Does Caffeine Consumption Increase the Risk of Miscarriage?

abstract & commentary

To determine whether the consumption of caffeine during pregnancy increases the risk of spontaneous abortion, Klebanoff and associates performed a nested case-control study, measuring serum paraxanthine, a marker of short-term caffeine intake, in 591 women who had spontaneous abortions at less than 140 days gestation and 2558 matched controls who gave birth to live infants at 28 weeks gestation or later. The mean duration of pregnancy was slightly more than 14 weeks among women with miscarriages and 39 weeks among controls. These patients had been enrolled in the Collaborative Perinatal Project between 1959-1966. While the mean serum paraxanthine concentration was significantly higher in women who had spontaneous abortions than in controls, the odds ratio for a spontaneous abortion was significantly increased (adjusted OR, 1.9; 95% CI 1.2-2.8) only in women with serum paraxanthine concentrations higher than 1845 ng/mL, corresponding to the 5% of control women with the highest concentrations.

Klebanoff et al conclude that only extremely high serum paraxanthine concentrations are associated with spontaneous abortion, suggesting that moderate consumption of caffeine is unlikely to increase the risk of miscarriage. (Klebanoff MA, et al. N Engl J Med 1999;341:1639-1644.)

Comment by Steven G. Gabbe, MD

The average per capita consumption of coffee in the United States is nearly eight pounds per year, the equivalent of more than 150 mg of caffeine per day. Whether caffeine consumption during pregnancy is associated with an increased risk of adverse outcomes including spontaneous abortion and low birthweight remains controversial. It is well known that caffeine readily crosses the placenta and that its half-life during pregnancy is prolonged. A cup of coffee contains approximately 100 mg of caffeine and tea about half that amount. In 1981, the FDA recommended that pregnant women "avoid caffeine-containing foods and drugs, if possible, or consume them only sparingly." Most studies have relied upon questionnaires to determine caffeine consumption. Klebanoff et al have measured serum paraxanthine, the primary metabolite of caffeine, as a biologic marker of caffeine consumption. They report an increased risk of miscarriage only in women with extremely high paraxanthine concentrations, the equivalent of consuming about six cups of coffee in a woman who does not smoke or about 11 cups of coffee in a smoker. The half-life of caffeine is considerably shorter in smokers.

While this information is reassuring, I concur with the advice in an editorial that accompanies this study.1 Eskenazi notes that a recent meta-analysis documented a small increase in the risk of spontaneous abortion and low birthweight in women who consumed more than 150 mg of caffeine daily, or roughly 1-2 cups of coffee per day. She advises, and I agree, that pregnant women should be advised to limit their caffeine intake.


1. Eskenazi B. N Engl J Med 1999;341:1688-1689.

In the recent study by Klebanoff et al, excessive caffeine consumption was associated with which of the following adverse pregnancy outcomes?

a. Congenital heart defects

b. Ectopic pregnancy

c. Spontaneous abortion

d. Placental abruption

e. Preterm birth