Developmental Toxicity of Caffeine and Related Fetal-Originated Disease

An increasing number of studies suggest that caffeine is detrimental to fetal development and can cause intrauterine dysplasia in offspring, leading to susceptibility to various diseases after birth, with potential multigenerational genetic effects. Prenatal caffeine exposure has been shown to have both direct toxic effects on the fetus by crossing the placenta and indirect effects by stimulating the maternal hypothalamic-pituitary-adrenal axis and opening the placental glucocorticoid barrier, which can result in overexposure of the fetus to maternal-originated glucocorticoids, leading to fetal multi-organ dysfunction. Therefore, the developmental toxicity of caffeine poses both immediate and long-term hazards. Intrauterine maternal-originated glucocorticoid overexposure caused by prenatal caffeine exposure can induce developmental programming changes in offspring, affecting the glucocorticoid-insulin-like growth factor 1 axis, hypothalamic-pituitary-adrenal axis, and the renin-angiotensin system, leading to postnatal susceptibility to various diseases. Epigenetics is involved in regulating the programming mechanisms of caffeine developmental toxicity. This chapter provides a comprehensive review of the short-term and long-term hazards and mechanisms of caffeine developmental toxicity, providing an experimental and theoretical basis for the analysis of the international hot theory of “Developmental Origins of Health and Disease”.