Explainer: Sudden infant death syndrome and new findings about butyrylcholinesterase

Disclaimer: I am not a medical professional or a scientist. This is a lay summary of popular and scientific coverage surrounding the event.

Sudden infant death syndrome (SIDS) is the leading cause of infant mortality in the Western world (Raven, 2018). It is a condition where a child less than one year old dies suddenly (“Sudden infant death syndrome,” 2017). For a diagnosis to be made, a cause of death must not be found after an autopsy and an investigation of the scene of death (“Sudden unexpected infant death,” 2013).

In the time since SIDS was originally indexed, nobody has been able to determine why it happens (“What causes SIDS?”, 2017). We’ve assumed that it’s multifactorial, i.e., that multiple risk factors have to line up (Kinney & Thach, 2009; Byard, 2018). Most of the proposed risk factors are temporary and are not intervenable, i.e., they can’t be prevented from happening — things like a specific inborn susceptibility and a specific time in development.

The only intervenable risk factor which has been proposed is the presence of environmental stressors, i.e., factors in the environment or in the way the environment directs the baby’s behaviour (Kinney & Thach, op. cit.). Environmental factors which have been proposed include co-sleeping, i.e., parents keeping their babies in the same bed as themselves, potentially causing the babies to suffocate; overheating; side sleeping; stomach sleeping; and prenatal exposure to nicotine (Fleming et al., 1993; Sullivan & Barlow, 2001; Bajanowski et al., 2007; Moon et al., 2007; Lavezzi et al., 2010; Moon, 2011; Moon & Fu, 2012; Carpenter et al., 2013; Horne, 2014; Moon et al., 2016; Carlin & Moon, 2017; Young & Shipstone, 2018; Anderson et al., 2019; “What causes SIDS?”, op. cit.).

The death of one’s child is an unimaginably traumatic experience. SIDS further compounds that. Like unexpected deaths from unknown causes in general, deaths from SIDS must be extensively investigated (Kinney & Thach, op. cit.). We’ve thought for some time, and with some degree of confidence, that the mechanism by which SIDS causes death is through hypoxia (Duncan & Byard, 2018), i.e., it deprives vital organs, particularly the brain, of oxygen. Because of this, SIDS has to be distinguished from other hypoxia-related deaths.

One cause of hypoxia-related death is intentional child murder by suffocation (Kinney & Thach, op. cit.). Another mechanism (Bajanowski et al., 2005) is shaken baby syndrome (SBS), thought to result from physical abuse by vigorous shaking, which may not, however, have been intended to kill — that doesn’t make it any better but it does make it different from murder. SBS is mechanically the same condition as whiplash in adults, but while whiplash mostly causes injuries to the muscles, ligaments and discs of the neck, SBS appears able to cut off oxygen to the brain (Miehl, 2005).

In cases of SIDS, suspicion of both murder through suffocation and involuntary manslaughter through SBS necessarily falls on parents, who are very probably innocent and grieving the loss of their child. Even without alleging criminal or unethical conduct, however, parents — and particularly mothers — whose children die of SIDS often bear the stigma of having been careless, even if they took every possible precaution.

Dr Carmel Harrington, a sleep medicine researcher at The Children’s Hospital at Westmead, in Western Sydney, NSW, is a mother whose son died of SIDS 29 years ago (“World first breakthrough could prevent SIDS,” 2022). On 6 May 2022, eBioMedicine, a division of The Lancet, published Harrington et al. (2022), who found that, compared to blood samples taken from healthy babies, blood samples from babies who died of SIDS contained considerably lower levels of butyrylcholinesterase (BCHE).

BCHE appears to play a role (Eggermont, 2014, pp. 278–280) in the ascending reticular activating system (ARAS), the part of the brain that regulates the ability to wake up (Tapia et al., 2013; Peters, 2020). The ARAS is the same system which causes adults with sleep apnea of the obstructive (OSA) or central (CSA) types to wake up if they stop breathing for too long. BCHE deficiency may prevent the ARAS from kicking in, meaning that a baby who stops breathing simply continues to not breathe, and never wakes up.

