Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies 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 0-2 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.

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.