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.     

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.     

Management of the third stage of labour: (for the Optimal Intrapartum Care series edited by Mercedes Bonet,Femi Oladapo and Metin Gülmezoglu)

The physiology of the third stage of labour is described. Active management reduces the risk of postpartum haemorrhage (PPH), due to the use of a uterotonic agent. Intramuscular Oxytocin 10 IU has the highest efficacy and lowest side effect profile, although ergometrine, carbetocin and misoprostol are also effective. The appropriate uterotonic in different settings such as home birth by unskilled attendants and at caesarean section is discussed. For the latter, there is less consensus on the optimal dose/route of oxytocin, this topic remaining on the research agenda. Delayed cord clamping enables transfusion of blood to the neonate and is recommended rather than early clamping. Controlled cord traction should only be performed by skilled birth attendants and confers minimal advantage in preventing retained placenta. The importance of early recognition of PPH, and preparedness, is emphasised. An approach to medical and surgical management of PPH is presented.     

Current strategies for the prevention of postpartum haemorrhage in the third stage of labour

PURPOSE OF REVIEW: Despite evidence that active management of the third stage of labour reduces the incidence of postpartum haemorrhage, expectant management is still widely practised. Factors accounting for this situation include the desire for a more natural experience of childbirth, the philosophy that active management is unnecessary in low-risk women, and avoidance of the adverse effects of conventional uterotonic agents. This review will evaluate the various strategies currently used for the prevention of primary postpartum haemorrhage. RECENT FINDINGS: Since publication of the first systematic review comparing active with expectant management in 1988, active management of the third stage using oxytocics has become increasingly adopted. Recent surveys, however, show that there are still wide variations in practice around the world. Recent interest has focused on the use of misoprostol for the prevention of postpartum haemorrhage. Carbetocin, an oxytocin receptor agonist, shows promise but has not been evaluated for use after vaginal births. SUMMARY: Active management of the third stage of labour is superior to expectant management in terms of blood loss, postpartum haemorrhage and other serious complications, but is associated with unpleasant side effects and hypertension when ergometrine is included. Intramuscular oxytocin results in fewer side effects. Oral and rectal misoprostol has been extensively assessed and found to be less effective than conventional oxytocics with more side effects. Until alternative regimes of misoprostol are studied in large controlled trials, misoprostol is not recommended for routine use in the third stage of labour. Of the remaining uterotonic agents evaluated, intramuscular carbetocin appears the most promising.     

Risk factors for primary postpartum haemorrhage

The objective of the study was to determine which background factors predispose women to primary postpartum haemorrhage (PPH) at the Obafemi Awolowo University Hospital. The study consisted of 101 women who developed PPH after a normal vaginal delivery and 107 women with normal unassisted vaginal delivery without PPH Both cases and controls were investigated for sociodemographic risk factors, medical and obstetric histories, antenatal events and labour and delivery outcomes. Data were abstracted from the medical and delivery records and risks were estimated by multivariate logistic regression. The results of the unvariate analysis revealed a number of potential risk factors for PPH but after adjustment by logistic regression three factors remained significant. These were prolonged second and third stages of labour and non-use of oxytocics after vaginal delivery. Previously hypothesised risk factors for PPH such as grand multiparity, primigravidity and previous episodes of PPH were not significantly associated with PPH. We conclude that primary PPH in this population is mostly associated with prolonged second and third stages of labour and non use of oxytocics. Efforts to reduce the incidence of PPH should not only be directed at proper management of labour but also training and retraining of primary health care workers and alternative health care providers in the early referral of patients with prolonged labour.     

Buccal misoprostol to prevent hemorrhage at cesarean delivery: a randomized study

OBJECTIVE: The purpose of this study was to assess the efficacy of buccal misoprostol to decrease uterine atony, hemorrhage, and the need for additional uterotonic agents during cesarean delivery. STUDY DESIGN: Patients who underwent cesarean delivery were assigned randomly to either 200-microg misoprostol or placebo placed in the buccal space. A dilute intravenous oxytocin infusion was given to all patients at delivery of the placenta. The primary outcome variable was the need for additional uterotonic agents. RESULTS: A total of 352 women received random assignments. Demographic and intrapartum characteristics were similar between the groups. More women in the placebo group required 1 additional uterotonic agent (43% vs 26%; P < .01; relative risk, 1.3; 95% CI, 1.10, 1.50). There was not a difference between the groups in the incidence of postpartum hemorrhage or a difference in preoperative and postoperative hemoglobin level. CONCLUSION: Buccal misoprostol reduces the need for additional uterotonic agents during cesarean delivery.     

