The pathological evidence for developmental delay in SIDS is reviewed from the Division of Neuropathology, The Hospital for Sick Children, University of Toronto, Toronto, Canada. Evidence of hypoxic ischemic insult to the brain includes astrogliosis and subcortical leukomalacia. Astrogliosis is most apparent in the region of the tegmentum in SIDS victims, a finding interpreted as hypoperfusion during episodes of bradycardia associated with apnea. Subcortical or periventricular leukomalacia was found in 21.6% of infants who died of SIDS. Term and prematurely born SIDS infants showed persistence of the reticular dendritic spines which suggests a delay of development to a mature, higher level of neuronal function. This delay may reflect a functional impairment of the higher levels of respiratory control in SIDS infants. A number of reports suggest alterations in neurotransmitter levels of catecholamines, beta endorphin, met-enkephalin, and substance P in SIDS. Examination of 36 infants who had died of SIDS showed that the mean number of small myelinated vagal fibers was significantly decreased in the SIDS infants compared with controls, suggesting an abnormal or delayed development of the vagus nerve. This finding was similar to that reported in a two year old infant dying of persistent infantile sleep apnea (Ondine’s curse). Elevated dopamine in the carotid bodies of SIDS victims suggests a role in pathogenesis: dopamine inhibits respiration by acting directly on the carotid bodies and the carotid body plays an important role in the development of respiratory maturation. The pineal gland influences diurnal rhythm and is significantly reduced in weight in SIDS patients compared to age matched controls; the significance of this reduction is unknown. Brains of SIDS victims born at term were significantly heavier than reference values matched for both age and body length. 
COMMENT. The authors emphasize a delay of neural maturation of both myelination and synapses in the etiology of SIDS. Other abnormalities such as brainstem astrogliosis may be secondary to hypoxic-ischemia. In Canada, the incidence of sudden infant death syndrome is 1.2 per 1000 live births. The peak age is 1-4 months. The highest incidence is in winter and more boys than girls are affected. A thorough autopsy ruled out SIDS in 10% of sudden unexpected deaths occurring under one year of age. The differential diagnoses included congenital heart disease, myocarditis, central nervous system trauma (child abuse), cardiomyopathy, encephalitis, meningitis, congenital diaphragmatic hernia, and medium chain acyl coenzyme deficiency. If an anatomical cause of death is found, the diagnosis is not SIDS. In SIDS the mechanism of death must be related to a central type of respiratory failure or cardiac dysrhythmia.