Cost-effectiveness of misoprostol to control postpartum hemorrhage in low-resource settings.

OBJECTIVE: To test the cost-effectiveness of training traditional birth attendants (TBAs) to recognize postpartum hemorrhage (PPH) and administer a rectal dose of misoprostol in areas with low access to modern delivery facilities. METHOD: A cost-effectiveness analysis, modeling two hypothetical cohorts of 10,000 women each giving birth with TBAs: one under standard treatment (TBA referral to hospital after blood loss >or=500 ml), and one attended by TBAs trained to recognize PPH and to administer 1000 microg of misoprostol at blood loss >or=500 ml. RESULT: The misoprostol strategy could prevent 1647 cases of severe PPH (range: 810-2920) and save $115,335 in costs of referral, IV therapy and transfusions (range: $13,991-$1,563,593) per 10,000 births. By preventing severe disease and saving money, it dominates the standard approach. CONCLUSION: Training TBAs to administer misoprostol to treat PPH has the potential to both save money and improve the health of mothers in low-resource settings.     

Misoprostol versus oxytocin for the reduction of postpartum blood loss.

OBJECTIVE: To compare the effect of 400 mug of oral misoprostol with 5 U of intravenous oxytocin in the reduction of postpartum blood loss and prevention of postpartum hemorrhage. METHODS: In a prospective, double-blind, randomized controlled trial conducted in a tertiary maternity hospital 622 women received either 400 mug of oral misoprostol or 5 U of intravenous oxytocin after delivery of the anterior shoulder or within 1 min of delivery. The primary outcome was a hematocrit drop of 10% or greater 24 h postpartum. The secondary outcomes were a hemoglobin drop of 30 mg/L or greater, the use of additional oxytocin, an estimated blood loss greater than 1000 mL, manual removal of the placenta, a blood transfusion, and shivering and fever (>or=38 degrees C) as adverse effects of misoprostol. RESULTS: There was no difference between the 2 groups regarding the primary outcome (a >or=10% hematocrit drop occurred in 3.4% and 3.7% of the participants in the oxytocin and misoprostol groups, P=0.98). The rate of use of additional oxytocin was higher in the misoprostol group (51% versus 40.5%, P=0.01). Shivering was confined to the misoprostol group (6.8%), and fever occurred in 12.5% of the women in the misoprostol group and 0.3% of the women in the oxytocin group. CONCLUSION: The routine use of 400 microg of oral misoprostol was no less effective than 5 U of intravenous oxytocin in reducing blood loss after delivery, as assessed by change in postpartum hematocrit. The adverse effects of misoprostol were mild and self-limiting.     

Rectal misoprostol versus intravenous oxytocin for prevention of postpartum hemorrhage

Objective

To assess the effectiveness of 800 μg of rectal misoprostol compared with an intravenous infusion of 5 IU of oxytocin as prophylaxis against postpartum hemorrhage (PPH).

Methods

A total of 514 women in labor were randomized into two groups (257 women in each). Within 1 minute of delivery of the anterior shoulder participants in group 1 received 800 μg of rectal misoprostol and 1 ampoule of normal saline in 5 mL lactated Ringer solution intravenously; group 2 received a rectal placebo tablet and 5 IU of oxytocin in 5 mL lactated Ringer solution intravenously.

Results

Both groups were comparable regarding the need for uterotonics, blood transfusion, and hematocrit drop of 10% or greater, 24 hours post partum (P = 0.54, P = 0.25, and P = 0.85, respectively). Fever was significantly higher among misoprostol patients (18.7% vs 0.8%, P < 0.001).

Conclusions

Routine use of 800 μg of rectal misoprostol was effective in reducing blood loss after delivery. We recommend the regimen for low-resource, busy obstetric settings.     

Reducing postpartum hemorrhage in Africa.

Postpartum hemorrhage (PPH) is the leading cause of maternal mortality in sub-Saharan Africa. This is being addressed by leading professional organizations, which point to the importance of a skilled attendant at birth. But they also emphasize that the active management of the third stage of labor is proven to reduce the incidence of PPH. In low-income settings, the prostaglandin misoprostol should be considered as it is low-cost, stable at room temperature and easy to administer.     

