(B-280) Risk of Newborn Congenital Abnormalities after Exposure to Misoprostol during Pregnancy: A Systematic Review and Meta-Analysis

Background: Misoprostol is a synthetic prostaglandin medication used to prevent and treat stomach and duodenal ulcers. Nonetheless, prenatal exposure to misoprostol is contraindicated due to its association with an increased risk of birth defects, abortion, premature labor or uterine rupture when administered to pregnant women.

Objectives: This study aimed to assess the embryotoxic risk associated with misoprostol exposure during pregnancy.

Methods: We performed a systematic search in the following databases: Medline, Embase, and Cochrane Central Register of Controlled Trials from inception to October 2024. The analysis included randomized controlled trials and observational studies that compared misoprostol to placebo in female patients who received therapy during pregnancy. We excluded patients who received therapy with the intention of abortion induction, and studies that lacked a comparator arm. The primary safety outcome was the occurrence of newborn congenital abnormalities in pregnant women who received misoprostol. Four reviewers independently screened and reviewed each study in pairs to assess its quality. Disagreement was resolved by consensus. Relevant information was were recorded in an Excel spreadsheet and analyzed using Comprehensive Meta-Analysis Software. The analysis utilized the odds ratios (OR) with the 95% Confidence Internal (CI) to assess the risk across individual studies, which were combined using meta-analysis.

Results: Six studies were included in the final analysis with of 6,499 pregnant females. The studies were conducted in the following countries: Brazil (3 studies), Turkey, Pakistan, and France. All included studies suggested a potential increase in the risk of congenital abnormalities, with OR range from 1.22 to 6.05. The pooled OR for newborn congenital abnormalities was estimated to be 1.88 (95% CI, 1.23 to 2.88) indicating a slight increase in the risk of developing congenital abnormalities among newborns of women who had been exposed to misoprostol during pregnancy.

Conclusions: The findings confirm an increased risk of newborn congenital abnormalities following exposure to misoprostol during pregnancy, as indicated in the product labeling. However, the significant safety concern warrants further investigations into the need of developing additional risk minimization measures.