Contemporary sudden infant death syndrome (SIDS) research is at an impasse, say experts, who are still unable to pinpoint the cause, or risk factors, after decades of effort and thousands of scholarly publications.
In a recent editorial in Springer’s World Journal of Paediatrics, Pontus M Siren, an independent researcher from Switzerland, wrote that there is no consensus on the underlying mechanism or coherent explanation for how diverse and seemingly unrelated risk factors contribute to the syndrome – and equally baffling, “is our inability to explain the cause of death in SIDS”.
One 2021 study – by vaccine critic Neil Z Miller – linked the syndrome to vaccinations, but that research was later retracted by Elsevier, reports Retraction Watch.
The study, published in Toxicology Reports, had suggested that 75% of SIDS cases reported occurred within seven days of vaccination, indicating that the fatalities were tied to immunisations.
Elsevier had launched an investigation into the paper after concerns from readers about potential research errors, but the author’s response did not “satisfactorily address” the concerns, particularly the “serious methodological flaws” in using the Vaccine Adverse Event Reporting System (VAERS) to infer a correlation between vaccination and SIDS, the publisher said when it removed the article.
The study joins several others relying on VAERS data that were subsequently retracted.
In his World of Paediatrics editorial, Siren wrote that in fact, compelling evidence seems to suggest SIDS may have a respiratory origin.
For 30 years, research into the syndrome has focused on the central nervous system (CNS) and on how dysfunctional homeostatic mechanisms controlling arousal, cardiorespiratory function, and neurotransmission may contribute to respiratory failure.
But despite significant efforts, this approach has failed to provide conclusive answers to the SIDS enigma.
Given the likely respiratory origin of the syndrome, it is surprising that the diaphragm – a vital ventilatory muscle – has been overlooked in the research, he suggested.
He wrote that around 13 300 scientific articles on SIDS were indexed in PubMed between 1960 and January 2026, the extensive research having explored the possible role of all cardiorespiratory organs in SIDS – with one notable exception.
During the same period, only 63 articles on “SIDS and diaphragm” were published. No clinical studies or trials, meta-analyses, or reviews are indexed. Typically, the diaphragm is not included in the pathological investigation of suspected SIDS cases.
Most of the articles do not examine the diaphragm’s role in the syndrome or do so only tangentially, while the pathological research and observational studies also don’t support the exclusion of the diaphragm as a possible contributing factor in SIDS.
Six publications highlighted significant pathological abnormalities in the diaphragms of affected infants. Three reported that SIDS cases have fewer type I (fatigue-resistant) diaphragm muscle fibres than controls.
The authors theorised that this may increase the risk of diaphragm fatigue, a hypothesis consistent with animal data showing that newborns with a low proportion of type I fibres are susceptible to fatigue.
Pathology of diaphragmatic fibres from 242 SIDS victims shows acute and recent muscle fibre necrosis accompanied by haemorrhages and oedema in 82% of the samples, consistent with persistent ventilatory effort under hypoxic conditions.
Silver and colleagues noted that diaphragmatic contraction band necrosis is characteristic of acute asphyxia and is prevalent in birth asphyxia and SIDS (11 of 26 and 19 of 30 cases, respectively).
Consistent with these results,, diaphragm muscle fibre ruptures and contraction bands were found in the SIDS infants and the control group, who died of asphyxia, strangulation, drowning, pneumonia, and undetermined causes.
Respiratory failure in SIDS
It is generally accepted that acute non-traumatic death results from either respiratory or cardiac failure. The possible role of heart dysfunction has been comprehensively investigated, but the evidence does not support a cardiac etiology for SIDS.
Rather, as Kinney and Thach argue, a large body of research, ranging from pathological and clinical data to heart rate and respiratory analyses of SIDS cases, suggests that the syndrome has a respiratory origin.
There is compelling evidence of both hypoxia and hypercapnia in SIDS, suggesting the syndrome is caused by dysfunction of the ventilatory pump, wrote Siren.
Kinney and Thach argued that SIDS has a respiratory pathway that begins hours or days prior to death and is progressive rather than sudden.
Infants first experience asphyxia and brain hypoperfusion, or both, without arousal. This is followed by increasing hypoxia and hypercapnia, loss of consciousness, hypoxic coma, extreme bradycardia, hypoxic gasping, sustained apnoea, and eventual death. There is evidence of intermittent and chronic hypoxia in SIDS.
Acute hypercapnic respiratory failure has three principal causes: (1) dysfunction of the CNS; (2) impairment of neuromuscular transmission; and (3) fatigue of the respiratory muscles.
These failure mechanisms – central, transmission, and peripheral – can occur independently or synergistically, and manifest similar clinical symptoms. The intensive investigation of the central and connective nervous system has not yielded definitive answers, nor has research identified consistent evidence of genetic abnormalities, trauma, deformities, or diseases of the nerves, rib cage, or muscles in SIDS cases.
The third failure mechanism, critical fatigue of the respiratory muscles, has been ignored by contemporary SIDS research.
Future directions
The diaphragm, a vital ventilatory muscle, has been overlooked. Infants six months and younger, particularly low birthweight babies and those born preterm, are susceptible to diaphragm fatigue, and poorly tolerate increases in ventilatory workload.
As McCool and Tzelepis suggested, the combination of diaphragmatic weakness and any process that increases the work of breathing may overwhelm the capacity of even a mildly weakened diaphragm.
SIDS infants typically present with multiple risk factors that impair diaphragm function or increase its workload: non-lethal infections and hypoxia can reduce the diaphragm’s force-generating capacity by 50%–80% and 20%–30%, respectively; and the prone position is associated with a significant reduction in diaphragm strength and endurance and REM sleep, with an 18% increase in diaphragmatic work.
The combined impact of these and other SIDS risk factors on diaphragm function in vulnerable infants should be investigated, suggested Siren, adding that his editorial was aimed at stimulating “a critical debate regarding the potential role of the diaphragm in the syndrome and to encourages readers to reconsider its exclusion from contemporary SIDS research”.
See more from MedicalBrief archives:
Combined prenatal smoking and drinking greatly increases SIDS risk — NIH study
Just a cigarette a day in pregnancy doubles Sudden Infant Death risk
Message on SIDS not getting through
High levels of serotonin found in infants who died of SIDS