米索前列醇用于预防产后出血的临床探讨

目的　探讨口服米索前列醇预防产后出血的价值。方法　采用回顾性资料分析方法 ,对我院2 0 0 1年 1月～ 2 0 0 2年 12月收住院的正常单胎头位足月妊娠经阴道试产者 16 0 0例随机分为两组。研究组 80 0例 ,在第二产程胎头娩出后即口服米索前列醇 6 0 0 μg ;对照组 80 0例 ,在胎头娩出后静脉予催产素 2 0U。观察产后2h出血量 ,产后出血发生率 ,新生儿窒息发生率及用药前后血压变化。结果　产后 2h出血量 ,研究组与对照组分别为 16 8 4 5± 6 0 5 6ml和 188 75± 95 32ml,两组比较差异有统计学意义 (P <0 0 1)。产后出血发生率 ,研究组与对照组分别为 1 2 5 %和 3 75 % ,两组比较差异有统计学意义 (P <0 0 1)。新生儿窒息发生率及用药前后血压变化对比差异无统计学意义 (P >0 0 5 )。结论　口服米索前列醇预防产后出血优于催产素 ,不仅能减少产后出血量 ,降低产后出血发生率 ,且给药方法简便、安全 ,便于推广应用。     

Controlling postpartum hemorrhage after home births in Tanzania.

OBJECTIVES: Determine safety of household management of postpartum hemorrhage (PPH) with 1000 microg of rectal misoprostol, and assess possible reduction in referrals and the need for additional interventions. METHODS: Traditional birth attendants (TBAs) in Kigoma, Tanzania were trained to recognize PPH (500 ml of blood loss). Blood loss measurement was standardized by using a local garment, the "kanga". TBAs in the intervention area gave 1000 microg of misoprostol rectally when PPH occurred. Those in the non-intervention area referred the women to the nearest facility. RESULTS: 454 women in the intervention and 395 in the non-intervention areas were eligible. 111 in the intervention area and 73 in the non-intervention had PPH. Fewer than 2% of the PPH women in the intervention area were referred, compared with 19% in the non-intervention. CONCLUSION: Misoprostol is a low cost, easy to use technology that can control PPH even without a medically trained attendant.     

Prevention of postpartum hemorrhage at home birth in Afghanistan

Objective

To test the safety, acceptability, feasibility, and effectiveness of community-based education and distribution of misoprostol for prevention of postpartum hemorrhage at home birth in Afghanistan.

Methods

A nonrandomized experimental control design in rural Afghanistan.

Results

A total of 3187 women participated: 2039 in the intervention group and 1148 in the control group. Of the 1421 women in the intervention group who took misoprostol, 100% correctly took it after birth, including 20 women with twin pregnancies. Adverse effect rates were unexpectedly lower in the intervention group than in the comparison group. Among women in the intervention group, 92% said they would use misoprostol in their next pregnancy. In the intervention area where community-based distribution of misoprostol was introduced, near-universal uterotonic coverage (92%) was achieved compared with 25% coverage in the control areas.

Conclusion

In Afghanistan, community-based education and distribution of misoprostol is safe, acceptable, feasible, and effective. This strategy should be considered for other countries where access to skilled attendance is limited.     

Uterine massage to reduce postpartum hemorrhage after vaginal delivery

Objective

To determine the effectiveness of sustained uterine massage started before delivery of the placenta in reducing postpartum hemorrhage.

Methods

A randomized controlled trial conducted in Egypt and South Africa between September 2006 and February 2009. A total of 1964 pregnant women were randomly allocated to 1 of 3 treatment groups: intramuscular oxytocin, sustained uterine massage, or both treatments. Blood loss within 30 minutes of delivery was recorded.

Results

The incidence of blood loss of 300 mL or more within 30 minutes of delivery was significantly higher in the massage group than in the massage plus oxytocin (RR 1.88; 95% CI, 1.29-2.74 in Assiut, and RR 1.3; 95% CI, 1.00-1.68 in SA) and the oxytocin only group (RR 1.7; 95% CI, 1.11-2.61 in Assiut, and RR 2.24; 95% CI, 1.54-3.27 in SA). In both centers, use of additional uterotonics was significantly higher in the uterine massage group compared with the other 2 groups.

