Sudden Infant Death Syndrome: History
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Subjects: Clinical Neurology
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Francesca Marinelli

Sudden infant death syndrome (SIDS) is defined as “the sudden death of an infant under 1 year of age which remains unexplained after thorough investigation including a complete autopsy, death scene investigation, and detailed clinical and pathological review”. 

  • Sudden Infant Death Syndrome

1. Introduction

Sudden infant death syndrome (SIDS) is defined as “the sudden death of an infant under 1 year of age which remains unexplained after thorough investigation including a complete autopsy, death scene investigation, and detailed clinical and pathological review” [1][2]. SIDS is characterized by an unexpected death during the sleeping period and it typically occurs in the first 12 months of age in a previously healthy infant. Most events take place in the child’s home; the out-of-home deaths are most frequent at a relative’s home or a child-care setting, especially if the child sleeps in prone position and in a stroller and/or car seat [3]. SIDS is a subcategory of Sudden Unexpected Infant Deaths (SUID) and represents nearly half of these cases; SUID includes SIDS of unknown cause and also events of strangulation in bed or accidental suffocation [4]. The peak of incidence of SIDS is around two to four months of age and 90% of cases occur before six months of age; prevalence of SIDS is higher in boys than girls, at a 3:2 ratio [5].

In the late 1980s prone sleep has been documented as a major risk factor for SIDS, leading in the 1990s to “back-to-sleep” campaigns which have had a great impact on reduction of SIDS rates [6]. SIDS infant mortality has decreased well over 50% for most countries, especially in the first few years after the beginning of national campaigns [7]. Alongside the SIDS prevention recommendations, perinatal care has experienced numerous other improvements, so it’s difficult to attribute the SIDS incidence drop to only the supine sleep practice [6]. Furthermore, the increasing rates of other causes of death such as strangulation in bed and accidental suffocation may represent another explanation of the decline in SIDS rates [8]. Over the first decade of this century, infant mortality from SIDS has experienced a continuous drop in some countries such as Australia, Canada, England and Wales, Germany, Japan and the Netherlands, while it has remained stationary in others, notably the USA and New Zealand [9]. Despite continuous public health efforts concentrating on the improvement of sleep conditions with a special focus on the high-risk groups [10][11], incidence of SIDS still continues to be high. In fact, SIDS still represents a prominent cause of infant death, occurring at a rate of 27/100,000 live births in the United Kingdom and 38/100,000 the United States [12][13]. In Italy incidence is about 1 out of 1000 live births [14]. Therefore, continuous research on the cause and prevention of SIDS is needed.

2. Pathogenesis and Risk Factors

The most recent evidence suggests that SIDS pathogenesis is a multifactorial condition that comprehends genetic, environmental and sociocultural factors [8]. The Triple-Risk Model, first described in 1994, affirms that SIDS occurs in infants with latent biological vulnerability (brainstem abnormality or genetic pattern), who is exposed to a trigger event or extrinsic risk factor (prone sleeping, airway obstruction) during a critical phase of development [15]. The combination of intrinsic and extrinsic factors which overlap during a period of respiratory, autonomic and cardiac development, usually occurring between two to four months of age, leads to a life-threatening event during a period of sleep. Failure of protective mechanisms during these episodes finally concludes with unexpected death. On the contrary, SIDS is less likely to occur with the removal of one of these factors [16][17].

