Maternal caffeine consumption and spontaneous abortion: a review of the epidemiologic evidence.

Since the 1980s, numerous studies have investigated whether caffeine intake during pregnancy affects the risk of spontaneous abortion. A clear consensus, however, has not been reached. Because of the public health importance of this question, we reviewed the results of 15 epidemiologic studies on this topic, with particular attention to the specific methodologic problems that would generate biased findings. These include selection and recall bias, confounding, several issues pertaining to exposure measurement, and the failure to account for fetal karyotype, caffeine metabolism, the timing of fetal demise, and the possibility that an effect of caffeine may be gestational age-specific. All of the studies reviewed suffer from important methodologic limitations that hinder both the interpretation of each study individually and the comparison of results across studies. Despite the fact that most epidemiologic studies have observed a positive association between maternal caffeine intake and the risk of spontaneous abortion, we conclude that the evidence must be considered to be equivocal, given the biases likely present and the fact that most of the potential biases would tend to overestimate any association. Until studies can overcome these limitations, evidence for a causal link between caffeine and spontaneous abortion will remain inconclusive.