Risks of miscarriage and inadvertent exposure to artemisinin derivatives in the first trimester of pregnancy: a prospective cohort study in western Kenya

• Type of Material: Article
• Authors: Stephanie Dellicour, Liverpool School of Tropical Medicine; Meghna Desai, Centers for Disease Control and Prevention; George Aol, Kenya Medical Research Institute; Martina Oneko, Kenya Medical Research Institute; Peter Ouma, Kenya Medical Research Institute; Godfrey Bigogo, Kenya Medical Research Institute; Deron C. Burton, Centers for Disease Control and Prevention; Robert Breiman, Emory University; Mary J. Hamel, Centers for Disease Control and Prevention; Laurence Slutsker, Centers for Disease Control and Prevention; Daniel Feikin, Centers for Disease Control and Prevention; Simon Kariuki, Kenya Medical Research Institute; Frank Odhiambo, Kenya Medical Research Institute; Jayesh Pandit, Bayer Healthcare; Kayla F. Laserson, Centers for Disease Control and Prevention; Greg Calip, University of Illinois at Chicago; Andy Stergachis, University of Washington; Feiko O. ter Kuile, Liverpool School of Tropical Medicine
• Language: English
• Date: 2015-11-18
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2015 Dellicour et al.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s12936-015-0950-6
• Title of Journal or Parent Work: Malaria Journal
• ISSN: 1475-2875
• Volume: 14
• Issue: 1
• Start Page: 461
• End Page: 461
• Grant/Funding Information: This work was partly supported by the Malaria in Pregnancy (MiP) Consortium, which is funded through a grant from the Bill and Melinda Gates Foundation to the Liverpool School of Tropical Medicine, UK and partly by the US Centers for Disease Control and Prevention (CDC), Division of Parasitic Diseases and Malaria through a cooperative agreement with Kenya Medical Research Institute (KEMRI), Center for Global Health Research (CGHR), Kisumu, Kenya.
• Keywords: Teratogenicity; Infectious Diseases; Tropical Medicine; ARTESUNATE; Parasitology; ARTEMETHER-LUMEFANTRINE; Life Sciences & Biomedicine; BIRTH-WEIGHT; ANTIMALARIAL-DRUG; MALARIA; DEVELOPMENTAL TOXICITY; Drug safety in pregnancy; Science & Technology; HEALTH; WOMEN; Miscarriage; MORBIDITY SURVEILLANCE; Anti-malarials; SAFETY; Pharmacovigilance
• Research Categories: Health Sciences, Public Health; Health Sciences, Pharmacology; Health Sciences, Obstetrics and Gynecology

Abstract

Background: The artemisinin anti-malarials are widely deployed as artemisinin-based combination therapy (ACT). However, they are not recommended for uncomplicated malaria during the first trimester because safety data from humans are scarce. Methods: This was a prospective cohort study of women of child-bearing age carried out in 2011-2013, evaluating the relationship between inadvertent ACT exposure during first trimester and miscarriage. Community-based surveillance was used to identify 1134 early pregnancies. Cox proportional hazard models with left truncation were used. Results: The risk of miscarriage among pregnancies exposed to ACT (confirmed + unconfirmed) in the first trimester, or during the embryo-sensitive period (≥6 to <13 weeks gestation) was higher than among pregnancies unexposed to anti-malarials in the first trimester: hazard ratio (HR) = 1.70, 95 % CI (1.08-2.68) and HR = 1.61 (0.96-2.70). For confirmed ACT-exposures (primary analysis) the corresponding values were: HR = 1.24 (0.56-2.74) and HR = 0.73 (0.19-2.82) relative to unexposed women, and HR = 0.99 (0.12-8.33) and HR = 0.32 (0.03-3.61) relative to quinine exposure, but the numbers of quinine exposures were very small. Conclusion: ACT exposure in early pregnancy was more common than quinine exposure. Confirmed inadvertent artemisinin exposure during the potential embryo-sensitive period was not associated with increased risk of miscarriage. Confirmatory studies are needed to rule out a smaller than three-fold increase in risk.