The Triple Risk Hypotheses in Sudden Infant Death Syndrome

• Published in: Pediatrics (Evanston) 2002-11, Vol.110 (5), p.e64-e64
• Main Authors: Guntheroth, Warren G, Spiers, Philip S
• Format: Article
• Language: English
• Subjects: Age Factors; Brain - pathology; Brain - physiopathology; Brain Diseases - embryology; Brain Diseases - pathology; Brain Diseases - physiopathology; Brain Stem - pathology; Brain Stem - physiopathology; Child Development - physiology; Comorbidity; Female; Fetal Diseases - epidemiology; Fetal Diseases - pathology; Fetal Diseases - physiopathology; Humans; Infant; Infant mortality; Infant, Newborn; Models, Theoretical; Pediatrics; Pregnancy; Prospective Studies; Risk Factors; Sudden Infant Death - epidemiology; Sudden Infant Death - pathology; Sudden infant death syndrome
• ISSN: 0031-4005; 1098-4275
• DOI: 10.1542/peds.110.5.e64

Sudden infant death syndrome (SIDS) victims were regarded as normal as a matter of definition (Beckwith 1970) until 1952 when Kinney and colleagues argued for elimination of the clause, "unexpected by history." They argued that "not all SIDS victims were normal," and referred to their hypothesis that SIDS results from brain abnormalities, which they postulated "to originate in utero and lead to sudden death during a vulnerable postnatal period." Bergman (1970) argued that SIDS did not depend on any "single characteristic that ordains a infant for death," but on an interaction of risk factors with variable probabilities. Wedgwood (1972) agreed and grouped risk factors into the first "triple risk hypothesis" consisting of general vulnerability, age-specific risks, and precipitating factors. Raring (1975), based on a bell-shaped curve of age of death (log-transformed), concluded that SIDS was a random process with multifactorial causation. Rognum and Saugstad (1993) developed a "fatal triangle" in 1993, with groupings similar to those of Wedgwood, but included mucosal immunity under a vulnerable developmental stage of the infant. Filiano and Kinney (1994) presented the best known triple risk hypothesis and emphasized prenatal injury of the brainstem. They added a qualifier, "in at least a subset of SIDS," but, the National Institute of Child Health and Development SIDS Strategic Plan 2000, quoting Kinney's work, states unequivocally that "SIDS is a developmental disorder. Its origins are during fetal development." Except for the emphasis on prenatal origin, all 3 triple risk hypotheses are similar. Interest in the brainstem of SIDS victims began with Naeye's 1976 report of astrogliosis in 50% of all victims. He concluded that these changes were caused by hypoxia and were not the cause of SIDS. He noted an absence of astrogliosis in some older SIDS victims, compatible with a single, terminal episode of hypoxia without previous hypoxic episodes, prenatal or postnatal. Kinney and colleagues (1983) reported gliosis in 22% of their SIDS victims. Subsequently, they instituted studies of neurotransmitter systems in the brainstem, particularly the muscarinic (1995) and serotenergic systems (2001). The major issue is when did the brainstem abnormalities, astrogliosis, or neurotransmitter changes occur and whether either is specific to SIDS. There is no published method known to us of determining the time of origin of these markers except that the injury causing astrog