Exposure to misoprostol and hormones during pregnancy and risk of congenital anomalies Exposição ao misoprostol e hormônios durante a gravidez e risco de anomalia congênita

This study evaluated the association between use of misoprostol and other drugs to induce menstruation, and congenital anomalies. A sample of 4,856 pregnant women 20 years and older were enrolled consecutively in prenatal services in the Unified National Health System, in six Brazilian State capitals. Data on socio-demographics and use of medicines were obtained using an interview from the 21st to 28th week of pregnancy. Other data, including information on delivery and diagnosis of congenital anomalies by the attending neonatal physician were obtained from patient charts. Potential confounders were adjusted by logistic regression. Use of drugs to induce menstruation was reported by 707 women (14.6%), of whom 120 (17%) reported use of misoprostol. After adjusting for the study center, a positive association was observed between misoprostol and congenital anomalies (OR = 2.64; 95%CI: 1.03-6.75); a positive association was also observed for sex hormones (OR = 2.24; 95%CI: 1.06-4.74). The results suggest that the use of misoprostol or sex hormones during pregnancy increases the risk of congenital anomalies. Misoprostol; Hormones; Abnormalities; Women's Health Introduction Misoprostol is a synthetic prostaglandin E1 analogue (PGE1), originally approved for the prevention and treatment of gastric ulcer. Its effectiveness has been investigated in elective medical abortions, labor induction, uterine evacuation following fetal death, postpartum hemorrhage, and cervical maturation, particularly in countries where abortion is legal 1,2. In Brazil, misoprostol has become the most popular recourse for inducing abortion, although this practice is illegal, with only two exceptions: cases in which the pregnant woman’s life is at risk, and pregnancies resulting from rape 3. Use of misoprostol by women seeking treatment at emergency services due to incomplete abortions calls attention to the resulting maternal health risk. Besides misoprostol, drugs containing estrogens and progestagens have been associated with attempted abortions 4,5,6,7. Maternal health risk is not the only problem associated with indiscriminate use of abortive substances. According to controlled clinical trials, medical abortions using misoprostol can lead to failed abortion in more than 10% of cases, requiring the use of a complementary abortive method 1. The single use of misoprostol is significantly less effective than combinations with mifepristone, methotrexate, or tamoxifen, and is not recommended in cases of firsttrimester medical abortion 1,8. In conditions ARTIGO ARTICLE Dal Pizzol TS et al. 1448 Cad. Saúde Pública, Rio de Janeiro, 24(6):1447-1453, jun, 2008 where illegal abortion is commonly performed, without adequate care and at inadequate doses, the use of misoprostol may fail to interrupt the pregnancy, thus generating anxiety concerning risk to the fetus 9. Case reports and case-control studies suggest that the use of misoprostol in unsuccessful abortions can be associated with congenital anomalies, including cranial nerve defects 10 and Möebius sequence 11,12. A systematic review of four case-control studies on the adverse effects of misoprostol on pregnancy outcome showed that prenatal exposure to misoprostol increases the odds of Möebius sequence and terminal transverse limb defects, as compared to unexposed individuals 13. However, the association between misoprostol and other types of congenital anomalies was not adequately elucidated in this analysis, due to interstudy heterogeneity. In this context, the objective of the current study is to evaluate the association between misoprostol and other widely used products for inducing menstruation, and congenital anomalies in fetuses and newborns. A letter with a preliminary analysis of the main findings presented in this article was published previously by the authors 14.