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

NCT03775954 | Recruiting

• 2 other identifiers: PRO00031598R01HL143485
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 2

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.

Conditions

High Risk Pregnancy; Long QT Syndrome; Intrauterine Fetal Death; Sudden Infant Death; Pregnancy Loss; Twin Twin Transfusion Syndrome; Birth Defect; Fetal Cardiac Disorder; Fetal Death; Brugada Syndrome; Fetal Tachycardia; Congenital Heart Disease; Fetal Hydrops; Twin Monochorionic Monoamniotic Placenta; Gastroschisis; Fetal Demise; Stillbirth; Fetal Arrhythmia; Fetal Cardiac Anomaly

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

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

  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

• 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.

  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)

• Unique "signature" electrophysiologic abnormalities

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

• Pregnancy outcomes

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

Study Arms (6)

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.

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.

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.

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.

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.

Diagnostic Test: Fetal Magnetocardiogram and Neonatal Electrocardiogram

6) Maternal medications and Fetal Tachycardia

Mothers 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.

Genetic: Substudy only: Maternal/Infant Pharmacogenomic assessment postnatally

Interventions

Fetal Magnetocardiogram and Neonatal Electrocardiogram DIAGNOSTIC_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.

1) Fetal Congenital Heart Disease; 2) History of fetal demise (Stillbirth); 3) Fetal hydrops, immune or non-immune; 4) Fetal gastroschisis; 5) Twin pregnancy, monochorionic

Substudy only: Maternal/Infant Pharmacogenomic assessment postnatally GENETIC

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.

6) Maternal medications and Fetal Tachycardia

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: This study involves pregnant women and subsequently-born neonate(s) of either gender.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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, 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University of Wisconsin, Madison: collaborator
• Tristan Technologies, Inc: collaborator
• Advancing a Healthier Wisconsin Endowment: collaborator

Study Sites (2)

University of Wisconsin - Madison

Madison, Wisconsin, 53715, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Related Publications (10)

• 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.

  PMID: 41126874 BACKGROUND

• 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.

  PMID: 24763516 BACKGROUND

• 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.

  PMID: 20418904 BACKGROUND

• 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.

  PMID: 24218437 BACKGROUND

• 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.

  PMID: 29527577 BACKGROUND

• 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.

  PMID: 32421437 BACKGROUND

• 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.

  PMID: 31394997 BACKGROUND

• 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.

  PMID: 36137723 BACKGROUND

• 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.

  PMID: 35904205 BACKGROUND

• 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.

  PMID: 36106782 BACKGROUND

Related Links

• Fetal MCG Research
• Children's Hospital of Wisconsin Herma Heart Institute
• NIH Seminar Dr. Strasburger is co-chair, speaks at 32 minutes, Dr. Wakai speaks at 62 minutes on fMCG and a participant speaks at 1::37 minutes on her experience in our study.

MeSH Terms

Conditions

Heart Defects, Congenital; Hydrops Fetalis; Gastroschisis; Fetal Death; Stillbirth; Long QT Syndrome; Sudden Infant Death; Fetofetal Transfusion; Congenital Abnormalities; Brugada Syndrome

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Erythroblastosis, Fetal; Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; alpha-Thalassemia; Thalassemia; Hemoglobinopathies; Genetic Diseases, Inborn; Immune System Diseases; Edema; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Hernia, Abdominal; Hernia; Pathological Conditions, Anatomical; Death; Pathologic Processes; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Death, Sudden; Infant Death; Anemia, Neonatal; Anemia; Infant, Newborn, Diseases

Study Officials

• Janette F Strasburger, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mara C Koffarnus, MD

CONTACT

414-266-4758; mkoffarn@mcw.edu

Gretchen Eckstein

CONTACT

414-266-3539; geckstein@chw.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 24, 2018
• First Posted: December 14, 2018
• Study Start: July 1, 2018
• Primary Completion (Estimated): November 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: March 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)