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Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise

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ClinicalTrials.gov Identifier: NCT03775954
Recruitment Status : Recruiting
First Posted : December 14, 2018
Last Update Posted : December 14, 2018
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
University of Wisconsin, Madison
Children's Hospital and Health System Foundation, Wisconsin
Shared Medical Technology, Inc.
Tristan Technologies, Inc
Information provided by (Responsible Party):
Janette F. Strasburger, Medical College of Wisconsin

Tracking Information
First Submitted Date October 24, 2018
First Posted Date December 14, 2018
Last Update Posted Date December 14, 2018
Actual Study Start Date July 1, 2018
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: December 13, 2018)
  • Heart rate variability using fMCG [ Time Frame: Comparison of procedures at 20-27 weeks gestation, and 30-37 weeks gestation ]
    To measure and compare the fMCG heart rate variability in five pregnancy conditions associated with fetal demise, to those of gestation matched normal fetuses.
  • Cardiac conduction [ Time Frame: Comparison of cardiac time intervals at 20-27 weeks gestation, 30-37 weeks gestation and at neonatal ECG at 0-2 weeks of age ]
    To measure and compare the fMCG cardiac time intervals in five pregnancy conditions associated with fetal demise, to those of gestation matched normal fetuses and to neonatal ECG at 2 weeks of age.
  • Cardiac repolarization [ Time Frame: Comparison of cardiac repolarization at 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-2 weeks of age. ]
    To measure and compare the fMCG cardiac repolarization patterns in five pregnancy conditions associated with fetal demise, to those of gestation matched normal fetuses, and to neonatal ECG at 2 weeks of age.
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: December 13, 2018)
  • Unique "signature" electrophysiologic abnormalities [ Time Frame: Comparison of findings at 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-2 weeks of age ]
    2a) To determine whether unique "signature" electrophysiologic abnormalities are present in any of these five maternal-fetal diseases, and 2b) to define at what trimester these develop. Understanding any unique findings could allow study of specific treatment strategies in the future. findings are first seen.
  • Pregnancy outcomes [ Time Frame: Comparison of findings at 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-2 weeks of age ]
    To correlate fMCG findings with 3a) outcomes of pregnancies (fetal demise, premature delivery, small for GA, 5 minute APGAR < 5, neonatal death) and 3b) fMCG cardiac time intervals with postnatal ECG intervals at 0-2 weeks of age.
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise
Official Title Fetal Electrophysiologic Abnormalities in High-risk Pregnancies Associated With Fetal Demise
Brief Summary Each year world-wide, 2.5 million fetuses die unexpectedly in the last half of pregnancy, 25,000 in the United States, making fetal demise ten-times more common than Sudden Infant Death Syndrome. This study will apply a novel type of non-invasive monitoring, called fetal magnetocardiography (fMCG) used thus far to successfully evaluate fetal arrhythmias, in order to discover potential hidden electrophysiologic abnormalities that could lead to fetal demise in five high-risk pregnancy conditions associated with fetal demise.
Detailed Description Fetal demise occurs in over 25,000 pregnancies annually in the US and over 2.5 million in pregnancies worldwide. Certain maternal-fetal-placental abnormalities can have a high risk of fetal demise. Despite advances in fetal surveillance with ultrasound and cardiotocography, the reduction in fetal mortality lags behind that of the neonate and has shown little decline in the past decade. This suggests that the type of fetal monitoring used may not be assessing the correct indicators of mortality. In all other age groups, electrocardiographic (ECG) and continuous heart rate (HR) monitoring are used in every intensive care unit or emergency setting; however, for the fetus, the ECG signal is nearly completely insulated and inaccessible. As the result, indirect assessment of cardiac rhythm is obtained using echocardiography/Doppler, but echo/Doppler does not have the precision to assess beat-to-beat HR variability and cannot assess cardiac repolarization at all. In this study, the investigators will evaluate five high risk conditions (major congenital heart disease in the fetus, fetal hydrops (immune and non-immune), monochorionic twin pregnancy, prior pregnancy ending in fetal demise, and gastroschisis) using Fetal Magnetocardiography (fMCG)which detects the natural magnetic signals accompanying the cardiac electrical signal. It is a new, safe, and non-invasive recording technique that has been performed for several decades, and has recently gained FDA approval for recording cardiac signals at all ages, including in the fetus. Normative data has been obtained at the University of Wisconsin - Madison