The rates of major malformations after gestational exposure to isotretinoin: a systematic review and meta-analysis

Obstet Gynecol Sci. 2021 Jul;64(4):364-373. doi: 10.5468/ogs.20373. Epub 2021 Mar 17.


Objective: Isotretinoin is among the most notorious human teratogens, documented originally as causing up to 30% of malformations. This systematic review and meta-analysis aimed to evaluate the rates of major malformation (MM) among isotretinoin-exposed pregnant women over the years through a systematic review and meta-analysis.

Methods: Eligible studies were searched and identified using various databases. Single-arm meta-analysis and meta-analysis of odd ratios among controlled studies were performed using Review Manager version 5.3.

Results: Ten eligible studies that combined 2,783 isotretinoin-exposed women were included in our study. The rate of MM weighted for the sample size was 15%. Three studies that included an unexposed comparison group were eligible for the meta-analysis. The pooled odds ratio of MM for isotretinoin-exposed women was 3.76. After 2006, the pooled odds ratio of MM for isotretinoin exposure was significantly lower at 1.04.

Conclusion: The current rate of MM in isotretinoin-exposed women was substantially lower after 2006.

Keywords: Congenital malformations; Isotretinoin; Meta-analysis; Pregnancy; Systematic review.