Identifying the causes of birth defects

Genetic and environmental factors, or some combination of these factors, can cause birth defects. For many years, March of Dimes grantees have been seeking to identify genes and environmental factors that cause or contribute to birth defects. Understanding the causes of birth defects is a crucial first step towards developing effective ways to prevent or treat them.

Some birth defects are caused by a mutation (change) in a single gene. In 1991, Stephen Warren, PhD, a March of Dimes grantee at Emory University in Atlanta, Georgia, identified the gene that causes fragile X syndrome, the most common inherited cause of mental retardation. Since then, scientists have learned that the mutation 'turns off' the fragile X gene so that it does not make the protein it normally makes.

The fragile X protein appears to regulate the production of a number of proteins that play key roles in the development and functioning of synapses, nerve-cell junctions where impulses are transmitted from one brain cell to another. Loss of the fragile X protein appears to disrupt communication at the synapses, contributing to the learning and behavioral problems associated with fragile X. Discovery of this gene and its workings are now leading to development of treatments. Dr. Warren and other scientists have identified drugs that may help correct synaptic miscommunication, and studies of their effectiveness have recently begun.

Many other birth defects appear to be caused by multiple genes and environmental exposures, adding to the complexity of understanding their causes. For example, March of Dimes grantees have discovered genes that contribute to heart defects and to cleft lip/palate, both of which are among the most common birth defects. However, in most cases, the causes of these defects remain unknown.

Grantees also aim to identify teratogens, environmental exposures that can cause birth defects. For example, in 1973, March of Dimes grantees were the first to link drinking alcohol during pregnancy to a specific pattern of birth defects and mental retardation they called fetal alcohol syndrome. Once a teratogen has been identified, pregnant women often can take steps to avoid it, thereby preventing birth defects.

However, there are more than 83,000 chemicals used in this country, with little information on the effects of most of them during pregnancy. Some grantees are working to provide pregnant women with the information they need to protect their babies. Mara Colleen Duncan, PhD, a grantee at the University of North Carolina at Chapel Hill is developing a novel system to test chemicals used in industry, agriculture, pharmaceuticals and in the home. "Because the elimination of all chemicals is impossible in modern life, the goal should be to identify those chemicals that are most harmful to a fetus and reduce exposure as much as possible," says Dr. Duncan.

Grantees also seek to improve understanding of how genes and environmental exposures may interact and contribute to birth defects, such as cleft lip/palate. A cleft is a gap or opening in a structure. Studies suggest that cigarette smoking during pregnancy may increase the risk of cleft lip/palate. Kathy Kay Svoboda, PhD, a grantee at Baylor College of Dentistry in Dallas, is trying to find out how.

Dr. Svoboda is exploring the possibility that maternal smoking may interfere with certain genes that regulate a specific stage of palate development. The palate begins to form in the earliest weeks of pregnancy from two separate sheets of tissue located along the sides of the tongue. These sheets of tissue grow toward each other, and by the seventh week of pregnancy, begin to fuse. A group of genes called growth factors appear to regulate the fusion of the palate. Dr. Svoboda believes that nicotine may change signals from these growth factors, possibly resulting in incomplete fusion and cleft palate. This study could improve understanding of the underlying causes of cleft lip/palate, and ultimately lead to new ways to prevent or treat this common birth defect.

Most common questions

Can birth defects be prevented?

Most birth defects cannot be prevented because their causes are not known. However, women can take a number of steps before and during pregnancy to reduce their risk [link to Birth Defects fact sheet]. These steps include taking a multivitamin containing 400 micrograms of folic acid daily starting before pregnancy and in early pregnancy. This helps to prevent serious birth defects of the brain and spinal cord, including spina bifida, and may also help prevent heart defects.

What are the most common birth defects?

Congenital heart defects are among the most common birth defects, affecting nearly 1 out of 100 babies in the United States. Some heart defects are mild, while others can be life-threatening. Other common birth defects include cleft lip/palate, Down syndrome and spina bifida (open spine), affecting about 1 in 700, 1 in 800 and 1 in 2,500 babies respectively.

What environmental factors may cause birth defects?

Environmental substances that can contribute to birth defects include alcohol, certain drugs/medications and infections. Women who drink heavily during pregnancy are at risk of having a baby with a pattern of mental and physical birth defects called fetal alcohol syndrome. Because even moderate or light drinking may harm a baby, women who are pregnant or planning pregnancy should not drink any alcohol. They also should avoid illegal drugs such as cocaine and Ecstasy, and ask their health care provider about the safety of any prescription and over-the-counter medications they take. Women also can take steps to help prevent certain infections such as toxoplasmosis and cytomegalovirus that can cause birth defects.

©2013 March of Dimes Foundation. The March of Dimes is a non-profit organization recognized as tax-exempt under Internal Revenue Code section 501(c)(3).