A Study to Compare the Efficacy of Misoprostol, Oxytocin, Methyl-ergometrine and Ergometrine–Oxytocin in Reducing Blood Loss in Active Management of 3rd Stage of Labor

Objectives

The purpose of the study was to compare the efficacy of misoprostol 400 μg per rectally, injection oxytocin 10 IU intramuscular, injection methylergometrine 0.2 mg intravenously and injection (0.5 mg ergometrine + 5 IU oxytocin) intramuscular on reducing blood loss in third stage of labor, duration of third stage of labor, effect on haemoglobin of the patient, need of additional oxytocics or blood transfusion and associated side effects and complications.

Study Design

A prospective non-randomized uncontrolled study was carried out in the Department of Obstetrics and Gynecology, SSG Hospital and Medical College, Baroda enrolling 200 women and dividing them into four groups. Active management of 3rd stage of labor was done using one of the 4 uterotonics as per the group of the patient. The main outcome measures were the amount of blood loss, the incidence of postpartum hemorrhage and a drop in hemoglobin concentration from before delivery to 24 h after delivery.

Results

Methylergometrine was found to be superior to rest of the drugs in the study with lowest duration of third stage of labor (P = 0.000096), lowest amount of blood loss (P = 0.000017) and lowest incidence of PPH (P = 0.03). There was no significant difference in the pre-delivery and the post-delivery hemoglobin concentration amongst the four groups with P = 0.061. The need of additional oxytocics and blood transfusion was highest with misoprostol as compared to all other drugs used in the study with P = 0.037 and 0.009, respectively. As regards side effects, misoprostol was associated with shivering and pyrexia in significantly high number of patients as compared to the other drugs used in the study while nausea, vomiting and headache were more associated with methylergometrine and ergometrine–oxytocin. However all the side effects were acceptable and preferable to the excessive blood loss.

Conclusion

Methylergometrine has the best uterotonic drug profile amongst the drugs used, strongly favouring its routine use as oxytocic for active management of third stage of labor. Misoprostol was found to cause a higher blood loss compared to other drugs and hence should be used only in low resource setting where other drugs are not available. The role of misoprostol in third stage of labor needs larger studies to be proved.     

Carbetocin versus sublingual misoprostol plus oxytocin infusion for prevention of postpartum hemorrhage at cesarean section in patients with risk factors: a randomized, open trail study

Objectives

To compare combined sublingual misoprostol plus oxytocin infusion with intravenous carbetocin for prevention of postpartum hemorrhage (PPH) in patients with risk factors during cesarean section (CS).

Methods

In this randomized study, 380 patients were randomly allocated to receive either combined 400 μg sublingual misoprostol before surgery plus 20 IU oxytocin after delivery of baby (n = 190) or intravenous 100 μg carbetocin (n = 190). The main outcome measure was requirement of additional pharmacological uterotonic. Secondary outcomes were the difference in preoperative and postoperative hemoglobin, estimated blood loss, incidence of blood transfusion and adverse effects.

Results

16.3 % of women who received sublingual misoprostol plus oxytocin infusion required additional uterotonic versus 13.7 % of women who received intravenous carbetocin with no significant difference (p = 0.27). No significant difference between treatment groups in preoperative and postoperative hemoglobin level change, estimated blood loss, incidence of blood transfusion was observed. Shivering and fever were significantly higher with misoprostol plus oxytocin (p = <0.001 and <0.001, respectively).

Conclusion

Both sublingual misoprostol plus oxytocin infusion and intravenous carbetocin are similarly effective for the prevention of PPH in patients with risk factors during CS.     

A continuum of care model for postpartum hemorrhage

The leading cause of maternal mortality is hemorrhage, generally occurring in the postpartum period. Current levels of PPH-related morbidity and mortality in low-resource settings result from institutional, environmental, cultural and social barriers to providing skilled care and preventing, diagnosing and treating PPH. Conventional uterotonics to prevent PPH are typically not available or practical for use in low-resource settings. In such deliveries, most often taking place at home or in rural health centers, underestimation of blood loss leads to a delay in diagnosis. Deficiencies in communication and transportation infrastructure impede transfer to a higher level of care. Inability to stabilize a patient who is in hemorrhagic shock rapidly results in death. To address these individual factors, we propose a continuum of care model for PPH, including routine use of prophylactic misoprostol or other appropriate uterotonic, a standardized means of blood loss assessment, availability of a non-pneumatic anti-shock garment, and systemization of communication, transportation, and referral. Such a multifaceted, systematic, contextualized PPH continuum of care approach may have the greatest impact for saving women's lives. This model should be developed and tested to be region-specific.     

