title: Risks of miscarriage and inadvertent exposure to artemisinin derivatives in the first trimester of pregnancy: a prospective cohort study in western Kenya.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Stephanie.Dellicour@lstmed.ac.uk.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Dellicour
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA. mud8@cdc.gov.
authors.forename: Meghna
authors.initials: M
authors.lastname: Desai
authors.affiliation: Kenya Medical Research Institute Centre for Global Health Research, Kisumu, Kenya. gaol@kemricdc.org.
authors.forename: George
authors.initials: G
authors.lastname: Aol
authors.affiliation: Kenya Medical Research Institute Centre for Global Health Research, Kisumu, Kenya. moneko@kemricdc.org.
authors.forename: Martina
authors.initials: M
authors.lastname: Oneko
authors.affiliation: Kenya Medical Research Institute Centre for Global Health Research, Kisumu, Kenya. pouma@kemricdc.org.
authors.forename: Peter
authors.initials: P
authors.lastname: Ouma
authors.affiliation: Kenya Medical Research Institute Centre for Global Health Research, Kisumu, Kenya. gbigogo@kemricdc.org.
authors.forename: Godfrey
authors.initials: G
authors.lastname: Bigogo
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA. akq7@cdc.gov.
authors.forename: Deron C
authors.initials: DC
authors.lastname: Burton
authors.affiliation: Global Health Institute, Emory University, Atlanta, GA, USA. rfbreiman@emory.edu.
authors.forename: Robert F
authors.initials: RF
authors.lastname: Breiman
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA. mlh8@cdc.gov.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Hamel
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA. lms5@cdc.gov.
authors.forename: Laurence
authors.initials: L
authors.lastname: Slutsker
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA. drf0@cdc.gov.
authors.forename: Daniel
authors.initials: D
authors.lastname: Feikin
authors.affiliation: Kenya Medical Research Institute Centre for Global Health Research, Kisumu, Kenya. skariuki@kemricdc.org.
authors.forename: Simon
authors.initials: S
authors.lastname: Kariuki
authors.affiliation: Kenya Medical Research Institute Centre for Global Health Research, Kisumu, Kenya. fodhiambo@kemricdc.org.
authors.forename: Frank
authors.initials: F
authors.lastname: Odhiambo
authors.affiliation: Bayer Healthcare, Nairobi, Kenya. jayesh_pandit@hotmail.com.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Pandit
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, USA. kel4@cdc.gov.
authors.forename: Kayla F
authors.initials: KF
authors.lastname: Laserson
authors.affiliation: Pharmacy Systems, Outcomes and Policy Department, University of Illinois at Chicago, Chicago, USA. gcalip@fredhutch.org.
authors.forename: Greg
authors.initials: G
authors.lastname: Calip
authors.affiliation: Departments of Pharmacy and Global Health, Schools of Pharmacy and Public Health, University of Washington, Seattle, USA. stergach@uw.edu.
authors.forename: Andy
authors.initials: A
authors.lastname: Stergachis
authors.affiliation: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Feiko.TerKuile@lstmed.ac.uk.
authors.forename: Feiko O
authors.initials: FO
authors.lastname: ter Kuile
mesh_terms: D000022:Abortion, Spontaneous / Q000139:chemically induced* / Q000453:epidemiology*; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects*; D037621:Artemisinins / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007630:Kenya; D008875:Middle Aged; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011446:Prospective Studies; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin