<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03775954</url>
  </required_header>
  <id_info>
    <org_study_id>PRO00031598</org_study_id>
    <secondary_id>R01HL143485</secondary_id>
    <nct_id>NCT03775954</nct_id>
  </id_info>
  <brief_title>Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise</brief_title>
  <official_title>Fetal Electrophysiologic Abnormalities in High-risk Pregnancies Associated With Fetal Demise</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical College of Wisconsin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Children's Hospital and Health System Foundation, Wisconsin</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Shared Medical Technology, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tristan Technologies, Inc</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical College of Wisconsin</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Each year world-wide, 2.5 million fetuses die unexpectedly in the last half of pregnancy,&#xD;
      25,000 in the United States, making fetal demise ten-times more common than Sudden Infant&#xD;
      Death Syndrome. This study will apply a novel type of non-invasive monitoring, called fetal&#xD;
      magnetocardiography (fMCG) used thus far to successfully evaluate fetal arrhythmias, in order&#xD;
      to discover potential hidden electrophysiologic abnormalities that could lead to fetal demise&#xD;
      in five high-risk pregnancy conditions associated with fetal demise.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Fetal demise occurs in over 25,000 pregnancies annually in the US and over 2.5 million in&#xD;
      pregnancies worldwide. Certain maternal-fetal-placental abnormalities can have a high risk of&#xD;
      fetal demise. Despite advances in fetal surveillance with ultrasound and cardiotocography,&#xD;
      the reduction in fetal mortality lags behind that of the neonate and has shown little decline&#xD;
      in the past decade. This suggests that the type of fetal monitoring used may not be assessing&#xD;
      the correct indicators of mortality. In all other age groups, electrocardiographic (ECG) and&#xD;
      continuous heart rate (HR) monitoring are used in every intensive care unit or emergency&#xD;
      setting; however, for the fetus, the ECG signal is nearly completely insulated and&#xD;
      inaccessible. As the result, indirect assessment of cardiac rhythm is obtained using&#xD;
      echocardiography/Doppler, but echo/Doppler does not have the precision to assess beat-to-beat&#xD;
      HR variability and cannot assess cardiac repolarization at all. In this study, the&#xD;
      investigators will evaluate five high risk conditions (major congenital heart disease in the&#xD;
      fetus, fetal hydrops (immune and non-immune), monochorionic twin pregnancy, prior pregnancy&#xD;
      ending in fetal demise, and gastroschisis) using Fetal Magnetocardiography (fMCG)which&#xD;
      detects the natural magnetic signals accompanying the cardiac electrical signal. It is a new,&#xD;
      safe, and non-invasive recording technique that has been performed for several decades, and&#xD;
      has recently gained FDA approval for recording cardiac signals at all ages, including in the&#xD;
      fetus. Normative data has been obtained at the University of Wisconsin - Madison Biomagnetism&#xD;
      Laboratory in 257 healthy fetuses by co-investigator Ronald T. Wakai, PhD. Over 550 serious&#xD;
      fetal arrhythmias have been evaluated to date. Fetal MCG has proven invaluable in fetal Long&#xD;
      QT Syndrome in identifying markers for risk of sudden death such as Torsades de Pointes&#xD;
      Ventricular Tachycardia (VT), T wave alternans, 2nd degree AV block, and QTc&gt;590 ms. To date,&#xD;
      fMCG has not been systematically applied to diseases that are not associated with&#xD;
      recognizable arrhythmias because the impact of silent conduction and repolarization defects&#xD;
      has been underappreciated. In this grant, the investigators hypothesize that beat-to-beat&#xD;
      fetal heart rate variability abnormalities and electrophysiologic abnormalities, are present&#xD;
      in five high risk maternal-fetal-placental conditions associated with fetal demise. The study&#xD;
      will determine which electrophysiologic abnormalities precede fetal demise or adverse&#xD;
      pregnancy outcome. Preliminary findings in healthy normal subjects in RO1HL063174 (Wakai)&#xD;
      show repolarization abnormalities in up to 5%, and some of these are modifiable once&#xD;
      recognized. Two hundred pregnant subjects will be studied over a 5 year period both at&#xD;
      referral (~20-27 weeks GA) and later in pregnancy at 30-37 weeks GA. fMCG results will be&#xD;
      compared to neonatal ECG (nECG) obtained at 0-4 weeks of life. This will determine whether&#xD;
      specific abnormal heart rate, rhythm and conduction patterns emerge that characterize the&#xD;
      condition, which will then allow the high risk obstetrician to better predict risk of fetal&#xD;
      demise in the future.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Anticipated">April 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2023</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Heart rate variability using fMCG</measure>
    <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</time_frame>
    <description>To measure and compare the fMCG heart rate variability in five pregnancy conditions associated with fetal demise, to those of gestation matched normal fetuses.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiac conduction</measure>
