In developed countries, sudden infant death syndrome (SIDS) is the most common cause of death for infants between 1 month and 1 year of age. The etiology of SIDS is likely to be multifactorial, and current paradigms often describe three overlapping elements of risk. Those elements are a critical developmental period, a vulnerable infant, and one or more exogenous stressors. In the triple-risk model, SIDS infants are described as having an underlying vulnerability in cardiorespiratory control in the central nervous system during a critical period when autonomic control is developing. This vulnerability might affect the response to exogenous stressors, including prone sleeping position, hypoxia, and increased carbon dioxide. In the common bacterial hypothesis and fatal triangle, the focus is on the stressors. In the first, a combination of common respiratory infections can cause SIDS in an infant during a developmentally vulnerable period. This theory also includes 3 factors of vulnerability: a genetic predisposition, a vulnerable developmental age, and infectious stressors. In the fatal triangle theory, infection, inflammation, and genetics each play a role in triggering a SIDS fatality. From our work in an animal model, we have found that rat pups die from a combination of infectious insults during a critical time of development. This is exacerbated by perinatal nicotine exposure, a condition shown to alter the autonomic response in exposed offspring. We are proposing that shock and cardiovascular collapse is a key element that links these theories.
American Heart Association (2005). 2005 American Heart Association (AHA) guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care (ECC) of pediatric and neonatal patients: Pediatric basic life support. Pediatrics , 117, e989-e1004.
2.
Beckwith, J.B. ( 1970). Discussion of terminology and definition of the sudden infant death syndrome. In A. B. Bergman , J. B. Beck, & G. C. Ray (Eds.), Sudden Infant Death Syndrome: Proceedings of the Second International Conference on the Causes of Sudden Death in Infants (pp. 14-22). Washington, DC: University of Washington Press.
3.
Berry, P.J. ( 1992). Pathological findings in SIDS. Journal of Clinical Pathology, 45(11 Suppl.), 11-16.
4.
Blackwell, C.C., Gordon, A.E., James, V.S., MacKenzie, D.A.C., Mogensen-Buchanan, M., el Ahmer, O.R., et al. (2002). The role of bacterial toxins in sudden infant death syndrome (SIDS). International Journal of Medical Microbiology, 291, 561-570.
5.
Blackwell, C.C., Moscovis, S.M., Gordon, A.E., Al Madani, O.M., Hall, S.T., Gleeson, M., et al. (2004). Ethnicity, infection and sudden infant death syndrome. FEMS Immunology and Medical Microbiology, 42, 53-65.
6.
Blackwell, C.C., Moscovis, S.M., Gordon, A.E., Al Madani, O.M., Hall, S.T., Gleeson, M., et al. (2005). Cytokine responses and sudden infant death syndrome: Genetic, developmental, and environmental risk factors. Journal of Leukocyte Biology, 78, 1242-1254.
7.
Blood-Siegfried, J., Nyska, A., Geisenhoffer, K., Lieder, H., Moomaw, C., Cobb, K., et al. (2004). Alteration in regulation of inflammatory response to influenza a virus and endotoxin in suckling rat pups: A potential relationship to sudden infant death syndrome. FEMS Immunology and Medical Microbiology, 42, 85-93.
8.
Blood-Siegfried, J., Nyska, A., Lieder, H., Joe, M., Vega, L., Patterson, R., et al. (2002). Synergistic effect of influenza a virus on endotoxin-induced mortality in rat pups: A potential model for sudden infant death syndrome. Pediatric Research, 52, 481-490.
9.
Blood-Siegfried, J., Rambaud, C., Nyska, A., & Germolec, D. ( 2008). Evidence for infection, inflammation and shock in sudden infant death: Parallels between a neonatal rat model of sudden death and infants who died of sudden infant death syndrome. Innate Immunity , 14, 145-152.
10.
Bone, R.C. ( 1996). Immunologic dissonance: A continuing evolution in our understanding of the systemic inflammatory response syndrome (SIRS) and the multiple organ dysfunction syndrome (MODS). Annals of Internal Medicine, 125, 680-687.
11.
Burchell, A., Lyall, H., Busuttil, A., Bell, E., & Hume, R. ( 1992). Glucose metabolism and hypoglycaemia in SIDS. Journal of Clinical Pathology, 45(11 Suppl.), 39-45.
12.
Dundar, M., Lanyon, W.G., & Connor, J.M. ( 1993). Scottish frequency of the common G985 mutation in the medium-chain acyl-CoA dehydrogenase (MCAD) gene and the role of MCAD deficiency in sudden infant death syndrome (SIDS). Journal of Inherited Metabolic Disease, 16, 991-993.
13.
Fifer, W.P., & Myers, M.M. ( 2002). Sudden fetal and infant deaths: Shared characteristics and distinctive features. Seminars in Perinatology, 26, 89-96.
14.