Biomagnetism Laboratory in 257 healthy fetuses by co-investigator Ronald T. Wakai, PhD. Over 550 serious fetal arrhythmias have been evaluated to date. Fetal MCG has proven invaluable in fetal Long QT Syndrome in identifying markers for risk of sudden death such as Torsades de Pointes Ventricular Tachycardia (VT), T wave alternans, 2nd degree AV block, and QTc>590 ms. To date, fMCG has not been systematically applied to diseases that are not associated with recognizable arrhythmias because the impact of silent conduction and repolarization defects has been underappreciated. In this grant, the investigators hypothesize that beat-to-beat fetal heart rate variability abnormalities and electrophysiologic abnormalities, are present in five high risk maternal-fetal-placental conditions associated with fetal demise. The study will determine which electrophysiologic abnormalities precede fetal demise or adverse pregnancy outcome. Preliminary findings in healthy normal subjects in RO1HL063174 (Wakai) show repolarization abnormalities in up to 5%, and some of these are modifiable once recognized. Two hundred pregnant subjects will be studied over a 5 year period both at referral (~20-27 weeks GA) and later in pregnancy at 30-37 weeks GA. fMCG results will be compared to neonatal ECG (nECG) obtained at 0-2 weeks of life. This will determine whether specific abnormal heart rate, rhythm and conduction patterns emerge that characterize the condition, which will then allow the high risk obstetrician to better predict risk of fetal demise in the future.
Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Current pregnancy complicated by one of the five diagnostic categories (fetal major congenital heart disease, prior unexplained Stillbirth at/after 20 weeks gestation, fetal hydrops, fetal gastroschesis, or monochorionic twin pregnancy.
Condition
  • High Risk Pregnancy
  • Congenital Heart Disease
  • Fetal Hydrops
  • Twin Monochorionic Monoamniotic Placenta
  • Gastroschisis
  • Fetal Demise
  • Stillbirth
  • Fetal Arrhythmia
  • Long QT Syndrome
  • Intrauterine Fetal Death
  • Sudden Infant Death
  • Pregnancy Loss
  • Twin Twin Transfusion Syndrome
  • Birth Defect
  • Fetal Cardiac Anomaly
  • Fetal Cardiac Disorder
  • Fetal Death
  • Brugada Syndrome
Intervention Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
Fetal Magnetocardiography (fMCG) is a new non-invasive diagnostic procedure that records tiny fetal cardiac signals similar to an Electrocardiogram or Holter monitor. The magnetometer has FDA clearance, and does not emit magnetic, electric or other energies. This is not an MRI. Examples of fetal MCG's can be found in the Links. The American Heart Association Scientific Statement on Fetal Diagnosis and Treatment (Circulation, 2014) has declared fMCG to be Class IIa for fetal heart rhythm abnormalities, meaning that benefit far exceeds risk. As part of this study, a neonatal electrocardiogram (nECG) will be obtained for comparison after the baby is born.
Study Groups/Cohorts
  • 1) Fetal Congenital Heart Disease
    Pregnancy with major fetal congenital heart disease, after 20 weeks gestation, and as neonate following delivery. Two fetal magnetocardiograms (fMCG) and 1 neonatal electrocardiogram (nECG) will be obtained and heart rate, rhythm, and conduction patterns will be compared.
    Intervention: Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
  • 2) History of fetal demise (Stillbirth)
    Pregnancy with a history of an unexplained fetal demise (stillbirth at 20 -40 weeks gestation) during any prior pregnancy. Two fetal magnetocardiograms (fMCG) and 1 neonatal electrocardiogram (nECG) will be obtained and heart rate, rhythm, and conduction patterns will be compared.
    Intervention: Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
  • 3) Fetal hydrops, immune or non-immune
    Pregnancy with fetal hydrops, immune or non-immune, at or after 20 weeks gestation. Two fetal magnetocardiograms (fMCG) and 1 neonatal electrocardiogram (nECG) will be obtained and heart rate, rhythm, and conduction patterns will be compared.
    Intervention: Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
  • 4) Fetal gastroschisis
    Pregnancy with fetal gastroschisis, at or after 20 weeks gestation. Two fetal magnetocardiograms (fMCG) and 1 neonatal electrocardiogram (nECG) will be obtained and heart rate, rhythm, and conduction patterns will be compared.
    Intervention: Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
  • 5) Twin pregnancy, monochorionic
    Twin pregnancy, monochorionic, with or without twin-twin transfusion syndrome, at or after 20 weeks gestation. Two fetal magnetocardiograms (fMCG) and 1 neonatal electrocardiogram (fMCG) will be obtained and heart rate, rhythm, and conduction patterns will be compared.
    Intervention: Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: December 13, 2018)
200
Original Estimated Enrollment Same as current
Estimated Study Completion Date April 30, 2022
Estimated Primary Completion Date April 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Current pregnancy complicated by one of the five diagnostic categories

