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High Risk PregnancyNCT03775954

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

An observational study of High Risk Pregnancy and Congenital Heart Disease, run by Medical College of Wisconsin at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Fetal Magnetocardiogram and Neonatal Electrocardiogram and Substudy only: Maternal/Infant Pharmacogenomic assessment postnatally
How many people
30 participants
Where
2 sitesUnited States
Study dates
1 Jul 2018to 30 Nov 2028
Phase
Observational
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

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.

Who may be able to join

  • 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
Show all 11Show fewer
  • 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, unless medically unable
  • 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.

Who cannot join

  • 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 at approximately 20 and 27 weeks GA, and again, if medical condition allows, between 30 and 37 weeks GA, then her infant will have an ECG between 0 and 4 weeks of age. 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 or at home.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Mara C Koffarnus, MD contact

414-266-4758

mkoffarn@mcw.edu

Gretchen Eckstein contact

414-266-3539

geckstein@chw.org

United States2 sites, 2 recruiting

  • University of Wisconsin - Madison

    Madison, Wisconsin, 53715

    Ronald T Wakai, PhD, rtwakai@wisc.edu

    Gretchen Eckstein, RN, BSN, 414-266-3539, geckstein@chw.org

    Recruiting

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

    Janette F Strasburger, MD, 414-266-2000, jstrasbu@mcw.edu

    Gretchen C Eckstein, RN, BSN, 414-266-3539 (Preferred), geckstein@chw.org

    Recruiting

Other trials in United States

About this study

Official title: Fetal Electrophysiologic Abnormalities in High-risk Pregnancies Associated With Fetal Demise

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.

Read the 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.

Being tested
Fetal Magnetocardiogram and Neonatal Electrocardiogram, Substudy only: Maternal/Infant Pharmacogenomic assessment postnatally
Keywords
Fetal Magnetocardiography, Stillbirth, Intrauterine Fetal Demise, Fetal Heart Rate Variability, Fetal Arrhythmias, High Risk Pregnancy, Pregnancy, Fetal Anomaly, Fetal Echocardiography, Non-Stress Testing, New Technology, Birth Defects, Fetal Research
Medical subject headings
Heart Defects, Congenital, Hydrops Fetalis, Gastroschisis, Fetal Death, Stillbirth, Long QT Syndrome, Sudden Infant Death, Fetofetal Transfusion

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fetal Magnetocardiogram and Neonatal ElectrocardiogramDiagnostic test

    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.

  • Substudy only: Maternal/Infant Pharmacogenomic assessment postnatallyGenetic

    See also section 6. Pharmacogenomics measure the way the liver breaks down medications. The systems controlling this are inherited, and mothers or infants can be normal, fast, ultrafast, or poor metabolizers for certain drugs. This study will attempt to improve future safety of cardiac drug treatments for both mother and fetus by evaluating the impact of PG.

Study groups in NCT03775954
Study groupRoleWhat they receive
1) Fetal Congenital Heart DiseasePregnancy 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.
Receives: 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.
Receives: Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
3) Fetal hydrops, immune or non-immunePregnancy 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.
Receives: Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
4) Fetal gastroschisisPregnancy 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.
Receives: Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
5) Twin pregnancy, monochorionicTwin 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.
Receives: Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram
6) Maternal medications and Fetal TachycardiaMothers who are taking medications that impact QT interval, and/or are used to treat either a maternal risk of arrhythmi (Inherited arrhythmia Syndromes) or used for fetal tachycardia management are eligible for the substudy evaluating maternal and infant pharmacogenomics. PG will be measured after delivery by RPRD, Inc with results conveyed to the subject by the PI. The results are not used for clinical management of the pregnancy.
Receives: Genetic: Substudy only: Maternal/Infant Pharmacogenomic assessment postnatally

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Heart rate variability using fMCG

    To measure and compare the fMCG heart rate variability in five pregnancy conditions associated with fetal demise, to those of gestation matched normal fetuses.

    Measured: Comparison of procedures at approximately 20-27 weeks gestation, at 30-37 weeks gestation, and at neonatal ECG at 0-4 weeks of age

  2. Cardiac conduction

    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 ECGs at 0-4 weeks of age.

    Measured: Comparison of cardiac time intervals at approximately 20-27 weeks gestation, 30-37 weeks gestation and at neonatal ECG at 0-4 weeks of age

  3. Cardiac repolarization

    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 ECGs at 0-4 weeks of age.

    Measured: Comparison of cardiac repolarization at approximately 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-4 weeks of age.

Secondary outcomes (2)

  1. Unique "signature" electrophysiologic abnormalities

    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.

    Measured: Comparison of findings at approximately 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-4 weeks of age

  2. Pregnancy outcomes

    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 0-4 weeks of age.

