Testing a home-based model of care using misoprostol for prevention and treatment of postpartum hemorrhage: results from a randomized placebo-controlled trial conducted in Badakhshan province, Afghanistan.

BACKGROUND: Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide. In Afghanistan, where most births take place at home without the assistance of a skilled birth attendant, there is a need for options to manage PPH in community-based settings. Misoprostol, a uterotonic that has been used as prophylaxis at the household level and has also been proven to be effective in treating PPH in hospital settings, is one possible option. METHODS: A double-blind, randomized placebo-controlled trial was conducted in six districts in Badakhshan Province, Afghanistan to test the effectiveness and safety of administering 800mcg sublingual misoprostol to women after a home birth for treatment of excessive blood loss. Consenting women were enrolled prior to delivery and given 600mcg misoprostol to self-administer orally as prophylaxis. Community health workers (CHW) were trained to observe for signs of PPH after delivery and if PPH was diagnosed, administer the study medication (misoprostol or placebo) and immediately refer the woman. A hemoglobin (Hb) decline of 2 g/dL or greater, measured pre- and post-delivery, served as the primary outcome; side effects, additional interventions, and transfer rates were also analyzed. RESULTS: Among the 1884 women who delivered at home, nearly all (98.7%) reported self-use of misoprostol for PPH prevention. A small fraction was diagnosed with PPH (4.4%, 82/1884) and was administered treatment. Hb outcomes, including the proportion of women with a Hb drop of 2 g/dL or greater, were similar between the study groups (misoprostol: 56.4% (22/39), placebo: 60.6% (20/33), p = 0.45). Significantly more women randomized to receive misoprostol experienced shivering (82.5% vs. placebo: 61.5%, p = 0.03). Other side effects were similar between study groups and none required treatment, including among the subset of 39 women, who received misoprostol for both of its PPH indications. CONCLUSIONS: While the study did not document a clinical benefit associated with misoprostol for treatment of PPH, study findings suggest that use of misoprostol for both prevention and treatment in the same birth as well as its use by lay level providers in home births does not result in any safety concerns. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov, number NCT01508429 Registered on December 1, 2011.

Using misoprostol to treat postpartum hemorrhage in home deliveries attended by traditional birth attendants.

OBJECTIVE: To explore the clinical and programmatic feasibility of using 800 µg of sublingual misoprostol to prevent and treat postpartum hemorrhage (PPH) during home delivery. METHODS: The present double-blind randomized controlled trial included women who underwent home deliveries in Chitral district, Khyber Pakhtunkhwa province, Pakistan, after presenting at healthcare facilities during the third trimester of pregnancy between May 28, 2012, and November 27, 2014. Participants were randomized in a 1:1 ratio to receive either 800 µg of misoprostol or placebo sublingually if PPH was diagnosed, having previously received a prophylactic oral dose of 600 µg misoprostol. The primary outcome, hemoglobin decrease of 20 g/L or greater from pre- to post-delivery assessment, was compared on a modified intention-to-treat basis. RESULTS: There were 49 patients allocated to receive misoprostol and 38 allocated to receive placebo; the incidence of a 20 g/L decrease in hemoglobin was similar between the groups (20/43 [47%] vs 19/33 [58%], respectively; P=0.335). CONCLUSION: There was no significant difference in clinical outcomes between the two trial arms. ClinicalTrials.gov:NCT01485562.

Oxytocin via Uniject (a prefilled single-use injection) versus oral misoprostol for prevention of postpartum haemorrhage at the community level: a cluster-randomised controlled trial.

BACKGROUND: Access to injectable uterotonics for management of postpartum haemorrhage remains limited in Senegal outside health facilities, and misoprostol and oxytocin delivered via Uniject have been deemed viable alternatives in community settings. We aimed to compare the efficacy of these drugs when delivered by auxiliary midwives at maternity huts. METHODS: We did an unmasked cluster-randomised controlled trial at maternity huts in three districts in Senegal. Maternity huts with auxiliary midwives located 3-21 km from the closest referral centre were randomly assigned (1:1; via a computer-generated random allocation overseen by Gynuity Health Projects) to either 600 µg oral misoprostol or 10 IU oxytocin in Uniject (intramuscular), stratified by reported previous year clinic volume (deliveries) and geographical location (inland or coastal). Maternity huts that had been included in a previous study of misoprostol for prevention of postpartum haemorrhage were excluded to prevent contamination. Pregnant women in their third trimester were screened for eligibility either during community outreach or at home-based prenatal visits. Only women delivered by the auxiliary midwives in the maternity huts were eligible for the study. Women with known allergies to prostaglandins or pregnancy complications were excluded. The primary outcome was mean change in haemoglobin concentration measured during the third trimester and after delivery. This study was registered with ClinicalTrials.gov, number NCT01713153. FINDINGS: 28 maternity hut clusters were randomly assigned-14 to the misoprostol group and 14 to the oxytocin group. Between June 6, 2012, and Sept 21, 2013, 1820 women were recruited. 647 women in the misoprostol group and 402 in the oxytocin group received study drug and had recorded pre-delivery and post-delivery haemoglobin concentrations, and overall 1412 women delivered in the study maternity huts. The mean change in haemoglobin concentrations was 3·5 g/L (SD 16·1) in the misoprostol group and 2·7 g/L (SD 17·8) in the oxytocin group. When adjusted for cluster design, the mean difference in haemoglobin decreases between groups was not significant (0·3 g/L, 95% CI -8·26 to 8·92, p=0·71). Both drugs were well tolerated. Shivering was common in the misoprostol group, and nausea in the oxytocin group. Postpartum haemorrhage was diagnosed in one woman allocated to oxytocin, who was referred and transferred to a higher-level facility for additional care, and fully recovered. No other women were transferred. INTERPRETATION: In terms of effects on haemoglobin concentrations, neither oxytocin nor misoprostol was significantly better than the other, and both drugs were safe and efficacious when delivered by auxiliary midwives. The programmatic limitations of oxytocin, including short shelf life outside the cold chain, mean that misoprostol could be more appropriate for community-level prophylaxis of postpartum haemorrhage. FUNDING: Bill & Melinda Gates Foundation.