    <time_frame>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</time_frame>
    <description>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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiac repolarization</measure>
    <time_frame>Comparison of cardiac repolarization at approximately 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-4 weeks of age.</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Unique &quot;signature&quot; electrophysiologic abnormalities</measure>
    <time_frame>Comparison of findings at approximately 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-4 weeks of age</time_frame>
    <description>2a) To determine whether unique &quot;signature&quot; 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.&#xD;
findings are first seen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pregnancy outcomes</measure>
    <time_frame>Comparison of findings at approximately 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-4 weeks of age</time_frame>
    <description>To correlate fMCG findings with 3a) outcomes of pregnancies (fetal demise, premature delivery, small for GA, 5 minute APGAR &lt; 5, neonatal death) and 3b) fMCG cardiac time intervals with postnatal ECG intervals at 0-4 weeks of age.</description>
  </secondary_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Anticipated">200</enrollment>
  <condition>High Risk Pregnancy</condition>
  <condition>Congenital Heart Disease</condition>
  <condition>Fetal Hydrops</condition>
  <condition>Twin Monochorionic Monoamniotic Placenta</condition>
  <condition>Gastroschisis</condition>
  <condition>Fetal Demise</condition>
  <condition>Stillbirth</condition>
  <condition>Fetal Arrhythmia</condition>
  <condition>Long QT Syndrome</condition>
  <condition>Intrauterine Fetal Death</condition>
  <condition>Sudden Infant Death</condition>
  <condition>Pregnancy Loss</condition>
  <condition>Twin Twin Transfusion Syndrome</condition>
  <condition>Birth Defect</condition>
  <condition>Fetal Cardiac Anomaly</condition>
  <condition>Fetal Cardiac Disorder</condition>
  <condition>Fetal Death</condition>
  <condition>Brugada Syndrome</condition>
  <arm_group>
    <arm_group_label>1) Fetal Congenital Heart Disease</arm_group_label>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2) History of fetal demise (Stillbirth)</arm_group_label>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3) Fetal hydrops, immune or non-immune</arm_group_label>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>4) Fetal gastroschisis</arm_group_label>
    <description>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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>5) Twin pregnancy, monochorionic</arm_group_label>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Fetal Magnetocardiogram and Neonatal Electrocardiogram</intervention_name>
    <description>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.</description>
    <arm_group_label>1) Fetal Congenital Heart Disease</arm_group_label>
    <arm_group_label>2) History of fetal demise (Stillbirth)</arm_group_label>
    <arm_group_label>3) Fetal hydrops, immune or non-immune</arm_group_label>
    <arm_group_label>4) Fetal gastroschisis</arm_group_label>
    <arm_group_label>5) Twin pregnancy, monochorionic</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Current pregnancy complicated by one of the five diagnostic categories (fetal major&#xD;
        congenital heart disease, prior unexplained Stillbirth at/after 20 weeks gestation, fetal&#xD;
        hydrops, fetal gastroschesis, or monochorionic twin pregnancy.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Current pregnancy complicated by one of the five diagnostic categories&#xD;
&#xD;
               -  prior unexplained Stillbirth at/after 20 weeks gestation&#xD;
&#xD;
               -  fetal major congenital heart defect&#xD;
&#xD;
               -  fetal hydrops&#xD;
&#xD;
               -  fetal gastroschisis&#xD;
&#xD;
               -  monochorionic twin pregnancy&#xD;
&#xD;
          -  Subject must be 18 years of age or older&#xD;
&#xD;
          -  Subject must be English speaking and must be able to read and sign the consent form in&#xD;
             English&#xD;
&#xD;
          -  Subject must be able to recline comfortably for 1-3 hours&#xD;
&#xD;
          -  Subject must be willing to complete all three procedures (fMCG, fMCG, nECG) as per&#xD;
             protocol, unless medically unable&#xD;
&#xD;
          -  Subject must be willing to allow us to review her and her infants prenatal, deliver,&#xD;
             and post-natal records to verify diagnosis, and clinical findings.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe claustrophobia not reduced by taking breaks, or by having the light on, or by&#xD;
             having someone in the room with them.&#xD;
&#xD;
          -  Active labor&#xD;
&#xD;
          -  Acute illness&#xD;
&#xD;
          -  Unable to recline comfortably with a pillow for more than 1-3 hours (assuming some&#xD;
             breaks are provided)&#xD;
&#xD;
          -  Weight over 450 lbs&#xD;
&#xD;
          -  An electric stimulation device (TENS unit, pacemaker, or nerve stimulator) that could&#xD;
             produce electric or magnetic noise.&#xD;
&#xD;
               -  Note that the Tristan 624 Magnetometer does not pose a risk to the subject's&#xD;
                  device, (since fMCG does not produce any energy or magnetism), but stimulators&#xD;
