Impact of intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine, dihydroartemisinin-piperaquine, and their combination on infant outcomes: A randomized controlled trial.

Abstract

Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine (IPTp-DP) is more effective than sulfadoxine-pyrimethamine (IPTp-SP) at reducing the burden of malaria in pregnancy in settings with high SP resistance. Paradoxically, IPTp-DP has been associated with lower birth weights compared with IPTp-SP. Whether the impacts of IPTp-DP extend after birth is unknown. We conducted a double-blind randomized controlled trial to compare malaria burden and growth among infants born to mothers who were randomized to monthly IPTp-SP, IPTp-DP, or IPTp-DP+SP. Infants were followed to 12 months of age by passive and active surveillance. The primary outcome was clinical malaria incidence; secondary outcomes included parasite prevalence by microscopy or quantitative PCR, and infant growth outcomes. Among 871 infants enrolled, there were 667 episodes of clinical malaria. Compared to infants whose mothers received IPTp-SP, malaria incidence was similar in infants whose mothers received IPTp-DP (incidence rate ratio [IRR] 1.04, 95% confidence interval (CI) 0.78-1.38) or IPTp-DP+SP (IRR=0.93, 95% CI 0.68-1.26). Overall parasite prevalence at monthly visits was 21.8%. Parasite prevalence was also similar between groups. The prevalence of wasting at birth was higher in infants whose mothers received IPTp-DP+SP (PR= 2.30, 95% CI 1.07, 4.97) or IPTp-DP (RR= 2.25, 95% CI 1.03, 4.94) than those that received IPTp-SP, but differences between groups resolved by 3-6 months of age. There were no significant differences in infant outcomes between the three IPTp arms apart from a transiently increased risk of wasting among infants born to mothers who received DP-containing IPTp regimens.