Use of isotretinoin among girls and women of childbearing age and occurrence of isotretinoin-exposed pregnancies in Germany: A population-based study.

Background: Exposure to isotretinoin during pregnancy must be avoided due to its teratogenicity, but real-world data on its use are scarce. We aimed to describe (i) isotretinoin use in women of childbearing age in Germany; (ii) the occurrence of isotretinoin-exposed pregnancies; and (iii) malformations among children exposed in utero. Methods and findings: Using observational data from the German Pharmacoepidemiological Research Database (GePaRD, claims data from approximately 20% of the German population), we conducted annual cross-sectional analyses to determine age-standardized prevalence of isotretinoin use between 2004 and 2019 among girls and women aged 13 to 49 years. In cohort analyses, we estimated the number of exposed pregnancies by assessing whether there was prescription supply overlapping the beginning of pregnancy (estimated supply was varied in sensitivity analyses) or a dispensation within the first 8 weeks of pregnancy. Data of live-born children classified as exposed in a critical period according to these criteria were reviewed to assess the presence of congenital malformations. The age-standardized prevalence of isotretinoin use per 1,000 girls and women increased from 1.20 (95% confidence interval [CI]: 1.16, 1.24) in 2004 to 1.96 (95% CI: 1.92, 2.01) in 2019. In the base case analysis, we identified 178 pregnancies exposed to isotretinoin, with the number per year doubling during the study period, and at least 45% of exposed pregnancies ended in an induced abortion. In sensitivity analyses, the number of exposed pregnancies ranged between 172 and 375. Among live-born children, 6 had major congenital malformations. The main limitation of this study was the lack of information on the prescribed dose, i.e., the supply had to be estimated based on the dispensed amount of isotretinoin. Conclusions: Isotretinoin use among girls and women of childbearing age increased in Germany between 2004 and 2019, and there was a considerable number of pregnancies likely exposed to isotretinoin in a critical period. This highlights the importance of monitoring compliance with the existing risk minimization measures for isotretinoin in Germany. Jonas Reinold and colleagues investigate how isotretinoin use has changed over a 15 year period in Germany and the potential for in-utero exposure. Author summary: Why was this study done?: Systemic (oral) isotretinoin is used in the treatment of moderate to severe acne. Given that isotretinoin is one of the strongest human teratogens known today, it is important to monitor the use of isotretinoin in girls and women of childbearing age as well as the occurrence of pregnancies exposed to this drug. There is a lack of population-based studies addressing these research questions. What did the researchers do and find?: Using a database covering 20% of the German population, we conducted cross-sectional analyses to assess the prevalence of isotretinoin use between 2004 and 2019 in girls and women of childbearing age. We found that the age-standardized prevalence of isotretinoin use increased from 1.20 to 1.96 per 1,000 girls/women during this period. In cohort analyses, we estimated the number of pregnancies likely exposed to isotretinoin in a critical period. In the base case analysis, we identified 178 of such pregnancies. Sensitivity analyses considering the recommended one-month washout period suggested that there could have been additional pregnancies exposed to isotretinoin because they started before the end of the washout period. What do these findings mean?: Isotretinoin use among girls and women of childbearing age increased in Germany between 2004 and 2019, and there were a considerable number of pregnancies likely exposed to isotretinoin in a critical period. This highlights the importance of monitoring compliance with the existing risk minimization measures for isotretinoin in Germany. It also seems important to increase awareness regarding the component of the pregnancy prevention program that recommends contraception also in the month after treatment cessation. The main limitation of this study was the lack of information on the prescribed dose of isotretinoin. We therefore estimated the dose based on the dispensed amount of isotretinoin and varied the underlying assumptions. [ABSTRACT FROM AUTHOR]

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