Objectives : The association between caffeine and pregnancy loss remains controversial due to limitations of prior studies such as relying on self-reported intake only, exposure measurement after clinical confirmation of pregnancy, and potential time-varying confounding by nausea/vomiting and lifestyle factors, which may be affected by prior caffeine exposure. Thus, our aim was to evaluate associations of preconception and early pregnancy serum caffeine, paraxanthine, and theobromine, self-reported intake of caffeinated beverages, and risk of pregnancy loss among 1228 reproductive-age women attempting pregnancy in the EAGeR trial during 2007-2011.
Methods : We estimated HRs and 95% CIs for any pregnancy loss, hCG loss (prior to ultrasound confirmation), and clinical loss (after ultrasound confirmation) according to caffeinated beverage intake and caffeine biomarkers measured at preconception and the 8th week of gestation using weighted adjusted Cox proportional hazards models.
Results : At preconception, 67%, 28%, and 9% of women reported any intake of caffeinated sodas, coffee, and tea, respectively. Preconception total caffeinated beverage intake of ≥3 vs. 0 cups/day was associated with 85% (95% CI: 1.18, 2.94) higher risk of any pregnancy loss, driven primarily by associations for hCG loss (HR: 2.88 (95% CI: 1.20, 6.91)). Caffeinated soda intake was associated with hCG loss (≥2 vs. < 2 cups/day HR: 2.11 (95% CI: 1.14, 3.89)), whereas caffeinated coffee intake was associated with clinical loss (≥2 vs. < 2 cups/day HR: 1.27 (95% CI: 1.02, 2.90)). Likewise, any detectable level of serum caffeine ( >0.2 vs. ≤0.2 ng/mL) at preconception was strongly associated with hCG loss (HR: 4.51 (95% CI: 1.36, 14.91)). Serum caffeine, paraxanthine, and theobromine measured at the 8th week of gestation were not associated with risk of loss.
Conclusions : Collectively, these data suggest that caffeine intake prior to pregnancy may increase risk of pregnancy loss, particularly in early gestation.
Funding Sources : Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH, Bethesda, MD.