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.     

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.     

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。     

Oral misoprostol in the third stage of labor.

OBJECTIVE: To compare the efficacy of intravenous ergometrine, intramuscular oxytocin, and oral misoprostol in the control of postpartum hemorrhage. METHODS: Mean blood loss, rates of blood loss between 500 and 1000 ml, hematocrit fall greater than 10%, and need for additional oxytocic agents and nature and rates of adverse effects were assessed in this prospective, randomized, controlled study. RESULTS: All outcomes were similar in the 3 groups. The main adverse effects in the misoprostol group were temperatures higher than 99 degrees F, which normalized within 2 h and shivering, which was mild and self-limiting. CONCLUSIONS: Oral misoprostol is as effective as conventional oxytocic agents in preventing postpartum hemorrhage and can be recommended for use in low-resource settings.     

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.     

Induction of labor with vaginal misoprostol plus oxytocin versus oxytocin alone

Objective

To compare the effect of an oxytocin infusion alone or preceded by an intravaginal application of misoprostol for labor induction in women with term pregnancies and a low Bishop score.

Methods

This study randomized 100 multiparous women with singleton pregnancies over 38 weeks and a Bishop score less than 6 to receive either a single 50-µg dose of misoprostol intravaginally 3 hours before initiation of the oxytocin infusion or only an oxytocin infusion. The time from induction to delivery, the route of delivery, and maternal and fetal outcomes were analyzed.

Results

The mean time from induction to delivery was 9.36 ± 1.97 hours in the misoprostol plus oxytocin group and 11.08 ± 3.23 in the oxytocin alone group (P = 0.002). The rates of vaginal delivery, 1- and 5-minute Agpar scores, placental abruption, and postpartum hemorrhage were similar between the 2 groups, as were the rates of admission to the neonatal intensive care unit. There were no cases of perinatal asphyxia.

Conclusion

A 50-µg intravaginal application of misoprostol before starting the oxytocin infusion is a more effective method of labor induction than an oxytocin infusion alone for our study population.     

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.     

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.     

Advance distribution of misoprostol for the prevention of postpartum hemorrhage in South Sudan

Objective

To determine if high uterotonic coverage can be achieved in South Sudan through a facility- and community-focused postpartum hemorrhage (PPH) prevention program.

Methods

The program was implemented from October 2012 to March 2013. At health facilities, active management of the third stage of labor (AMTSL) was emphasized. During prenatal care and home visits, misoprostol was distributed to pregnant women at approximately 32 weeks of pregnancy for the prevention of PPH at home births. Data on uterotonic coverage and other program outcomes were collected through facility registers, home visits, and postpartum interviews.

Results

In total, 533 home births and 394 facility-based births were reported. Misoprostol was distributed in advance to 787 (84.9%) pregnant women, of whom 652 (82.8%) received the drug during home visits. Among the women who delivered at home, 527 (98.9%) reported taking misoprostol. A uterotonic for PPH prevention was provided at 342 (86.8%) facility-based deliveries. Total uterotonic coverage was 93.7%. No adverse events were reported.

Conclusion

It is feasible to achieve high coverage of uterotonic use in a low-resource and postconflict setting with few skilled birth attendants through a combination of advance misoprostol distribution and AMTSL at facilities. Advance distribution through home visits was key to achieving high coverage of misoprostol use.     

Rectal misoprostol versus intravenous oxytocin for the prevention of postpartum hemorrhage after vaginal delivery

OBJECTIVE: To compare rectally administered misoprostol to intravenously administered oxytocin for the management of third-stage labor. STUDY DESIGN: Subjects were randomized to receive two, 200-microg misoprostol tablets rectally (study medication) plus 2 mL saline in Ringer's lactate intravenously or two lactose tablets rectally plus 20 units oxytocin in Ringer's lactate intravenously (control medication). Blood loss was determined by estimation, measurement, and change in hematocrit values from admission to postpartum day 1. Subjects were excluded if cesarean delivery was required. RESULTS: A total of 325 women underwent analysis. By estimation, 21% of subjects and 15% of controls had postpartum hemorrhage (P =.17). By using measured blood loss, we determined that 70 of 154 (46%) study subjects and 61 of 161 (38%) control subjects had postpartum hemorrhage (P =.17). For 36 (23%) misoprostol subjects and 18 (11%) oxytocin subjects at least one additional agent was required to control bleeding (P =.004). CONCLUSION: Rectal misoprostol (400 microg) was no more effective than intravenous oxytocin in preventing postpartum hemorrhage.     

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.     

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.     

Using Uniject to increase the use of prophylactic oxytocin for management of the third stage of labor in Latin America

Objective

To evaluate a multifaceted intervention for effectiveness in increasing the use of prophylactic oxytocin by birth attendants (obstetricians, midwives, and nurses) working in small maternity hospitals in Argentina.

Methods

A before-and-after quasi-experimental study was conducted in 5 small maternity hospitals. The study intervention consisted of training birth attendants in the active management of the third stage of labor, distributing oxytocin in Uniject (Hipofisina BIOL Uniject; Laboratorios BIOL, Buenos Aires, Argentina), and using posters as reminders. The primary outcome was the rate of prophylactic oxytocin use in the 6 months before and the 6 months of the intervention period. Secondary outcomes included use of controlled cord traction and uterine massage, and birth attendants' acceptance of the use of oxytocin in Uniject.