    • prior unexplained Stillbirth at/after 20 weeks gestation
    • fetal major congenital heart defect
    • fetal hydrops
    • fetal gastroschisis
    • monochorionic twin pregnancy
  • Subject must be 18 years of age or older
  • Subject must be English speaking and must be able to read and sign the consent form in English
  • Subject must be able to recline comfortably for 1-3 hours
  • Subject must be willing to complete all three procedures (fMCG, fMCG, nECG) as per protocol
  • Subject must be willing to allow us to review her and her infants prenatal, deliver, and post-natal records to verify diagnosis, and clinical findings.

Exclusion Criteria:

  • Severe claustrophobia not reduced by taking breaks, or by having the light on, or by having someone in the room with them.
  • Active labor
  • Acute illness
  • Unable to recline comfortably with a pillow for more than 1-3 hours (assuming some breaks are provided)
  • Weight over 450 lbs
  • An electric stimulation device (TENS unit, pacemaker, or nerve stimulator) that could produce electric or magnetic noise.

    • Note that the Tristan 624 Magnetometer does not pose a risk to the subject's device, (since fMCG does not produce any energy or magnetism), but stimulators themselves can cause interference for our recordings. Some devices may still qualify, and discussion with study nurse may be useful if subject has a pacemaker or similar device.

The subject will have a single 2-3 hour fetal magnetocardiogram between 20 and 27 weeks GA, and again between 30 and 37 weeks GA, then return with her infant between 0 and 2 weeks of age for a single neonatal electrocardiogram. Subjects will be paid a nominal fee for their participation each time, as well as transportation reimbursement if >25 miles. For subjects traveling a long distance, the ECG may be performed locally.

Sex/Gender
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: This study involves pregnant women and subsequently-born neonate(s) of either gender.
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Janette F Strasburger, MD 414-955-5673 jstrasbu@mcw.edu
Contact: Mara C Koffarnus, MA 414-266-4758 mkoffarn@mcw.edu
Listed Location Countries United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03775954
Other Study ID Numbers PRO00031598
R01HL143485 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Plan Description: Only de-identified data can be released
Responsible Party Janette F. Strasburger, Medical College of Wisconsin
Study Sponsor Medical College of Wisconsin
Collaborators
  • National Heart, Lung, and Blood Institute (NHLBI)
  • University of Wisconsin, Madison
  • Children's Hospital and Health System Foundation, Wisconsin
  • Shared Medical Technology, Inc.
  • Tristan Technologies, Inc
Investigators
Principal Investigator: Janette F Strasburger, MD Medical College of Wisconsin
PRS Account Medical College of Wisconsin
Verification Date December 2018