                  themselves can cause interference for our recordings. Some devices may still&#xD;
                  qualify, and discussion with study nurse may be useful if subject has a pacemaker&#xD;
                  or similar device.&#xD;
&#xD;
        The subject will have a single 2-3 hour fetal magnetocardiogram at approximately 20 and 27&#xD;
        weeks GA, and again, if medical condition allows, between 30 and 37 weeks GA, then her&#xD;
        infant will have an ECG between 0 and 4 weeks of age. Subjects will be paid a nominal fee&#xD;
        for their participation each time, as well as transportation reimbursement if &gt;25 miles.&#xD;
        For subjects traveling a long distance, the ECG may be performed locally or at home.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <gender_description>This study involves pregnant women and subsequently-born neonate(s) of either gender.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janette F Strasburger, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical College of Wisconsin</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Mara C Koffarnus, MD</last_name>
    <phone>414-266-4758</phone>
    <email>mkoffarn@mcw.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Gretchen Eckstein</last_name>
    <phone>414-266-3539</phone>
    <email>geckstein@chw.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of Wisconsin - Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53715</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ronald T Wakai, PhD</last_name>
      <email>rtwakai@wisc.edu</email>
    </contact>
    <contact_backup>
      <last_name>Gretchen Eckstein, RN, BSN</last_name>
      <phone>414-266-3539</phone>
      <email>geckstein@chw.org</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Medical College of Wisconsin</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53226</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Janette F Strasburger, MD</last_name>
      <phone>414-266-2000</phone>
      <email>jstrasbu@mcw.edu</email>
    </contact>
    <contact_backup>
      <last_name>Gretchen C Eckstein, RN, BSN</last_name>
      <phone>414-266-3539 (Preferred)</phone>
      <email>geckstein@chw.org</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.medphysics.wisc.edu/wp/research/biomagnetism/</url>
    <description>Fetal MCG Research</description>
  </link>
  <link>
    <url>http://www.chw.org/medical-care/herma-heart</url>
    <description>Children's Hospital of Wisconsin Herma Heart Institute</description>
  </link>
  <link>
    <url>https://datascience.nih.gov/news/nih-virtual-workshop-near-term-applications-of-quantum-sensing-technologies-in-biomedical-sciences,https://www.youtube.com/watch?v=5Z74MiJ4j8o</url>
    <description>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.</description>
  </link>
  <reference>
    <citation>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. Erratum In: Circulation. 2014 May 27;129(21):e512.</citation>
    <PMID>24763516</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>20418904</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>24218437</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>29527577</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>32421437</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>31394997</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>36137723</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>35904205</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>36106782</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>October 24, 2018</study_first_submitted>
  <study_first_submitted_qc>December 13, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 14, 2018</study_first_posted>
  <last_update_submitted>March 16, 2023</last_update_submitted>
  <last_update_submitted_qc>March 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical College of Wisconsin</investigator_affiliation>
    <investigator_full_name>Janette F. Strasburger</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Fetal Magnetocardiography</keyword>
  <keyword>Stillbirth</keyword>
  <keyword>Intrauterine Fetal Demise</keyword>
  <keyword>Mobile Medical Technologies</keyword>
  <keyword>Fetal Heart Rate Variability</keyword>
  <keyword>Fetal Arrhythmias</keyword>
  <keyword>High Risk Pregnancy</keyword>
  <keyword>Pregnancy</keyword>
  <keyword>Fetal Anomaly</keyword>
  <keyword>Fetal Echocardiography</keyword>
  <keyword>Non-Stress Testing</keyword>
  <keyword>New Technology</keyword>
  <keyword>Birth Defects</keyword>
  <keyword>Fetal Research</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastroschisis</mesh_term>
    <mesh_term>Stillbirth</mesh_term>
    <mesh_term>Fetal Death</mesh_term>
    <mesh_term>Hydrops Fetalis</mesh_term>
    <mesh_term>Heart Diseases</mesh_term>
    <mesh_term>Arrhythmias, Cardiac</mesh_term>
    <mesh_term>Heart Defects, Congenital</mesh_term>
    <mesh_term>Long QT Syndrome</mesh_term>
    <mesh_term>Brugada Syndrome</mesh_term>
    <mesh_term>Fetofetal Transfusion</mesh_term>
    <mesh_term>Congenital Abnormalities</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Death</mesh_term>
    <mesh_term>Infant Death</mesh_term>
    <mesh_term>Sudden Infant Death</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Only de-identified data can be released</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03775954
org study id: PRO00031598
secondary id: R01HL143485
nct id: NCT03775954
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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.
