Pregnancy outcomes after first-trimester treatment with artemisinin derivatives versus non-artemisinin antimalarials: a systematic review and individual patient data meta-analysis.

"Declaration of interests We declare no competing interests."

"AcknowledgmentsWe thank all study participants and study teams. In addition, we thank the WHO International Birth Defect Panel for their review of all cases of congenital anomalies from the WHO TDR Pilot Pregnancy Registry, the Pregnancy Registry in Burkina Faso, and the Assessment of the Safety of Antimalarial Drug Use During Early Pregnancy studies. We are grateful to Lewis Holmes (Medical Genetics and Metabolism Unit, MassGeneral Hospital for Children, Boston, MA, USA) and Asher Ornoy (Hebrew University Hadassah Medical School and Adelson School of Medicine, Ariel University, Israel) for their valuable feedback on the manuscript. This meta-analysis was partly funded by the Medicines for Malaria Venture and WHO. The Worldwide Antimalarial Resistance Network, which supported the curation of the data for this Article, is supported by The Bill & Melinda Gates Foundation. The findings and conclusions in this Article are those of the authors and do not necessarily represent the official position of the US Centers for Disease Control and Prevention."

"This systematic review and IPD meta-analysis was done according to a registed protocol (PROSPERO CRD42015032371) and is reported according to the PRISMA-IPD statement. The results of the previous systematic review, including studies published up to November, 2015, are reported elsewhere. We did an updated literature search for studies published between Nov 1, 2015, and Dec 21, 2021, by use of MEDLINE, Embase, and the Malaria in Pregnancy Library. The newly identified studies were combined with those identified in the previous literature search, which included studies published before 2015. A full list of search terms used is provided in the . In addition, malaria researchers were contacted for any other potential data sources, inlcuding unpublished studies. 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."