title: Clarithromycin in early pregnancy and the risk of miscarriage and malformation: a register based nationwide cohort study.
abstract: BACKGROUND
  The antibiotic clarithromycin has been associated with fetal loss in animals and a study has found a doubling in the frequency of miscarriages among women using clarithromycin in pregnancy. The aim of the study was to investigate whether clarithromycin use in early pregnancy was associated with an increased risk for miscarriages and major malformations.
  
  
  METHODS
  We conducted a nationwide cohort study including all women in Denmark with a known conception between 1997 and 2007. The Fertility Database was used to identify all women giving birth and the National Hospital Register was used to identify all women with a record of miscarriage or induced abortion. Prescription data was obtained from the National Prescription Register. The primary outcome was the number of miscarriages and offspring with major congenital malformations among users of clarithromycin compared to non-users.
  
  
  RESULTS
  We identified 931 504 pregnancies (705 837 live births, 77 553 miscarriages, and 148 114 induced abortions). 401 women redeemed a prescription of clarithromycin in the first trimester of which 40 (10.0%) experienced a miscarriage and among the live born nine (3.6%) had offspring with malformations. The hazard ratio (HR) of having a miscarriage after exposure to clarithromycin was 1.56 (CI95% 1.14-2.13). There was no increased hazard of having a miscarriage when being exposed to penicillin or erythromycin. There was no increased prevalence (OR = 1.03 (CI95% 0.52-2.00)) of having offspring with malformations after exposure to clarithromycin.
  
  
  CONCLUSIONS
  We found an increased hazard of miscarriage but no increased prevalance of having offspring with malformations among women redeeming a prescription of clarithromycin in early pregnancy. This is supported by previous studies in animals and humans. However, further research is required to explore the possible effect of treatment indication on the associations found.
authors.affiliation: Laboratory of Clinical Pharmacology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. jta@rh.dk
authors.forename: Jon Trærup
authors.initials: JT
authors.lastname: Andersen
authors.forename: Morten
authors.initials: M
authors.lastname: Petersen
authors.forename: Espen
authors.initials: E
authors.lastname: Jimenez-Solem
authors.forename: Kasper
authors.initials: K
authors.lastname: Broedbaek
authors.forename: Nadia Lyhne
authors.initials: NL
authors.lastname: Andersen
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.forename: Niels
authors.initials: N
authors.lastname: Keiding
authors.forename: Henrik Enghusen
authors.initials: HE
authors.lastname: Poulsen
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000453:epidemiology; D000022:Abortion, Spontaneous / Q000453:epidemiology / Q000209:etiology*; D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects; D017291:Clarithromycin / Q000009:adverse effects*; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D006801:Humans; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D015995:Prevalence; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D017291:Clarithromycin