Thalidomide Embryopathy Health Article

Definition

The term thalidomide embryopathy (TE) is used to describe a specific pattern of birth defects caused by a mother's use of the drug thalidomide during her pregnancy. The drug is able to cross the placenta and reaches the developing embryo, causing parts of the embryo's body to form abnormally. The most common birth defects observed in infants with TE include structural abnormalities of the arms, legs, ears, and eyes, although other organs may also be affected. The most harmful time to use thalidomide is during the first three to six weeks of pregnancy.

Description

Thalidomide was originally marketed in Germany in October 1957 as a safe, inexpensive, and effective sedative. Its use was later expanded to include treatment of insomnia, anxiety, upset stomach, and morning sickness during pregnancy. Prior to its release onto the market, thalidomide had been tested in rodents and had been deemed safe; human studies were not performed. It was made available in at least 46 countries. However, the drug was never approved for marketing in the United States due to concerns about the medication's potential side effects, one of which, peripheral neuropathy, was first recognized in 1960. Symptoms of peripheral neuropathy, or nerve damage, include burning, numbness, or tingling in the arms, legs, hands, or feet. The damage may not be reversible even after stopping the medication. Early in the 1960s, an increased number of infants with severe abnormalities of the arms and legs were observed in Germany, Great Britain, and Australia. Once it became clear that the mothers of these infants had taken thalidomide while pregnant, a connection was made between the drug and the birth defects. In 1961, the drug was withdrawn from the worldwide market. It has since become known as a powerful human teratogen, a drug or other agent proven to cause birth defects. The experience with thalidomide also led to greater overall attention to the potential effects of drug and other environmental exposures on a developing fetus, and to improved legislation regarding testing requirements before a new drug is released to the public.

Although the use of thalidomide decreased dramatically after 1961, it remained available in the United States and other countries on a "compassionate use" basis: physicians could obtain special permission to treat ill patients they believed could significantly benefit from the drug. Over time, it became clear that thalidomide is effective in the treatment of a number of medical conditions. This surprising resurgence of thalidomide has, in turn, led to concern over the possibility of another generation of children born with thalidomide-related birth defects. The manufacturer of thalidomide, Celgene Corporation, is working in close partnership with the U.S. Food and Drug Administration (FDA) to tightly control the use of the drug and to maintain close follow-up on all individuals to whom it is prescribed. The drug is marketed under the brand name Thalomid.

Limb abnormalities are the most readily identified, and most well known, type of birth defect caused by prenatal thalidomide exposure. However, other types of physical problems may also occur in an exposed infant. In addition to limb abnormalities, TE may include abnormalities of the ears, eyes, kidneys, heart, intestinal tract, and nervous system. Mental retardation has been reported in approximately 5% of older individuals with TE.

Genetic profile

TE is not an inherited medical condition. However, thalidomide is a known teratogen. Therefore, women who use this medication while pregnant are at risk of having infants with physical, and possibly mental, birth defects. A woman who does not use thalidomide during pregnancy cannot have a child with TE. As of 2001, it is still not entirely clear how thalidomide causes birth defects. One hypothesis is that the drug prevents formation of new blood vessels. Research is continuing in this area.