K A Hahn1, L A Wise2, K J Rothman3, E M Mikkelsen4, S B Brogly5, H T Sørensen6, A H Riis4, E E Hatch5. 1. Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA kahahn@bu.edu. 2. Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA Slone Epidemiology Center, Boston University, Boston, MA 02215, USA. 3. Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA RTI Health Solutions, Research Triangle Park, NC 12194 USA. 4. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. 5. Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA. 6. Department of Epidemiology, Boston University School of Public Health, Boston, MA 02118, USA Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.
Abstract
STUDY QUESTION: Is caffeine and caffeinated beverage consumption associated with the risk of spontaneous abortion (SAB)? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: Caffeine has been hypothesized as a risk factor for SAB since the 1980s; however, results from previous studies have been conflicting. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 5132 Danish women planning pregnancy and enrolled from 2007 to 2010. PARTICIPANTS/MATERIALS, SETTING, 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS, REASONS FOR CAUTION: The observed results may be affected by non-differential exposure misclassification, reverse causation and residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTERESTS: 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.
STUDY QUESTION: Is caffeine and caffeinated beverage consumption associated with the risk of spontaneous abortion (SAB)? SUMMARY ANSWER: 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. WHAT IS KNOWN ALREADY: Caffeine has been hypothesized as a risk factor for SAB since the 1980s; however, results from previous studies have been conflicting. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 5132 Danish women planning pregnancy and enrolled from 2007 to 2010. PARTICIPANTS/MATERIALS, SETTING, 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. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS, REASONS FOR CAUTION: The observed results may be affected by non-differential exposure misclassification, reverse causation and residual confounding. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTERESTS: 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.
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