Decentralizing postabortion care in Senegal with misoprostol for incomplete abortion.

OBJECTIVE: To expand access to postabortion care (PAC) services in Senegal by introducing misoprostol as a first-line treatment at the community level. METHODS: The present prospective study enrolled 481 women seeking treatment for incomplete abortion at 11 community health posts in Senegal between September 2011 and August 2012. Participants were given 400 µg of sublingual misoprostol and asked to return to the clinic 1 week later to confirm clinical status. At study completion, all women were asked to respond to a series of questions regarding their experience with this method. All care was provided by nurse midwives. RESULTS: All but three of the study women (99.4%; 474/477) had successful complete abortion after taking misoprostol. Almost all women were satisfied or very satisfied with the treatment (99.6%; 469/471), would select the method again if needed (98.9%; 465/470), and would recommend the method to a friend (99.8%; 468/469). CONCLUSION: The results provide further evidence that 400 µg of misoprostol is highly effective for first-line treatment of incomplete abortion. Furthermore, this regimen can be fully provided by nurse midwives, and can be easily and successfully introduced in community health settings where other methods of PAC may not previously have been available. Clinicaltrials.gov: NCT01939457.

Misoprostol as first-line treatment for incomplete abortion at a secondary-level health facility in Nigeria.

OBJECTIVE: To determine the feasibility of introducing misoprostol as first-line treatment for incomplete abortion at a secondary-level health facility. METHODS: An open-label prospective study was conducted in a secondary-level health facility in Nigeria. Eligible women diagnosed with incomplete abortion received 400-µg sublingual misoprostol as first-line treatment. Nurse-midwives took the lead in diagnosis, counseling, treatment, and assessment of final outcome. The primary outcome was the proportion of women who completed the abortion process. RESULTS: Complete evacuation was achieved in 83 of 90 (92.2%) eligible women. The most common adverse effects were abdominal pain/cramps (58 [64.4%]), heavy bleeding (21 [23.3%]), spotting (15 [16.7%]), and fever/chills (11 [12.2%]). More than 90% of women reported that the procedure was satisfactory, that pain and adverse effects were tolerable, and that bleeding was acceptable. Eighty-four (93.3%) and 86 (95.6%) women, respectively, would use the method in the future and recommend it to friends. CONCLUSION: Misoprostol is an effective, safe, and acceptable method for treating incomplete abortion. It can be successfully used as first-line treatment by nurse-midwives. Success rates over 90% are consistent with findings from previous studies in which drug administration was controlled solely by physicians.

Misoprostol in the management of the third stage of labour in the home delivery setting in rural Gambia: a randomised controlled trial.

OBJECTIVE: To assess the effectiveness of 600 microg oral misoprostol on postpartum haemorrhage (PPH) and postpartum anaemia in a low income country home birth situation. DESIGN: Double blind randomised controlled trial. SETTING: Twenty-six villages in rural Gambia with 52 traditional birth attendants (TBAs). SAMPLE: One thousand, two hundred and twenty-nine women delivering at home under the guidance of a trained TBA. METHODS: Active management of the third stage of labour using three 200-microg misoprostol tablets and placebo or four 0.5-mg ergometrine tablets (standard treatment) and placebo. Tablets were taken orally immediately after delivery. MAIN OUTCOME MEASURES: Measured blood loss, postpartum haemoglobin (Hb), difference between Hb at the last antenatal care visit and three to five days postpartum. RESULTS: The misoprostol group experienced lower incidence of measured blood loss > or =500 mL and postpartum Hb <8 g/dL, but the differences were not statistically significant. The reduction in postpartum (compared with pre-delivery) Hb > or = 2 g/dL was 16.4% with misoprostol and 21.2% with ergometrine [relative risk 0.77; 95% confidence interval (CI) 0.60-0.98; P= 0.02]. Shivering was significantly more common with misoprostol, while vomiting was more common with ergometrine. Only transient side effects were observed. CONCLUSIONS: Six hundred micrograms of oral misoprostol is a promising drug to prevent life-threatening PPH in this setting.

Effectiveness of lifesaving skills training and improving institutional emergency obstetric care readiness in Lam Dong, Vietnam.

Essential obstetric care is promoted as the prime strategy to save women's lives in developing countries. We measured the effect of improving lifesaving skills (LSS) capacity in Vietnam, a country in which most women deliver in health facilities. A quasi-experimental study was implemented to assess the impact of LSS training and readiness (availability of essential obstetric equipment, supplies, and medication) on the diagnosis of life-threatening obstetric conditions and appropriate management of labor and birth. The intervention (LSS training and readiness) was provided to all clinics and hospitals from 1 of 3 demographically similar districts in southcentral Vietnam, to hospitals only in another district, with the third district serving as the comparison group. Detection of life-threatening obstetric conditions increased in both experimental clinics and hospitals, but the intervention only improved the management of these conditions in hospitals. Management of life-threatening obstetric conditions is most effective in hospitals. The intervention did not clearly benefit women delivering in clinics.

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.