Published online by Cambridge University Press: 20 July 2018
Three research areas derived from human studies of epidemiology, pathology, and sleep in infants have made contributions to our understanding of sudden infant death syndrome (SIDS). Epidemiological studies of infants who died of SIDS have identified a variety of risk factors associated with increased and decreased risk of SIDS (1-7), including prone sleeping position (8, 9), maternal cigarette smoking during pregnancy, and heat stress in the infant, often related to overheated environments, excessive bed clothing, or other unsafe sleeping practices (8, 10, 11). Additional risk factors include a recent upper respiratory tract infection, bed sharing, prematurity, and intrauterine and/or postnatal hypoxic stress.
Similar progress in understanding the origins of SIDS has been made by pathologists analysing the brains of infants who died and were classified as SIDS. Analyses of brain tissue from these infants have consistently revealed a high prevalence of abnormalities in the brainstem serotoninergic system including an increased number of serotonergic neurons, a higher proportion of serotonergic neurons displaying immature morphology, decreased tissue levels of serotonin (5-HT) and its synthetic enzyme, tryptophan hydroxylase 2 (TPH2), and decreased 5-HT receptor binding intensity both in serotonergic nuclei themselves and in several nuclei that are important in cardiorespiratory control (9, 12-16). Similar serotonin system deficits have been described in infants who died of asphyxia (17). There has been persistent speculation that infants who died of SIDS suffered from hypoxia (i.e. low oxygen levels) at some time preceding death (18-22), and hypoxia appeared to delay maturation of the brain in infants who died of SIDS (19-21, 23, 24).
Finally, sleep studies in the infants who subsequently died of SIDS have revealed a sequence of repetitive episodes of hypoxia preceding, or following, apnea and/or bradycardia, followed by autoresuscitative efforts to restore normal breathing and arouse from sleep (25-28). Death occurred when the autoresuscitation or arousal following prolonged apnea failed to restore regular breathing and adequate oxygenation. Many infants experienced sequences of multiple hypoxic apneic events from which they recovered, only to succumb to a final event in which autoresuscitation and/or arousal failed.