Expanding uterotonic protection following childbirth through community-based distribution of misoprostol: Operations research study in Nepal

Objective

To determine feasibility of community-based distribution of misoprostol for preventing postpartum hemorrhage (PPH) to pregnant woman through community volunteers working under government health services.

Methods

Implemented in one district in Nepal. The primary measure of performance was uterotonic protection after childbirth, measured using pre- and postintervention surveys (28 clusters, each with 30 households). Maternal deaths were ascertained through systematic health facility and community-based surveillance; causes of death were assigned based on verbal autopsy.

Results

Of 840 postintervention survey respondents, 73.2% received misoprostol. The standardized proportion of vaginal deliveries protected by a uterotonic rose from 11.6% to 74.2%. Those experiencing the largest gains were the poor, the illiterate, and those living in remote areas.

Conclusion

Community-based distribution of misoprostol for PPH prevention can be successfully implemented under government health services in a low-resource, geographically challenging setting, resulting in much increased population-level protection against PPH, with particularly large gains among the disadvantaged.     

Randomized Double Masked Trial of Zhi Byed 11, a Tibetan Traditional Medicine,Versus Misoprostol to Prevent Postpartum Hemorrhage in Lhasa,Tibet

The objective of this study was to compare a Tibetan traditional medicine (the uterotonic Zhi Byed 11 [ZB11]) to oral misoprostol for prophylaxis of postpartum hemorrhage (PPH). We conducted a double‐blind randomized controlled trial at three hospitals in Lhasa, Tibet, People's Republic of China. Women (N = 967) were randomized to either ZB11 or misoprostol groups. Postpartum blood loss was measured in a calibrated blood collection drape. The primary combined outcome was incidence of PPH, defined as measured blood loss (MBL) ≥ 500 mL, administration of open label uterotonics, or maternal death. We found that the rate of the combined outcome was lower among the misoprostol group (16.1% versus 21.8% for ZB11; P = .02). Frequency of PPH was lower with misoprostol (12.4% versus 17.4%; P = .02). There were no significant differences in MBL > 1000 mL or mean or median MBL. Fever was significantly more common in the misoprostol group (P = .03). The rate of combined outcome was significantly lower among women receiving misoprostol. However, other indices of obstetric hemorrhage were not significantly different.     

Efficacy of rectal misoprostol as second-line therapy for the treatment of primary postpartum hemorrhage

OBJECTIVE: To assess the efficacy of rectal misoprostol as second-line therapy in the management of primary postpartum hemorrhage (PPH) as compared to methylergonovine maleate. STUDY DESIGN: This was a retrospective cohort study. Charts from July 2000 to February 2005 were reviewed. Inclusion criteria were patients between 37 and 42 weeks' gestational age who received a clinical diagnosis of PPH following delivery of a singleton pregnancy and who required a second uterotonic following initial oxytocin therapy. The control group represented those receiving methylergonovine maleate (18 patients), and the study group consisted of those receiving misoprostol (40 patients). RESULTS: There was no significant difference in maternal age, gestational age, parity or type of delivery between the 2 groups. There was no significant difference between the 2 groups in the need for blood transfusion (methylergonovine maleate group, 0/18 [0%], misoprostol group, 5/40 [12.5%] [p = 0.11]), the need for third-line medical therapy (methylergonovine maleate group, 10/18 [55.5%], misoprostol group, 22/40 [55%] [p = 0.961) or the need for any surgical intervention (methylergonovine maleate, 4/18 [22.2%], misoprostol 5/40 [12.5%] [p = 0.51]). CONCLUSION: This limited study suggests that rectal misoprostol is comparable to methergine as second-line therapy for the treatment of 1 primary postpartum hemorrhage.     

The effect of prophylactic oral tranexamic acid plus buccal misoprostol on blood loss after vaginal delivery: a randomized controlled trial

Objective: The objective of this study is to evaluate the effect of prophylactic oral tranexamic acid (TA) plus buccal misoprostol on the amount of blood loss after vaginal delivery in women at low risk for post-partum hemorrhage (PPH).

Materials and methods: The study was a randomized open label clinical trial conducted in a tertiary University Hospital between January 2016 and June 2017. We included women who delivered vaginally with a singleton pregnancy. They were randomized into three groups: group I (women received 10?IU oxytocin IV after delivery of the baby), group II (women received 600?µg buccal misoprostol after delivery of the baby), and group III (women received 1000?mg oral TA at the end of the first stage of labor plus 600 µg buccal misoprostol after delivery of the baby). In each group, pre- and post-delivery pulse rate, blood pressure, temperature, and hemoglobin level were evaluated. Additionally, the amount of blood loss, need for blood transfusion, need for additional uterotonics, and side effects of the study medications were recorded.

