Pregnancy 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-analysis

• Main Authors: Makoto Saito, Rashid Mansoor, Kalynn Kennon, Anupkumar R. Anvikar, Elizabeth A. Ashley, Daniel Chandramohan, Lauren M. Cohee, Umberto D’Alessandro, Blaise Genton, Mary Ellen Gilder, Elizabeth Juma, Linda Kalilani-Phiri, Irene Kuepfer, Miriam K. Laufer, Khin Maung Lwin, Steven R. Meshnick, Dominic Mosha, Atis Muehlenbachs, Victor Mwapasa, Norah Mwebaza, Michael Nambozi, Jean-Louis A. Ndiaye, François Nosten, Myaing Nyunt, Bernhards Ogutu, Sunil Parikh, Moo Kho Paw, Aung Pyae Phyo, Mupawjay Pimanpanarak, Patrice Piola, Marcus J. Rijken, Kanlaya Sriprawat, Harry K. Tagbor, Joel Tarning, Halidou Tinto, Innocent Valéa, Neena Valecha, Nicholas J. White, Jacher Wiladphaingern, Kasia Stepniewska, Rose McGready, Philippe J. Guérin
• Format: Article
• Language: English
• Published: BMC 2020-06-01
• Series: BMC Medicine
• Subjects: Falciparum malaria; Pregnancy; Treatment; Safety; Stillbirth; Small for gestational age
• Online Access: http://link.springer.com/article/10.1186/s12916-020-01592-z

Abstract 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.