Gilbert, R., Rudd, P., Berry, P.J., Fleming, P.J., Hall, E., White, D.G., et al. (1992). Combined effect of infection and heavy wrapping on the risk of sudden unexpected infant death. Archives of Disease in Childhood, 67, 171-177.
15.
Gordon, A.E., MacKenzie, D.A.C., el Ahmer, O.R., Al Madani, O.M., Braun, J.M., Weir, D.M., et al. (2002). Evidence for a genetic component in sudden infant death syndrome. Child Care Health and Development, 28, 27-29.
16.
Gozal, D. ( 1996). Deficient heat shock protein expression: A potential mechanism for the sudden infant death syndrome. Medical Hypotheses , 46, 52-54.
17.
Guntheroth, W.G., & Spiers, P.S. ( 2001). Thermal stress in sudden infant death: Is there an ambiguity with the rebreathing hypothesis? Pediatrics, 107, 693-698.
18.
Harper, R.M. ( 2000). Sudden infant death syndrome: A failure of compensatory cerebellar mechanisms? Pediatric Research, 48, 140-142.
19.
Harper, R.M. ( 2001). Autonomic control during sleep and risk for sudden death in infancy. Archives Italiennes De Biologie, 139, 185-194.
20.
Harper, R.M., Kinney, H.C., Fleming, P.J., & Thach, B.T. ( 2000). Sleep influences on homeostatic functions: Implications for sudden infant death syndrome. Respiration Physiology, 119, 123-132.
21.
Harrison, L.M., Morris, J.A., Telford, D.R., Brown, S.M., & Jones, K. ( 1999). The nasopharyngeal bacterial flora in infancy: Effects of age, gender, season, viral upper respiratory tract infection and sleeping position. FEMS Immunology and Medical Microbiology , 25, 19-28.
22.
Hazinski, M., & Jenkins, M. ( 2002). Shock, multiple organ dysfunction syndrome, and burns in children. In K. McCance, & S. Huether (Eds.), Pathophysiology: The biologic basis for disease in adults and children (4th ed., pp. 1513-1540). Mosby Inc.
23.
Henshaw, C. ( 2005). Alterations in blood pressure. In L. Cop-stead, & J. Banasik (Eds.), Pathophysiology. Philadelphia : WB Saunders.
24.
Hodgman, J.E., & Siassi, B. ( 1999). Prolonged QTc as a risk factor for SIDS. Pediatrics, 103, 814-815.
25.
Holgate, S.T., Walters, C., Walls, A.F., Lawrence, S., Shell, D.J., Variend, S., et al. (1994). The anaphylaxis hypothesis of sudden infant death syndrome (SIDS): Mast cell degranulation in cot death revealed by elevated concentrations of tryptase in serum. Clinical and Experimental Allergy, 24, 1115-1122.
26.
Huang, Z.G., Wang, X., Evans, C., Gold, A., Bouairi, E., & Mendelowitz, D. (2004). Prenatal nicotine exposure alters the types of nicotinic receptors that facilitate excitatory inputs to cardiac vagal neurons. Journal of Neurophysiology, 92, 2548-2554.
27.
Kahn, A., Groswasser, J., Rebuffat, E., Sottiaux, M., Blum, D., Foerster, M., et al. (1992). Sleep and cardiorespiratory characteristics of infant victims of sudden death: a prospective case-control study. Sleep, 15, 287-292.
28.
Kinney, H.C., Filiano, J.J., & Harper, R.M. ( 1992). The neuropathology of the sudden infant death syndrome. A review. Journal of Neuropathology and Experimental Neurology , 51, 115-126.
29.
Kinney, H.C., Filiano, J.J., & White, W.F. ( 2001). Medullary serotonergic network deficiency in the sudden infant death syndrome: Review of a 15-year study of a single dataset . Journal of Neuropathology and Experimental Neurology, 60, 228-247.
30.
Krous, H.F. ( 1984). Sudden infant death syndrome: Pathology and pathophysiology . Pathology Annals, 19, 1-14.
31.
Lingappa, V., & Farey, K. ( 2000a). Command control of organ systems. In Physiological medicine: A clinical approach to basic medical physiology (pp. 113-153). Newyork: McGraw-Hill.
32.
Lingappa, V., & Farey, K. ( 2000b). Fluid, electrolyte, acid-base and blood pressure regulation . In Physiological medicine: A clinical approach to basic medical physiology (pp. 455-510). Newyork: McGraw-Hill .
33.
Lundemose, J.B., Smith, H., & Sweet, C. ( 1993). Cytokine release from human peripheral blood leucocytes incubated with endotoxin with and without prior infection with influenza virus: Relevance to the sudden infant death syndrome. International Journal of Experimental Pathology, 74, 291-297.
34.
Maron, B.J., Clark, C.E., Goldstein, R.E., & Epstein, S.E. ( 1976). Potential role of QT interval prolongation in sudden infant death syndrome. Circulation, 54, 423-430.
