International Journal of Gynecology and Obstetrics- Reducing maternal mortality due to elective abortion: Potential impact of misoprostol in low-resource settings

Publication date: 2007

ty o C.C. Harper a,⁎, K. Bl J.T. Henderson a, P.D a Bixby Center for Reproductive H Gynecology and Reproductive Scie Abstract Over 99% of deaths due to abortion occur in developing countries. Maternal deaths due to reduce mortality due to abortion. Empirical testing of the hypothesis with data collected from KEYWORDS ava i l ab l e a t www.sc i enced i r ec t . com www.e l sev i e r. co International Journal of Gynecology and Obstetrics (2007) 98, 66–69 developing countries could help to inform and improve the use of misoprostol in those settings. © 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. 1. Introduction Unsafe abortion is a preventable public health threat in developing regions, where over 99% of deaths due to abortion occur [1]. This article assesses the potential of misoprostol (Cytotec®, Pfizer, New York, NY) to induce elective abortion explore this hypothesis, estimates of the mortality reduc- tions possible if misoprostol were to replace riskier abortion techniques are presented. Medical abortion has been shown to be safe and effective in developing countries [2–4]. It does not require anesthesia or a hospital setting, and holds promise to increase access to safe abortion where surgical abortion is unsafe or unavail- abortion are preventable. Increasing the use ofmisoprostol for elective abortion could have a notable impact on maternal mortality due to abortion. As a test of this hypothesis, this study estimated the reduction in maternal deaths due to abortion in Africa, Asia and Latin America. The estimates were adjusted to changes in assumptions, yielding different possible scenarios of low and high estimates. This simple modeling exercise demonstrated that increased use of misoprostol, an option for pregnancy termination already available to many women in developing countries, could significantly Maternal mortality; Misoprostol abortion; Medical abortion as a simple intervention to reduc ⁎ Corresponding author. University 3333 California Street, Ste. 335, San Fr +1 415 922 6448. E-mail address: harperc@obgyn.uc 0020-7292/$ - see front matter © 200 All rights reserved. doi:10.1016/j.ijgo.2007.03.009 anchard b, D. Grossman b, . Darney a ealth Research and Policy, Department of Obstetrics, nces, University of California, San Francisco, San Francisco, CA, USA ridge, MA, USA ved in revised form 2 March 2007; accepted 15 March 2007 b Ibis Reproductive Health, Camb Received 2 November 2006; recei low-resource settings SPECIAL ARTICLE Reducing maternal mortali Potential impact of misopr e maternal mortality. To of California, San Francisco, ancisco, CA, USA 94118. Tel.: sf.edu (C.C. Harper). 7 International Federation of G due to elective abortion: stol in m/ loca te / i j go able. The World Health Organization (WHO) added mifepris- tone and misoprostol to its Essentials Medicines List for developing countries [5]. Mifepristone is expensive and is not approved in many countries. Misoprostol, a prostaglandin E1 analogue, is inexpensive, stable at room temperature, widely ynecology and Obstetrics. Published by Elsevier Ireland Ltd. g re d m abo 67Reducing maternal mortality due to elective abortion: Potential impact of misoprostol Table 1 Estimates of deaths due to abortion in developin Number unsafe Number maternal Proportion attempting Estimate medical available and used off-label for many obstetric/gynecologic conditions. Although not as effective as mifepristone–mis- oprostol, misoprostol-alone has been studied for first and second-trimester abortions [6,7]. abortions [1] deaths to unsafe abortion medical abortion (%) (deaths per abortions) a 1st trimester Developing regions 18,400,000 67,500 20 20 20 10 40 20 40 10 60 20 60 10 80 20 80 10 Africa 4,200,000 29,800 20 20 20 10 40 20 40 10 60 20 60 10 80 20 80 10 Asia c 10,500,000 34,000 20 20 20 10 40 20 40 10 60 20 60 10 80 20 80 10 Latin America 3,700,000 3700 20 20 20 10 40 20 40 10 60 20 60 10 80 20 80 10 a 80% of all abortions assumed to occur in 1st trimester and 20% in 2 b 10% of medical abortions in 1st trimester and 15% in 2nd trimester as abortion. c Excluding Japan, Australia, and