This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator.
The specific aim of this project is to test whether exposure to volatile environmental toxicants is a risk factor for congenital heart disease. Specifically, we hypothesize that increased exposure to trichloroethylene is associated with an increased risk for congenital heart disease. Further, we hypothesize that risk is conferred by an excess amount of a particular metabolite whose concentrations are determined by two enzymes, alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1), both of which are genetically polymorphic. In the original application, we proposed to measure the compounds of interest in the blood and urine samples of ~7000 pregnant women early in pregnancy. Based on these exposures, we planned to select infants for cardiac ECHOs prior to delivery. Because women in the Milwaukee area, particularly minority women, present for prenatal care late in pregnancy, we have not been successful in recruiting sufficient numbers of patients to have sufficient power. NIH has approved an alteration in study design to a case-control method. As such, we will be enrolling mother-infant pairs with and without congenital heart disease during the first week postpartum. Maternal exposure will be determined using GCMS analysis of maternal blood and urine samples. Fetal exposure will be assessed by measuring these compounds in infant meconium. Maternal and infant genotypes for ADH1C and CYP2E1*D will be determined. Both case and control infants will have cardiac ECHOs.
The specific aims, hypotheses and laboratory methods are unchanged from the original GCRC application. In addition, the level of involvement of the GCRC is unchanged from previous. However, the enrollment will occur at CHW and FMLH, rather than St. Joseph's Hospital and Aurora-Sinai Medical Center. As such, nurses from the pediatric satellite unit will be directly involved in recruitment. Enrollment of an additional 850 (425 mother infant pairs) patients over the next three years is planned.
Showing the most recent 10 out of 380 publications
