Effectiveness of Intermittent Preventive Treatment With Dihydroartemisinin‐Piperaqunine Against Malaria in Pregnancy in Tanzania: A Randomized Controlled Trial

Intermittent preventive treatment in pregnancy with sulfadoxine‐pyrimethamine (IPTp‐SP) to prevent malaria and adverse birth outcomes is threatened by Plasmodium falciparum resistance to sulfadoxine‐pyrimethamine. We investigated the effectiveness of intermittent preventive treatment in pregnancy with monthly dihydroartemisinin‐piperaquine (IPTp‐DHP) as an alternative option to IPTp‐SP. A total of 956 malaria‐free (malaria rapid diagnostic test (MRDT) negative) pregnant women from moderate malaria transmission areas in Tanzania were enrolled and randomized to receive monthly IPTp‐DHP ( n = 478) or IPTp‐SP ( n = 478) and followed for maternal and birth outcomes. The primary outcome was the prevalence of histopathologically confirmed placental malaria (active or past infection). Secondary outcomes were overall malaria at delivery, symptomatic‐malaria, parasitemia during pregnancy, and adverse birth outcomes as a composite of spontaneous‐abortion, premature birth, stillbirth, and low birth weight (LBW) fetal anemia. Outcome differences between treatment groups were expressed as the protective efficacy (PE), defined as 1‐prevalence ratios or 1‐incidence rate ratio. The prevalence of histopathologically confirmed placental malaria was significantly lower in IPTp‐DHP (2.5%, 12/478) than IPTp‐SP (8.2%, 39/478); PE = 69% (95% confidence interval (CI): 42–84, P < 0.001). The prevalence of maternal malaria at delivery was significantly lower in IPTp‐DHP (8.2%) than IPTp‐SP (18.2%, P < 0.001). The incidence per person‐years at risk for symptomatic‐malaria (0.02 vs. 0.12, P = 0.002) and parasitemia during pregnancy (0.28 vs. 0.67, P < 0.001) were significantly lower in the IPTp‐DHP group than in the IPTp‐SP group. The prevalence of any adverse birth outcomes (composite) was not significantly ( P = 0.06) different between IPTp‐DHP (17.9%) and IPTp‐SP (23.8%). However, the prevalence of LBW (4.6% vs. 9.6%, P = 0.003) was significantly lower in IPTp‐DHP compared with IPTp‐SP. We report superior protective efficacy of monthly IPTp‐DHP against malaria in pregnancy and LBW than IPTp‐SP.