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

Stephanie Dellicour, Meghna Desai, George Aol, Martina Oneko, Peter Ouma, Godfrey Bigogo, Deron C. Burton, Robert F. Breiman, Mary J. Hamel, Laurence Slutsker, Daniel Feikin, Simon Kariuki, Frank Odhiambo, Jayesh Pandit, Kayla F. Laserson, Greg Calip, Andy Stergachis, Feiko O. Ter Kuile

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article number461
JournalMalaria journal
Volume14
Issue number1
DOIs
StatePublished - Nov 18 2015
Externally publishedYes

Keywords

  • Anti-malarials
  • Drug safety in pregnancy
  • Miscarriage
  • Pharmacovigilance
  • Teratogenicity

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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