How Did Research on Medication Safety in Pregnancy Define, Develop and Advance the Field of Pharmacoepidemiology?

Abstract

According to the Centers for Disease Control and Prevention, 1 in the United States, 90% of pregnant women take medication during pregnancy. Nearly every pregnant woman faces the decision about whether to take medication and requires information to determine how to best protect her own health and the health of the fetus. Guidance on the safety of medications utilized during pregnancy was once scarce, and the consequences of this lack of information were sometimes devastating. The infamous "thalidomide disaster" in 1961 is one example. Thalidomide was marketed in Europe as a mild hypnotic and after its release, a dramatic increase was seen in the frequency of a severe and previously rare birth defect known as phocomelia, the absence of limbs or parts of limbs. 2 Epidemiologic studies associated its cause with in utero exposure to thalidomide, 3e9 which led to regulatory changes in both the United States and Europe. In the United Kingdom, the Committee on the Safety of Medicines was established in 1968, and in the United States the Kefauver-Harris Amendments strengthened the requirements for the proof of drug safety. These legislative changes led to what has become the current drug-approval process. The field of pharmacoepidemiology, the study of the use of and the effects of drugs in large numbers of people, 10,11 emerged in response to the need for research on the impact of medication usage on the public's health. The advent of pharmacoepidemiology followed a long period during which information regarding medication safety was provided solely by preapproval clinical trials, and medication use in clinical practice settings was not incorporated into regulatory direction. The reliance on preapproval clinical studies, which generally excluded large proportions of the population, such as pregnant women, resulted in inadequate safety data as study-inclusion criteria limited generalizability. Even with the expanded inclusion of pregnant women in clinical research, safety data are limited as the small samples observed are often inadequate for the detection of rare outcomes. Today, large-scale pharmacoepidemiologic studies spanning continents guide the World Health Organization's recommendations on the safe use of medications in pregnancy, such as the use of the highly effective artemisinin antimalarial treatments previously precluded from use in pregnant women based solely on embryotoxicity studies in animals. 12 We chose to introduce the field of pharmacoepidemiology to the readers of Clinical Therapeutics with two papers that illustrate the development of the field through seminal research on medication safety in pregnancy. The historical importance of early studies on in utero exposure to medications and adverse pregnancy and birth outcomes is described, as is the development of new and evolving data sources and methods that can be applied to other research areas as well. Multiple robust administrative data sources exist for use in performing population-based studies in pregnant women, with linkage to outcomes among t...