Birth defects rates are rising. Major birth defects are found in 3 to 4 of every 100 births, and more defects become evident in the first few months of life. Of 38 birth defects monitored by the Centers for Disease Control and Prevention, the incidence of 27 increased between 1979 and 1989, only 2 decreased, and the rest were essentially unchanged. Whether due to increased reporting or a genuine overall rise, the figures show we are not winning in the effort against birth defects.

In contrast to these gloomy statistics, however, human observational studies have shown how some major defects can be prevented. Among the best known examples is the discovery that the B-vitamin folic acid can help prevent neural tube defects. These defects occur in about 3,000 babies in the U.S. each year, and 1,000 more are electively aborted. Many more probably die by miscarriage.

In the 1950s it was found that a drug called aminopterin, which antagonizes the actions of folic acid, could cause neural tube defects. In addition, neural tube defects tend to cluster where diets are low in the vitamin. Further studies showed that giving folic acid supplements to women helps prevent these defects.

Human studies showed their power again when fetal alcohol syndrome was identified, explaining a combination of facial abnormalities, brain involvement, and growth retardation. Identifying the syndrome meant that these defects could then be prevented.

In a stunning example of this kind of non-invasive, ethical human research, a recent study showed how the incidence of cerebral palsy and mental retardation could be cut dramatically. Researchers studying very low-birth-weight infants in Georgia discovered that if their mothers had a preeclampsia, a syndrome of high blood pressure late in pregnancy, there was much less risk of brain hemorrhages in their babies. It soon became clear that what was protecting the babies was not their mothers’ preeclampsia, but the magnesium sulfate used to treat it. The researchers then examined other cases where magnesium was given during pregnancy and found that, indeed, magnesium could potentially prevent 63 percent of cases of cerebral palsy and 49 percent of cases of mental retardation.

The importance of these findings cannot be overstated. Neural tube defects, fetal alcohol syndrome, cerebral palsy, and mental retardation create life-long challenges for affected individuals and an enormous financial burden for families and for society as a whole. An estimated $90 million was spent in 1990 alone to care for individuals with spina bifida born in the preceding decade.

The Need for Further Human Studies

For most birth defects, genetic and environmental causes are too obscure to permit the planning of prevention programs. A much greater investment in human observational studies is essential.

Congenital heart defects, for example, remain enigmatic. They are found in 5 to 10 of every 1,000 live births, and many more are diagnosed later in life. Most research on heart defects has focused on diagnosis and treatment; little is known about their causes. However, epidemiologic studies have produced important leads. For example, hypoplastic left heart syndrome, a potentially lethal defect, is associated with excess vitamin A exposure, maternal diabetes, and maternal upper respiratory infection during the first trimester.

Cleft palate and cleft lip occur in 0.9 per 1,000 live births in the U.S. As with heart defects, research has focused on surgical treatments rather than causes. However, studies have suggested that both genetic and environmental factors, including smoking, viruses, fever, and medications, play important roles. Chemical exposures in fathers may play a role, too, either through effects on DNA or because chemicals in the father’s clothing affect the mother. A British study of 14,415 children with birth defects found an increased incidence of cleft palate among children of food processors, metal miners and smelters, painters, and motor vehicle operators.

Defects of the arms or legs are known to be caused by genetic factors, as well as by alcohol, legal and illegal drugs, diabetes, and mechanical factors. The most notorious example, thalidomide, was banned in 1962, although it is now finding new uses as a treatment for leprosy and AIDS-related disorders. Epidemiologic and clinical studies suggest that the incidence of limb defects may be reduced by genetic counseling and by limiting drug exposures to the extent possible. However, further human studies are needed to establish additional prevention strategies.

Similarly, defects of the esophagus, stomach, or intestine can result from both genetic and environmental factors, but more study is needed to ascertain their causes.

The Need for a New Research Initiative

Research in heart disease started with large human population studies that showed the role of risk factors, such as high cholesterol levels and smoking. Research then progressed to human clinical intervention trials that proved the value of changing these risk factors. The same research sequence is essential for birth defects. The research advances described above for neural tube defects, fetal alcohol syndrome, cerebral palsy, and mental retardation show the power of population-based research, and make it clear that such studies are needed much more broadly. Sadly, this kind of research has never been fully pursued for most common birth defects.

Birth defects are rarer than heart disease and cancer, however, so research studies must access cases from much larger populations. Existing birth defect registries have limitations, and none is exploited to the extent it could be.

The Centers for Disease Control and Prevention (CDC) also sponsors the Metropolitan Atlanta Congenital Defects Program, which monitors approximately 40,000 births each year through Atlanta-area hospitals. This program provides supplemental data on 300 infants with birth defects and 100 population-based control infants each year, including retrospective interviews on nutrition, substance use, and environmental factors affecting either the mother or father, blood and urine samples from subjects and parents, and a DNA bank. Another CDC program, the Metropolitan Atlanta Developmental Disabilities Surveillance Program, monitors the prevalence of mental retardation, cerebral palsy, and visual and hearing impairment in children between the ages of three and ten.

The California Birth Defects Monitoring Program includes data for about half of all births in California, based on medical records and, if available, information from genetic clinics and chromosome laboratories. It investigates birth defect clusters based on the reports of health officials and community members, but cannot identify clusters for defects occurring at less than ten times the expected rate. If the “expected” rate of a given defect is chronically elevated due to long-standing exposure to a teratogen, current high rates will not be identified as abnormal.

The largest privately operated birth defects registry is the Environmental Birth Defects Registry run by the Association of Birth Defect Children, which investigates birth defect patterns by comparing, for example, defects found in children of Vietnam veterans and children of non-veterans. It includes data on late, difficult-to-diagnose disorders, such as learning disabilities and immune dysfunction. In 1995, the registry had approximately 3,000 cases in its database.

To be useful, birth defect databases need to be large and detailed. Defects that occur only a few times in every 10,000 births present obvious challenges, even for the largest registries. Nonetheless, the dramatic success of recent human population studies demonstrates their potential for reducing the incidence of birth defects. Carefully planned epidemiologic studies should be the highest priority in birth defect research.

Neal D. Barnard, M.D., Beverly Greenwold, M.D., and Suzanne McCaffrey contributed to this report.