Beverly Winikoff

Safety, efficacy, and acceptability of medical abortion in China, Cuba, and India: A comparative trial of mifepristone-misoprostol versus surgical abortion

OBJECTIVE We investigated safety, efficacy, and acceptability of an oral regimen of medical abortion compared with surgical abortion in three developing countries. STUDY DESIGN Women (n = 1373) with amenorrhea < or = 56 days chose either surgical abortion (as provided routinely) or 600 mg of mifepristone followed after 48 hours by 400 micrograms of misoprostol. This is the appropriate design for studying safety, efficacy, and acceptability among women selecting medical abortion over available surgical services. RESULTS The medical regimen had more side effects, particularly bleeding, than did surgical abortion but very few serious side effects. Failure rates for medical abortion, although low, exceeded those for surgical abortion: 8.6% versus 0.4% (China), 16.0% versus 4.0% (Cuba), and 5.2% versus 0% (India). Nearly half of failures among medical clients were not true drug failures, however, but surgical interventions not medically necessary (acceptability failures or misdiagnoses). Women were satisfied with either method, but more preferred medical abortion. CONCLUSION Medical abortion can be safe, efficacious, and acceptable in developing countries.

The obstetrician's opportunity: Translating “breast is best” from theory to practice

The superiority of breast-feeding to artificial feeding of infants has been well established for nutritional, biochemical, antiinfective, psychological, economic, and contraceptive reasons. The promotion of breast-feeding should, therefore, be a high-priority concern of health workers. Both provision of information and support to expectant mothers and changes in hospital routines in the perinatal period have been shown capable of dramatically increasing the incidence and duration of breast-feeding in populations studied. Moreover, these interventions are interventions are quite specific, effective, manageable, and affordable. Obstetricians have a special responsibility and capacity to promote breast-feeding given their contact with women throughout pregnancy and their influence on hospital birth routines. A greater commitment on the part of obstetricians to promote breast-feeding could accelerate and extend the current shift back to breast-feeding, to the benefit of mothers and their babies in all socioeconomic groups.

The effects of birth spacing on child and maternal health.

Child and maternal mortality and morbidity are examined in relation to the interval between pregnancies. Most data available pertain to child mortality. Very little reliable information links child morbidity or maternal health detriments to short birth spacing. The evidence on child mortality suggests that very short intervals (conceptions less than six months after a birth) are detrimental to survival of the second child, but these results must be viewed in light of the methodological difficulties of studies of this subject. Policy implications of the data are perhaps less clear than is sometimes assumed.

Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial.

BACKGROUND Oxytocin, the standard of care for treatment of post-partum haemorrhage, is not available in all settings because of refrigeration requirements and the need for intravenous administration. Misoprostol, an effective uterotonic agent with several advantages for resource-poor settings, has been investigated as an alternative. This trial established whether sublingual misoprostol was similarly efficacious to intravenous oxytocin for treatment of post-partum haemorrhage in women not exposed to oxytocin during labour. METHODS In this double-blind, non-inferiority trial, 9348 women not exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at four hospitals in Ecuador, Egypt, and Vietnam (one secondary-level and three tertiary-level facilities). 978 (10%) women were diagnosed with primary post-partum haemorrhage and were randomly assigned to receive 800 microg misoprostol (n=488) or 40 IU intravenous oxytocin (n=490). Providers and women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the time of initial treatment. This study is registered with ClinicalTrials.gov, number NCT00116350. FINDINGS All randomly assigned participants were analysed. Active bleeding was controlled within 20 min with study treatment alone for 440 (90%) women given misoprostol and 468 (96%) given oxytocin (relative risk [RR] 0.94, 95% CI 0.91-0.98; crude difference 5.3%, 95% CI 2.6-8.6). Additional blood loss of 300 mL or greater after treatment occurred for 147 (30%) of women receiving misoprostol and 83 (17%) receiving oxytocin (RR 1.78, 95% CI 1.40-2.26). Shivering (229 [47%] vs 82 [17%]; RR 2.80, 95% CI 2.25-3.49) and fever (217 [44%] vs 27 [6%]; 8.07, 5.52-11.8) were significantly more common with misoprostol than with oxytocin. No women had hysterectomies or died. INTERPRETATION In settings in which use of oxytocin is not feasible, misoprostol might be a suitable first-line treatment alternative for post-partum haemorrhage.

