Reproductive results associated with misoprostol and other substances utilized for interruption of pregnancy

Abstract

Sir, In Brazil, the main use of misoprostol is to induce abortion, even though this practice is illegal. There are only two situations in which abortion is not a criminal act: when the pregnant woman’s life is at risk and when pregnancy has resulted from rape or incest. The use of misoprostol as an abortion-inducing substance may lead to a situation in which the pregnancy is not lost [1], thereby generating anxiety regarding the risk to the fetus and the pregnant woman. Case and case-control studies have suggested that the use of misoprostol in unsuccessful abortions may be associated with congenital malformations, for example in children with limb reduction defects and/or Mobius Sequence [2, 3] and anomalies of the central nervous system [4]. However, in one cohort study correlating the use of misoprostol with teratogenic effects, no difference was found in the rates of congenital malformations between 86 cases of exposure to misoprostol during pregnancy and 86 cases without exposure to this drug [5]. In this letter, we report an association observed between the use of misoprostol during the first trimester of pregnancy and congenital malformation of the child or fetal death, from the Brazilian Study of Gestational Diabetes, a cohort of women attending prenatal services at public hospitals in six Brazilian cities, between February 1991 and June 1995. Data relating to the use of misoprostol and other substances with the potential to induce abortion during the pregnancy (obtained during the first phase of the cohort) and data relating to the neonate’s state of health (obtained during the third phase of the cohort) were analyzed. Interviews were held with 5,564 women aged 20 years or over who were between their 21st week and 28th week of pregnancy (Table 1). Information on the use of substances with the potential to induce abortion was obtained from the interviews with the pregnant women. The diagnosis of congenital malformation was made by the attending doctor and entered in the pregnant woman’s records. The present analysis included the pregnant women who were followed through to the third phase of the cohort, thus resulting in a sample of 4,862 women (87.4% of the initial sample). Use of substances with the potential to induce abortion was reported by 707 pregnant women (14.6%); of these, 120 declared that they had used misoprostol during the first trimester of pregnancy. More cases of congenital malformation were found in the group exposed to misoprostol than in the unexposed group (RR=2.39), with threshold significance (95% CI 0.99–5.80) (Table 2). Using a logistic regression model that included the variables of skin color, marital situation and research center, the risk increased slightly (RR=2.61; 95% CI 1.01–6.75). The malformations that occurred in the sample of pregnant women who made use of misoprostol were: syndactyly, twisted foot, meningomyelocele, microcephaly and fingernail defects. A significant difference was also observed between the women with and without exposure to misoprostol, in relation to fetal death (RR=2.63; 95% CI 1.17–5.88 (Table 3). After adjustment using the regression model, the relative risk increased to 3.21 (95% CI 1.34–7.68). The data available in the literature on the effects on the fetus and child mostly come from case reports and case-control studies of limited sample size. Moreover, they do not include adverse events other than the congenital malformations that are important for the outcome of the pregnancy. The prospective populationbased study that included a cohort of 86 cases and 86 externally selected controls did not have sufficient T. da Silva Dal Pizzol (&) University of Passo Fundo, Rua Paissandu, 1973, apto 604, Passo Fundo, Rio Grande do Sul, 99010-102, Brasil E-mail: tatiane@saude.upf.tche.br