Results: There was a statistically significant lower hemoglobin level and higher blood loss in the misoprostol group compared with oxytocin group and TA plus misoprostol group (p?=?.0001). There was a statistically significant higher hemoglobin level and lower blood loss in the TA plus misoprostol group compared with the oxytocin group (p?=?.004 and .043, respectively). PPH occurred in 16.7% of women in the misoprostol group compared 1.7% in the oxytocin group and no cases of PPH in the TA plus misoprostol group (p?=?.0001).

Conclusions: In settings like rural area or home delivery in which oxytocin is not available, alternative oral TA plus buccal misoprostol may be considered as an effective line in prevention of PPH.     

Randomized Controlled Trial of Rectal Misoprostol Versus Oxytocin in Third Stage Management

Objective: To compare rectal misoprostol with oxytocin for routine management of the third stage of labour.Study design: A total of 240 parturient women were randomized, at three University of Toronto teaching hospitals, to receive either rectal misoprostol (400 µg) after delivery of the infant or parenteral oxytocin (5 units IV or 10 units IM) with the delivery of the anterior shoulder, when possible, or 5 units IV or IM after the delivery of the placenta.The primary outcome measure was change in hemoglobin (Δ[Hgb]) from admission in early labour to day one postpartum.Setting: The labour ward of three University of Toronto teaching hospitals: St. Michaels, Toronto General, and Mount Sinai.Population: Labouring women either nulliparous or muciparous with no known risk for excessive third stage blood loss; vertex presentation; no previous Caesarean delivery; induced, spontaneous, or augmented labour.Results: No difference in Δ[Hgb] was observed between the two groups; the Δ[Hgb] in the oxytocin and misoprostol groups were 1.43 g/L (95% confidence interval [Cl], 1.2–1.6 g/L) and 1.59 g/L (95% Cl, 1.4–1.8 g/L) respectively (p = 0.35). Secondary outcome measures (excessive third stage bleeding, duration of third stage of labour, need for manual removal of the placenta or the need for additional oxytocics) did not differ between the two groups.Conclusion: Rectal misoprostol is of equivalent efficacy to parenteral oxytocin for the prevention of primary postpartum hemorrhage. Rectal misoprostol is an appropriate uterotonic agent for routine management of the third stage of labour.     

Sublingual misoprostol versus intramuscular oxytocin for prevention of postpartum hemorrhage in low-risk women

ObjectiveTo compare sublingual misoprostol with intramuscular oxytocin for prevention of postpartum hemorrhage (PPH) in low-risk vaginal birth.MethodsIn a prospective, randomized, double-blind trial, 530 women without risk of PPH were randomly allocated to receive either 400 μg of misoprostol sublingually or 10 units of oxytocin intramuscularly within 1 minute of delivery. The outcome measures were incidence of PPH, postpartum blood loss, drop in hemoglobin level in 24 hours, need for additional uterotonic drug, incidence of adverse effects, and need for blood transfusion. Student t, χ², Mann–Whitney U, and Fisher exact tests were used for comparison.ResultsIncidence of postpartum hemorrhage (≥ 500 mL) and postpartum blood loss in the misoprostol group were similar to those in the oxytocin group (6% versus 5.7%, P = 0.85; 153 mL versus 146 mL, P = 0.36). Shivering and pyrexia were encountered more often in the misoprostol than in the oxytocin group (shivering: 19% versus 0.8%, P < 0.001, relative risk [RR] 0.86, 95% confidence interval [CI] 0.82–0.90; pyrexia: 2.3% versus 0%, P = 0.03, RR 0.97, 95% CI 0.95–0.99).ConclusionThe efficacy of 400 μg of misoprostol administered sublingually was equivalent to that of 10 units of oxytocin given intramuscularly for prevention of PPH in low-risk vaginal delivery.     

