Pharmacological Safety in Pregnancy: A Systematic Review On the Use of Potentially Teratogenic Drugs

Abstract

Objective: To assess the prevalence of potentially teratogenic drug utilization by pregnant women: overall and in the periconceptional period. Methods: The electronic database PubMed/Medline was searched for the following keywords: «pharmacoepidemiology», «pregnancy», «drug use», «safety», «pregnancy risk category», «fetal risk», «teratogen». The systematic analysis included 28 studies published in English from January 2006 to 23 December 2015. Results. The review shows that the study designs and the choices for data analysis and presentation of results differ largely across published studies. In the USA and Canada, measured rates of maternal use of contraindicated drugs (FDA category X) during pregnancy ranged from 2.4% to 5.3% (1.1–5.0% in the first trimester).The use of drugs with positive evidence of risk (FDA category D) ranged from 5.8% to 39.6% (2.7–6.0%). In European countries, proportions of women using drugs of risk categories X and D ranged from 1.0% to 4.9% (0.31–3.2%) and from 2.0% to 5.9% (1.6–3.7%), respectively. In developing countries, respective proportions of women ranged within 0.2–2.1% and 1.9–11.4%. In early pregnancy (the first trimester), the proportion of women taking potentially teratogenic drugs was high if compared with the second and third trimesters. The use of contraindicated drugs during pregnancy fastly decreases compared with the period before conception. Although the reduction of use of drugs with positive evidence of risk is less marked, possibly, with relation of their efficacy for the treatment of chronic conditions. On the base of analyzed studies, the reference list of potentially teratogenic drugs was formed. Conclusion. The results of published literature confirm differences in study methods that make it difficult to compare the application of potentially teratogenic drugs in pregnancy. The fundamental challenge remains an insufficiency or lack of available information on the evidence of risk to fetus cuased by the drugs that are most widely used in pregnancy.