This discovery is significant because if further research verifies a strong link between low BCHE and SIDS, it may be possible to develop screening to identify infants at risk of SIDS before they can die, and then to develop medical interventions to massively reduce or prevent SIDS altogether (Connell & Vidal, 2022; Ravikumar, 2022; Van de Riet, 2022).

References

Anderson, T.M., Lavista Ferres, J.M., Ren, S.Y., Moon, R.Y., Goldstein, R.D., … & Mitchell, E.A. (2019, April 1). Maternal smoking before and during pregnancy and the risk of sudden unexpected infant death. Pediatrics, 143(4), e20183325. doi:10.1542/peds.2018-3325. Retrieved 14 May 2022.

Bajanowski, T., Vennemann, M., Bohnert, M., Rauch, E., Brinkmann, B., & Mitchell, E.A. (2005, April 14). Unnatural causes of sudden unexplained deaths initially thought to be sudden infant death syndrome. International Journal of Legal Medicine, 119, 213–216. doi:10.1007/s00414-005-0538-8. Retrieved 14 May 2022.

Bajanowski, T., Brinkmann, B., Mitchell, E.A., Vennemann, M.M., Leukel, H.W., … & Beike, J. (2007, February 7). Nicotine and cotinine in infants dying from sudden infant death syndrome. International Journal of Legal Medicine, 122, 23–28. doi:10.1007/s00414-007-0155-9. Retrieved 14 May 2022.

Byard, R.W. (2018). Chapter 1: Sudden infant death syndrome — Definitions. In J.R. Duncan & R.W. Byard (Eds.), SIDS — Sudden infant and early childhood death: The past, the present and the future. University of Adelaide Press; US National Library of Medicine. Retrieved 14 May 2022.

Carlin, R.F., & Moon, R.Y. (2017, February). Risk factors, protective factors, and current recommendations to reduce sudden infant death syndrome: A review. JAMA Pediatrics, 171(2), 175–180. doi:10.1001/jamapediatrics.2016.3345. Retrieved 14 May 2022.

Carpenter, R., McGarvey, C., Mitchell, E.A., Tappin, D.M., Vennemann, M.M., … & Carpenter, J.R. (2013, May 20). Bed sharing when parents do not smoke: Is there a risk of SIDS? An individual level analysis of five major case–control studies. BMJ Open, 3(5), e002299. doi:10.1136/bmjopen-2012-002299. Retrieved 14 May 2022.

Connell, C., & Vidal, P. (2022, May 8). Sydney researchers find enzyme marker to help detect babies at higher risk of SIDS. ABC News (Australian Broadcasting Corporation). Retrieved 14 May 2022.

Duncan, J.R., & Byard, R.W. (2018). Chapter 2: Sudden infant death syndrome — An overview. In J.R. Duncan & R.W. Byard (Eds.), SIDS — Sudden infant and early childhood death: The past, the present and the future. University of Adelaide Press; US National Library of Medicine. Retrieved 14 May 2022.

Eggermont, J.J. (2014). Noise and the brain: Experience dependent developmental and adult plasticity. Elsevier Academic Press. doi:10.1016/C2011-0-06149-5. Retrieved 14 May 2022.

Fleming, P.J., Levine, M.R., Azaz, Y., Wigfield, R., & Stewart, A.J. (1993, August). Interactions between thermoregulation and the control of respiration in infants: Possible relationship to sudden infant death. Acta Paediatrica, 82(s390), 57–59. doi:10.1111/j.1641-2227.1993.tb12878.x. Retrieved 14 May 2022.

Harrington, C.T., Al Hafid, N., & Waters, K.A. (2022, May 6). Butyrylcholinesterase is a potential biomarker for sudden infant death syndrome. eBioMedicine, 80, 104041. doi:10.1016/j.ebiom.2022.104041. Retrieved 14 May 2022.

Horne, R.S.C. (2014, January 10). Effects of prematurity on heart rate control: Implications for sudden infant death syndrome. Expert Review of Cardiovascular Therapy, 4(3), 335–343. doi:10.1586/14779072.4.3.335. Retrieved 14 May 2022.

Kinney, H.C., & Thach, B.T. (2009, August 20). The sudden infant death syndrome. New England Journal of Medicine, 361, 795–805. doi:10.1056/NEJMra0803836. Retrieved 14 May 2022.