A randomized, controlled trial comparing effect of oral misoprostol and intravenous syntocinon on intra-operative blood loss during cesarean section

BACKGROUND: Oxytocics are routinely used in an attempt to prevent excessive blood loss during cesarean section. Misoprostol, a potent uterotonic agent, has been reported to be useful in the prevention and treatment of postpartum hemorrhage by several investigators but its use during cesarean section has not been described. The objective of this study was to randomly compare the effectiveness of oral misoprostol with intravenous syntocinon on blood loss during elective cesarean sections under regional anesthesia. METHODS: Sixty pregnant women were randomized either to receive misoprostol 400 micrograms orally or syntocinon 10 IU intravenously during cesarean section. The primary outcome measure was intra-operative blood loss as estimated by physicians, and by values of preoperative and postoperative hemoglobin concentration and hematocrit. Demographic characteristics of the subjects and outcomes were compared using chi-square test for categorical and two-sample t-test for continuous data. RESULTS: Baseline characteristics in terms of age, body weight, parity, gestational age and indications for cesarean section were similar in both groups. The estimated blood loss was 545 ml (CI 476-614) in misoprostol group and 533 ml (CI 427-639) in syntocinon group (p = 0.85). Differences in preoperative and postoperative hemoglobin and hematocrit values were also similar in both groups. Two women in the misoprostol group and three in the syntocinon group (p=0.64) required additional oxytocics. One patient in each group required blood transfusion. No serious side effects were noted in either group. CONCLUSION: Oral misoprostol appears to be safe and as effective as intravenous syntocinon in reduction of intra-operative blood loss during elective cesarean section under regional anesthesia and merits further investigation.     

A randomized clinical trial comparing oral misoprostol with synthetic oxytocin or syntometrine in the third stage of labour

This is a multicentre, blocked, randomized trial to compare the efficacy of oral misoprostol 400 microg with current injectable uterotonic agents (oxytocin/ Syntometrine) used prophylactically in the third stage of labour. Main outcome measures were blood loss, use of a second uterotonic agent and difference in haemoglobin level from antepartum to postpartum. Data analysis from 863 women showed a statistically significant increase in both the mean blood loss (p < 0.001) and the rate of postpartum haemorrhage > 500 mL, (RR 2.72: 95% C1 1.73-4.27) in the misoprostol group compared to the oxytocin/Syntometrine group. The use of a second uterotonic agent was higher in the misoprostol group (RR 2.89: 95% Cl 2.00-4.18) as well as a greater decrease in postpartum haemoglobin (p = 0.015). Oral misoprostol 400 microg is significantly less effective than the traditional intramuscular uterotonic agents currently used and therefore cannot be considered as a viable option to these agents in the management of the third stage of labour.     

Active management of the third stage at Caesarean section: a randomised controlled trial of misoprostol versus Syntocinon

The objective of this trial was to investigate whether 500 microg oral misoprostol given immediately after delivery of the neonate at Caesarean section is as effective as a bolus intravenous injection of 10 iu Syntocinon in stimulating uterine contractions and thereby reducing blood loss. Forty women undergoing elective or emergency Caesarean section were included in a placebo-controlled randomised trial. Group 1 received oral misoprostol and a placebo intravenous bolus and Group 2 received intravenous Syntocinon and oral placebo tablets. The main outcome measures were estimated blood loss at Caesarean section, drop in serum haemoglobin, and the need for additional uterotonic agents. We found that there was no significant difference (p = 0.75) in estimated blood loss between the two groups. No differences were observed in the decrease in haemoglobin, requirement for additional oxytocics, the need for blood transfusion or the degree of shivering in each group (p > 0.05 in each case). We concluded that oral misoprostol could be used as an alternative oxytocic agent for the third stage at Caesarean section. However, there is an obvious need for a larger randomised controlled trial to be undertaken. Previous published studies have concentrated on vaginal births and further studies should be extended to Caesarean deliveries.     

A double-blind randomized controlled trial of oral misoprostol and intramuscular syntometrine in the management of the third stage of labor

BACKGROUND: The aim of this study was to compare the efficacy and safety of oral misoprostol 400 mug with intramuscular syntometrine in the management of the third stage of labor. MATERIAL AND METHODS: This was a double-blind randomized controlled trial conducted in a tertiary care hospital. Three hundred and fifty-five women randomized to receive either oral misoprostol 400 mug or intramuscular syntometrine in the third stage of labor were studied. The change in hemoglobin level from before to 48 h after delivery, use of additional oxytocics and treatment related side effects were the main outcome measures. RESULTS: There were no significant differences between the two groups in terms of the change in hemoglobin level and mean blood loss. The incidence of shivering was significantly higher in the misoprostol group whilst that of vomiting was significantly higher in the syntometrine group. There were no differences in the incidence of nausea, headache, diarrhea and pyrexia between the two groups. CONCLUSION: Orally administered misoprostol at a dose of 400 mug is an acceptable alternative in preventing post-partum blood loss, as measured by the peri-partum change in hemoglobin level and was not associated with an increased incidence of side effects.