Coteratogenic effects of caffeine.

Coteratogenicity studies have been carried out using various physical and chemical agents along with caffeine. For ionizing radiation in mice, enhancement of teratogenic responses (cleft palate, limb malformations) was noted with single systemic bolus doses of 50 to 200 mg/kg. Studies in rats with ethanol or nicotine reveal only an additive effect with caffeine. There are mixed results with chemical carcinogens and caffeine with some studies showing enhancement and others showing that caffeine inhibits the teratogenic effect of some carcinogens. The time of treatment, at the time of carcinogen exposure for the inhibition and later in the gestation period for the enhancement, appears to be the critical factor. For a variety of pharmaceutical agents (acetazolamide, mitomycin C, hydroxyurea, 5-fluorouracil), caffeine was shown to enhance the teratogenic effect of the agent. With 5-azacytidine in rats, caffeine suppressed limb malformations. Administration of inhibitors of beta-adrenergic function reduces the teratogenic effect of caffeine in mice. The interpretation of the experimental studies in terms of human hazard is complicated by the general use of high-dose bolus exposures which are not typical of human exposures, and the use of test systems that are not readily applicable to humans. The studies in human populations show clearly that caffeine itself has no link to negative birth outcome, and in the few instances where it has been examined there appears to be no interaction between coffee consumption and either alcohol consumption or smoking on pregnancy outcome.