Artemether–lumefantrine should be considered the preferred treatment for uncomplicated Plasmodium falciparum malaria in the first trimester of pregnancy, investigators conclude based on results of a systematic review and individual patient data (IPD) meta-analysis.
The primary endpoint used in the analysis was adverse pregnancy outcome (a composite of either miscarriage, stillbirth, or major congenital anomalies). The one-stage IPD meta-analysis used shared-frailty Cox models and produced these results: “We identified seven eligible studies that included 12 cohorts. All 12 cohorts contributed IPD, including 34,178 pregnancies, 737 with confirmed first-trimester exposure to ABTs and 1,076 with confirmed first-trimester exposure to non-ABTs. Adverse pregnancy outcomes occurred in 42 (5.7%) of 736 ABT-exposed pregnancies compared with 96 (8.9%) of 1,074 non-ABT-exposed pregnancies in the first trimester (adjusted hazard ratio [aHR] 0.71, 95% CI 0.49–1.03). Similar results were seen for the individual components of miscarriage (aHR = 0.74, 0.47–1.17), stillbirth (aHR = 0.71, 0.32–1.57), and major congenital anomalies (aHR = 0.60, 0.13–2.87). The risk of adverse pregnancy outcomes was lower with artemether–lumefantrine than with oral quinine in the first trimester of pregnancy (25 [4.8%] of 524 vs 84 [9.2%] of 915; aHR 0.58, 0.36–0.92).”
“We found no evidence of embryotoxicity or teratogenicity based on the risk of miscarriage, stillbirth, or major congenital anomalies associated with ABT during the first trimester of pregnancy,” the authors conclude. “Given that treatment with artemether–lumefantrine was associated with fewer adverse pregnancy outcomes than quinine, and because of the known superior tolerability and antimalarial effectiveness of [artemisinin-based combination therapies], artemether–lumefantrine should be considered the preferred treatment for uncomplicated Plasmodium falciparum malaria in the first trimester. If artemether–lumefantrine is unavailable, other ACTs (except artesunate–sulfadoxine–pyrimethamine) should be preferred to quinine. Continued active pharmacovigilance is warranted.”