Multiple extrinsic risk factors for SIDS in the sleep environment of the infants have been examined. Prone sleeping appears to be the most significant risk factor for SIDS. In fact, it is likely to be associated with re-breathing expired gases, suffocation, overheating and decreased arousal [18]. Infants in side lying position are also at high risk to roll into prone position while sleeping [19]. Other factors related to the sleeping environment involve soft bedding, sleeping with blankets, pillows, soft objects, bumper pads, head or face covered during sleep, bedsharing (especially co-sleeping on a couch or sofa) and room or infant overheating [20]. Maternal smoking during pregnancy is associated with a fivefold increase in SIDS events, and postnatal smoking exposure further increases the risk [21][22][23]. In fact, it’s been demonstrated that smoking during pregnancy contributes to the risk due to the disruption of arousal patterns in the sleeping baby along with impairment of autonomic system and cardiovascular response: uterine exposure reduces lung compliance and volume, alters arousal mechanisms and decreases heart rate variability in response to stress, all factors that can negatively affect a baby’s ability to respond appropriately to the environment [24][25]. A recent study showed a linear correlation between number of cigarettes smoked daily during pregnancy and the risk of a SUID event. Furthermore, quitting smoking over the three trimesters is strongly associated with great reduction of SUID risk but also diminution of cigarettes smoked daily contributes to a small decrease in risk [26]. Additional risk factors include maternal alcohol use, young maternal age (under 20 years) and poor prenatal care [27]. The combined exposure of alcohol and tobacco beyond the first trimester of pregnancy appears to have a synergistic effect on the risk for SIDS events [28]. Co-sleeping associated with recent use of alcohol or drugs by the parents also increases the risk significantly [29]. The strong association between smoking, alcohol consumption and drugs utilization may also explain, in part, the interaction described between co-sleeping and smoking [29][30][31][32]. Bottle-feeding is associated with increased risk, while the use of a pacifier and breastfeeding appear to be protective factors [27][33][34]. Some studies suggest that a significant part of SIDS cases may be closely related to sub-clinical infection processes [35][36]. In a study conducted by Goldwater et al. in 2020, significantly heavier thymus and brain were found in SIDS victims compared to non-SIDS controls. This finding is related to immune responses in the brain and thymus associated with possible subclinical infections [37].

Intrinsic risk factors are male gender, population subgroups such as non-Hispanic black infants, American Indian or Alaska Native infants [8][38] and prematurity. Preterm birth or low birth weight increases the risk of SIDS events three to four times, suggesting that altered intrauterine environment may contribute to the pathogenesis [39]. Additionally, smoking during pregnancy increases the risk of premature delivery [40]. Furthermore, research suggests that disorders of homeostasis, neuroregulation and cardiorespiratory function associated with brain and brainstem anomalies play an important role in SIDS [16]. In particular, serotonin brainstem abnormalities have been identified in up to 70% of infants who have died of SIDS [16]. Since the serotonin system is associated with several homeostatic functions, these anomalies may possibly lead to a network dysfunction that affects arousal and cardiorespiratory functions [41][42]. In addition to brain vulnerabilities, research has focused on identifying genetic variants related to defects involving autonomic and metabolic functions, neurotransmission and cardiac repolarization, suggested to contribute to SIDS infant’s “underlying vulnerability” [2][43][44]. Thus, certain infants may have a genetic predisposition to SIDS or an underlying abnormality in the brainstem, which becomes manifest when the infant experiences environmental challenges (hypoxia, asphyxia, hypercarbia, overheating) during sleep and differentiates a SIDS infant from a healthy infant. In fact, infants without the underlying conditions present an efficient protective brainstem response to homeostatic challenges which promptly manage to avoid SIDS occurrence [2]. The combination of multiple extrinsic and intrinsic factors leads to asphyxia. Vulnerable infants are not able to respond with arousal that prevents re-breathing or apnea. Consequently, asphyxia leads to bradycardia and insufficient gasping breathing, which eventually terminate with death [45].

Most of these life-threatening events occur during the sleep period. In fact, sleep is associated with a reduction of blood pressure, heart rate, respiratory rate and muscle tone, especially in the upper airways. During sleep phases protective reflexes to hypoxia and hypercapnia are also depressed. Blood pressure, cerebral oxygenation and cerebral vascular homeostasis are decreased in the prone position [46][47]. In fact, term infants between two to four months of age show a depressed baroreflex response and decreased arousal in the prone position [48][49]. In premature babies these characteristics in prone position are mostly marked [50][51]. These considerations highlight, indeed, the increased risk of SIDS occurring during sleeping, mainly in the prone position during specific infant development windows.

