Fetal and Neonatal Magnetophysiology

Fetal research and clinical practice has been hampered by a lack of suitable investigational techniques. Currently, ultrasound is the only widely used method of studying fetal anatomy and physiology, but it has significant limitations for assessment of cardiac rhythm. The proposed study will allow us to investigate fetal magnetocardiography (fMCG) as a new tool for the study of normal and abnormal fetal heart rate and rhythm, with a goal of demonstrating probable benefit from use of the device in patients with serious fetal arrhythmia. We propose a study that will last 1-2 years and will provide data to aid in assessing the safety and effectiveness of fMCG for diagnosis and management of patients with abnormal fetal heart rate and rhythm. We hope that the data from the study will support a Humanitarian Device Exemption (HDE) application for the subject device. The safety and efficacy study designs are described below. High-risk subjects will undergo echocardiography as part of their routine clinical management, and our results will be compared to the echocardiography results, as well as with postnatal ECG, when available. (Since many arrhythmias resolve prior to birth, either due to resolution of disease or due to treatment, only a limited number of diseases allow postnatal comparison). For rhythms that persist after birth, the diagnostic utility of fMCG and echocardiography will be assessed by computing the sensitivity (Sn) and specificity (Sp) relative to postnatal ECG for the following prenatal modalities: (i) the fMCG, (ii) the original (referral) echo, (iii) if available, the in-lab echocardiogram at the time of the fMCG study. Secondary endpoints will assess changes in diagnosis and in clinical management due to the additional information provided by fMCG, compared to the information provided by echocardiography alone.

Study Overview

• Status: Completed
• Conditions: Long QT Syndrome; Fetal Arrhythmia; Abnormality in Fetal Heart Rate or Rhythm
• Intervention / Treatment: Device: magnetocardiography; Device: fetal echocardiography; Device: postnatal ECG

• Study Type: Observational
• Enrollment (Actual): 39

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin-Madison

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

We plan to study a total of 180 subjects. Sixty will be pregnant women with uncomplicated pregnancies; 120 will be pregnant women with pregnancies complicated by fetal arrhythmia or a condition that puts the fetus at risk of fetal arrhythmia. We refer to these cases as "high-risk" due to the presence of or risk of arrhythmia to the fetus. The pregnant mothers will be age 18 or older. They will be studied as early as 15 weeks' gestation and may be asked to return, if their physician determines that additional fMCG studies are necessary.

Description

Inclusion Criteria:

Normal subjects: normal, healthy adult women with uncomplicated pregnancies

High-risk cohort: The primary inclusion criterion is diagnosis of serious fetal arrhythmia, which is defined as sustained low or high heart rate. Low heart rate, or bradycardia, and high heart rate, or tachycardia, are based on normative values for gestation (usually below 110 -120 beats/min, or above 160-180 beats/min). Intermittent bradycardia and tachycardia are also important to detect because these arrhythmias may become incessant over the course of pregnancy and have implications for patient management. Abnormal repolarization, such as long QT syndrome (LQTS), is another important class of arrhythmia. Fetuses with a family history of LQTS or a suspicious rhythm (low heart rate, intermittent AV block, or ventricular tachycardia) will also be studied.

Exclusion Criteria:

The pregnant women subjects must by aged 18 or older. High-risk subjects cannot participate if their physician in consultation with the lead physician of the study does not grant permission for them to participate in the study due to risk of travel or other reason.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
normal; pregnant women with uncomplicated pregnancies	Device: magnetocardiography; recording of magnetic heart activity; Other Names: MCG; fetal magnetocardiography; Device: fetal echocardiography; fetal echocardiography; Other Names: Doppler ultrasound; M-mode ultrasound; 2d ultrasound
high-risk; pregnant women with pregnancies complicated by fetal arrhythmia or the risk of fetal arrhythmia	Device: magnetocardiography; recording of magnetic heart activity; Other Names: MCG; fetal magnetocardiography; Device: fetal echocardiography; fetal echocardiography; Other Names: Doppler ultrasound; M-mode ultrasound; 2d ultrasound; Device: postnatal ECG; postnatal ECG; Other Names: electrocardiography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Experiencing Symptoms	Percentage of subjects experiencing symptoms	15-40 weeks' gestation
Percentage of Subjects Experiencing Adverse Events Unrelated to Device	Percentage of subjects experiencing adverse events unrelated to device	15 weeks' gestation till up to 1 month after birth
Number of Participants With Concordance of fMCG and Postnatal ECG for Diagnosis of Long QT Syndrome	Number of Participants with Concordance of fMCG and Postnatal ECG for Diagnosis of Long QT Syndrome based on measurement of rate-corrected QT interval (QTc)	Birth to age 1 week
Percentage of Subjects Experiencing Adverse Events Related to Device	Percentage of Subjects Experiencing Adverse Events Related to Device	15 weeks' gestation till up to 1 month after birth

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Fetuses With a Family History of Long QT Syndrome Who a Change in Diagnosis Due to fMCG	Percentage of fetuses with a family history of long QT syndrome who a change in diagnosis due to fMCG	15 weeks' gestation to birth
Percentage of Fetuses With a Family History of Long QT Syndrome Who Had a Change in Management Due to fMCG	Percentage of fetuses with a family history of long QT syndrome who had a change in management due to fMCG	15 weeks' gestation to birth

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Medical College of Wisconsin; Shared Medical Technology, Inc.
• Investigators: Principal Investigator: Ronald Wakai, Ph.D., University of Wisconsin, Madison; Study Director: Janette Strasburger, M.D., Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: July 11, 2013
• First Submitted That Met QC Criteria: July 16, 2013
• First Posted (Estimate): July 19, 2013

Study Record Updates

• Last Update Posted (Actual): May 29, 2019
• Last Update Submitted That Met QC Criteria: May 15, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: long QT syndrome; fetal heart rate; fetus; fetal arrhythmia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Congenital Abnormalities; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Arrhythmias, Cardiac; Long QT Syndrome
• Other Study ID Numbers: 2013-0362; R01HL063174 (U.S. NIH Grant/Contract)