Lavezzi, A.M., Corna, M.F., & Matturri, L. (2010, July 19). Ependymal alternations in sudden intrauterine unexplained death and sudden infant death syndrome: Possible primary consequence of prenatal exposure to cigarette smoking. Neural Development, 5, 17. doi:10.1186/1749-8104-5-17. Retrieved 14 May 2022.

Miehl, N.J. (2005, Fall). Shaken baby syndrome. Journal of Forensic Nursing, 1(3), 111–117. doi:10.1111/j.1939-3938.2005.tb00027.x. Retrieved 14 May 2022.

Moon, R.Y. (2011, November 1). SIDS and other sleep-related infant deaths: Expansion of recommendations for a safe infant sleeping environment. Pediatrics, 128(5), 1030–1039. doi:10.1542/peds.2011-2284. Retrieved 14 May 2022.

Moon, R.Y., Darnall, R.A., Feldman-Winter, L., Goodstein, M.H., & Hauck, F.R. (2016, November 1). SIDS and other sleep-related infant deaths: Updated 2016 recommendations for a safe infant sleeping environment. Pediatrics, 138(5), e20162938. doi:10.1542/peds.2016-2938. Retrieved 14 May 2022.

Moon, R.Y., Horne, R.S.C., & Hauck, F.R. (2007, November 3). Sudden infant death syndrome. The Lancet, 370(9598), 1578–1587. doi:10.1016/S0140-6736(07)61662-6. Retrieved 14 May 2022.

Moon, R.Y., & Fu, L. (2012, July 1). Sudden infant death syndrome: An update. Pediatrics in Review, 33(7), 314–320. doi:10.1542/pir.33-7-314. Retrieved 14 May 2022.

Peters, B. (2020, August 5). Reticular activating system and your sleep: How brain disturbances disrupt sleep patterns (R. Collins, Ed.). Verywell Health (Dotdash Media, Inc.). Retrieved 14 May 2022.

Raven, L. (2018). Chapter 4: Sudden infant death syndrome — History. In J.R. Duncan & R.W. Byard (Eds.), SIDS — Sudden infant and early childhood death: The past, the present and the future. University of Adelaide Press; US National Library of Medicine. Retrieved 14 May 2022.

Ravikumar, V. (2022, May 12). What causes sudden infant death syndrome? New breakthrough might point to answers. Miami Herald (The McClatchy Company, LLC). Retrieved 14 May 2022.

Sudden infant death syndrome (2017, January 31). US National Institute of Child Health and Human Development. Retrieved 14 May 2022.

Sudden unexpected infant death (2013, March 7). US National Center for Chronic Disease Prevention and Health Promotion; Internet Archive. Retrieved 14 May 2022.

Sullivan, F.M., & Barlow, S.M. (2001, April). Review of risk factors for sudden infant death syndrome. Paediatric and Perinatal Epidemiology, 15(2), 144–200. doi:10.1046/j.1365-3016.2001.00330.x. Retrieved 14 May 2022.

Tapia, J.A., Trejo, A., Linares, P., Alva, J.M., Kristeva, R., & Manjarrez, E. (2013, October 24). Reticular activating system of a central pattern generator: Premovement electrical potentials. Physiological Reports, 1(5). doi:10.1002/phy2.129. Retrieved 14 May 2022.

Van de Riet, E. (2022, May 13). Groundbreaking new study finds possible explanation for SIDS. WDBJ 7 (Gray Media Group, Inc.). Retrieved 14 May 2022.

What causes SIDS? (2017, January 31). US National Institute of Child Health and Human Development. Retrieved 14 May 2022.

World first breakthrough could prevent SIDS (2022, May 7). Sydney Children’s Hospitals Network; New South Wales Health. Retrieved 14 May 2022.

Young, J., & Shipstone, R. (2018). Chapter 11 — Shared sleeping surfaces and dangerous sleeping environments. In J.H. Duncan & R.W. Byard (Eds.), SIDS — Sudden infant and early childhood death: The past, the present and the future. University of Adelaide Press; US National Library of Medicine. Retrieved 14 May 2022.


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