Conclusion

Uterine massage was less effective than oxytocin for reducing blood loss after delivery. When oxytocin was used, there was no additional benefit from uterine massage. The effectiveness of uterine massage in the absence of oxytocin was not studied. ACTRN: 12609000372280.     

Drape estimation vs. visual assessment for estimating postpartum hemorrhage.

OBJECTIVE: To compare (1) visual estimation of postpartum blood loss with estimation using a specifically designed blood collection drape and (2) the drape estimate with a measurement of blood loss by photospectrometry. METHODS: A randomized controlled study was performed with 123 women delivered at the District Hospital, Belgaum, India. The women were randomized to visual or drape estimation of blood loss. A subsample of 10 drape estimates was compared with photospectrometry results. RESULTS: The visual estimate of blood loss was 33% less than the drape estimate. The interclass correlation of the drape estimate to photospectrometry measurement was 0.92. CONCLUSION: Drape estimation of blood loss is more accurate than visual estimation and may have particular utility in the developing world. Prompt detection of postpartum hemorrhage may reduce maternal morbidity and mortality in low-resource settings.     

Community-based distribution of misoprostol for treatment or prevention of postpartum hemorrhage: Cost-effectiveness, mortality, and morbidity reduction analysis

Objective

To compare the cost-effectiveness of community-based distribution of misoprostol for prevention with misoprostol for treatment of postpartum hemorrhage (PPH).

Methods

A Monte Carlo simulation depicted mortality and anemia-related morbidity attributable to PPH among 3 scenarios of 10 000 women delivering at home in rural India: (1) standard management; (2) standard management plus 800 µg of sublingual misoprostol for PPH treatment; and (3) standard management plus 600 µg of prophylactic oral misoprostol. The model included costs of drugs, birth attendant training, and transport for women who did not respond to misoprostol.

Results

Misoprostol lowered mortality by 70% and 81% in scenarios 2 and 3, respectively. Scenarios 2 and 3 raise costs by 6% and 35%, respectively. Incremental cost per disability-adjusted life year (DALY) saved is estimated at $6 and $170, respectively.

Conclusion

Both interventions were more effective at decreasing mortality and anemia than standard management. The most efficient scale-up plan would focus initially on increasing coverage with the treatment strategy ($6 per DALY).     

Factors associated with acute postpartum hemorrhage in low-risk women delivering in rural India.

OBJECTIVE: Postpartum hemorrhage (PPH), a major cause of maternal mortality and morbidity in low-income countries, can occur unpredictably. This study examined the sociodemographic, clinical, and perinatal characteristics of low-risk women who experienced PPH. METHODS: This analysis was conducted using data on 1620 women from a randomized trial testing oral misoprostol for prevention of PPH in rural India. RESULTS: Of the women, 9.2% experienced PPH. No maternal or sociodemographic factors and few perinatal factors differed between women with PPH and those without, other than treatment with misoprostol. Having fewer than 4 prenatal visits and lack of iron supplementation increased the risk for PPH (P<0.001 and P=0.037, respectively). Several factors unknown until the second stage of labor (perineal tear and birth weight) were also associated (P=0.003). CONCLUSIONS: Among women at low risk for PPH, there were few factors associated with further risk. Given that PPH can occur without warning, rural communities should consider ways to increase both primary prevention (iron supplementation, AMTSL) and secondary prevention of PPH (availability of obstetric first aid, availability of transport, and availability of emergency obstetric care).     

Oral misoprostol for prevention of postpartum hemorrhage by paramedical workers in India.

