Footnotes Contributors: RI, HN, CA, BBM, AK-M, ROO, AKM, ADM and BTO designed the intervention and the study

Brefeldin A ATPase and participated in supervising patient care. RI and HN performed the data analysis. RI wrote the first draft and all participated in data interpretation and provided a critical review of the manuscript. Funding: The study was funded by the Government of Uganda. RI is partly supported by the Wellcome Trust through a Director’s discretionary research funds. Competing interests: None. Ethics approval: Makerere University School of Medicine Research and Ethics Committee. Provenance and peer review: Not commissioned; externally peer reviewed. Data sharing statement: No additional data are available.
Isotretinoin, a vitamin A derivative, is licensed in the European Union (EU) since 1983 and is indicated for systemic treatment of severe acne (such as nodular or conglobate acne

or acne at risk of permanent scarring) in patients resistant to adequate courses of standard therapy with systemic antibacterials and topical therapy.1 The teratogenic potential is an important characteristic of isotretinoin. Animal studies already suggested teratogenic effects in humans and isotretinoin has been contraindicated for use during pregnancy since the very beginning of the marketing authorisation. Despite this contraindication, the first cases of congenital anomalies after isotretinoin use during pregnancy were documented already in 1983.2 As described by Lammer et al3 in 1985, isotretinoin embryopathy consists of craniofacial, cardiac, thymic and central

nervous system defects. They found a relative risk of 26 for this group of major congenital malformations after systemic isotretinoin exposure during some parts of the first 10 weeks after conception.3 Elective termination of pregnancy (ETOP) was decided in more than 50% of exposed pregnancies and 20% of the remaining pregnancies ended in a first trimester spontaneous abortion.3 Reports of congenital anomalies after isotretinoin use accumulated and consequently, in 1988 the marketing authorisation holder of isotretinoin implemented a world-wide Pregnancy Prevention Programme (PPP) to better prevent pregnancies among systemic isotretinoin users.4 The PPP included an educational programme for prescribers and patients including material to be used in counselling women about the need to prevent pregnancy AV-951 while taking isotretinoin. Conditions for prescribing included a negative pregnancy test, the use of reliable contraception and a signed patient consent form.4 In 2003, a review of isotretinoin by the European Medicine Agency (EMA) resulted in a compulsory European harmonised PPP for all isotretinoin containing products.1 The elements of the European wide PPP are listed in box 1. Box 1 Elements of the European Union isotretinoin pregnancy prevention programme 1.