Misoprostol for women's health: a review.

OBJECTIVE To review published literature on misoprostol for womens health indications to provide a synthesis of available information and highlight areas in need of additional research. DATA SOURCES: Studies were identified through searches of medical literature databases including MEDLINE, Cochrane Database, and Popline, in addition to a review of references from identified articles. STUDY SELECTION: We included all studies reported in English and published before March 31, 2001, which evaluated the efficacy of misoprostol alone for labor and delivery, evacuation of the uterus after pregnancy failure and induced abortion. Studies were not excluded based on quality or sample size. TABULATION, INTEGRATION, AND RESULTS: Misoprostol shows promise for all of the womens health indications addressed. Currently available data, though, are often hard to interpret because of variations in regimen, dose, and outcome measures. The low cost, ease of administration and storage, and widespread availability of misoprostol make it particularly appealing for developing countries. Because many of the womens health problems for which misoprostol could be prescribed currently cause significant mortality and morbidity, increased access to and information on use of misoprostol could help improve womens health especially where these problems are most severe. CONCLUSION Further research is needed to identify optimal regimens for misoprostol for obstetric and gynecologic health indications. Registering misoprostol with national drug regulatory authorities for any of several womens health indications could help increase access to and safe use of this drug. Provider training would be a logical subsequent step.

Assessing the role of family planning in reducing maternal mortality.

It is widely believed that family planning has important benefits for both maternal and child health. Despite this, little work has been done to quantify the potential effect of family planning in reducing maternal mortality. This paper assesses the impact of family planning in averting maternal deaths, and discusses the overall ability of risk strategies to address the bulk of maternal mortality. The practical difficulties of providing effective contraception to populations with high maternal mortality are addressed, and the need for maternal health care services as an adjunct to useful family planning programs is emphasized. Although family planning cannot by itself cause a substantial reduction in risk of pregnancy, the combined strategies of general fertility reduction, abortion services, and family planning for high-risk groups might effectively address about half of all maternal mortality in the developing world. Pregnancy and delivery care have the potential for saving large numbers of lives with appropriate interventions. It is concluded that reproductive risks can be reduced only by preventing unwanted pregnancies and protecting maternal health during wanted ones.

Effects of iron supplementation on maternal hematologic status in pregnancy.

OBJECTIVES Prenatal iron supplementation has been the standard recommendation for reducing maternal anemia in developing countries for the past 30 years. This article reviews the efficacy of iron supplementation on hemoglobin levels in pregnant women in developing countries. METHODS Data from randomized controlled trials published between 1966 and 1998 were pooled. Meta-analyses of the relative change in maternal hemoglobin associated with iron supplementation were stratified by initial hemoglobin levels, duration of supplementation, and daily gestational supplement dose and supplementation with other nutrients. RESULTS Iron supplementation raises hemoglobin levels. Its effects are dose dependent and are related to initial hematologic status. The extent to which iron supplementation can reduce maternal anemia is unclear. CONCLUSIONS The extent to which maternal hemoglobin levels can be increased by recommended prenatal supplementation is limited and has uncertain physiological benefits. Other approaches, including food fortification and prevention and treatment of other causes of anemia, require methodologically rigorous evaluation to find effective answers to this global problem.

Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: a double-blind, randomised, non-inferiority trial

BACKGROUND Oxytocin, the gold-standard treatment for post-partum haemorrhage, needs refrigeration, intravenous infusion, and skilled providers for optimum use. Misoprostol, a potential alternative, is increasingly used ad hoc for treatment of post-partum haemorrhage; however, evidence is insufficient to lend support to recommendations for its use. This trial established whether sublingual misoprostol is non-inferior to intravenous oxytocin for treatment of post-partum haemorrhage in women receiving prophylactic oxytocin. METHODS In this double-blind, non-inferiority trial, 31 055 women exposed to prophylactic oxytocin had blood loss measured after vaginal delivery at five hospitals in Burkina Faso, Egypt, Turkey, and Vietnam (two secondary-level and three tertiary-level facilities). 809 (3%) women were diagnosed with post-partum haemorrhage and were randomly assigned to receive 800 mug misoprostol (n=407) or 40 IU intravenous oxytocin (n=402). Providers and women were masked to treatment assignment. Primary endpoints were cessation of active bleeding within 20 min and additional blood loss of 300 mL or more after treatment. Clinical equivalence of misoprostol would be accepted if the upper bound of the 97.5% CI fell below the predefined non-inferiority margin of 6%. All outcomes were assessed from the time of initial treatment. This study is registered with ClinicalTrials.gov, number NCT00116350. FINDINGS All randomly assigned participants were analysed. Active bleeding was controlled within 20 min after initial treatment for 363 (89%) women given misoprostol and 360 (90%) given oxytocin (relative risk [RR] 0.99, 95% CI 0.95-1.04; crude difference 0.4%, 95% CI -3.9 to 4.6). Additional blood loss of 300 mL or greater after treatment occurred for 139 (34%) women receiving misoprostol and 123 (31%) receiving oxytocin (RR 1.12, 95% CI 0.92-1.37). Shivering (152 [37%] vs 59 [15%]; RR 2.54, 95% CI 1.95-3.32) and fever (88 [22%] vs 59 [15%]; 1.47, 1.09-1.99) were significantly more common with misoprostol than with oxytocin. Six women had hysterectomies and two women died. INTERPRETATION Misoprostol is clinically equivalent to oxytocin when used to stop excessive post-partum bleeding suspected to be due to uterine atony in women who have received oxytocin prophylactically during the third stage of labour.

A randomized trial of misoprostol compared with manual vacuum aspiration for incomplete abortion.

Objective: To compare the safety, efficacy, and acceptability of misoprostol and manual vacuum aspiration for the treatment of incomplete abortion in a hospital setting in Kampala, Uganda. Methods: Three hundred seventeen women with clinically diagnosed incomplete first-trimester abortions were randomized to treatment with either manual vacuum aspiration or 600 &mgr;g misoprostol orally to complete their abortions. All women received antibiotics posttreatment and were followed up 1–2 weeks later. Results: Regardless of treatment allocation, nearly all women in this study successfully completed their abortions with either oral misoprostol or manual vacuum aspiration (96.3% versus 91.5%, relative risk 1.05, 95% confidence interval 0.98–1.14). Complications were less frequent in those receiving misoprostol than those having manual vacuum aspiration (0.9% versus 9.8%, relative risk 0.1, 95% confidence interval 0.01–0.78). In the 6 hours after treatment, women using misoprostol reported heavier bleeding but lower levels of pain than those treated with manual vacuum aspiration. Rates of acceptability were similarly high among women in the 2 treatment groups, with 94.2% and 94.7% of women reporting that their treatment was satisfactory or very satisfactory in the misoprostol and manual vacuum aspiration groups, respectively. Conclusion: For treatment of first-trimester uncomplicated incomplete abortion, both manual vacuum aspiration and 600 &mgr;g oral misoprostol are safe, effective, and acceptable treatments. Based on availability of each method and the wishes of individual women, either option may be presented to women for the treatment of incomplete abortion. Level of Evidence: I

Analysis of failure in medical abortion

Medical abortion opens a new choice to women wishing to terminate a pregnancy. Increasingly, providers in the developing and developed world will begin to offer this option. Yet, the nomenclature and concepts used for measuring failure of surgical abortion are not directly adaptable because of important differences inherent in the method and in the way it is offered in a given setting. We propose that failures in medical abortion should be defined as a surgical intervention (whether vacuum aspiration or dilatation and curettage) performed for any reason. Such instances may be further classified into three types: user choice interventions, provider choice or error interventions, and true drug failures requiring intervention. Further description and examples of each type are given.