Magnetocardiography for the Fetus at Risk for Stillbirth
Janette F. Strasburger
INTRODUCTION
For half a century, the superb diagnostic capabilities of ultrasound and echocardiography have been the primary tools for fetal cardiac rhythm diagnosis. However, fetal magnetocardiography (fMCG) (Part 2, Chapter 3) has taken our understanding to a new level by allowing us to delve into the electrophysiology of these rhythms. With these advances, it should be possible to explore the hypothesis that fMCG may uncover electrophysiologic findings that predispose to the risk of stillbirth. This possibility has been largely unexplored in the field of fetal medicine. Such an approach would be facilitated by 25 years of experience in the Biomagnetism Laboratory at the University of Wisconsin-Madison, where medical physicists and fetal cardiologists have developed normal values for fetal cardiac intervals and repolarization characteristics over a wide range of gestational ages.1,2,3 These studies have diagnosed repolarization abnormalities in fetuses with atrioventricular (AV) block, long QT syndrome (LQTS), and congenital heart disease.4,5,6,7,8,9 Serial studies of 132 ostensibly normal pregnancies where fMCG-detected QRS-T discordance and ST depression or elevation suggest underlying abnormalities in fetuses thought to be normal by traditional obstetrical parameters.10 In addition, these studies have shown that treatment can positively effect the electrophysiology of fetuses with conduction system and structural heart disease. This chapter will summarize current information about stillbirth and describe a new study utilizing fMCG. This study proposes to evaluate electrophysiologic findings in fetuses at risk for stillbirth to find markers predicting in utero demise. It is currently evaluating five at-risk groups: mono-dichorionic twins, fetuses with gastroschisis or congenital heart disease, and mothers with a prior history of stillbirth, or those with fetal hydrops.
FETAL MAGNETOCARDIOGRAPHY (fMCG)
FMCG has been described in Part 2, Chapter 3. As previously discussed, fMCG produces no magnetism or energy and is a completely safe passive receiver for cardiac electric and magnetic signals. Currently, fMCG is limited to medical physics laboratories rather than labor and delivery wards. Though approved by the Food and
Drug Administration (FDA) for the indication of fetal cardiac recording with a Class IIa indication for fetal arrhythmia, superconducting quantum interference device (SQUID) magnetometers are extremely expensive to operate. The expense is due to the need to cool the SQUIDs with liquid helium as described in Part 2, Chapter 3. Newer sensors are being developed that use optically pumped magnetometers rather than cryogenics; this change is expected to significantly reduce cost. Optically pumped magnetometers are not yet approved for use in the fetus, but in the Biomagnetism Laboratory at University of Wisconsin-Madison, over 50 pregnant women have undergone this procedure without incident. The quality of the data is equal to that obtained using the SQUID.11
Drug Administration (FDA) for the indication of fetal cardiac recording with a Class IIa indication for fetal arrhythmia, superconducting quantum interference device (SQUID) magnetometers are extremely expensive to operate. The expense is due to the need to cool the SQUIDs with liquid helium as described in Part 2, Chapter 3. Newer sensors are being developed that use optically pumped magnetometers rather than cryogenics; this change is expected to significantly reduce cost. Optically pumped magnetometers are not yet approved for use in the fetus, but in the Biomagnetism Laboratory at University of Wisconsin-Madison, over 50 pregnant women have undergone this procedure without incident. The quality of the data is equal to that obtained using the SQUID.11
STILLBIRTH
Stillbirth is defined as the unexpected in utero death of the fetus at a gestational age (GA) of ≥20 weeks. Almost 25,000 stillbirths occur each year in the United States, more than seven times the frequency of sudden infant death syndrome (SIDS). Worldwide, an estimated 2.5 million stillbirths occur each year. Stillbirth peaks in late gestation12,13,14 and has a lifetime impact on the mother and other family members. The cause of at least 30% of stillbirths is unknown. Over 200 risk factors have been associated with stillbirth, such as placenta, cord and membrane complications, and fetal anomalies (FIG. 6.2.1A). Stillbirth also has acute and chronic, intrinsic, and extrinsic triggers.12,13,15,16,17 Non-Hispanic black women have almost double the stillbirth rates of other races; Native Americans and Pacific Islanders also are at high risk (FIG. 6.2.1B). The reasons for these disparities are unclear, but epigenetic risk is proposed. Common genetic polymorphisms may also increase this risk.
While the rate of stillbirth has declined over decades, the decreasing rate has not kept pace with the decline of neonatal and infant deaths (FIG. 6.2.2A). This is especially true of stillbirths at 20 to 28 weeks GA (FIG. 6.2.2B). Even if the pregnancy is at increased risk of stillbirth, the timing of delivery to avert such a death is imperfectly predicted, and the obstetrician often chooses between delivering a live baby prematurely and risking a stillbirth.
Little is known of the mechanisms of stillbirth, and tools to identify and monitor the at-risk fetus are limited. Thus, the presence of electrophysiologic abnormalities such as conduction or repolarization prior to stillbirth is unknown. What is needed is a more sensitive monitoring tool to identify the cardiac sequelae of hypoxia and acidosis. To date, monitoring capabilites of fMCG can provide these data.
Known Maternal and Fetal Risk Factors for Stillbirth
Stillbirth is seen in 2% to 30% of major congenital heart defects (especially when chromosomal abnormalities or extracardiac defects are present),18 in 30% of fetal hydrops cases,19,20,21 and in 5% of subsequent pregnancies in women who have had a prior unexplained fetal demise.14,22,23 Monochorionic twins have a 0.5% to 15% mortality,24,25,26 and gastroschisis has a 4.8% to 10% fetal mortality.27,28,29 The only obstetrical disease with an increased stillbirth associated with fetal conduction system disease
is intrahepatic cholestasis (IHC). It is known that bile acids have an arrhythmogenic effect, and in a case series, the fetuses of pregnant women with IHC had significantly longer PR intervals than controls.30 In a case report, treatment of IHC with ursodeoxycholic acid reduced the mother’s symptoms and shortened the fetal AV interval from 163 to 143 ms.31
is intrahepatic cholestasis (IHC). It is known that bile acids have an arrhythmogenic effect, and in a case series, the fetuses of pregnant women with IHC had significantly longer PR intervals than controls.30 In a case report, treatment of IHC with ursodeoxycholic acid reduced the mother’s symptoms and shortened the fetal AV interval from 163 to 143 ms.31