Introduction

Unexpected and unexplained death of an infant of less than 1 year is commonly known as sudden infant death syndrome (SIDS), which is one of the three subtypes under the broader category of sudden unexpected infant death (SUID).

A study conducted in the University Hospital of São João of Portugal with parents and healthcare professionals showed that 67.7% parents were aware of SIDS, and 47.5% of parents knew that supine position as the safest against SIDS (Fernandes et al., 2020). The cause of SIDS remains unknown, despite after extensive investigation, including autopsy, examination of the death scene, and review of medical history (Fernandes et al., 2020).

However, one study showed that SIDS is more likely to occur during colder months. Although some viruses and bacteria have been identified in infant autopsies, none have been definitively linked to SIDS (Fernandes et al., 2020).

Recent statistics

A study showed that 1 in 10 babies are born preterm (born before 37 weeks of gestation), totalling 15 million globally. Between 1993-1996 in the UK, SIDS infants were four times more likely than controls to be preterm (20% vs. 5%) or have low birth weight (<2500 g) (23% vs. 5%) (Rosemary SC. Horne et al., 2024). A New Zealand study (1986-2000) found consistently higher SIDS rates in preterm infants. In the US (2012-2013), SIDS rates were significantly higher among preterm infants (22.61%) than term infants (10.79%) (Rosemary SC. Horne et al., 2024).

In the United States, 22% of post neonatal deaths are attributed to sudden infant death syndrome (Hauck & Tanabe, 2008). Getahun et al. (2004) collected and analysed SIDS data between 1995-1998 and reported a continuous decrease in incidence rates. The decreasing trend was statistically significant ( P < .001) with 87.6 per 100,000 live births for 1995, and 75.7 per 100,000 for 1998 (Getahun et al., 2004).

Theories & Causes behind the SIDS

At the Lino Rossi Research Centre at the University of Milan, researchers conduct extensive research into sudden infant deaths using real case studies as part of a long-term program focused on understanding causes. Since the enactment of an Italian law in 2006, a legal framework was established, making it a requirement to carry out a detailed post-mortem examination, with parental consent, for any sudden and unexplained death of an infant under one year. This ensures that such investigations are systematically conducted. The Lino Rossi Research Centre fulfils this legal obligation and, in doing so, uses the data and findings from these examinations as a key component of its long-term research programme into sudden infant death, with a particular focus on the autonomic nervous system (Lavezzi, 2015).

The researchers examined 150 cases of SID of babies who died suddenly between 1 and 11 months old and discovered that 70% of the infants showed structural and biochemical abnormalities in the central nervous system (CNS) (Lavezzi, 2015).

Whilst the Kölliker–Fuse nucleus (KFN), a part of the brainstem that controls breathing appeared normal, researchers discovered elevated levels of brain-derived neurotrophic factor (BDNF) in the CNS, along with decreased expression of neuronal nuclear antigen (NeuN) in the same region, a marker of healthy nerve cells (Lavezzi, 2015). These observations suggest abnormalities in the development and function of key brainstem areas responsible for autonomic control of vital functions, such as breathing and heart rate, which may contribute to the mechanisms underlying SIDS.

Figure 1: Immunohistochemical staining of the Kölliker–Fuse nucleus showing BDNF expression in neuronal cytoplasm. This illustrates altered neurotrophic factor distribution reported in SIDS cases (Lavezzi, 2015).

Risk Factors for SIDS

Risks associated with sudden infant death syndrome are smoking during pregnancy, exposing an infant to cigarette smoke in the early months after birth, soft bedding, premature birth, co-sleeping in unsafe conditions and covered airways ( Changing concepts of sudden infant death syndrome , 2000). Some of the additional risk factors include:

• Exposed to exogenous stress like prone sleeping

• Overheating

• Head-covering

• Sleep deprivation

• Infection

Mechanisms for SIDS

SIDS is believed to result from multiple reasons as explained by the Triple Risk hypothesis. The model (Figure 1) suggests that death may occur when three conditions overlap: a vulnerable infant (e.g., preterm), a critical development stage period between 2-4 months, and an external stressor (like sleeping in the prone position). The model emphasises that all three factors must be present for the risk to result in death (Rosemary SC. Horne et al., 2024).

Figure 2: The Triple Risk Model shows the three overlapping factors, a vulnerable infant, a critical developmental period, and an exogenous stress. This model shows that death can occur when a vulnerable infant due to factors like genetic factors, preterm birth, maternal smoking or alcohol consumption exposures is in a critical developmental period between 0-6 months of age with impaired autonomic and arousal control. (Rosemary SC. Horne et al., 2024).

