[MikeWaters]

I know you would love to say that caffeine is good for you, but the evidence is increasingly against it.

http://content.nejm.org/cgi/content/full/341/22/1688

The article by Klebanoff and colleagues1 in this issue of the Journal adds to the growing body of literature examining the association of caffeine intake with adverse pregnancy outcomes and developmental problems. This study reports an association between spontaneous abortions, primarily in the second trimester, and unusually high levels of consumption of caffeine, equivalent to more than six cups of coffee a day.

Unlike previous studies, in which exposure was estimated from the women's reports of the amount of caffeinated beverages they consumed, Klebanoff et al. used a biologic marker of caffeine intake, the levels of the caffeine metabolite paraxanthine in serum, to estimate exposure. Estimation of exposure on the basis of women's own reports is problematic, both because of potentially inaccurate or biased reports and because the amount of caffeine in a cup of tea or coffee differs greatly, depending on the method of preparation.2 The use of a biologic marker of exposure may help to reduce misclassification. Nevertheless, a single serum measurement, as used in the study by Klebanoff et al., may not accurately reflect a woman's exposure during the critical period of fetal development, since in early pregnancy the half-life of caffeine is short (approximately three to seven hours) and caffeine intake may vary markedly during pregnancy because of nausea and food aversion.

Given the results of the study by Klebanoff et al.,1 can we now conclude that the consumption of caffeine at usual levels during pregnancy is safe? The weight of the evidence still suggests otherwise. A recent meta-analysis3 concluded that there is a small increase in the crude risk of both spontaneous abortion (odds ratio, 1.4; 95 percent confidence interval, 1.3 to 1.5) and low birth weight (odds ratio, 1.5; 95 percent confidence interval, 1.4 to 1.6) in women who consume more than 150 mg of caffeine, or roughly one to two cups of coffee, per day. Furthermore, on the basis of studies in animals, spontaneous abortion and low birth weight may not be the most sensitive end points to use in determining the in utero effects of caffeine consumption.