Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis
Issued Date
2023-01-14
Resource Type
ISSN
01406736
eISSN
1474547X
Scopus ID
2-s2.0-85146250546
Pubmed ID
36442488
Journal Title
The Lancet
Volume
401
Issue
10371
Start Page
118
End Page
130
Rights Holder(s)
SCOPUS
Bibliographic Citation
The Lancet Vol.401 No.10371 (2023) , 118-130
Suggested Citation
Saito M., McGready R., Tinto H., Rouamba T., Mosha D., Rulisa S., Kariuki S., Desai M., Manyando C., Njunju E.M., Sevene E., Vala A., Augusto O., Clerk C., Were E., Mrema S., Kisinza W., Byamugisha J., Kagawa M., Singlovic J., Yore M., van Eijk A.M., Mehta U., Stergachis A., Hill J., Stepniewska K., Gomes M., Guérin P.J., Nosten F., ter Kuile F.O., Dellicour S. Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis. The Lancet Vol.401 No.10371 (2023) , 118-130. 130. doi:10.1016/S0140-6736(22)01881-5 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/82459
Title
Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis
Author(s)
Saito M.
McGready R.
Tinto H.
Rouamba T.
Mosha D.
Rulisa S.
Kariuki S.
Desai M.
Manyando C.
Njunju E.M.
Sevene E.
Vala A.
Augusto O.
Clerk C.
Were E.
Mrema S.
Kisinza W.
Byamugisha J.
Kagawa M.
Singlovic J.
Yore M.
van Eijk A.M.
Mehta U.
Stergachis A.
Hill J.
Stepniewska K.
Gomes M.
Guérin P.J.
Nosten F.
ter Kuile F.O.
Dellicour S.
McGready R.
Tinto H.
Rouamba T.
Mosha D.
Rulisa S.
Kariuki S.
Desai M.
Manyando C.
Njunju E.M.
Sevene E.
Vala A.
Augusto O.
Clerk C.
Were E.
Mrema S.
Kisinza W.
Byamugisha J.
Kagawa M.
Singlovic J.
Yore M.
van Eijk A.M.
Mehta U.
Stergachis A.
Hill J.
Stepniewska K.
Gomes M.
Guérin P.J.
Nosten F.
ter Kuile F.O.
Dellicour S.
Author's Affiliation
Infectious Diseases Data Observatory
WorldWide Antimalarial Resistance Network
Institut de Recherche en Sciences de la Santé
Centro de Investigação em Saúde de Manhiça CISM
Faculty of Tropical Medicine, Mahidol University
The Institute of Medical Science, The University of Tokyo
Centre Hospitalier Universitaire de Kigali
Copperbelt University
Tropical Diseases Research Centre Ndola
Universidade Eduardo Mondlane
Makerere University
Ifakara Health Institute
Amani Medical Research Centre Tanga
Kenya Medical Research Institute
Moi University
University of California, Los Angeles
Centers for Disease Control and Prevention
Liverpool School of Tropical Medicine
University of Ghana
Göteborgs Universitet
University of Washington
Nuffield Department of Medicine
UNICEF
University of Cape Town
Icon
WorldWide Antimalarial Resistance Network
Institut de Recherche en Sciences de la Santé
Centro de Investigação em Saúde de Manhiça CISM
Faculty of Tropical Medicine, Mahidol University
The Institute of Medical Science, The University of Tokyo
Centre Hospitalier Universitaire de Kigali
Copperbelt University
Tropical Diseases Research Centre Ndola
Universidade Eduardo Mondlane
Makerere University
Ifakara Health Institute
Amani Medical Research Centre Tanga
Kenya Medical Research Institute
Moi University
University of California, Los Angeles
Centers for Disease Control and Prevention
Liverpool School of Tropical Medicine
University of Ghana
Göteborgs Universitet
University of Washington
Nuffield Department of Medicine
UNICEF
University of Cape Town
Icon
Other Contributor(s)
Abstract
Background: Malaria in the first trimester of pregnancy is associated with adverse pregnancy outcomes. Artemisinin-based combination therapies (ACTs) are a highly effective, first-line treatment for uncomplicated Plasmodium falciparum malaria, except in the first trimester of pregnancy, when quinine with clindamycin is recommended due to concerns about the potential embryotoxicity of artemisinins. We compared adverse pregnancy outcomes after artemisinin-based treatment (ABT) versus non-ABTs in the first trimester of pregnancy. Methods: For this systematic review and individual patient data (IPD) meta-analysis, we searched MEDLINE, Embase, and the Malaria in Pregnancy Library for prospective cohort studies published between Nov 1, 2015, and Dec 21, 2021, containing data on outcomes of pregnancies exposed to ABT and non-ABT in the first trimester. The results of this search were added to those of a previous systematic review that included publications published up until November, 2015. We included pregnancies enrolled before the pregnancy outcome was known. We excluded pregnancies with missing estimated gestational age or exposure information, multiple gestation pregnancies, and if the fetus was confirmed to be unviable before antimalarial treatment. The primary endpoint was adverse pregnancy outcome, defined as a composite of either miscarriage, stillbirth, or major congenital anomalies. A one-stage IPD meta-analysis was done by use of shared-frailty Cox models. This study is registered with PROSPERO, number CRD42015032371. Findings: 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 1076 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 1074 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). Interpretation: 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. 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 ACTs, artemether–lumefantrine should be considered the preferred treatment for uncomplicated P 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. Funding: Medicines for Malaria Venture, WHO, and the Worldwide Antimalarial Resistance Network funded by the Bill & Melinda Gates Foundation.