SIDS Prevention Strategies

A study finding showed a dramatic decrease in SIDS rates was observed after “Back to Sleep” campaigns to prevent SIDS (Jullien, 2021).

The NICE guideline ‘Postnatal care up to 8 weeks after birth’ provides following recommendations:

• “Recognise that co-sleeping can be intentional or unintentional. Discuss this with parents and carers and inform them that there is an association between co-sleeping (parents or carers sleeping on a bed or sofa or chair with an infant) and SIDS.”

• “Inform parents and carers that the association between co-sleeping (sleeping on a bed or sofa or chair with an infant) and SIDS is likely to be greater when they, or their partner, smoke.”

• “Inform parents and carers that the association between co-sleeping (sleeping on a bed or sofa or chair with an infant) and SIDS may be greater with parental or carer recent alcohol consumption, or parental or carer drug use, or low birthweight or premature infants.”

The American Academy of Paediatrics (AAP) provide recommendations for a safe sleep environment that apply to all infants up to 12 months of age that are very similar to the NICE guidelines (Jullien, 2021).

Some of the prevention strategies are:

• Sleep in supine decubitus position

• Place infants in prone position with supervision when awake

• Place infants on firm sleep surface

• Avoid overheating & head-covering while sleeping

• Delay the use of pacifier until breastfeeding is firmly established

• Avoid smoking during pregnancy, in the pregnant woman’s environment, and in the infant’s environment.

• Pregnant women should obtain regular prenatal care.

• Mothers should breastfeed exclusively or feed with expressed milk for 6 months

• Pregnant women should avoid alcohol and illicit drug use during pregnancy and after the birth. (Jullien, 2021).

Conclusion

SIDS remains a significant public health concern. Research highlights that vulnerabilities in brain development, particularly within Kölliker–Fuse nucleus, may play a role. While the KFN structure itself appeared normal in examined cases, biochemical abnormalities were observed in the central nervous system (CNS), including elevated levels of brain-derived neurotrophic factor (BDNF) and decreased expression of neuronal nuclear antigen (NeuN), a marker of healthy nerve cells. These CNS changes, when combined with external stressors and critical developmental stages, can increase the risk of SIDS (Lavezzi, 2015). Global studies report higher SIDS risk in preterm and low birth weight infants, emphasises the importance of early education. Prevention strategies, such as promoting safe sleep environments, avoiding exposure to tobacco smoke, encouraging breastfeeding, and spreading awareness regarding SIDS risk factors and prevention strategies in parents have been proven effective to significantly reduce the SIDS rates (Jullien, 2021). Future studies tracking heart rate variability in neonatal units may help identify at-risk infants earlier and implement preventive strategies more effectively. (Rosemary SC. Horne et al., 2024). Public education, especially for parents, remains essential in reducing SIDS risk.

References

Changing concepts of sudden infant death syndrome: Implications for infant sleeping environment and sleep position. (2000). Pediatrics, 105 (3), 650–656. https://doi.org/10.1542/peds.105.3.650

Fernandes, S. C., Luca, F. de, Oliveira, C. S., & Maria, S. (2020). Sudden infant death syndrome: What healthcare professionals and parents know about how to prevent it in Portugal. The Yale Journal of Biology and Medicine, 93 (4), 475. https://pmc.ncbi.nlm.nih.gov/articles/PMC7513448/

Getahun, D., Amre, D., Rhoads, G. G., & Demissie, K. (2004). Maternal and obstetric risk factors for sudden infant death syndrome in the United States. Obstetrics & Gynecology, 103 (4), 646–652. https://doi.org/10.1097/01.aog.0000117081.50852.04

Hauck, F. R., & Tanabe, K. O. (2008). International trends in sudden infant death syndrome: Stabilization of rates requires further action. Pediatrics, 122 (3), 660–666. https://doi.org/10.1542/peds.2007-0135

Horne, R. S. C., Harrewijn, I., & Hunt, C. E. (2024). Physiology during sleep in preterm infants: Implications for increased risk for the sudden infant death syndrome. Sleep Medicine Reviews, 78 , 101990. https://doi.org/10.1016/j.smrv.2024.101990

Jullien, S. (2021). Sudden infant death syndrome prevention. BMC Pediatrics, 21 (S1). https://doi.org/10.1186/s12887-021-02536-z

Lavezzi, A. M. (2015). A new theory to explain the underlying pathogenetic mechanism of sudden infant death syndrome. Frontiers in Neurology, 6 . https://doi.org/10.3389/fneur.2015.00220