Meta-analysis informed the updated WHO guidelines for treatment of uncomplicated malaria in the first trimester of pregnancy
A new WWARN meta-analysis commissioned by the World Health Organization (WHO), which informed a change to its treatment guidelines for malaria has been published in The Lancet.
The study provides evidence that artemether-lumefantrine should now replace quinine as the treatment of choice in the first trimester of pregnancy. Although there is limited data on specific artemisinin-based combination therapies (ACTs) other than artemether-lumefantrine, the other ACTs (including artesunate-amodiaquine, artesunate-mefloquine and dihydroartemisinin-piperaquine but not artesunate–sulfadoxine–pyrimethamine) may be considered for use where artemether-lumefantrine is not available, given the demonstrated poorer outcomes of quinine treatment, along with the challenges of adherence to a seven-day course of treatment.
ACTs are already recommended for treatment in second and third trimesters. This study, the largest of its kind, was a collaborative effort between over 20 research groups with data from over 34,000 pregnancies from 12 cohort studies in ten countries collected over more than 20 years.
The meta-analysis results suggest that first-trimester treatment with artemisinin-based treatment is as safe and possibly more effective than non-artemisinin-based treatments, including quinine-based regimens. Importantly, artemether-lumefantrine, the ACT with the most safety data, was associated with 42% fewer adverse pregnancy outcomes (pregnancy loss or major congenital malformations) than oral quinine in the first trimester.
All participating research groups kindly agreed to share their individual patient data (IPD) of 34,178 pregnancies with WWARN. The data included 737 pregnancies with confirmed first-trimester exposure to artemisinin-based treatment and 1,076 with confirmed exposure to other antimalarials. It has taken over 20 years to collect these data, illustrating the difficulty of obtaining quality data on the safety of antimalarials in pregnancy.
