The role of pharmacoepidemiology in pharmacovigilance: rational drug use in pregnancy.

The most important objective of the Hungarian Case-Control Surveillance of Congenital Abnormalities is the postmarketing surveillance of the teratogenic effects of drugs. This dataset includes 22,865 pregnant women who had offspring with congenital abnormalities and 38,151 pregnant women who had healthy babies between 1980 and 1996. Their case-control analysis is appropriate to assess the risks and benefits of drug treatments during pregnancy. Of about 4000 drugs used in Hungary, 35 seemed to be human teratogens. Only a small proportion (about 1%) of congenital abnormalities is traceable to teratogenic drugs in humans. Hungarian studies were not able to confirm the teratogenicity of tetracyclines (doxycycline) and some other drugs, but indicated the beneficial effect of clotrimazole in the prevention of undescended testis related to preterm birth. Periconceptional multivitamin/folic acid supplementation can reduce the first occurrence of neural-tube defects, oral clefts, cardiovascular malformations, and urinary tract defects. At present the teratogenicity of drugs is exaggerated and the benefits of drug treatment during pregnancy are underestimated. This unbalanced risk-benefit assessment initiated disadvantageous decisions, e.g. planned pregnancies are terminated because of the supposed false teratogenic risk of drugs; pregnant women with acute or chronic diseases are not treated adequately and it causes exacerbation of the illness or fetal complications; the necessary drug treatments are connected with a permanent psychological stress. In conclusion, the anxiety and fear created by the notion that nearly all drugs cause congenital abnormalities is more harmful than the effect of proven human teratogenic drugs themselves.