This entry is adapted from the peer-reviewed paper 10.3390/life11030184

References

  1. Krous, H.F.; Beckwith, J.B.; Byard, R.W.; Rognum, T.O.; Bajanowski, T.; Corey, T.; Cutz, E.; Hanzlick, R.; Keens, T.G.; Mitchell, E.A. Sudden Infant Death Syndrome and Unclassified Sudden Infant Deaths: A Definitional and Diagnostic Approach. Pediatrics 2004, 114, 234–238.
  2. Kinney, H.C.; Richerson, G.B.; Dymecki, S.M.; Darnall, R.A.; Nattie, E.E. The Brainstem and Serotonin in the Sudden Infant Death Syndrome. Annu. Rev. Pathol. Mech. Dis. 2009, 4, 517–550.
  3. Kassa, H.; Moon, R.Y.; Colvin, J.D. Risk Factors for Sleep-Related Infant Deaths in In-Home and Out-of-Home Settings. Pediatrics 2016, 138, e20161124.
  4. Behnam-Terneus, M.; Clemente, M. SIDS, BRUE, and Safe Sleep Guidelines. Pediatr. Rev. 2019, 40, 443–455.
  5. Shapiro-Mendoza, C.K.; Tomashek, K.M.; Anderson, R.N.; Wingo, J. Recent National Trends in Sudden, Unexpected Infant Deaths: More Evidence Supporting a Change in Classification or Reporting. Am. J. Epidemiol. 2006, 163, 762–769.
  6. Goldstein, R.D.; Trachtenberg, F.L.; Sens, M.A.; Harty, B.J.; Kinney, H.C. Overall Postneonatal Mortality and Rates of SIDS. Pediatrics 2016, 137, e20152298.
  7. Hauck, F.R.; Tanabe, K.O. International Trends in Sudden Infant Death Syndrome: Stabilization of Rates Requires Further Action. Pediatrics 2008, 122, 660–666.
  8. Moon, R.Y.; Fu, L. Sudden Infant Death Syndrome: An Update. Pediatr. Rev. 2012, 33, 314–320.
  9. Taylor, B.J.; Garstang, J.; Engelberts, A.; Obonai, T.; Cote, A.; Freemantle, J.; Vennemann, M.; Healey, M.; Sidebotham, P.; A Mitchell, E.; et al. International comparison of sudden unexpected death in infancy rates using a newly proposed set of cause-of-death codes. Arch. Dis. Child. 2015, 100, 1018–1023.
  10. National Institute of Child Health and Human Development, National Institutes of Health. Safe to Sleep Campaign. Available online: (accessed on 27 October 2020).
  11. Heron, M. Deaths: Leading Causes for 2014. Natl. Vital Stat. Rep. 2016, 65, 1–96.
  12. Matthews, T.J.; MacDorman, M.F. Infant mortality statistics from the 2010 period linked birth/infant death data set. Natl. Vital Stat. Rep. 2013, 62, 1–26.
  13. Patel, V. Unexplained Deaths in Infancy, England and Wales: 2018. Available online: (accessed on 27 October 2020).
  14. Sindrome Della Morte in Culla. Epidemiologia. Available online: (accessed on 27 October 2020).
  15. Filiano, J.J.; Kinney, H.C. A Perspective on Neuropathologic Findings in Victims of the Sudden Infant Death Syndrome: The Triple-Risk Model. Neonatology 1994, 65, 194–197.
  16. Moon, R.Y.; Task Force on Sudden Infant Death Syndrome. SIDS and Other Sleep-Related Infant Deaths: Evidence Base for 2016 Updated Recommendations for a Safe Infant Sleeping Environment. Pediatrics 2016, 138, e20162940.
  17. Goldstein, R.D.; Kinney, H.C.; Willinger, M. Sudden Unexpected Death in Fetal Life Through Early Childhood. Pediatrics 2016, 137.
  18. Groswasser, J.; Simon, T.; Scaillet, S.; Franco, P.; Kahn, A. Reduced Arousals Following Obstructive Apneas in Infants Sleeping Prone. Pediatr. Res. 2001, 49, 402–406.
  19. Li, D.-K.; Petitti, D.B.; Willinger, M.; McMahon, R.M.; Odouli, R.; Vu, H.; Hoffman, H.J. Infant Sleeping Position and the Risk of Sudden Infant Death Syndrome in California, 1997-2000. Am. J. Epidemiol. 2003, 157, 446–455.
