Fig. 12.   Mechanisms underlying the adverse effects of prenatal nicotine on neonatal adrenomedullary function and their potential role in SIDS. In the fetus or neonate, the tissue responds autonomously to hypoxia so that catecholamines are released even though innervation is not functional. Ordinarily, the onset of innervation replaces the autonomous response with reflexly mediated release. With prenatal nicotine exposure, chronic, drug-induced depolarization of the chromaffin cells forces them into terminal differentiation prematurely so that autonomous responsiveness is lost before the onset of innervation, leading to an inability to respond to hypoxia. As shown at the bottom, normal rats are protected from the effects of hypoxia because they maintain adrenal catecholamine secretion at all times by autonomous or reflex mechanisms; the loss of autonomous response occurs only with the onset of reflex responses. In the nicotine group, the premature loss of the autonomous response opens a window of vulnerability in which neither process can contribute to catecholamine release. With further development, this window closes with the onset of functional innervation.