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Rapid Responses: Rapid Responses published:
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Misoprostol is a teratogenic drug
- María Reverte (10 May 2008)
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Response Misoprostol is a teratogenic drug
- Annette Aronsson, Staffan Bergstrom (13 May 2008)
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Foetal effects of inappropriate misoprostol use: wider issues must be addressed to minimise foetal risk
- Brian T Wilson (20 May 2008)
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Re: Foetal effects of inappropriate misoprostol use: wider issues must be addressed to minimise foetal risk
- Annette Aronsson, Staffan Bergstrom (24 May 2008)
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María Reverte, Professor of Pharmacolgy, PhD, MD Universidad de Salamanca, Facultad de Medicina. Av. Alfonso X El Sabio s/n. 37007 Salamanca. SPAIN
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Dear Sir, The editorial of Bergström & Aronsson (1) reflex a particular point of vie about the possible use of misoprostol for women´s reproductive health. The idea is not new. In 1991 Norma et al (2) have written about the use of misoprostol as an abortive drug. However, the results were not so good. It has been observered that misoprostol is a teratogenic drug for human (3), used orally and vaginally, and mice (4). People of Latin-America (5), remember very well the tragic history of more than one thousand of children how are abnormal, after their mothers decide to use misoprostol as an abortive. 1 Bergström S, Aronsson A (2008). Misoprostol in resource poor countries. Is cheap and effective, yet is availability remains restricted. BMJ 2008;336:1032. 2 Norma JE, Thong KJ, Baird DT (1991). Uterine contractility and induction of abortion in early pregnancy by misoprostol and mifeprostone. Lancet;338:1233-6. 3 Oriol IM, Castillo EE (200). Epidemiological assessment of misoprostol teratogenicity. J Obstet Gynaecol;107:519. 4. Paumgartten FJ, Magalhaes-de-Souza CA, de Carvalho RR, Chahoud I. Embriotoxicity effect of misoprostol in the mouse. Braz J Med Biol Res;28:355-61. 5. Castilla EE, Orioli IM (1994). Teratogenicity of misoprostol: data from the Latin-American Collaborative Study of Congenital Malformations. Am J Med Genet 51: 165-162. Competing interests: None declared |
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Annette Aronsson, Obstetrician Karolinska University Hospital SE-171 76, Staffan Bergstrom
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Dear Sir In a comment to our editorial misoprostol in resource poor countries, Reverte made a remark that misoprostol is a teratogenic drug (1). Exposure to misoprostol in early pregnancy has been associated with multiple genital defects. Mutagenicity studies of misoprostol have been negative and misoprostol has been shown not to be embryotoxic, foetotoxic or teratogenic (2) The defects may be due to a disturbed blood supply during contractions, induced by misoprostol(3). The absolute risk of malformation after exposure to misoprostol is low (less than 10 per 1000 births(3). The risk must be placed in context. For women without access to safe legal abortion, misoprostol is an option to an unsafe abortion. 1 Reverte M. Misoprostol is a teratogenic drug. BMJ 2008;336:1032. 2 Pastuszak AL,Schuler L, Speck-Martins CE et al. Use of misoprostol during pregnancy and Mobius`syndrome in infants. N Engl J Med 1998;338:1881-5. 3 Tang OS, Gemzell-Danielsson K, Ho PC. Int J Gyn Obs 2007;99,S160-7 Competing interests: None declared |
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Brian T Wilson, MB BS, PhD Department of Paediatrics, University Hospital of North Tees, Stockton on Tees. TS19 8PE. UK.
