Induction of Labor: The Misoprostol Controversy

Alisa B. Goldberg, MD, MPH, Deborah A. Wing, MD

Disclosures

J Midwifery Womens Health. 2003;48(4) 

In This Article

Abstract and Introduction

Abstract

Misoprostol (Cytotec) is safe and effective for induction of labor, although it is not approved by the Food and Drug Administration (FDA) for use in pregnancy. In August 2000, the manufacturer of misoprostol warned against its use in pregnancy because of its abortifacient properties and cited reports of maternal and fetal deaths when misoprostol was used to induce labor, fueling the misoprostol controversy. More than 45 randomized trials including more than 5400 women have found vaginal misoprostol to be more effective than oxytocin or vaginal prostaglandin E2 at effecting vaginal delivery within 24 hours. Cesarean delivery rates with vaginal misoprostol are lower than with oxytocin alone, but similar to prostaglandin E2. There have been no significant differences in the frequency of serious adverse maternal or neonatal outcomes with low-dose misoprostol compared with oxytocin or prostaglandin E2; however, the relative risk of rare adverse outcomes with misoprostol is unknown. The data suggest that absolute risks are low when misoprostol is used appropriately. We recommend 25 mcg vaginally every 4 to 6 hours for carefully selected patients in closely monitored settings. Whether misoprostol will prove to be the most cost-effective agent for inducing labor in women with an unfavorable cervix remains to be determined.

Introduction

Misoprostol is a prostaglandin E1 analogue approved by the Food and Drug Administration (FDA) for the prevention and treatment of peptic ulcer disease in patients taking non-steroidal anti-inflammatory drugs. It has also become an important drug in obstetric and gynecologic practice because of its uterotonic and cervical ripening activity. Misoprostol is useful in the management of elective medical and surgical abortion, miscarriage, induction of labor, and postpartum hemorrhage. In contrast to other prostaglandin preparations, misoprostol does not require refrigeration or parenteral administration. It is also inexpensive. Misoprostol may play a particularly important role in the practice of obstetrics and gynecology in resource-poor countries where refrigeration is not available, the cost of other prostaglandin preparations is prohibitively expensive, and maternal mortality rates are high. Misoprostol has perhaps the greatest potential to save women's lives around the world by preventing or treating postpartum hemorrhage where no safe alternative treatments exist.[1]

On August 23, 2000, the manufacturer of misoprostol (Cytotec, Searle) distributed a letter to clinicians in the United States warning them against the use of misoprostol in pregnant women. The letter stated that Cytotec administration by any route is contraindicated in pregnancy because it can cause abortion. The manufacturers also cited reports of uterine rupture and maternal and fetal deaths when Cytotec was used to induce labor. They stated that "in addition to the known and unknown acute risks to the mother and fetus, the effect of Cytotec on the later growth [and] development...of the child when Cytotec is used for induction of labor...has not been established."[2] That letter generated a nationwide reaction and considerable controversy. Many hospitals removed misoprostol from their formularies, and pregnant women lost access to the drug for any indication. In a response issued in December of 2000,[3] the American College of Obstetricians and Gynecologists (ACOG) reaffirmed their previous position, originally published in 1999,[4] that substantial evidence supports the use of misoprostol for induction of labor. The controversy over the use of misoprostol for induction of labor continues as misoprostol is put on trial by the media and in courtrooms around the country. We know that misoprostol is effective for induction of labor, but how does it compare with other agents routinely used for this indication with regards to safety? The purpose of this article is to address this question, to summarize the evidence supporting the use of misoprostol for induction of labor, and to describe why controversy surrounds its use.

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