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Pregnancy Exposure Registries

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Abstract

Scientifically valid data on the safety of drug use during pregnancy are a significant public health need. Data are rarely available on the fetal effects of in utero exposure in human pregnancies, particularly when a drug is first marketed. Data from animal reproductive toxicology studies, which function as a screen for potential human teratogenicity, are usually all that is available in a product’s labelling. For practising clinicians, translating known animal risks into an accurate assessment of teratogenic risks in their patients is very difficult, if not impossible. Without human data on the effects of in utero drug exposure, it is difficult for physicians and other healthcare providers (e.g. genetic counsellors) to adequately counsel patients about fetal risks. Therefore, a pregnant woman may decide to unnecessarily terminate a wanted pregnancy or forego needed drug therapy. In spite of the lack of data on the safety of drug use during human pregnancies, pregnant women are exposed to drugs either as prescribed therapy or inadvertently before pregnancy is known (over one-half of pregnancies are unplanned). Because little is known about the teratogenic potential of a drug in humans before marketing, post-marketing surveillance of drug use in pregnancy is critical to the detection of drug-induced fetal effects. The existing passive mechanism of spontaneous reporting of adverse drug effects is inadequate to routinely detect drug-induced fetal risks or lack of such risks. Therefore, post-marketing pregnancy exposure registries are being increasingly used to proactively monitor for major fetal effects and to describe margins of safety associated with drug exposure during pregnancy. However, differing methodological rigour has been applied to the development of pregnancy exposure registries. It is important that all pregnancy registries develop epidemiologically sound written study protocols a priori. It is only through the use of rigourous methodology and procedures that data from pregnancy exposure registries will withstand scientific scrutiny. Successful recruitment of an adequate number of exposed pregnancies, aggressive follow-up, and complete and accurate ascertainment of pregnancy outcome are critical attributes of a well-designed registry.

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Acknowledgments

The authors have received no sources of funding that were used to assist in producing this article. The authors have no potential conflicts of interest that may be directly relevant to the contents of this manuscript. This article is based on the August 2002 US FDA Guidance for Industry: Establishing Pregnancy Exposure Registries, which represents the FDA’s thinking on this topic at that time. For the full text of the guidance see {rshttp://www.fda.gov/cder/guidance/3626fnl.pdf. Any deviations from that guidance contained in this article are minor and included for clarification and should not be construed as representing changes in the policies or position of the US FDA.

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Authors and Affiliations

  1. Pregnancy Labeling Task Force, HFD-020, Center for Drug Evaluation and Research, US Food and Drug Administration, 5600 Fishers Lane, Rockville, Maryland, 20874, USA

    Dianne L. Kennedy, Kathleen Uhl & Sandra L. Kweder

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  1. Dianne L. Kennedy
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  2. Kathleen Uhl
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  3. Sandra L. Kweder
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Correspondence to Dianne L. Kennedy.

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Kennedy, D.L., Uhl, K. & Kweder, S.L. Pregnancy Exposure Registries. Drug-Safety 27, 215–228 (2004). https://doi.org/10.2165/00002018-200427040-00001

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