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
Open Access
- 2 June 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in BMC Medicine
- Vol. 18 (1), 1-17
- https://doi.org/10.1186/s12916-020-01592-z
Abstract
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. 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. 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). 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.Funding Information
- Bill and Melinda Gates Foundation
- ExxonMobil Foundation
- University of Oxford Clarendon Fund
This publication has 64 references indexed in Scilit:
- Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysisThe Lancet, 2013
- Impact of malaria during pregnancy on pregnancy outcomes in a Ugandan prospectivecohort with intensive malaria screening and prompt treatmentMalaria Journal, 2013
- Does Malaria Affect Placental Development? Evidence from In Vitro ModelsPLOS ONE, 2013
- Plasmodium falciparum parasitaemia in the first half of pregnancy, uterine and umbilical artery blood flow, and foetal growth: a longitudinal Doppler ultrasound studyMalaria Journal, 2012
- Artemether-lumefantrine to treat malaria in pregnancy is associated with reduced placental haemozoin deposition compared to quinine in a randomized controlled trialMalaria Journal, 2012
- A Novel Histological Grading Scheme for Placental Malaria Applied in Areas of High and Low Malaria TransmissionThe Journal of Infectious Diseases, 2010
- Longitudinal Studies of Plasmodium falciparum Malaria in Pregnant Women Living in a Rural Cameroonian Village with High Perennial TransmissionThe American Journal of Tropical Medicine and Hygiene, 2010
- Impact of maternal malaria and under-nutrition on intrauterine growth restriction: a prospective ultrasound study in Democratic Republic of CongoEpidemiology and Infection, 2008
- Malaria in pregnancy and the endemicity spectrum: what can we learn?Trends in Parasitology, 2004
- The Sick Placenta—The Role of MalariaPlacenta, 2004