Thalidomide was suspected of causing the once rare forms of skeletal limb defects in babies primarily due to the results of several cross-sectional and case-control studies conducted in the early 1960s. As summarized by Leck (1979), three such epidemiologic studies had led to conclusive evidence implicating thalidomide as the teratogen responsible for the most devastating birth defects tragedy of the last century.

In Germany, Lenz and Knapp (1962) obtained evidence of thalidomide taken by mothers during pregnancy in 41 out of 46 phocomelia or amelia cases. This high percentage led them to accept the hypothesis that the drug and the defects were causally related, despite the fact that a case-control study was not actually carried out. Weicher et al. (1962) on the other hand conducted a more extensive epidemiologic study, in which they retrospectively contrasted the exposure rates between 50 case of birth deformities and 90 controls. Weicher et al. found 34 of the cases and only 2 of the controls with the mother taking thalidomide in pregnancy. Meanwhile, in Australia, McBride (1963) observed 41 babies born to women prescribed thalidomide at the hospital during the first 16 weeks of pregnancy. Of these thalidomide user cases, 34% (14 cases) had skeletal limb defects. This percentage is significantly greater than the 0.24% (52 cases) seen retrospectively in the 21,485 other babies (i.e., those with non-user mothers) born between 1957 and 1962 in the same Sydney area.