  20. Ruys, J.H.; De Jonge, G.A.; Brand, R.; Engelberts, A.C.; A Semmekrot, B. Bed-sharing in the first four months of life: A risk factor for sudden infant death. Acta Paediatr. 2007, 96, 1399–1403.
  21. Mitchell, E.; Milerad, J. Smoking and the Sudden Infant Death Syndrome. Rev. Environ. Health 2006, 21, 81–104.
  22. Dietz, P.M.; England, L.J.; Shapiro-Mendoza, C.K.; Tong, V.T.; Farr, S.L.; Callaghan, W.M. Infant Morbidity and Mortality Attributable to Prenatal Smoking in the U.S. Am. J. Prev. Med. 2010, 39, 45–52.
  23. MacDorman, M.F.; Cnattingius, S.; Hoffman, H.J.; Kramer, M.S.; Haglund, B. Sudden Infant Death Syndrome and Smoking in the United States and Sweden. Am. J. Epidemiol. 1997, 146, 249–257.
  24. Fifer, W.P.; Fingers, S.T.; Youngman, M.; Gomez-Gribben, E.; Myers, M.M. Effects of alcohol and smoking during pregnancy on infant autonomic control. Dev. Psychobiol. 2009, 51, 234–242.
  25. Richardson, H.L.; Walker, A.M.; Horne, R.S.C. Maternal smoking impairs arousal patterns in sleeping infants. Sleep 2009, 32, 515–521.
  26. Anderson, T.M.; Ferres, J.M.L.; Ren, S.Y.; Moon, R.Y.; Goldstein, R.D.; Ramirez, J.-M.; Mitchell, E.A. Maternal Smoking Before and During Pregnancy and the Risk of Sudden Unexpected Infant Death. Pediatrics 2019, 143, e20183325.
  27. Hauck, F.R.; Thompson, J.M.D.; O Tanabe, K.; Moon, R.Y.; Vennemann, M.M. Breastfeeding and Reduced Risk of Sudden Infant Death Syndrome: A Meta-analysis. Pediatrics 2011, 128, 103–110.
  28. Elliott, A.J.; Kinney, H.C.; Haynes, R.L.; Dempers, J.D.; Wright, C.; Fifer, W.P.; Angal, J.; Boyd, T.K.; Burd, L.; Burger, E.; et al. Concurrent prenatal drinking and smoking increases risk for SIDS: Safe Passage Study report. EClinicalMedicine 2020, 19, 100247.
  29. Blair, P.S.; Sidebotham, P.; Evason-Coombe, C.; Edmonds, M.; Heckstall-Smith, E.M.A.; Fleming, P. Hazardous cosleeping environments and risk factors amenable to change: Case-control study of SIDS in south west England. BMJ 2009, 339, b3666.
  30. Scragg, R.; Mitchell, E.A.; Taylor, B.J.; Stewart, A.W.; Ford, R.P.; Thompson, J.M.; Allen, E.M.; Becroft, D.M. Bed sharing, smoking, and alcohol in the sudden infant death syndrome. New Zealand Cot Death Study Group. BMJ 1993, 307, 1312–1318.
  31. Blair, P.S.; Fleming, P.J.; Smith, I.J.; Platt, M.W.; Young, J.; Nadin, P.; Berry, P.J.; Golding, J.; The CESDI SUDI Research Group. Babies sleeping with parents: Case-control study of factors influencing the risk of the sudden infant death syndrome. BMJ 1999, 319, 1457–1461.
  32. Carpenter, R.G.; Irgens, L.M.; Blair, P.S.; England, P.D.; Fleming, P.; Huber, J.; Jorch, G.; Schreuder, P. Sudden unexplained infant death in 20 regions in Europe: Case control study. Lancet 2004, 363, 185–191.
  33. Hauck, F.R.; Omojokun, O.O.; Siadaty, M.S. Do Pacifiers Reduce the Risk of Sudden Infant Death Syndrome? A Meta-analysis. Pediatrics 2005, 116, e716–e723.
  34. Moon, R.Y.; Tanabe, K.O.; Yang, D.C.; Young, H.A.; Hauck, F.R. Pacifier Use and Sids: Evidence for a Consistently Reduced Risk. Matern. Child Health J. 2012, 16, 609–614.
  35. Goldwater, P.N. Sudden Infant Death Syndrome, Infection, Prone Sleep Position, and Vagal Neuroimmunology. Front. Pediatr. 2017, 5.
