Ignite Creation Date:
2024-05-06 @ 8:59 AM
Last Modification Date:
2024-10-26 @ 12:08 PM
Study NCT ID:
NCT02876380
Status:
COMPLETED
Last Update Posted:
2022-02-21
First Post:
2016-08-08
Brief Title:
Prospective Identification of Long QT Syndrome in Fetal Life
Sponsor:
University of Colorado Denver
Organization:
University of Colorado Denver
Study Overview
Official Title:
Prospective Identification of Long QT Syndrome in Fetal Life
Status:
COMPLETED
Status Verified Date:
2022-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Fetal LQTS
Brief Summary:
The postnatal diagnosis of Long QT Syndrome LQTS is suggested by a prolonged QT interval on 12 lead electrocardiogram ECG strengthened by a positive family history andor characteristic arrhythmias and confirmed by genetic testing However for several reasons such LQTS testing cannot be performed successfully before birth First fetal ECG is not possible and direct measure of the fetal QT interval by magnetocardiography is limited to fewer than 10 sites world-wide Second while genetic testing can be performed in utero there is risk to the pregnancy and the fetus Third although some fetuses present with arrhythmias easily recognized as LQTS torsade des pointes TdP andor 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 FHRGestational 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
Immediate Goal The investigators propose a multicenter pre-birth observational cohort study to develop a Fetal Heart Rate FHRGestational 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
Detailed Description:
Ascertainment of LQTS an inherited arrhythmia disorder in a group of conditions known as the channelopathies is challenging before birth Recently in a retrospective study it was reported that a gestational age dependent bradycardia allows a much higher recognition of genotype positive LQTS than the standard obstetrical gestational age independent definition of bradycardia Mitchell 2012
However the fetal heart rate in pregnancies with maternal or paternal LQTS diagnosed prior to the pregnancy has not been evaluated prospectively from the first trimester to birth Nor is it known if the fetal heart rate gestational age profile might be mutation specific In addition the use of fetal heart rate to successfully distinguish between LQTS and normal fetuses of pregnancies in which a parent has a known mutation has not been tested
The investigators believe that fetuses with an LQTS mutation born to families in which the mother or father has an LQTS mutation will have slower heart compared to fetuses shown after birth not to have the family mutation If the investigators hypothesis is correct these findings could be applied to the general population of pregnant women to prospectively identify fetuses with LQTS and without a known family history Since a fetal proband has been led to the identification of unsuspecting family members prospectively identifying affected fetuses would increase ascertainment of life-threatening mutations in all ages Cuneo 2013
However the fetal heart rate in pregnancies with maternal or paternal LQTS diagnosed prior to the pregnancy has not been evaluated prospectively from the first trimester to birth Nor is it known if the fetal heart rate gestational age profile might be mutation specific In addition the use of fetal heart rate to successfully distinguish between LQTS and normal fetuses of pregnancies in which a parent has a known mutation has not been tested
The investigators believe that fetuses with an LQTS mutation born to families in which the mother or father has an LQTS mutation will have slower heart compared to fetuses shown after birth not to have the family mutation If the investigators hypothesis is correct these findings could be applied to the general population of pregnant women to prospectively identify fetuses with LQTS and without a known family history Since a fetal proband has been led to the identification of unsuspecting family members prospectively identifying affected fetuses would increase ascertainment of life-threatening mutations in all ages Cuneo 2013
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None