Research Explores Environmental Causes of Birth Defects

Amidst the joy of bringing a new child into the world lurks a lingering fear of every new parent: Is my baby healthy? In fact, each year in America, approximately 150,000 infants - about 1 in 28 - are born with a birth defect, according to the March of Dimes. A birth defect is defined as an abnormal structure, function or metabolism (body chemistry) that results in physical or mental disability, or is fatal. Birth defects are the leading cause of death in the first year of life.

Scientists believe most birth defects are caused by a complex mix that could include such factors as genetic predisposition, environmental exposure and lifestyle choices. Yet, in 60% to 70% of cases, the precise cause of the birth defect is unknown. Research being conducted at the Medical College of Wisconsin may someday help determine some of those causes.

One of the leading researchers in the field is Ronald Hines, PhD, Medical College of Wisconsin Professor of Pediatrics and Associate Director of the Children's Research Institute. His work involves investigating whether genetic predisposition and exposure to certain environmental agents could lead to birth defects. Along with D. Gail McCarver, MD, Associate Professor of Pediatrics in Neonatology (Neonatal-Perinatal Medicine), he is co-director of the Birth Defects Research Center, a joint venture of the Medical College and Children's Hospital. Dr. McCarver serves as a member of the Scientific Advisory and Policy Committee for the Children's Research Institute.

"In an approximate $4 million study funded by the National Institute of Environmental Health Sciences, work being conducted by Dr. McCarver is investigating genetic susceptibility of pregnant women to environmental exposure, specifically to volatile organic compounds such as methanol, toluene and trichloroethylene," says Dr. Hines. "She is concerned about chronic exposure to these toxic substances, not necessarily high or peak levels at a certain times during pregnancy." Residents of southeastern Wisconsin are exposed to relatively high levels of all three compounds, Dr. Hines notes. He says many factors are involved, including a high concentration of relatively low-level emitters, the type of manufacturing historically present in the area, and weather patterns relative to manufacturing sites in northern Illinois.

Found in Common Products
Methanol, also known as wood alcohol, is found in fertilizer and occurs in decaying organic material. It's added to gasoline, paint strippers, aerosol spray paints, wall paints, carburetor cleaners, and windshield washer products. Toluene is found everywhere in the environment and in a vast range of products, including gasoline, plastics, electronics, sweeteners, detergents, furniture, and pharmaceuticals. One of the major sources of exposure to toluene is cigarette smoke. Trichloroethylene, or TCE, can be found in such consumer products as aerosol paint and paint removers, automotive sealants, certain laundry and dry cleaning products, vinyl flooring, and correction fluid.

Thanks to the mapping of the human genome, scientists now have a better tool to understand variation in the genes encoding the enzymes responsible for the transformation of chemicals in the body - a process that is beneficial in many cases, but damaging in others. With a better understanding of these genes and the role their encoded products play in biotransformation, researchers like Dr. Hines also can study when certain enzymes become active in this transformation process during development.

Although the cause of most birth defects is still not determined, scientists do know ingestion of or exposure to certain compounds can affect developing fetuses. "We know toluene can affect the fetus in ways similar to alcohol," he says. "Alcohol, toluene, lead, mercury (found in fish), arsenic, cadmium and sidestream cigarette smoke can promote structural and functional birth defects, or affect the overall growth of the fetus."

Learning disabilities that show up in children may also stem from exposure to some chemicals during prenatal development, "but it's often difficult to assess if or when exposure occurred, because it's based on the parent's recall long after the actual exposure," Dr. Hines adds. "That's one of the reasons we embarked on this research, so we could quantify exposure with more accuracy."

To help track the link between exposure and birth defects, Dr. McCarver and her colleagues collect and analyze blood and urine samples from women volunteers during pregnancy for volatile organic compounds. They also use questionnaires that examine alcohol consumption during pregnancy and examine the genes encoding the enzymes responsible for the transformation of these compounds in both the child and the mother.

Environmental causes alone are thought to be linked to between 2% and 3% of birth defects. However, the combination of environmental exposure and genetic susceptibility is probably linked to between 20% and 30% of birth defects, Dr. Hines says.

Birth defects thought to be linked to environmental causes include cardiac defects and other structural defects such as cleft lip and palate, as well as reproductive defects.

National Children's Study
Recently, the Medical College of Wisconsin and the University of Wisconsin-Madison were selected as one of the first groups to participate in the largest long-term study ever conducted in the United States of the environment's effects on human health and development. The goal of the study is to improve the health and well-being of children.

The study calls for recruiting women of childbearing age and following their offspring from preconception or during the first or second trimester until age 21. The National Children's Study eventually plans on enrolling 100,000 children nationwide, including 1,200 children from Waukesha County. The five-year, $16.2 million contract will be led by co-principal investigators Christine E. Cronk, ScD, Associate Professor of Pediatrics at the Medical College, and Maureen Durkin, PhD, DrPH, Associate Professor of Population Health Sciences at UW-Madison.

Meantime, until the study's results are known, are there safe levels of exposure to these chemical compounds? Yes, Dr. Hines says, noting "the dose makes the poison." Low levels of many toxic compounds are usually not harmful. Could some have a cumulative effect over time that is hazardous? "Yes," he says, "bioaccumulation is a possibility. It can vary according to the chemical and vary among populations."

In addition to genetic predisposition and environmental exposure, lifestyle choices can also result in exposure to compounds that increase the risk of birth defects in pregnant women. These include alcohol, some over-the-counter medicines, and certain foods and food additives.

For women who are pregnant or plan to be, Dr. Hines recommends a common sense approach - avoid alcohol and cigarette smoke, and don't use over-the-counter medications without consulting a physician. As for those volatile organic compounds - methanol, toluene and trichloroethylene - he recommends pregnant women avoid contact with products known to contain them. "If at all possible, don't pump gasoline when you're pregnant, for example, and avoid direct contact with pesticides and paint removers."

Dr. Hines recommends with women with questions about environmental hazards call the Froedtert & The Medical College of Wisconsin Fetal Concerns Program (414-805-4776) or the Poison Control Center (1-800-222-1222). He also recommends they visit the March of Dimes web site.

Barbara Abel
HealthLink Contributing Writer

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.