This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110KCNQ1 mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29–41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute; P<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute; P<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (r=0.700; P<0.001), and postnatal QTc (r=−0.762; P<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (−10 beats per minute per added mutation; P<1.0×10–23). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted −7 beats per minute, P<0.0001.

Conclusions—In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias.

Place, publisher, year, edition, pages
2015. Vol. 8, no 4, 806-814 p.
Keyword [en]
arrhythmias, cardiac, genotype, genetic association studies, heart rate, long QT syndrome
National Category
Cardiac and Cardiovascular Systems
URN: urn:nbn:se:umu:diva-108470DOI: 10.1161/CIRCEP.114.002552ISI: 000359740500011PubMedID: 26019114OAI: diva2:855636
Available from: 2015-09-22 Created: 2015-09-11 Last updated: 2016-05-18Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Winbo, AnnikaLindh, MariaDiamant, Ulla-BrittPersson, JohanRydberg, Annika
By organisation
In the same journal
Circulation: Arrhythmia and Electrophysiology
Cardiac and Cardiovascular Systems

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 52 hits
ReferencesLink to record
Permanent link

Direct link