35.
McCance, K. ( 2002). Structure and function of the cardiovascualr and lymphatic systems. In K. McCance, & S. Huether (Eds.), Pathophysiology: The biologic basis for disease in adults and children (4th ed., pp. 930-979). St Louis: Mosby Inc.
36.
Molony, N., Blackwell, C.C., & Busuttil, A. ( 1999). The effect of prone posture on nasal temperature in children in relation to induction of staphylococcal toxins implicated in sudden infant death syndrome. FEMS Immunology and Medical Microbiology, 25, 109-113.
37.
Morris, J.A. ( 1999). The common bacterial toxins hypothesis of sudden infant death syndrome. FEMS Immunology and Medical Microbiology , 25, 11-17.
38.
Morris, J.A., Haran, D., & Smith, A. ( 1987). Hypothesis: Common bacterial toxins are a possible cause of the sudden infant death syndrome. Medical Hypotheses , 22, 211-222.
39.
Navarro, H.A., Seidler, F.J., Eylers, J.P., Baker, F.E., Dobbins, S.S., Lappi, S.E., et al. (1989). Effects of prenatal nicotine exposure on development of central and peripheral cholinergic neurotransmitter systems. Evidence for cholinergic trophic influences in developing brain. Journal of Pharmacology and Experimental Therapeutics, 251, 894-900.
40.
Platt, M.S., Yunginger, J.W., Sekulaperlman, A., Irani, A.M.A., Smialek, J., Mirchandani, H.G., et al. (1994). Involvement of mast-cells in sudden-infant-death-syndrome . Journal of Allergy and Clinical Immunology, 94, 250-256.
41.
Poets, C.F., Meny, R.G., Chobanian, M.R., & Bonofiglo, R.E. (1999). Gasping and other cardiorespiratory patterns during sudden infant deaths. Pediatric Research, 45, 350-354.
42.
Rambaud, C., Guibert, M., Briand, E., Grangeot-Keros, L., Coulomb-L’Hermin, A., & Dehan, M. ( 1999). Microbiology in sudden infant death syndrome (SIDS) and other childhood deaths. FEMS Immunology and Medical Microbiology , 25, 59-66.
43.
Raza, M.W., & Blackwell, C.C. (1999). Sudden infant death syndrome, virus infections and cytokines. FEMS Immunology and Medical Microbiology, 25, 85-96.
44.
Raza, M.W., el Ahmer, O.R., Ogilvie, M.M., Blackwell, C.C., Saadi, A.T., Elton, R.A., et al. (1999). Infection with respiratory syncytial virus enhances expression of native receptors for non-pilate. Neisseria meningitidis on HEp-2 cells. FEMS Immunology and Medical Microbiology, 23, 115-124.
45.
Reid, G.M. ( 1998). Sudden infant death syndrome and the modulation of neuropeptides released during shock. Medical Hypotheses , 51, 23-26.
46.
Rognum, T.O., & Saugstad, O.D. (1993). Biochemical and immunological studies in SIDS victims. Clues to understanding the death mechanism. Acta Paediatrica Supplement, 82(Suppl. 389), 82-85.
47.
Sawczenko, A., & Fleming, P.J. ( 1996). Thermal stress, sleeping position, and the sudden infant death syndrome. Sleep, 19(10 Suppl.), S267-S270.
48.
Schwarz, A. ( 2006). Shock Retrieved March, 9, 2006, from http://www.emedicine.com/PED/topic3047.htm.
49.
Slotkin, T.A., Lappi, S.E., McCook, E.C., Lorber, B.A., & Seidler, F.J. ( 1995). Loss of neonatal hypoxia tolerance after prenatal nicotine exposure: Implications for sudden infant death syndrome. Brain Research Bulletin, 38, 69-75.
50.
Slotkin, T.A., Saleh, J.L., McCook, E.C., & Seidler, F.J. ( 1997). Impaired cardiac function during postnatal hypoxia in rats exposed to nicotine prenatally: Implications for perinatal morbidity and mortality, and for sudden infant death syndrome. Teratology , 55, 177-184.
51.
Taylor, B.J., Williams, S.M., Mitchell, E.A., & Ford, R.P. ( 1996). Symptoms, sweating and reactivity of infants who die of SIDS compared with community controls. New Zealand National Cot Death Study Group. Journal of Paediatrics and Child Health, 32, 316-322.
52.
Wedgewood, R.J. ( 1972). Review of USA experience. In F. E. Camps & R. G. Carpente (Eds.), Sudden and unexplained deaths in infancy (cot deaths): Vol. 28. Bristol England: Wright.
53.
Willinger, M., James, L.S., & Catz, C. ( 1991). Defining the sudden infant death syndrome (SIDS): Deliberations of an expert panel convened by the National Institute of Child Health and Human Development. Pediatric Pathology, 11, 677-684.