Results

The use of prophylactic oxytocin showed a median rate of 14.6% at baseline and 85.6% during the intervention period. 96% of birth attendants reported that the Uniject device facilitated oxytocin 1administration.

Discussion

Prophylactic oxytocin in the third stage of labor is a beneficial intervention with current low use, particularly in low- and middle-income countries. If the results shown in the present study were further replicated, this strategy could be an effective method for improving prophylactic oxytocin use in other similar Latin American hospitals.     

Comparison of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor

Objective

To compare the efficacy and adverse effects of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor (AMTSL).

Methods

A double-blind randomized trial of 300 women with a healthy singleton pregnancy allocated into 4 groups to receive either: 400 µg or 600 µg of sublingual misoprostol, 5 IU of intravenous oxytocin, or 200 µg of intravenous methylergometrine. The primary outcome measure was blood loss in the third and fourth stage of labor; secondary measures were duration of the third stage of labor, changes in hemoglobin levels, and adverse effects.

Results

Patients who received 600 µg of misoprostol had the lowest blood loss (96.05 ± 21.1 mL), followed by 400 µg of misoprostol (126.24 ± 49.3 mL), oxytocin (154.7 ± 45.7 mL), and methylergometrine (223.4 ± 73.7 mL) (P < 0.01). Shortest mean duration of the third stage of labor (5.74 minutes) was with 600 µg of misoprostol, while methylergometrine had the longest (6.83 minutes) (P < 0.05). Pyrexia was observed in the misoprostol groups, and raised blood pressure in the methylergometrine group (P < 0.001). The 24-hour postpartum hemoglobin level was similar among the groups (P > 0.05).

Conclusion

Administration of 600 µg of sublingual misoprostol was more effective than 400 µg of misoprostol, intravenous oxytocin, and intravenous methylergometrine for AMTSL.     

刺激乳头对产后出血的影响：（附300例分析）

本文对1992年8月至1992年12月在辽宁省彰武县正常分娩、非高危妊娠的300例产妇进行产后出血的前瞻性研究。其中200例为实验组,当胎儿前肩娩出后刺激双侧乳头以增强子宫收缩;另选条件相似的100例产妇为对照,不作任何干预,对比第三产程时间及产后2小时和产后24小时的出血量。结果证明:胎儿前肩娩出后刺激乳头能减少产后出血发生率,对照组产后出血发生率为20％,刺激乳头组产后出血发生率仅为10.51％,二组差异显著,P<0.05。此方法简便易行,适于推广应用。     

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).     

Preventing postpartum hemorrhage in low-resource settings.

OBJECTIVES: To review the literature to determine the most effective methods for preventing postpartum hemorrhage (PPH), the single most important cause of maternal death worldwide. METHODS: Systematic review of published randomized controlled trials and relevant reviews. RESULTS: Review of the literature confirms that active management of the third stage of labor, especially the administration of uterotonic drugs, reduces the risk of PPH due to uterine atony without increasing the incidence of retained placenta or other serious complications. Oxytocin is the preferred uterotonic drug compared with syntometrine, but misoprostol also can be used to prevent hemorrhage in situations where parenteral medications are not available (e.g. at home births in developing countries). CONCLUSIONS: The use of active management of the third stage of labor to prevent PPH due to uterine atony should be expanded, especially in developing country settings.     

Misoprostol use during the third stage of labor.

OBJECTIVES: To systematically review the efficacy of misoprostol compared with placebo or other uterotonics in preventing maternal morbidity associated with the third stage of labor. METHODS: We identified, retrieved, evaluated, abstracted data, and assessed the quality of all published studies (from January 1996 to May 2002) which assessed misoprostol's efficacy in minimizing uterine blood loss during the third stage of labor. Seventeen studies included 28170 subjects; of these, approximately one-half received misoprostol with the remainder receiving either a placebo or another uterotonic agent. An estimate of the odds ratio (OR) and risk difference for dichotomous outcomes was calculated using a random- and fixed-effects model. Continuous outcomes were pooled using a variance-weighted average of within-study difference in means. RESULTS: In assessing studies comparing misoprostol with placebo, those who received oral misoprostol had a decreased risk of needing additional uterotonics (OR 0.64, 95% confidence interval 0.46, 0.90). Compared with placebo, use of misoprostol was associated with an increased risk for shivering and pyrexia. In contrast, in studies comparing misoprostol with oxytocin, oxytocin was associated with significantly lower rates of postpartum hemorrhage, maternal shivering and pyrexia. In studies comparing misoprostol with Syntometrine, misoprostol was associated with higher rates of the need for additional uterotonic agent as well as shivering. CONCLUSIONS: Misoprostol was inferior to oxytocin and other uterotonics with regard to any of the third stage of labor outcomes assessed. However, when compared to placebo, misoprostol had a decreased risk of needing additional uterotonics. Thus, in less-developed countries where administration of parenteral uterotonic drugs may be problematic, misoprostol represents a reasonable agent for the management of the third stage of labor. Additional randomized clinical trials examining objective outcome measures (i.e. need for blood transfusion or 10% hemoglobin change) may further define benefits and risks of misoprostol use during the third stage of labor.