title: [The thalidomide experience: review of its effects 50 years later].
abstract: This year is the 50(th) anniversary of the discovery that the drug thalidomide causes birth defects and should therefore be considered as a teratogen. However, despite the existence of several other drugs that are also human teratogens, thalidomide continues to cause concern among health professionals as well as the general population. The objectives of this article are to make a short historical review of the discovery that this drug severely alters the embryo development, the critical period of gestation and the identification of the real effect of thalidomide. For the first time an analysis is provided to identify the type of malformations for which thalidomide really increases the risk. The proportions of the different types of malformations groups from the series of patients considered to be affected by thalidomide from the literature were compared with the proportions of the same malformations groups in non-exposed infants from the Spanish Collaborative Study of Congenital Malformation (ECEMC). The aim of the analysis was to calculate the relative frequencies of 13 groups of malformations observed in series of patients exposed to thalidomide, by comparison with the same groups of defects in 1,491 patients with limb malformations from the ECEMC consecutive newborn infants, non-exposed to thalidomide. The results showed that the groups with the most classical limb malformations attributed to thalidomide (phocomelia, thumb absence/hypoplasia) had a significantly very higher frequency in exposed cases than in the ECEMC's cases. However, cases presenting with only lower limb malformations were 3 times less frequent in thalidomide cases than in those of ECEMC. Finally, other groups presented the same frequency as those observed in the ECEMC's cases. The results of the 2 last groups, strongly suggests that they were not due to the effect of thalidomide. In addition to the short historical review of the teratogenicity risk of thalidomide, and their new therapeutic properties, it is documented that, as it happens with all other currently known human teratogens, not all malformations observed in infants prenatally exposed to thalidomide were caused by this drug. Finally, it is discussed the paradox that the «feared» thalidomide drug causing a great human drama affecting about 10,000 infants has led to a formidable contribution to the scientific knowledge, and large range of therapeutic applications.
authors.affiliation: Departamento de Farmacología, Facultad de Medicina, Universidad Complutense de Madrid. Madrid, España. mlmartinez.frias@isciii.es
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Martínez-Frías
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000266:history; D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000266:history / Q000494:pharmacology; D004480:Ectromelia / Q000139:chemically induced* / Q000266:history; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D049673:History, 20th Century; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000737:chemistry / Q000266:history; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000266:history / Q000494:pharmacology; D011247:Pregnancy; D013723:Teratogens / Q000266:history / Q000494:pharmacology*; D013792:Thalidomide / Q000009:adverse effects* / Q000737:chemistry / Q000266:history
chemical_list: D020533:Angiogenesis Inhibitors; D006993:Hypnotics and Sedatives; D007166:Immunosuppressive Agents; D013723:Teratogens; D013792:Thalidomide