Makoto SaitoMakoto SaitoMakoto SaitoRashid MansoorKalynn KennonAnupkumar R. AnvikarElizabeth A. AshleyDaniel ChandramohanLauren M. CoheeUmberto D'AlessandroBlaise GentonMary Ellen GilderElizabeth JumaLinda Kalilani-PhiriIrene KuepferMiriam K. LauferKhin Maung LwinSteven R. MeshnickDominic MoshaAtis MuehlenbachsVictor MwapasaNorah MwebazaMichael NamboziJean Louis A. NdiayeFrançois NostenFrançois NostenMyaing NyuntBernhards OgutuSunil ParikhMoo Kho PawAung Pyae PhyoMupawjay PimanpanarakPatrice PiolaMarcus J. RijkenKanlaya SriprawatHarry K. TagborJoel TarningHalidou TintoInnocent ValéaNeena ValechaNicholas J. WhiteNicholas J. WhiteJacher WiladphaingernKasia StepniewskaKasia StepniewskaRose McGreadyRose McGreadyPhilippe J. GuérinCentre Universitaire de Médecine Générale et Santé PubliqueUniversity of Health and Allied Sciences, GhanaUniversity of Malawi College of MedicineMedical Research Council Laboratories GambiaInstitut Pasteur du CambodgeMakerere UniversityIfakara Health InstituteUniversite Cheikh Anta DiopKenya Medical Research InstituteShoklo Malaria Research UnitUniversity Medical Center UtrechtLondon School of Hygiene & Tropical MedicineThe University of North Carolina at Chapel HillNational Institute of Malaria Research IndiaUniversitat BaselSwiss Tropical and Public Health Institute (Swiss TPH)University of Washington, SeattleMahosot Hospital, LaoUniversity of Maryland School of MedicineMahidol UniversityNuffield Department of MedicineDuke UniversityYale UniversityMyanmar Oxford Clinical Research UnitInfectious Diseases Data Observatory (IDDO)Institut de Recherche en Sciences de la SantéWorldWide Antimalarial Resistance Network (WWARN)Tropical Diseases Research Centre2020-08-252020-08-252020-06-02BMC Medicine. Vol.18, No.1 (2020)174170152-s2.0-85085676994https://repository.li.mahidol.ac.th/handle/20.500.14594/58135© 2020 The Author(s). Background: Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Individual patient data (IPD) meta-analysis was conducted to compare the association between antimalarial treatments and adverse pregnancy outcomes, including placental malaria, accompanied with the gestational age at diagnosis of uncomplicated falciparum malaria infection. Methods: A systematic review and one-stage IPD meta-analysis of studies assessing the efficacy of artemisinin-based and quinine-based treatments for patent microscopic uncomplicated falciparum malaria infection (hereinafter uncomplicated falciparum malaria) in pregnancy was conducted. The risks of stillbirth (pregnancy loss at ≥ 28.0 weeks of gestation), moderate to late preterm birth (PTB, live birth between 32.0 and < 37.0 weeks), small for gestational age (SGA, birthweight of < 10th percentile), and placental malaria (defined as deposition of malaria pigment in the placenta with or without parasites) after different treatments of uncomplicated falciparum malaria were assessed by mixed-effects logistic regression, using artemether-lumefantrine, the most used antimalarial, as the reference standard. Registration PROSPERO: CRD42018104013. Results: Of the 22 eligible studies (n = 5015), IPD from16 studies were shared, representing 95.0% (n = 4765) of the women enrolled in literature. Malaria treatment in this pooled analysis mostly occurred in the second (68.4%, 3064/4501) or third trimester (31.6%, 1421/4501), with gestational age confirmed by ultrasound in 91.5% (4120/4503). Quinine (n = 184) and five commonly used artemisinin-based combination therapies (ACTs) were included: artemether-lumefantrine (n = 1087), artesunate-amodiaquine (n = 775), artesunate-mefloquine (n = 965), and dihydroartemisinin-piperaquine (n = 837). The overall pooled proportion of stillbirth was 1.1% (84/4361), PTB 10.0% (619/4131), SGA 32.3% (1007/3707), and placental malaria 80.1% (2543/3035), and there were no significant differences of considered outcomes by ACT. Higher parasitaemia before treatment was associated with a higher risk of SGA (adjusted odds ratio [aOR] 1.14 per 10-fold increase, 95% confidence interval [CI] 1.03 to 1.26, p = 0.009) and deposition of malaria pigment in the placenta (aOR 1.67 per 10-fold increase, 95% CI 1.42 to 1.96, p < 0.001). Conclusions: The risks of stillbirth, PTB, SGA, and placental malaria were not different between the commonly used ACTs. The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs. Reduction of malaria-associated adverse birth outcomes requires effective prevention in pregnant women.Mahidol UniversityMedicinePregnancy outcomes and risk of placental malaria after artemisinin-based and quinine-based treatment for uncomplicated falciparum malaria in pregnancy: A WorldWide Antimalarial Resistance Network systematic review and individual patient data meta-analysisReviewSCOPUS10.1186/s12916-020-01592-z