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In their editorial, “Misoprostol in resource poor countries,” Bergstrom and Aronsson champion the use of this prostaglandin E1 analogue in reducing postpartum haemorrhage, and as a cheap, effective abortifacient(1). The authors attribute the poor availability of this drug in some areas to the manufacturer’s attitudes to marketing and note that it is widely available on the black market, yet fail to discuss the historical reasons for this, and the foetal effects of misoprostol, resulting in some bias in their paper. The use of oral misoprostol as an over-the-counter abortifacient became common in countries where termination is illegal, notably in Latin America. A study in Brazil in 1991 highlighted this issue(2), but instead of discussing the intrinsic problems concerning family planning and the role of termination in society, the Brazilian Ministry of Health restricted sales of misoprostol, driving it onto the black market. The effectiveness of oral misoprostol in terminating pregnancies is dose dependent, and does not result in sustained uterine contractions in the same way that vaginal or sublingual administration does(3). Lack of information among those using oral misoprostol, and increased cost of the drug as a black market commodity results in women taking inappropriate doses for their intended outcome. This is not unexpected – patients rely on doctors and pharmacists to provide an appropriate dose of medication, at an appropriate purity, via the most appropriate route: none of these can be guaranteed on the street. Oral misoprostol causes intense uterine contraction(3,4), impairing uterine artery flow(5). This causes downstream hypoxic damage and can result in striking features of vascular disruption in the surviving foetus, including Möbius syndrome, hydrocephalus, scalp defects, arthrogryposis, syndactyly and tissue loss in limbs, and equinovarus club foot(6,7). In order to minimise the potential long-term risk to surviving infants, the argument should therefore be about the appropriateness of family planning, and the national attitudes that govern the availability and legality of safe, effective termination in these countries. Unless these issues have been resolved, the argument should not be about the use of misoprostol per se. References 1. Bergstrom S, Aronsson A. Misoprostol in resource poor countries. BMJ. 2008; 336:1032. 2. Coelho HI, Misago C, da Fonseca WV, et al. Selling abortifacients over the counter in pharmacies in Fortaleza, Brazil. Lancet. 1991; 338:247. 3. Aronsson A, Bygdeman M, Gemzell-Danielsson K. Effects of misoprostol on uterine contractility following different routes of administration. Hum Reprod. 2004; 19:81-4. 4. Christin-Maitre S, Bouchard P, Spitz IM. Medical termination of pregnancy. N Engl J Med. 2000; 342:946-56. 5. Los FJ, Brandenburg H, Niermeijer MF. Vascular disruptive syndromes after exposure to misoprostol or chorionic villus sampling. Lancet. 1999; 353:843-4. 6. Gonzalez CH, Marques-Dias MJ, Kim CA et al. Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy. Lancet. 1998; 351:1624-7. 7. Coelho KE, Sarmento MF, Veiga CM, et al. Misoprostol embryotoxicity: clinical evaluation of fifteen patients with arthrogryposis. Am J Med Genet. 2000; 95:297-301. Competing interests: None declared |
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Annette Aronsson, Obstetrician Karolinska University Hospital SE-171 76 Stockholm, Staffan Bergstrom
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Dear Sir In a response to our editorial on misoprostol in resource poor countries Wilson made a comment on misoprostol and foetal effects in Brazil (1). In Brazil abortion is only permitted to save the life of the woman or in case of rape. When misoprostol was approved in Brazil for the treatment of gastric ulcer 1986, it was also used for pregnancy termination and a reduction in abortion morbidity was seen (2). Only two years later the government restricted the sales of misoprostol. At the same time the first cases of birth defects associated with misoprostol was reported (3). Case reports indicated the potential of teratogenicity of misoprostol (4,5). In three case-control studies, there was a higher prevalence of birth effects among misoprostol-exposed children (6,7,8), but the absolute risk is low. Abortion attempts may involve pharmaceuticals, insertion of a root, twig or catheter into the uterus, a dilatation and curettage procedure performed improperly by an unskilled provider, ingestion of harmful substances and trauma to the abdomen (9) Wilson also recommends family planning and legal safe abortion. Tragically, already in 1967 The World Health Organization stated that abortions are a serious public health problem. At The International Conference on Population and Development 1994, governments were urged to deal with unsafe abortion and in 1999 The Assembly in New York agreed that in circumstances where abortion is not against the law, such abortion should be safe. In spite of all this, and also a rise in the use of contraceptive globally, one woman still dies every eight minute in a low-income country due to complications from unsafe abortion. (1) Wilson BT. BMJ, 2008 May 20. Foetal effects of inappropriate misoprostol use: wider issues must be addressed to minimise foetal risk (2) Faundes A, Santos LC et al. Post- abortion complications after interruption of pregnancy with misoprostol. Advances in Contraception. 1996;12(1):1-9 (3) Schonhofer PS. Brazil: Misuse of misoprostol as an abortifacient may induce malformations. Lancet 1991;332:1534-5 (4) Gonzalez CH, Marques-Dias MJ, Kim CA et al. Congenital abnormalities in Brazilian children associated with misoprostol misuse in first trimester of pregnancy. Lancet 1998;351:1624-5 (5) Coelho KE, Sarmento MF, Veiga CM et al. Am J Med Genet 2000;95:297-301 (6) Pastuszak AL, Schuler L, Speck-Martins CE et al. Use of misoprostol durig pregnancy and Mobius`syndrome in infants. N Engl J Med 1998,338:1881 -5 (7) Orioli IM, castilla EE. Epidemiological assessments of misoprostol teratogenicity.BJOG 107(4):519-2 (8) Vargas FK, Schuber-Faccini L et al 2000. Prenatal exposure to misoprostol and vascular disruption defects. A case control study. Am J med Genet 95(4):302-6. (9) Unsafe abortion. Fifth edition. World Health Organization (10) Alan Guttmacher Institute 2007. www.guttmacher.org/pubs/fb_IAW.html Competing interests: None declared |
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