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

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

Affiliations
  • 1Korean Mothersafe Counselling Center, Pregnancy & Breastfeeding Medicines Information Center, Seoul, Korea
  • 2Department of Obstetrics and Gynecology, Inje University Ilsan Paik Hospital, Goyang, Korea
  • 3Department of Obstetrics and Gynecology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea
  • 4Department of Obstetrics and Gynecology, National Medical Center, Seoul, Korea
  • 5Clinical Research Center, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
  • 6Motherisk Israel and Adelson faculty of Medicine, Ariel University, Ariel, Israel

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.

Keyword

Isotretinoin; Congenital malformations; Pregnancy; Meta-analysis; Systematic review

Figure

  • Fig. 1 Database flow chart for meta-analysis.

  • 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 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 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.


Cited by  1 articles

Pregnancy and neonatal outcomes after periconceptional exposure to isotretinoin in Koreans
Eun-Hwan Cha, NaeRy Kim, Ho-Seok Kwak, Hae Ji Han, Sung Hong Joo, June-Seek Choi, Kyoung-Chul Chun, Young-Ah Kim, Jae-Whoan Koh, Jung Yeol Han
Obstet Gynecol Sci. 2022;65(2):166-175.    doi: 10.5468/ogs.21354.


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