New Zealand. gions ortality to rtion Estimated number Estimated number Estimated percent Misoprostol abortion regimens of varying doses and routes of administration have been tested in developing regions [8–10]. Efficacy ofmisoprostol-alone for first-trimester abortion ranges from about 88–96%, but may be lower in legally restricted 100,000 deaths to medical abortion b maternal deaths to all abortions reduction maternal deaths 2nd trimester 200 1781 57,266 15.2 100 891 56,376 16.5 200 3562 47,032 30.3 100 1781 45,251 33.0 200 5343 36,798 45.5 100 2672 34,127 49.4 200 7124 26,564 60.6 100 3562 23,002 65.9 200 407 24,902 16.4 100 203 24,699 17.1 200 813 20,004 32.9 100 407 19,598 34.2 200 1220 15,106 49.3 100 610 14,497 51.4 200 1626 10,209 65.7 100 813 9396 68.5 200 1016 28,964 14.8 100 508 28,456 16.3 200 2033 23,929 29.6 100 1016 22,912 32.6 200 3049 18,893 44.4 100 1525 17,369 49.8 200 4066 13,858 59.2 100 2033 11,825 65.2 200 358 3400 8.1 100 179 3220 13.0 200 716 3000 16.2 100 358 2714 25.9 200 1074 2799 24.4 100 537 2261 38.9 200 1433 2498 32.5 100 716 1782 51.8 nd trimester. sumed to “fail” and were given prevailing mortality rates for unsafe 68 C.C. Harper et al. settings [11]. A consensus regimen has been published for early abortion (through 9 weeks gestation), consisting of 800 mcg vaginal misoprostol, repeated after 24 h [12]. Misoprostol regimens for second-trimester abortion have shown effective- ness from approximately 85–91%, although a consensus regi- men does not yet exist [6]. Studies in China have shown success using 400 μg vaginal misoprostol every 3–6 h, up to 5 doses in 24 h [13,14]. Little research has been conducted on the safety and effectiveness of misoprostol used in less controlled settings [15]. Misoprostol was used, however, outside of clinics in Brazil and the Dominican Republic before a consensus regimen was reached, and was associated with fewer infections and abortion complications [16,17]. The paucity of mortality data, particularly where abortion is legally restricted, necessitates an estimation approach in measuring the impact of misoprostol abortion. Estimates can be used to inform maternal health interventions. This article uses a simple modeling approach with high and low mortality rates and varies an assumption that is amenable to intervention, the proportion of women choosing medical abortion. The model yields eight different scenarios per region, ranging from minimal to maximum impact. 2. Materials and methods Maternal deaths due to abortion in developing regions are estimated as a whole and then separately for Africa, Asia and Latin America. The model assumed that factors influencing pregnancy, abortion, and mortality rates remain at current levels (e.g. women in reproductive age, contraceptive pre- valence, pregnancies, poverty and urbanization rates, women at risk of unsafe abortion). 2.1. Mortality rates, by trimester Mortality rates for mifepristone–misoprostol are estimated at 0.8–1.5 deaths per 100,000 abortions in the U.S.,[18,19] and mortality in the second trimester is approximately 10-fold higher [20]. Almost 90% of abortions are first trimester,[21] but in low- resource settings, delays are likely longer. Mortality associated with misoprostol abortion will be higher where access to emergency medical services is poor, particularly for second- trimester abortions, which account for most abortion deaths [22,23]. The model assumed two different sets of mortality rates, low and high, for misoprostol abortion in developing regions, and varied the rates by trimester. The low series is 10 deaths per 100,000 abortions in the first trimester and 100 deaths per 100,000 abortions in the second trimester. The high series is 20 deaths per 100,000 abortions (first trimester) and 200 per 100,000 (second trimester). First-trimester rates were applied to 80% of medical abortions. 2.2. Proportion of women using medical abortion The proportion of women at risk of unsafe abortion who choose medical abortion was varied to assess the impact on mortality. The proportion varies widely and is likely to continue to change over time as awareness and practice change. Estimates started at 20% and ranged to an outside figure of 80% of abortions. In the U.S. about 25% of women choose medical abortion, in France and Scotland 60–70%, and in China 30–70% [24,25]. A study in India showed a range of 0–80%, depending on the provider [26]. 