Medical College of Wisconsin

Dr. Michael E. Mitchell, Primary Investigator
Milwaukee, WI
Research Project: Non-Invasive Indicator of Fetal Well Being for Unborn Infants with Congenital Heart Disease
Amount funded: $40,000 (Year 1)

Early and accurate non-invasive tools to monitor fetal well-being prior to the development of a critical fetal illness are urgently needed in perinatal medicine and particularly important in the unborn infant with congenital heart disease. Currently, the only methods available for the monitoring of fetal well being are indirect and late measurements such as heart rate monitoring or biophysical profile, which alert physicians to problems after they have developed. There is a compelling need to develop a sensitive and specific non-invasive test to assess the fetal well being in order to improve pregnancy outcomes for children with congenital heart disease.

Fragmented cell free fetal DNA (cff-DNA) circulates in maternal plasma at detectable levels from week 5 onward. Cost-effective detection and precise quantification of circulating fetal DNA from maternal plasma at the percent level (1% or greater) is now possible. Our preliminary work suggests that acute changes in fetal well being in unborn infants with congenital heart disease may result in dramatically decreased levels of circulating cff-DNA in maternal plasma. These data suggest that changes from baseline levels of circulating cff-DNA may be an early indicator of decreased fetal metabolism, development of fetal compromise and subsequent fetal loss. The goal of this project is to conduct a longitudinal prospective study to analyze the relationship of circulating cff-DNA in maternal plasma with the well being of fetuses with congenital heart disease. Studies will be done in both a fetal lamb model of induced fetal distress and in pregnant women with antenatally diagnosed fetal congenital heart disease who are at increased risk of fetal loss.