Prospective Identification of Long QT Syndrome in Fetal Life

Overview

About this study

The postnatal diagnosis of Long QT Syndrome (LQTS) is suggested by a prolonged QT interval on 12 lead electrocardiogram (ECG),a positive family history and/or characteristic arrhythmias and confirmed by genetic testing.  LQTS testing cannot be performed successfully before birth as   fetal ECG is not possible and direct measure of the fetal QT interval by magnetocardiography is limited. Genetic testing can be performed in utero, but there is risk to the pregnancy and the fetus. Although some fetuses present with arrhythmias easily recognized as LQTS (torsade des pointes (TdP) and/or 2° atrioventricular (AV) block, this is uncommon, occurring in <25% of fetal LQTS cases. Rather, the most common presentation of fetal LQTS is sinus bradycardia, a subtle rhythm disturbance that often is unappreciated to be abnormal. Consequently, the majority of LQTS cases are unsuspected and undiagnosed during fetal life, with dire consequences. For example, maternal medications commonly used during pregnancy can prolong the fetal QT interval and may provoke lethal fetal ventricular arrhythmias. But the most significant consequence is the missed opportunity for primary prevention of life threatening ventricular arrhythmias after birth because the infant is not suspected to have LQTS before birth. The over-arching goal of the study is to overcome the barriers to prenatal detection of LQTS. The investigators plan to do so by developing an algorithm using fetal heart rate (FHR) which will discriminate fetuses with or without LQTS. Immediate Goal: The investigators propose a multicenter pre-birth observational cohort study to develop a Fetal Heart Rate (FHR)/Gestational Age (GA) algorithm from a cohort of fetuses recruited from 13 national and international centers where one parent is known by prior genetic testing to have a mutation in one of the common LQTS genes: potassium voltage-gated channel subfamily Q member 1 (KCNQ1), potassium voltage-gated channel subfamily H member 2 (KCNH2), or sodium voltage-gated channel alpha subunit 5 (SCN5A). The investigators have chosen this population because 1) These mutations are the most common genetic causes of LQTS, and 2) Offspring will have high risk of LQTS as inheritance of these LQTS gene mutations is autosomal dominant. Thus, progeny of parents with a known mutation are at high (50%) risk of having the same parental LQTS mutation. The algorithm will be developed using FHR measured serially throughout pregnancy. All offspring will undergo postnatal genetic testing for the parental mutation as the gold standard for diagnosing the presence or absence of LQTS.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria - Prospective Arm:

  • Mothers and fathers, 18-45 years of age.
  • Pregnant women with a previously identified mutation in a known LQTS gene or pregnant women whose partner (and the father of the baby) has a previously identified mutation in a known LQTS gene will be invited to participate. If the pregnant partner of a man with a LQTS gene is enrolled, then the man/father of child will be enrolled as well.
  • Women at 7-30 weeks of gestation.
  • Mothers with a previously identified mutation in a known LQTS gene or whose partner (father of the baby) has a previously identified mutation in a known LQTS gene that have had a child that was born after April 1, 2016.
  • Newborns for ECG data collection post-delivery.

Exclusion Criteria - Prospective Arm:

  1. Phenotype positive but genotype negative pregnant woman or father of the fetus.
  2. Fetuses with congenital or chromosomal anomaly identified before or after birth.
  3. Pregnant women who present beyond 30 weeks of pregnancy.

Inclusion Criteria - Retrospective Arm:

  • Mothers and fathers, 18-45 years of age.
  • Children conceived between January 1, 2013 and April 1, 2016.
  • Women with a previous pregnancy and a known LQTS gene or where the father of the baby had a known LQTS gene.
  • Women with a mutation in a known LQTS gene.
  • Women whose partner/father of the baby has a mutation in a known LQTS gene (the father of the child will be enrolled if mother of child is enrolled).
  • Newborns for ECG data collection post-delivery

Exclusion Criteria - Retrospective Arm:

  • Phenotype positive but genotype negative pregnant woman or father of the fetus.
  • Fetuses with congenital or chromosomal anomaly identified before or after birth.
  • Fetal heart rate data unavailable prior to 30 weeks of pregnancy.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Michael Ackerman, M.D., Ph.D.

Open for enrollment

Contact information:

Kaylie Briske

(507)266-0470

Briske.Kaylie@mayo.edu

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

.
CLS-20271980

Mayo Clinic Footer