OBJECTIVE: To study whether paramedical workers from rural primary health centers in India are able to administer oral misoprostol and actively manage the third stage of labor to prevent postpartum hemorrhage (PPH). METHOD: Cluster randomization was used to enroll 1200 women at 30 peripheral health centers from 5 states in India, 600 forming the study's intervention group (active management of the third stage of labor with 600 mug of oral misoprostol) and 600 forming the comparison group (in which the current government guidelines for the prevention of PPH were followed). The primary outcome was blood loss after delivery, which was measured using a calibrated blood collection drape. RESULTS: Age, literacy level, occupation, and gravidity were similar in the 2 groups. More than 70% of women in both groups had moderate anemia (hemoglobin level <10 g/dL). Paramedical workers followed instructions in almost all deliveries in the intervention group (99%). There was a significant reduction in duration of the third stage of labor (7.9 +/- 4.2 min vs. 10.9 +/- 4.3 min; p < .001) and median blood loss after delivery (100 mL vs. 200 mL; p < .001) in the intervention group. Overall, a low incidence of PPH was observed (<1%) in both groups. A greater number of women had moderate to severe shivering (12.7% vs. 0.5%) and a temperature higher than 38 degrees C (9.7% vs. 4.3%) in the intervention group, which was statistically significant. CONCLUSION: Simple interventions can be easily implemented in rural health care settings to reduce the blood loss during labor. This finding has significant implications for developing countries, in which the prevalence of anemia is high.     

A double-blind, randomized, placebo-controlled trial of misoprostol and routine uterotonics for the prevention of postpartum hemorrhage

Objective

To assess the effects of 400-μg sublingual misoprostol plus routine uterotonics on postpartum hemorrhage.

Methods

A double-blind, placebo-controlled, randomized study was performed. After delivery of the child, eligible women received routine uterotonics and were randomly allocated to receive 400-μg misoprostol or placebo sublingually. The primary outcome measure was blood loss of at least 500 mL within 1 hour of taking the trial tablets.

Results

In total, 672 women received misoprostol and 673 received placebo. The baseline data were similar for both groups. Misoprostol plus routine uterotonics reduced postpartum blood loss, but the effect was not significant for blood loss of at least 500 mL (relative risk [RR] 0.96; 95% confidence interval [CI], 0.63-1.45) or blood loss of at least 1000 mL (RR 0.50; 95% CI, 0.15-1.66). Misoprostol also reduced the need for non-routine oxytocin, manual removal of the placenta, and hysterectomy, but these differences were not significant either. Misoprostol was associated with pyrexia and moderate/severe shivering. There was no death in either group.

Conclusion

Misoprostol plus routine uterotonics resulted in modest reductions of blood loss in the third stage of labor, but the effects did not reach statistical significance. Larger studies are recommended.     

Misoprostol in preventing postpartum hemorrhage: a meta-analysis.

OBJECTIVE: To assess misoprostol's ability to prevent postpartum hemorrhage (PPH) where no alternatives exist. Comparison to oxytocics demonstrates how similarly misoprostol achieves a level of effectiveness-obtainable only in hospitals-in remote locations around the world. METHOD: Using the Mantel-Haenszel fixed-effects model and the DerSirmonian and Laird random-effects model, summary statistics indicated that misoprostol's excess risk of PPH was only 4% when compared to oxytocics. RESULT: This risk difference was well within the range of expected results for all uterotonic agents and does not warrant branding misoprostol as an inferior drug. CONCLUSION: Conventional uterotonic drugs should not be used to set the lowest-accepted level of effectiveness in settings where they are entirely unsuitable. Continuing to weigh the benefits of one effective drug against another only delays the distribution of misoprostol in countries where it is the only feasible choice and must be measured against no treatment at all.     

Introduction of misoprostol for prevention of postpartum hemorrhage at the community level in Senegal

Objective

To demonstrate that training ensures correct administration of oral misoprostol by auxiliary midwives for prevention of postpartum hemorrhage (PPH) among women giving birth at the community level in Senegal.

Methods

A 6-day training program for auxiliary midwives and supervisors, including 1 day of PPH prevention training and a practicum of 10 deliveries at health centers and 3 deliveries at maternity huts, was conducted in 2 Senegalese districts in June–July 2009. Data were collected between July and December 2009 on the administration of oral misoprostol by trained auxiliary midwives among 245 women giving birth at health centers, health posts, and maternity huts.

