A preventable teratology: isotretinoin

It was concerning to read Henry and colleagues’ study on the poor adherence to pregnancy prevention while women are taking isotretinoin.1

This drug was first licensed in 1982 in the United States, and the first reports on concerns about birth defects occurred within a year. Recommendations from the Teratology Society were first published in 1991.2

The reported risk for isotretinoin embryopathy is 35% for an embryo or fetus that is exposed beyond the 15th day after conception.3 The evidence supports the exposure to the embryo or fetus as the risk, not the use of the medication before conception. The embryopathy is well described, with craniofacial, cardiovascular and central nervous system (CNS) “disruptive” anomaly patterns.

Subnormal intelligence was also reported in a prospectively collected cohort of 31 five-year-old children exposed prenatally, with 19% having a full-scale intelligence quotient (IQ) less than 70 and 28% having an IQ in the 71–85 range.4 The intellectual deficit was not always associated with the finding of other non-CNS major disruptive anomalies: 6 of 10 children with borderline IQ had no identified major anomalies (all the children with severe IQ deficit had other identified major anomalies).

This evidence point is important for the clinical use of ultrasound screening of the exposed embryo or fetus for congenital anomalies and having the conclusion of “no anomalies, therefore not affected.”

Henry and colleagues’ results indicate that a much stronger warning and more counselling are likely required to prevent pregnancy. The teratology messaging needs to start first with the prescribing physician and informed consent from the patient. However, there needs to be stronger oversight from industry and the dispensing pharmacist (who should ask, “What birth control method will you be using while you are taking this medication?”).

Improved knowledge translation about teratology and changes to the prescribing process clearly fit into the Choosing Wisely theme. This type of exposure to the embryo or fetus is entirely preventable. Isotretinoin embryopathy is not an acceptable pregnancy outcome, even when one considers patients’ autonomy and their choice of method for preventing pregnancy.