DESPITE many decades of sudden infant death syndrome research, mainstream researchers have not yet constructed a congruent and plausible patho-mechanism for these deaths.
Most research so far has been arbitrary in terms of epidemiology and pathology and has had little, if any, regard to the findings in physiologically monitored SIDS cases captured on memory monitors, or consistency of pathological findings.
However, an infection model of SIDS may provide some answers. Because of the importance of the gut microbiome in the development of the infant immune system and maintaining the physiological integrity of the gut, I was part of a team that conducted an investigation into the gut microbiome of SIDS and live babies.
Previous sterile site findings and earlier research showed that Staphylococcus aureus and Escherichia coli were more often found in babies who died from SIDS than in those who died from other causes. Based on this work, we developed a hypothesis, similar to one outlined earlier, proposing that a brief bacteraemia occurred prior to death.
The hypothesis included pathogen recognition defectiveness supported by the finding of immune response (IR) gene defects, eg, IL-10 low-producer polymorphism. Bacteraemic episodes are common in early life, so “normal” babies who lack genetic IR defects would be better able to cope with these events and survive the bacteraemia without an adverse outcome.
The bacteraemia could result from defective gut wall integrity or defences. An altered or “abnormal” gut microbiome may influence gut defences or cause possible inflammation and therefore could affect translocation of pathogens such as S. aureus and certain pathotypes of E. coli resident in the infant gut. Extraintestinal and uropathogenic E. coli pathotypes are overrepresented in SIDS cases as is S. aureus.
Our research showed significant changes in gut microflora occurred with age and these differed significantly between SIDS and “control” babies, suggesting that factors influencing colonisation of the gut in SIDS infants during the first few months of life differ from those of live comparison babies. This could imply that the gut itself, and/or the innate and/or adaptive immune systems of SIDS infants are compromised in some way. We suggest an “abnormal” gut microbiome could be responsible.
The research also showed the gut microbiome of SIDS babies differs from that of normal babies, particularly the overarching finding of significantly more babies dying while lying prone, with S. aureus colonisation, than babies similarly colonised but dying in other positions (supine/side). This supports the hypothesis that prone sleep position increases the risk of such colonisation and therefore provides a congruent explanation as to why sleeping prone increases SIDS risk. There was a highly significant association between prone sleeping and S. aureus in both gut and a sterile site.
Considered together with our findings, the theory that bacterial infection plays a role in the final events of SIDS is supported by a large body of evidence — sterile site swabs indicate bacteraemia and we know that bacteraemia is a profound inducer of hypoxaemia (seen in the terminal stages); there is evidence that fever precedes some SIDS deaths; and pathological findings of intrathoracic petechiae, heavy wet lungs and liquid blood/elevated fibrin degradation products that are all compatible with a process of bacterial sepsis, together with the physiological findings of hypoxaemia and bradycardia and asystole followed by gasping. These observations point to the possibility that bacterial sepsis/toxaemia is the final event in SIDS pathogenesis.
Therefore, arguments in favour of respiratory or brainstem compromise, one could contend, evaporate.
Our microbiome findings raise the possibility for trials of a prevention program to provide the “correct” microbiome to babies early in life. If sustained colonisation is achievable, this would be a simple and relatively cheap and novel approach to help eliminate this tragic and enigmatic condition.
Professor Paul Goldwater is a consultant in clinical microbiology and infectious diseases at SA Pathology (at the Women’s & Children’s Hospital, Adelaide).