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.
observational model: Cohort
time perspective: Prospective
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
description: To measure and compare the fMCG heart rate variability in five pregnancy conditions associated with fetal demise, to those of gestation matched normal fetuses.
measure: Cardiac conduction
time frame: 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
description: 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.
measure: Cardiac repolarization
time frame: Comparison of cardiac repolarization at approximately 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-4 weeks of age.
description: 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.
measure: Unique "signature" electrophysiologic abnormalities
time frame: Comparison of findings at approximately 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-4 weeks of age
description: 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.
measure: Pregnancy outcomes
time frame: Comparison of findings at approximately 20-27 weeks gestation, 30-37 weeks gestation and neonatal ECG at 0-4 weeks of age
description: 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.
arm group label: 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.
arm group label: 2) History of fetal demise (Stillbirth)
description: 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.
arm group label: 3) Fetal hydrops, immune or non-immune
description: 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.
arm group label: 4) Fetal gastroschisis
description: 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.
arm group label: 5) Twin pregnancy, monochorionic
description: 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 type: Diagnostic Test
intervention name: Fetal Magnetocardiogram and Neonatal Electrocardiogram
description: 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.
arm group label: 1) Fetal Congenital Heart Disease
arm group label: 2) History of fetal demise (Stillbirth)
arm group label: 3) Fetal hydrops, immune or non-immune
arm group label: 4) Fetal gastroschisis
arm group label: 5) Twin pregnancy, monochorionic
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
gender description: This study involves pregnant women and subsequently-born neonate(s) of either gender.
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Janette F Strasburger, MD
role: Principal Investigator
affiliation: Medical College of Wisconsin
last name: Mara C Koffarnus, MD
phone: 414-266-4758
email: mkoffarn@mcw.edu
last name: Gretchen Eckstein
phone: 414-266-3539
email: geckstein@chw.org
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
url: https://www.medphysics.wisc.edu/wp/research/biomagnetism/
description: Fetal MCG Research
url: http://www.chw.org/medical-care/herma-heart
description: Children's Hospital of Wisconsin Herma Heart Institute
url: https://datascience.nih.gov/news/nih-virtual-workshop-near-term-applications-of-quantum-sensing-technologies-in-biomedical-sciences,https://www.youtube.com/watch?v=5Z74MiJ4j8o
description: 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.
citation: 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. Erratum In: Circulation. 2014 May 27;129(21):e512.
PMID: 24763516
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
citation: 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
responsible party type: Principal Investigator
investigator affiliation: Medical College of Wisconsin
investigator full name: Janette F. Strasburger
investigator title: Professor
mesh term: Gastroschisis
mesh term: Stillbirth
mesh term: Fetal Death
mesh term: Hydrops Fetalis
mesh term: Heart Diseases
mesh term: Arrhythmias, Cardiac
mesh term: Heart Defects, Congenital
mesh term: Long QT Syndrome
mesh term: Brugada Syndrome
mesh term: Fetofetal Transfusion
mesh term: Congenital Abnormalities
mesh term: Syndrome
mesh term: Death
mesh term: Infant Death
mesh term: Sudden Infant Death
sharing ipd: No
ipd description: Only de-identified data can be released