Abstract
BackgroundMalaria 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.MethodsA 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.ResultsOf 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).ConclusionsThe 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.
Highlights
Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development
Higher parasitaemia before treatment was associated with a higher risk of small for gestational age (SGA) and deposition of malaria pigment in the placenta
The risk of SGA was high among pregnant women infected with falciparum malaria despite treatment with highly effective drugs
Summary
Malaria in pregnancy, including asymptomatic infection, has a detrimental impact on foetal development. Malaria during pregnancy has adverse impacts on the foetus including increased risks of pregnancy loss (i.e. miscarriage or stillbirth) [1, 2], preterm birth (PTB) [3, 4], intrauterine growth restriction (IUGR), and small for gestational age (SGA) [3, 5, 6]. The most widely reported adverse impact of malaria in pregnancy is low birthweight (LBW), commonly defined as birthweight less than 2500 g and used as a proxy for foetal growth [11, 12]. LBW does not distinguish between being “born to early” (or PTB) or “born to small” (or IUGR), or both, which are associated with different neonatal mortality and morbidity. An advance in the last decade is that an international standard foetal growth chart defining SGA has become available [15] permitting standardized comparison using SGA to summarize the evidence of the impact of malaria on foetal growth
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