Results

All participating women received the correct administration of oral misoprostol; however, few women delivering in the community-based maternity huts received the supervision that is locally required to administer misoprostol. Women were willing to pay for some or all of the costs of misoprostol for PPH prevention.

Conclusion

Timely management of PPH is essential to reduce maternal mortality. With limited training, auxiliary midwives achieved the correct administration of oral misoprostol that can attain this goal. Community delivery supervised by a skilled attendant limits access to, and need not be a requirement for, PPH prevention.     

Prevention and treatment of postpartum hemorrhage: new advances for low-resource settings

Postpartum hemorrhage due to uterine atony is the primary direct cause of maternal mortality globally. Management strategies in developed countries involve crystalloid fluid replacement, blood transfusions, and surgery. These definitive therapies are often not accessible in developing countries. Long transports from home or primary health care facilities, a dearth of skilled providers, and lack of intravenous fluids and/or a safe blood supply often create long delays in instituting appropriate treatment. We review the evidence for active management of third-stage labor and for the use of specific uterotonics. New strategies to prevent and manage postpartum hemorrhage in developing countries, such as community-based use of misoprostol, oxytocin in the Uniject delivery system, the non-inflatable antishock garment to stabilize and resuscitate hypovolemic shock, and the balloon condom catheter to treat intractable uterine bleeding are reviewed. New directions for clinical and operations research are suggested.     

高龄妊娠对产后出血的影响

目的探讨孕妇高龄是否对产后出血产生影响。 方法采用回顾性研究方法对2009年1月1日至2014年12月31日在广州医科大学附属第三医院妇产科住院分娩的年龄≥18岁单胎产妇28 839例的临床资料进行分析,按照孕妇分娩年龄进行分组,≥35岁为高龄组(3 670例),18～34岁为适龄组(25 169例),比较两组产后出血发病率、首发病因和妊娠结局;采用独立样本t检验、秩和检验、χ²检验对数据进行统计学分析。 结果本研究总的产后出血发生率为3.75%(1 081/28 839);高龄组产后出血发病率4.66%(171/3670),比适龄组产后出血发病率3.62%(910/25 169)高(χ²＝9.673,P＝0.002)。高龄组产后出血首发病因分别为：子宫收缩乏力(55.55%)、胎盘因素(39.77%)、软产道裂伤(3.51%)、凝血功能障碍(1.17%)。高龄组平均住院天数、顺产产后出血量、子宫切除率、转重症监护病房比例、输红细胞比例均高于适龄组,分别为(9.36±0.59)d和(6.42±0.96)d,(799.09±30.55)ml和(742.44±11.34)ml,12.87%和4.51%,5.8%和2.75%,28.65%和17.25%,P均<0.05。 结论高龄妊娠的孕妇更容易发生产后出血,且结局较差,子宫收缩乏力及胎盘因素是主要原因。     

米索前列醇预防剖宫产术后出血的临床研究

目的观察米索前列醇用于剖宫产预防产后出血的效果。方法选择１８２例剖宫产者,随机分为米索前列醇组、米索前列醇＋催产素组及催产素组。米索前列醇组６０例,术中打开腹膜时口服米索前列醇６００μｇ。米索前列醇＋催产素组６４例,术中打开腹膜时口服米索前列醇６００μｇ,胎儿娩出后宫体肌内注射催产素２０ＩＵ。催产素组５８例,胎儿娩出后宫体肌内注射催产素２０ＩＵ,再静脉滴注催产素２０ＵＩ。以上各组观察术中及术后２小时内出血量。结果术中及术后２小时平均出血量,米索前列醇组为２１２±５６０ｍｌ;米索前列醇＋催产素组为２０８±５５４ｍｌ;催产素组为３４５±６４７ｍｌ。米索前列醇组与催产素组比较,差异有极显著性（Ｐ＜００１）。米索前列醇组与米索前列醇＋催产素组比较,差异无显著性（Ｐ＞００５）。结论米索前列醇促进子宫收缩作用强于催产素,能较好地预防剖宫产术后出血,且用药方便、安全。