Thalidomide Embryopathy

Prenatal testing usually includes a detailed ultrasound to look at the baby’s body and organs. Ultrasound is useful because it can detect many birth defects, but may not be able to detect all potential problems caused by thalidomide exposure.

In this 1950s, thalidomide was first marketed as a safe sedative with minimal side effects and sold under a variety of drug names. The drug was also combined with other medications to treat a variety of conditions including migraines, asthma, hypertension, and nausea.

Several years after the introduction of thalidomide, doctors began noticing an increase in limb abnormalities in populations where thalidomide was widely used and prescribed. The teratogenic effects of thalidomide were discovered in the 1960s, and subsequently, thalidomide was taken off of the market.

Some children with thalidomide embryopathy experience mental retardation or have behavioral conditions like autism. In a study of 86 patients with thalidomide embryopathy, 4-5% were diagnosed with autism. This is a 50-fold increase over the general population incidence of autism.

Thalidomide is a sedative agent that changes the body’s immune response by reducing the ability of the body to grow new blood vessels. Today, it is used for treatment of several medical conditions, including leprosy, cancer, and complications from HIV infection.

Thalidomide embryopathy is a collection of abnormalities that result in an infant that has been exposed to the drug thalidomide in utero, or during pregnancy, at critical times of development. The most recognizable effects of thalidomide embryopathy are limb reduction defects, including complete absence of limbs. Other abnormalities including cardiac, or heart, defects, gastrointestinal defects, and abnormalities of the external ear are also commonly associated with thalidomide embryopathy.

A teratogen is a substance or agent that can cause birth defects in a developing embryo. Different types of teratogens exist including radiation, chemicals, drugs, and maternal infections.

Thalidomide embryopathy is caused by exposure of a developing fetus to the drug thalidomide at important times during development. Thalidomide is considered a teratogen.

The symptoms, or defects, of thalidomide embryopathy can be divided into four separate groups:

There is a critical period during development in which exposure to thalidomide can cause the most damage to a developing fetus. This time period is between 34-50 days after the last menstrual period, or 20-36 days after fertilization.

If you suspect a pregnancy, miss a period, or have a positive pregnancy test, stop thalidomide use immediately. If you become pregnant during treatment, contact your health care provider right away. They can discuss whether you should continue discontinuing your medication, as well as options for prenatal testing.

There are no studies that suggest the use of thalidomide in men causes an increased risk of birth defects. However, thalidomide is excreted in semen. Therefore, it is recommended that men taking thalidomide use condoms during intercourse, and for 28 days after stopping thalidomide.

To date, there have been studies on pregnancy outcomes in women who only used thalidomide prior to conception. All of the known infants with thalidomide-related birth defects were exposed during the first trimester of pregnancy.

During the 1950s before the effects of thalidomide were known, over 4,000 infants were born with the features of thalidomide embryopathy to mothers who had used the drug. Additionally, in South America where thalidomide is widely prescribed for the treatment of leprosy, 35 infants with thalidomide embryopathy have been reported. Regulatory agencies hope that with the extensive research and education efforts about the effects of thalidomide, they can help prevent another generation of infants with thalidomide embryopathy.

There is at least a 20% risk to have a baby with thalidomide-related birth defects like shortened or missing limbs, missing ears, and other problems like heart defects, gastrointestinal defects, and kidney abnormalities. Currently, there are no clinical trials available on thalidomide exposure in pregnancy.

Despite extensive research on thalidomide, the teratogenic mechanisms, or how the drug causes the symptoms seen in thalidomide embryopathy, are still unclear. Some researchers believe it may involve inhibiting DNA transcription, and as a result, disrupts the creation of blood vessels. However, there is no clear answer on how thalidomide causes the observed symptoms.

Exposure to thalidomide in the first few days of the sensitive period (days 20-24) affected the development of the ears and eyes, while exposure during days 24-31 affected upper limb development, and exposure during days 24-31 affected lower limb development.

Thalidomide is different from other teratogens in the fact that the dosage, or amount, a woman takes does not seem to affect the type or severity of the effects seen. The timing of the exposure, rather than the amount of the exposure seems to be the most significant factor in the type and severity of the defects seen.

The rate of fetal and infant death with maternal thalidomide use is estimated to be as high as 40% or greater. The cause of death is usually due to the severe birth defects caused by thalidomide exposure.

Currently, there are no reports linking thalidomide use and infertility. However, because thalidomide can damage a developing fetus early in a pregnancy, sometimes before a woman recognizes she is pregnant, it is important to use very effective methods of birth control. It is recommended that two different and reliable methods of birth control be used if a woman is taking thalidomide.

Thalidomide embryopathy occurs as a result of exposure to the drug thalidomide, not due to any genetic causes. An individual has to be exposed to thalidomide during the critical period to develop thalidomide embryopathy.

To date, there have been 38 children born to individuals with thalidomide embryopathy. There were no increase in malformation or functional abnormalities in their children.

The use of thalidomide while breastfeeding has not been studied. Based on its chemical properties, it is expected that thalidomide would pass into breast milk, and subsequently, the baby. However, the exact effects of thalidomide on a breastfed infant are unknown. Therefore, it is not recommended that women breastfeed while taking thalidomide.

Thalidomide embryopathy may also be referred to as fetal thalidomide syndrome.

The Thalidomide Society was formed in 1962 by parents of children affected by thalidomide. This group helps to fight for compensation for children and families affected by the drug and provide support. Their website can be found at http://www.thalidomidesociety.org/ . For women who have been exposed to thalidomide during pregnancy, other helpful source is Mother to Baby. http://www.mothertobaby.org They can be reached at 1-866-626-6847

To be safe, it is recommended women stop use of thalidomide one month before trying to conceive to reduce the risk of thalidomide-related birth defects.