    Measured: Comparison of findings at approximately 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-4 weeks of age

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2018
  2. Study start1 Jul 2018
  3. Primary completion30 Nov 2028 (estimated)
  4. Study completion30 Nov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03775954
Sponsor's protocol ID
PRO00031598
Other IDs
R01HL143485
Status last verified
Feb 2026
First submitted
24 Oct 2018
Last updated
4 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Only de-identified data can be released

Publications

  • Strasburger JF. Fetal magnetocardiography: Using quantum technologies to define fetal rhythm, conduction, and repolarization prior to birth. Am Heart J Plus. 2025 Sep 4;59:100593. doi: 10.1016/j.ahjo.2025.100593. eCollection 2025 Nov.

    PubMed 41126874

  • Donofrio MT, Moon-Grady AJ, Hornberger LK, Copel JA, Sklansky MS, Abuhamad A, Cuneo BF, Huhta JC, Jonas RA, Krishnan A, Lacey S, Lee W, Michelfelder EC Sr, Rempel GR, Silverman NH, Spray TL, Strasburger JF, Tworetzky W, Rychik J; American Heart Association Adults With Congenital Heart Disease Joint Committee of the Council on Cardiovascular Disease in the Young and Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Council on Cardiovascular and Stroke Nursing. Diagnosis and treatment of fetal cardiac disease: a scientific statement from the American Heart Association. Circulation. 2014 May 27;129(21):2183-242. doi: 10.1161/01.cir.0000437597.44550.5d. Epub 2014 Apr 24.

    PubMed 24763516

  • Strasburger JF, Wakai RT. Fetal cardiac arrhythmia detection and in utero therapy. Nat Rev Cardiol. 2010 May;7(5):277-90. doi: 10.1038/nrcardio.2010.32.

    PubMed 20418904

  • Cuneo BF, Strasburger JF, Yu S, Horigome H, Hosono T, Kandori A, Wakai RT. In utero diagnosis of long QT syndrome by magnetocardiography. Circulation. 2013 Nov 12;128(20):2183-91. doi: 10.1161/CIRCULATIONAHA.113.004840.

    PubMed 24218437

  • Batie M, Bitant S, Strasburger JF, Shah V, Alem O, Wakai RT. Detection of Fetal Arrhythmia Using Optically-Pumped Magnetometers. JACC Clin Electrophysiol. 2018 Feb;4(2):284-287. doi: 10.1016/j.jacep.2017.08.009. No abstract available.

    PubMed 29527577

  • Strand S, Strasburger JF, Cuneo BF, Wakai RT. Complex and Novel Arrhythmias Precede Stillbirth in Fetuses With De Novo Long QT Syndrome. Circ Arrhythm Electrophysiol. 2020 May;13(5):e008082. doi: 10.1161/CIRCEP.119.008082. Epub 2020 May 18.

    PubMed 32421437

  • Strand S, Lutter W, Strasburger JF, Shah V, Baffa O, Wakai RT. Low-Cost Fetal Magnetocardiography: A Comparison of Superconducting Quantum Interference Device and Optically Pumped Magnetometers. J Am Heart Assoc. 2019 Aug 20;8(16):e013436. doi: 10.1161/JAHA.119.013436. Epub 2019 Aug 9.

    PubMed 31394997

  • Wacker-Gussmann A, Strasburger JF, Wakai RT. Fetal Magnetocardiography Alters Diagnosis and Management in Fetal Congenital Heart Disease and Cardiomyopathy. JACC Clin Electrophysiol. 2022 Sep;8(9):1159-1161. doi: 10.1016/j.jacep.2022.04.012. Epub 2022 Jun 29. No abstract available.

    PubMed 36137723

  • Wacker-Gussmann A, Strasburger JF, Wakai RT. Contribution of Fetal Magnetocardiography to Diagnosis, Risk Assessment, and Treatment of Fetal Arrhythmia. J Am Heart Assoc. 2022 Aug 2;11(15):e025224. doi: 10.1161/JAHA.121.025224. Epub 2022 Jul 29.

    PubMed 35904205

  • Strasburger JF, Eckstein G, Butler M, Noffke P, Wacker-Gussmann A. Fetal Arrhythmia Diagnosis and Pharmacologic Management. J Clin Pharmacol. 2022 Sep;62 Suppl 1(Suppl 1):S53-S66. doi: 10.1002/jcph.2129.

    PubMed 36106782

Questions about this trial

What is this clinical trial studying?

An observational study of High Risk Pregnancy and Congenital Heart Disease, run by Medical College of Wisconsin at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Mara C Koffarnus, MD (414-266-4758, mkoffarn@mcw.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Heart rate variability using fMCG (time frame: Comparison of procedures at approximately 20-27 weeks gestation, at 30-37 weeks gestation, and at neonatal ECG at 0-4 weeks of age). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03775954, which also lists 10 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.

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