title: Superiority of 3 over 2 doses of intermittent preventive treatment with sulfadoxine-pyrimethamine for the prevention of malaria during pregnancy in mali: a randomized controlled trial.
abstract: BACKGROUND
  In 2003, Mali introduced intermittent preventive therapy in pregnancy (ITPp) with sulfadoxine-pyrimethamine (SP) for the control of malaria in pregnancy, consisting of 2 doses of SP given in the 2nd and 3rd trimester. This widely used regimen, although very effective, leaves many women unprotected from malaria during the last 4-to-8 weeks of gestation, which is a pivotal period for fetal weight gain. The aim of the study was to compare the efficacy and safety of 3-dose versus 2-dose IPTp-SP for the prevention of placental malaria and associated low birth weight (LBW).
  
  
  METHODS
  We conducted a parallel-group, open-label, individually randomized controlled superiority trial involving 814 women of all gravidity, enrolled from April 2006 through March 2008. All women were seen at least 3 times and received either 2 (n = 401) or 3 (n = 413) doses of IPTp-SP. The primary endpoint measured was placental malaria, LBW, preterm births, and maternal anemia were secondary endpoints, and severe maternal skin reactions and neonatal jaundice were safety endpoints.
  
  
  RESULTS
  Among the 96% of study subjects who were followed up until delivery, the prevalence of placental malaria was 2-fold lower in the 3-dose group (8.0%) than in the 2-dose group (16.7%); the adjusted prevalence ratio (APR) was 0.48 (95% confidence interval [CI], 0.32-0.71). LBW and preterm births were also reduced; the prevalence of LBW was 6.6% in the 3-dose group versus 13.3% in the 2-dose group (APR, 0.50; 95% CI, 0.32-0.79), and the prevalence of preterm births was 3.2% versus 8.9% (APR, 0.37; 95% CI, 0.19-0.71). No significant reductions in maternal anemia or differences in safety endpoints were observed.
  
  
  CONCLUSIONS
  Adding a third dose of ITPp-SP halved the risk of placental malaria, LBW, and preterm births in all gravidae, compared with the standard 2-dose regimen, in this area of highly seasonal transmission with low levels of SP resistance.
  
  
  BACKGROUND
  ISRCTN 74189211.
authors.affiliation: Department of Health System Information, National Directorate of Health, University of Bamako, Bamako, Mali.
authors.forename: Oumou S Maïga
authors.initials: OS
authors.lastname: Diakite
authors.forename: Oumou M
authors.initials: OM
authors.lastname: Maiga
authors.forename: Kassoum
authors.initials: K
authors.lastname: Kayentao
authors.forename: Boubacar T
authors.initials: BT
authors.lastname: Traoré
authors.forename: Abdoulaye
authors.initials: A
authors.lastname: Djimde
authors.forename: Bouyagui
authors.initials: B
authors.lastname: Traoré
authors.forename: Mouctar
authors.initials: M
authors.lastname: Diallo
authors.forename: Mouctar
authors.initials: M
authors.lastname: Traoré
authors.forename: Aissata
authors.initials: A
authors.lastname: Ongoiba
authors.forename: Didier
authors.initials: D
authors.lastname: Doumtabé
authors.forename: Safiatou
authors.initials: S
authors.lastname: Doumbo
authors.forename: Mamadou S
authors.initials: MS
authors.lastname: Traoré
authors.forename: Antoine
authors.initials: A
authors.lastname: Dara
authors.forename: Oumar
authors.initials: O
authors.lastname: Guindo
authors.forename: Diawara M
authors.initials: DM
authors.lastname: Karim
authors.forename: Siraman
authors.initials: S
authors.lastname: Coulibaly
authors.forename: Flabou
authors.initials: F
authors.lastname: Bougoudogo
authors.forename: Feiko O
authors.initials: FO
authors.lastname: Ter Kuile
authors.forename: Martin
authors.initials: M
authors.lastname: Danis
authors.forename: Ogobara K
authors.initials: OK
authors.lastname: Doumbo
mesh_terms: D000293:Adolescent; D000328:Adult; D000740:Anemia / Q000517:prevention & control; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects; D018890:Chemoprevention / Q000009:adverse effects / Q000379:methods*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007230:Infant, Low Birth Weight; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000517:prevention & control; D008288:Malaria / Q000517:prevention & control*; D008302:Mali; D008875:Middle Aged; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000517:prevention & control*; D047928:Premature Birth / Q000517:prevention & control; D011739:Pyrimethamine / Q000008:administration & dosage* / Q000009:adverse effects; D012871:Skin Diseases / Q000139:chemically induced; D013413:Sulfadoxine / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D004338:Drug Combinations; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011739:Pyrimethamine