Correspondence

Correction

Use of Misoprostol during Pregnancy and Möbius' Syndrome in Infants

N Engl J Med 1998; 339:1553-1554November 19, 1998

Article

To the Editor:

In their paper describing the association between the reported use of misoprostol in unsuccessful attempts to terminate pregnancy and Möbius' syndrome in infants, Pastuszak et al. (June 25 issue)1 conclude that the “administration of misoprostol during pregnancy should be strongly discouraged, given the drug's low efficacy and its likelihood of causing fetal malformations.” We disagree. The suitability of administering misoprostol during pregnancy depends entirely on the intended effect. If the desired outcome is the medical termination of unwanted pregnancy, cervical priming before vacuum aspiration, or prevention of postpartum hemorrhage, concern about potential fetal malformation is misplaced, and the drug's safety and efficacy for the woman should be the chief issue. If misoprostol is intended to induce labor, concern about its effects on the infant are clearly in order, but Möbius' syndrome is not a threat.

Recent clinical data show that misoprostol is safe and efficacious for many uses during pregnancy,2,3 especially for the termination of unwanted pregnancy. Misoprostol, in conjunction with mifepristone or methotrexate, is safe and effective for the termination of early pregnancy. In France and China, for example, early abortion regimens involving mifepristone and misoprostol have been used by more than 1 million women, with success rates in the range of 92 to 95 percent.4 Moreover, misoprostol alone may also be safe and effective for early abortion; the success rate for a vaginal regimen is over 90 percent.5,6

Misoprostol has a number of advantages over other drugs and methods traditionally used for the reproductive health indications noted above. It is inexpensive, stable in a variety of climates, and widely available because of its use for gastrointestinal indications. Censure of the use of misoprostol during pregnancy inappropriately discourages its potential use, under supervision, for these indications, to the detriment of women's health worldwide. Cautions about misoprostol should be limited to its use in women with early pregnancy who intend to continue their pregnancies to term.

Kelly Blanchard, M.Sc.
Beverly Winikoff, M.D., M.P.H.
Population Council, New York, NY 10017

Charlotte Ellertson, Ph.D.
Population Council, 04000 Mexico, D.F., Mexico

6 References

1. 1

   Pastuszak AL, Schuler L, Speck-Martins CE, et al. Use of misoprostol during pregnancy and Möbius' syndrome in infants. N Engl J Med 1998;338:1881-1885
   Full Text | Web of Science | Medline

2. 2

   Sanchez-Ramos L, Peterson DE, Delke I, Gaudier FL, Kaunitz AM. Labor induction with prostaglandin E₁ misoprostol compared with dinoprostone vaginal insert: a randomized trial. Obstet Gynecol 1998;91:401-405
   CrossRef | Web of Science | Medline

3. 3

   el-Refaey H, O'Brien P, Morafa W, Walder J, Rodeck C. Use of oral misoprostol in the prevention of postpartum haemorrhage. Br J Obstet Gynaecol 1997;104:336-339
   CrossRef | Medline

4. 4

   Grimes DA. Medical abortion in early pregnancy: a review of the evidence. Obstet Gynecol 1997;89:790-796
   CrossRef | Web of Science | Medline

5. 5

   Carbonell JL, Varela L, Velazco A, Fernandez C, Sanchez C. The use of misoprostol for abortion at ≤9 weeks' gestation. Eur J Contracept Reprod Health Care 1997;2:181-185
   CrossRef | Medline

6. 6

   Carbonell JL, Varela L, Velazco A, Fernandez C. The use of miso-prostol for termination of early pregnancy. Contraception 1997;55:165-168
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: We thank Blanchard et al. for their comments. We agree that “the suitability of administering misoprostol during pregnancy depends entirely on the intended effect.” Our study was not intended as a review of the beneficial effects or efficacy of misoprostol for off-label indications, but rather as a post-marketing–surveillance approach to evaluate the magnitude of adverse effects of misoprostol after its use during the first trimester of pregnancy. The study was prompted by requests from physicians seeking information about the risk–benefit ratio of misoprostol when used to treat gastric ulcers in pregnant women or in women of childbearing age. Of paramount concern was the potential for prolonged fetal exposure during organogenesis to a drug prescribed for reasons specific to the mother.

A review of the published evidence led us to hypothesize that fetal exposure to misoprostol early in the first trimester, with continued progression of pregnancy to term, might be associated with Möbius' syndrome. Our decision to perform a case–control study was predicated on the fact that, in the absence of free access to abortion, Brazilian women commonly identify misoprostol as an abortifacient,1,2 and consequently, the prevalence of misoprostol use in pregnancy there has been estimated at 10 percent.3

In labeling misoprostol as a new teratogen in our article, we underscored the biologic plausibility of vascular disruption or an ischemic event in the embryonic brain stem as the cause of fetal damage. Our conclusion that the administration of misoprostol during pregnancy should be discouraged was made in the context of our study population — that is, women who tried to induce abortion early in the first trimester, using oral doses of misoprostol that were ineffective for this purpose.

The correct name of one author is Synthia Lordello, not Cordello, as published.

Anne L. Pastuszak, M.Sc.
Hospital for Sick Children, Toronto, ON M5G 1X8, Canada

Lavinia Schüler, M.D., Ph.D.
Universidade Federal do Rio Grande do Sul, 90046-900 Porto Alegre, Brazil

3 References

1. 1

   Clandestine abortion: a Latin American reality. New York: Alan Guttmacher Institute, 1994.
   

2. 2

   Singh S, Wulf D. Estimated levels of induced abortion in six Latin American countries. Int Fam Plann Perspect 1994;20:4-13
   CrossRef

3. 3

   Costa SH, Vessey MP. Misoprostol and illegal abortion in Rio de Janeiro, Brazil. Lancet 1993;341:1258-1261
   CrossRef | Web of Science | Medline

Citing Articles (3)

Citing Articles

1. 1

   Marilyn T. Miller, Kerstin Strömland, Liana Ventura, Maria Johansson, Jose M. Bandim, Christopher Gillberg. (2005) Autism associated with conditions characterized by developmental errors in early embryogenesis: a mini review. International Journal of Developmental Neuroscience 23:2-3, 201-219
   CrossRef

2. 2

   Julia K. Terzis, Ernst Magnus Noah. (2003) Dynamic Restoration in Möbius and Möbius-Like Patients. Plastic and Reconstructive Surgery 111:1, 40-55
   CrossRef

3. 3

   &NA;. (1998) Misoprostol 'safe and effective' for the termination of early pregnancy. Reactions Weekly &NA;:729, 2
   CrossRef