Project Description Narrative:
As many as 85% of pregnant women take at least one prescription medication during their pregnancies. Over 250 drugs in the U.S. market, many of them over the counter, have the potential to pass readily to the fetus, and can prolong cardiac electrocardiographic (ECG) time intervals. In certain fetuses, such as those with inherited arrhythmia syndromes (IASs), those exposed to multiple QT prolonging medications, or those with severe illnesses, this can lead to fetal rhythm and conduction abnormalities that are silent, potentially lethal, and cannot be detected by ultrasound alone. Another factor impacting the fetus's ECG is maternal metabolism of drugs, which is controlled by certain genes for liver metabolism (Cytochrome P450). When a mother has ultra-fast metabolism or ultra-slow metabolism, it can impact drug levels, fetal exposure, and response to treatment. This project will study fetal heart rhythm effects of medications in 30 mother/fetal pairs after 15 weeks gestation over two years using a non-invasive safe method of recording the magnetic heart signal, called fetal magnetocardiography (fMCG). The research team will evaluate pharmacogenomics of the mother and infant in pregnancies with arrhythmias and develop predictive models of drug metabolism to establish optimal dosing regimens in the future.
The research team seeks to show that Wisconsin can lead the nation in advancement of new technology to support Obstetrics, which has historically seen the lowest investment in innovation of any of the medical specialties, with a goal of making pregnancy safer. Wisconsin is unique within the United States for having such a strong collaboration for medical device development for pregnancy between its two major medical universities that spans two decades, and directly benefits women in this state by providing sophisticated cardiac monitoring for the fetus, similar to what is available in an intensive care unit. fMCG uses quantum sensing, a safe listening technology to sense natural ECG-like signals from the fetal heart. Patients come from across the country and Canada to the biomagnetism laboratory for assessment.
The research team hypothesizes that developing an integrated pharmacodynamics model of pregnancy antiarrhythmic drug therapy incorporating and informed by electrophysiologic, pharmacologic, pharmacogenomic, and clinical data will, in the future, make treatment with drugs during pregnancy safer for women in Wisconsin and across the country by providing specific dosing ranges based on response to therapy.
This project will positively impact health and/or health equity in Wisconsin by developing new clinical technologies to improve pregnancy care and prevent stillbirth. Stillbirth rates for minority women of color are almost double those of the Caucasian population. While arrhythmias have a symmetric distribution, pharmacogenomic variants that alter drug metabolism are more common in minority populations.