title: Caffeine and caffeinated beverage consumption and risk of spontaneous abortion.
abstract: OBJECTIVE
  Is caffeine and caffeinated beverage consumption associated with the risk of spontaneous abortion (SAB)?
  
  
  CONCLUSIONS
  While preconceptional caffeine consumption was not materially associated with an increased risk of SAB, consumption during early pregnancy was associated with a small increased risk of SAB, although the relation was not linear.
  
  
  BACKGROUND
  Caffeine has been hypothesized as a risk factor for SAB since the 1980s; however, results from previous studies have been conflicting.
  
  
  METHODS
  This prospective cohort study included 5132 Danish women planning pregnancy and enrolled from 2007 to 2010.
  
  
  METHODS
  Participants were women who conceived after entry into the Snart-Gravid cohort and who were aged 18-40, in a stable relationship with a male partner, and did not use fertility treatments to conceive. Women reported their daily caffeine and caffeinated beverage consumption on questionnaires before conception and during early pregnancy. All exposure measurements were prospective with respect to outcome ascertainment. We estimated hazard ratios (HRs) of SAB for categories of caffeine consumption in milligrams (mg) per day and the corresponding 95% confidence intervals (CIs) using Cox proportional hazards regression models with gestational weeks as the time scale.
  
  
  RESULTS
  There were 732 women (14.3%) who were identified as having a SAB. In the preconceptional period, caffeine consumption was not materially associated with SAB risk (HR comparing ≥300 with <100 mg/day: 1.09; 95% CI: 0.89, 1.33). In early pregnancy, the HRs for 100-199, 200-299 and ≥300 mg/day of caffeine consumption were 1.62 (95% CI: 1.19, 2.22), 1.48 (95% CI: 1.03, 2.13) and 1.23 (95% CI: 0.61, 2.46), respectively, compared with that for <100 mg/day.
  
  
  CONCLUSIONS
  The observed results may be affected by non-differential exposure misclassification, reverse causation and residual confounding.
  
  
  CONCLUSIONS
  This is the largest study to date of prospectively measured, preconception caffeine consumption and risk of SAB. We were able to reduce the likelihood of differential left truncation bias and recall bias present in other analyses.
  
  
  BACKGROUND
  Snart-Gravid was funded by the NICHD (R21-050264). Dr. Hahn's work was funded in part by the BU Reproductive, Perinatal, and Pediatric Epidemiology Training Grant NIH #T32HD052458. There are no competing interests.
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA kahahn@bu.edu.
authors: K A
authors: KA
authors: Hahn
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA Slone Epidemiology Center, Boston University, Boston, MA 02215, USA.
authors: L A
authors: LA
authors: Wise
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA RTI Health Solutions, Research Triangle Park, NC 12194 USA.
authors: K J
authors: KJ
authors: Rothman
authors: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors: E M
authors: EM
authors: Mikkelsen
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA.
authors: S B
authors: SB
authors: Brogly
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors: H T
authors: HT
authors: Sørensen
authors: Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
authors: A H
authors: AH
authors: Riis
authors: Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA.
authors: E E
authors: EE
authors: Hatch
mesh_terms: D000022:Abortion, Spontaneous / Q000175:diagnosis* / Q000209:etiology*; D000293:Adolescent; D000328:Adult; D001628:Beverages; D002110:Caffeine / Q000009:adverse effects*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005306:Fertilization; D006801:Humans; D015994:Incidence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D002110:Caffeine
keywords: caffeine; coffee; cohort study; spontaneous abortion