Caffeine is teratogenic to rodents at high dosage levels (44). Effects such as cleft palates and ectrodactyly result from administration of lOOmg/kg/d or more, but only when given in a single dose by gavage or injection. Increased fetal absorption and decreased fetal weight also occur at these levels, which approach lethality. True teratogenic responses have usually been associated with dosages that result in maternal toxicity. Delayed bone ossification is observed at much lower levels, but this effect is rapidly compensated postnatally.

The role of caffeine in the outcome of human pregnancy is generally determined by retrospective questioning. Studies have been based on beverage consumption recall and are therefore inexact with regard to the amount of caffeine ingested or the effects of other beverage components. There is no clear evidence of teratogenic effects due to caffeine (45). Conflicting data exist concerning the relationship between maternal caffeine consumption and infant birth weight (46). Since caffeine crosses the placental barrier, it is possible for high concentrations to occur in the neonate (47). Most medical advice cautions against high caffeine intake during pregnancy.

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