Association of Intra-Uterine Exposure to Drugs with Congenital Defects: The Thalidomide Effect

Thalidomide was first synthesised in 1954 and subsequently marketed in 1956. In pre-clinical studies, thalidomide was found to have no apparent side effects. Consequently, it was distributed as an ”over-the-counter” drug and used by pregnant women in order to combat morning sickness. In 1961, a significant increase of congenital limb defects in prenatally-exposed newborns became evident. As a result, thalidomide was withdrawn from the market, due to its severe teratogenic effects. It has been estimated that about 6,000 children were affected with thalidomide embryopathy. The clinical findings of the embryopathy are unusual and characteristic.

Despite the fact that scientists have studied thalidomide over the years, its pharmacokinetics, metabolism and teratogenic mechanisms have never been fully understood.

In recent years, thalidomide has been rediscovered and used for the treatment of several immunological diseases and inflammatory dermatoses, especially lepromatous leprosy. A specific programme (STEPS) to support the appropriate use of thalidomide is being implemented in the United States, in order to avoid thalidomide related birth defects; whereas, on the other hand, an increase of thalidomide embryopathy in newborns from under developed countries has been noted.