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

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

Eun Jeong Choi  1   2 , NaeRy Kim  1   3 , Ho-Seok Kwak  1 , Hae Ji Han  1 , Kyoung-Chul Chun  2 , Young-Ah Kim  2 , Jae-Whoan Koh  2 , Jung Yeol Han  1   2 , Sung Hong Joo  1   4 , Ji Sung Lee  5 , Gideon Koren  6
Affiliations

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

Eun Jeong Choi et al. Obstet Gynecol Sci. 2021 Jul.

Abstract

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.

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Conflict of interest statement

Conflict of interest

The authors declare no conflict of interest. The authors alone are responsible for the content and writing of this paper.

Figures

Fig. 1
Fig. 1
Database flow chart for meta-analysis.
Fig. 2
Fig. 2
Random-effect single-arm meta-analysis of major malformation prevalence in isotretinoin exposure of the 10 included studies. CI, confidence interval.
Fig. 3
Fig. 3
Meta-analysis of odd ratios: the major congenital malformation in birth of isotretinoin exposed women with subgroup analysis of the studies published before 2006 vs. after. CI, confidence interval.
Fig. 4
Fig. 4
The rate of elective abortion in isotretinoin-exposed pregnancy as per published studies (Lammer et al. [3], Dai et al. [4], Mitchell et al. [19], Cheetham et al. [16], Bérard et al. [15], Garcia-Bournissen et al. [17], Schaefer et al. [20], Shin et al. [10], Henry et al. [18], and MacDonald et al. [22]). The average rate of elective abortion was 42% during 4 weeks before conception and 57% during pregnancy.
See this image and copyright information in PMC

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