title: Effectiveness and safety of misoprostol distributed to antenatal women to prevent postpartum haemorrhage after child-births: a stepped-wedge cluster-randomized trial.
abstract: BACKGROUND
  Oral misoprostol, administered by trained health-workers is effective and safe for preventing postpartum haemorrhage (PPH). There is interest in expanding administration of misoprostol by non-health workers, including task-shifting to pregnant women themselves. However, the use of misoprostol for preventing PPH in home-births remains controversial, due to the limited evidence to support self-administration or leaving it in the hands of non-health workers. This study aimed to determine if antenatally distributing misoprostol to pregnant women to self-administer at home birth reduces PPH.
  
  
  METHODS
  Between February 2013 and March 2014, we conducted a stepped-wedge cluster-randomized trial in six health facilities in Central Uganda. Women at 28+ weeks of gestation attending antenatal care were eligible. Women in the control-arm received the standard-of-care; while the intervention-arm were offered 600 mcg of misoprostol to swallow immediately after birth of baby, when oxytocin was not available. The primary outcome (PPH) was a drop in postpartum maternal haemoglobin (Hb) by ≥ 2 g/dl, lower than the prenatal Hb. Analysis was by intention-to-treat at the cluster level and we used a paired t-tests to assess whether the mean difference between the control and intervention groups was statistically significant.
  
  
  RESULTS
  97% (2466/2545) of eligible women consented to participate; 1430 and 1036 in the control and intervention arms respectively. Two thousand fifty-seven of the participants were successfully followed up and 271 (13.2%) delivered outside a health facility. There was no significant difference between the study group in number of women who received a uterotonic at birth (control 80.4% vs intervention 91.4%, mean difference = -11.0%, 95% confidence interval [CI] -25.7% to 3.6%, p = 0.11). No woman took misoprostol before their baby's birth. Shivering and fever were 14.9% in the control arm compared to 22.2% in the intervention arm (mean difference = -7.2%, 95% CI -11.1% to -3.7%), p = 0.005). There was a slight, but non-significant, reduction in the percentage of women with Hb drop ≥ 2g/dl from 18.5% in the control arm to 11.4% in the intervention arm (mean difference = 7.1%, 95% CI -3.1% to 17.3%, p = 0.14). Similarly, there was no significant difference between the groups in the primary outcome in the women who delivered at home (control 9.6% vs intervention 14.5%, mean difference -4.9; 95% CI -12.7 to 2.9), p = 0.17).
  
  
  CONCLUSIONS
  This study was unable to detect a significant reduction in PPH following the antenatal distribution of misoprostol. The study was registered with Pan-African Clinical Trials Network ( PACTR201303000459148, on 19/11/2012).
authors.affiliation: Department of Obstetrics and Gynaecology, Makerere University College of Health Sciences, PO Box 7072, Kampala, Uganda. ononge2006@yahoo.com.
authors.forename: Sam
authors.initials: S
authors.lastname: Ononge
authors.affiliation: Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street WC1E 7HT, London, UK.
authors.forename: Oona M R
authors.initials: OM
authors.lastname: Campbell
authors.affiliation: School of Public Health, Makerere University College of Health Sciences, PO Box 7072, Kampala, Uganda.
authors.forename: Frank
authors.initials: F
authors.lastname: Kaharuza
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, Keppel Street WC1E 7HT, London, UK.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lewis
authors.affiliation: MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, Keppel Street WC1E 7HT, London, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Fielding
authors.affiliation: Department of Obstetrics and Gynaecology, Makerere University College of Health Sciences, PO Box 7072, Kampala, Uganda.
authors.forename: Florence
authors.initials: F
authors.lastname: Mirembe
mesh_terms: D000284:Administration, Oral; D000328:Adult; D016000:Cluster Analysis; D036861:Delivery, Obstetric / Q000379:methods; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000453:epidemiology / Q000209:etiology; D006454:Hemoglobins / Q000187:drug effects; D006700:Home Childbirth; D006801:Humans; D016595:Misoprostol / Q000008:administration & dosage* / Q000009:adverse effects; D010120:Oxytocics / Q000008:administration & dosage* / Q000009:adverse effects; D006473:Postpartum Hemorrhage / Q000517:prevention & control*; D049590:Postpartum Period / Q000097:blood / Q000187:drug effects*; D011247:Pregnancy; D012646:Self Administration; D012768:Shivering; D014454:Uganda; D055815:Young Adult
chemical_list: D006454:Hemoglobins; D010120:Oxytocics; D016595:Misoprostol