The risk of spontaneous abortion was increased with high levels, but not with moderate levels, of caffeine consumption

OBJECTIVE To determine if caffeine consumption during pregnancy is associated with an increased risk of spontaneous abortion. DESIGN Nested case-control study within a cohort of pregnant women assembled in the period 1959-1966. SETTING 12 prenatal clinics in the USA. SUBJECTS Cases were 591 women, mean age 27 years, who had a spontaneous abortion prior to 20 (mean 14) weeks gestation. Controls were 2558 women, mean age 25 years, who had a live birth after 28 (mean 39) weeks gestation and who were matched to cases by centre and gestarional age at blood sampling (mean 11 weeks). 46% of cases and 39% of controls were smokers. INTERVENTION Scrum paraxanthine, a metabolite of caffeine, was measured in serum samples taken during pregnancy and stored frozen for more than 30 years. MAIN OUTCOME MEASURES Odds ratio (OR, 95% CI) for spontaneous abortion by serum paraxanthine level, compared to those with a level < 50 ng/mL, adjusted for smoking, age, and race. MAIN RESULTS 82% of both the cases and controls had serum paraxanthine levels > 50 ng/mL, but the mean level was higher in the cases (752 vs 583 ng/mL, p < 0.001). In women with a scrum paraxanthine level of 50-1845 ng/mL (20th-94th percentile of controls, analysed in eight subgroups) the OR for spontaneous abortion was not significantly different from women with a level < 50 ng/mL (range of OR's 0.7-1.1*) and no trend towards a dose effect was observed. However, in women with a level > 1845 ng/mL (12% of cases and 8% of controls), the OR for spontaneous abortion was 1.9 (1.2-2.8). This association of a high paraxanthine level with spontaneous abortion was similar for women who had a spontaneous abortion before or after 14 weeks gestation, and for women with and without vomiting in pregnancy. CONCLUSION The risk of spontaneous abortion was increased 2-fold in women with very high scrum paraxanthine levels (roughly equivalent to daily coffee consumption of > 5 cups in a non-smoker or > 10 cups in a smoker), but was not increased in women with moderate caffeine consumption.