Pregnancy registries and spontaneous reports are essential pharmacovigilance tools to evaluate drug safety during pregnancy.
The aim of this study was to evaluate postmarket capture of exposed pregnancies.
Pregnancy registries for drugs and biologics were identified in a systematic review. Through a standardized questionnaire, manufacturers provided information on (1) pregnancy registry enrollment and retention, and (2) worldwide receipt of spontaneous reports for exposed pregnancies. A validated algorithm for live-birth pregnancies allowed calculation of exposure rates per 100,000 live births using claims data.
Among 34 products with a pregnancy registry, median (interquartile range) registry enrollment was 36 pregnancies (5–258) and median spontaneous report capture was 450 pregnancies (89–1192). Products used in >20/100,000 live births had a median registry enrollment of 490 pregnancies and median capture of 1061 spontaneously reported exposed pregnancies. Lower median registry enrollment and spontaneous report capture was observed for products used in 0.5–20/100,000 live births (36 from registries, 541 spontaneous reports) and <0.5/100,000 live births (3 from registries, 41 spontaneous reports). Among 24 registries enrolling ≥10 pregnancies, median capture of pregnancy outcomes (e.g. live birth, spontaneous abortion) was 83.9%. For 19 registries enrolling ≥10 infants, the median proportion of infants achieving protocol-specified follow-up was 89.9% for up to 4 weeks post-birth, 75.0% for 1–5 months, and 57.1% for ≥6 months.
Relatively higher product utilization among pregnant women predicted greater pregnancy registry enrollment. For products rarely used during pregnancy, registry enrollment was low and differences in registry enrollment compared with worldwide spontaneous report receipt were most pronounced. Products with very low utilization levels during pregnancy may require a combination of worldwide pharmacovigilance, pregnancy registries, and additional study methods to achieve adequate surveillance.
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Conflict of interest
Steven Bird, Kate Gelperin, Lockwood Taylor, Leyla Sahin, Hoda Hammad, Susan Andrade, Mohamed Mohamoud, Sengwee Toh, and Christian Hampp have no conflicts of interest to declare that are directly relevant to the content of this study. This study represents the opinions of the authors and not necessarily those of the FDA. Susan Andrade received a grant from Pfizer Inc. unrelated to this study or any drugs evaluated in our study. No other conflicts are present.
Sentinel is funded by the US FDA. No other funding was received for this study.
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Bird, S.T., Gelperin, K., Taylor, L. et al. Enrollment and Retention in 34 United States Pregnancy Registries Contrasted with the Manufacturer’s Capture of Spontaneous Reports for Exposed Pregnancies. Drug Saf 41, 87–94 (2018). https://doi.org/10.1007/s40264-017-0591-5