2.3. Mortality rates for medical abortion failures An estimated 10% of first-trimester and 15% of second-trimester medical abortions are assumed to fail. Failures were assigned prevailing mortality rates for unsafe abortion, taken from WHO estimates (18.4 million unsafe abortions, 67,500 maternal deaths) in developing regions [1]. Corresponding WHO mortality rates are: 366.8 per 100,000 unsafe abortions in developing regions, 709.5 in Africa, 323.8 in Asia, and 100.0 in Latin America/Caribbean. In sum, the model assumed a low and high series of mortality rates, by trimester, and varied the proportion of women choosing medical abortion to assess the impact on mortality. The remaining procedures, along with medical abortion failures, are subject to prevailing mortality rates for unsafe abortion. The total number of deaths was compared to deaths currently attributed to unsafe abortion. The final column of Table 1 shows the estimated percent reduction in maternal deaths. 3. Results Results show that under conditions of high mortality rates, there is a 15% reduction in mortality if 20% of procedures are misoprostol-induced; 30% reduction in mortality if the proportion of procedures rises to 40%; and a 45% reduction with 60% misoprostol-induced, which represents 30,500 lives saved annually. Relying on the low series of mortality rates, with 20% of abortions misoprostol-induced, the improve- ments are similar at 16.5%; at 40% misoprostol-induced a 33% mortality reduction; and at 60% misoprostol-induced, a 49% mortality reduction. Improvements depend heavily on the proportion using medical abortion, rather than on whether low or high estimates for mortality are used. While the higher mortality estimates would be more likely in Africa and Asia, the low rates of 10 per 100,000 for first trimester and 100 per 100,000 for second trimester are more likely for Latin America. At low mortality in Latin America with 40% of abortions misoprostol-induced, a 26% reduction in maternal deaths can be achieved, and in Africa and Asia, 33% and 30% respectively, using the high series of mortality rates. 4. Discussion These estimated mortality reductions are notable, whether high mortality rates, as might occur in Africa or parts of Asia, or low, are used as the basis of the estimate. While countries where mortality rates are highest stand the most to gain, these simple estimates show that even in Latin America, more widespread use of misoprostol-induced abortion could lead to a large reduction in maternal mortality. The more widespread misoprostol abortion is, the greater the gains. Abortion-related mortality has decreased in Latin America where some abortions are already misoprostol-induced, and acceptability of misoprostol was found to be high [27]. However, neither women nor health practitioners have wide- spread knowledge of the consensus regimen nor of the abortion process itself [28]. Informed use of misoprostol, particularly Technologies Project and Gynuity Health Projects. July 28, 2003. Washington, DC. 69Reducing maternal mortality due to elective abortion: Potential impact of misoprostol knowledge of the consensus regimen and where to seek post- abortion care, is necessary to realize the full benefits. Given higher mortality with second-trimester termination, initiating the regimen early in pregnancy could dramatically affect mortality. Women seeking abortion have shown them- selves capable of calculating pregnancy duration, although rural womenmay present at later gestational ages [29,30]. For misoprostol abortion to have the greatest impact onmortality, timely access to post-abortion care at hospitals or clinics is necessary. Women may not recognize when they require care for bleeding, and post-abortion care, including urgent care for complications and treatment of incomplete and unsafe abortion, is not always available [31]. Current estimates of abortions and maternal deaths are likely underestimates [32]. The model here used conservative numbers where data are scarce. Research is needed to document actual mortality rates as misoprostol use increases in developing regions. 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