  36. Moscovis, S.M.; Gordon, A.E.; Al Madani, O.M.; Gleeson, M.; Scott, R.J.; Hall, S.T.; Burns, C.; Blackwell, C. Genetic and Environmental Factors Affecting TNF-α Responses in Relation to Sudden Infant Death Syndrome. Front. Immunol. 2015, 6, 374.
  37. Goldwater, P.N.; Kelmanson, I.A.; Little, B.B. Increased thymus weight in sudden infant death syndrome compared to controls: The role of sub-clinical infections. Am. J. Hum. Biol. 2020, e23528.
  38. Maged, M.; Rizzolo, D. Preventing sudden infant death syndrome and other sleep-related infant deaths. J. Am. Acad. Physician Assist. 2018, 31, 25–30.
  39. Bigger, H.R.; Silvestri, J.M.; Shott, S.; Weese-Mayer, D.E. Influence of increased survival in very low birth weight, low birth weight, and normal birth weight infants on the incidence of sudden infant death syndrome in the United States: 1985–1991. J. Pediatr. 1998, 133, 73–78.
  40. Ostfeld, B.M.; Schwartz-Soicher, O.; Reichman, N.E.; Teitler, J.O.; Hegyi, T. Prematurity and Sudden Unexpected Infant Deaths in the United States. Pediatrics 2017, 140, e20163334.
  41. Weese-Mayer, D.E.; Berry-Kravis, E.M.; Zhou, L.; Maher, B.S.; Curran, M.E.; Silvestri, J.M.; Marazita, M.L. Sudden Infant Death Syndrome: Case-Control Frequency Differences at Genes Pertinent to Early Autonomic Nervous System Embryologic Development. Pediatr. Res. 2004, 56, 391–395.
  42. Jacobs, B.L.; Azmitia, E.C. Structure and function of the brain serotonin system. Physiol. Rev. 1992, 72, 165–229.
  43. Weese-Mayer, D.E.; Ackerman, M.J.; Marazita, M.L.; Berry-Kravis, E.M. Sudden Infant Death Syndrome: Review of implicated genetic factors. Am. J. Med. Genet. Part A 2007, 143A, 771–788.
  44. Van Norstrand, D.W.; Ackerman, M.J. Genomic risk factors in sudden infant death syndrome. Genome Med. 2010, 2, 86.
  45. Sridhar, R.; Thach, B.T.; Kelly, D.H.; Henslee, J.A. Characterization of successful and failed autoresuscitation in human infants, including those dying of SIDS. Pediatr. Pulmonol. 2003, 36, 113–122.
  46. Yiallourou, S.R.; Walker, A.M.; Horne, R.S.C. Effects of sleeping position on development of infant cardiovascular control. Arch. Dis. Child. 2008, 93, 868–872.
  47. Wong, F.Y.; Witcombe, N.B.; Yiallourou, S.R.; Yorkston, S.; Dymowski, A.R.; Krishnan, L.; Walker, A.M.; Horne, R.S.C. Cerebral oxygenation is depressed during sleep in healthy term infants when they sleep prone. Pediatrics 2011, 127, e558–e565.
  48. Horne, R.S.; Ferens, D.; Watts, A.-M.; Vitkovic, J.; Lacey, B.; Andrew, S.; Cranage, S.M.; Chau, B.; Adamson, T. The prone sleeping position impairs arousability in term infants. J. Pediatr. 2001, 138, 811–816.
  49. Yiallourou, S.R.; Walker, A.M.; Horne, R.S.C. Prone sleeping impairs circulatory control during sleep in healthy term infants: Implications for SIDS. Sleep 2008, 31, 1139–1146.
  50. Fyfe, K.L.; Yiallourou, S.R.; Wong, F.Y.; Odoi, A.; Walker, A.M.; Horne, R.S.C. Cerebral oxygenation in preterm infants. Pediatrics 2014, 134, 435–445.
  51. Witcombe, N.B.; Yiallourou, S.R.; Walker, A.M.; Horne, R.S.C. Blood pressure and heart rate patterns during sleep are altered in preterm-born infants: Implications for sudden infant death syndrome. Pediatrics 2008, 122, e1242–e1248.
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