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

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 0-4 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


Primary Outcome

Heart rate variability using fMCG

Secondary Outcome

 Unique "signature" electrophysiologic abnormalities

Condition

High Risk Pregnancy

Intervention

Fetal Magnetocardiogram and Neonatal Electrocardiogram

Study Arms / Comparison Groups

 1) Fetal Congenital Heart Disease
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Diagnostic Test

Estimated Enrollment

200

Start Date

July 1, 2018

Completion Date

April 30, 2022

Primary Completion Date

April 30, 2022

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.
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Janette F Strasburger, MD, 414-266-4758, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03775954

Organization ID

PRO00031598

Secondary IDs

R01HL143485

Responsible Party

Principal Investigator

Study Sponsor

Medical College of Wisconsin

Collaborators

 National Heart, Lung, and Blood Institute (NHLBI)

Study Sponsor

Janette F Strasburger, MD, Principal Investigator, Medical College of Wisconsin


Verification Date

October 2019