Crib Death: Sudden Unexplained Death of Infants — The Pathologist’s Viewpoint

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Inflammatory responses in sudden infant death syndrome – past and present views

Like them, he believes SIDS is a real condition, but said the system could benefit from better terminology and stricter definitions. Rather than squelch research, Dr. For Ms. Cormier, not a day goes by that she doesn't think about her daughter, Quinn, who would have turned 3 this summer.

Crib Death - Sudden Infant Death Syndrome (SIDS)

Now that more time has passed, she said she can understand why some medical examiners want to call deaths such as Quinn's undetermined. They were here. This is a space where subscribers can engage with each other and Globe staff. Non-subscribers can read and sort comments but will not be able to engage with them in any way.

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If you are looking to give feedback on our new site, please send it along to feedback globeandmail. If you want to write a letter to the editor, please forward to letters globeandmail. Camps, forensic pathologist, wrote a memorandum to the Ministry of Health. A preliminary study confirmed the weakness of the accidental suffocation hypothesis, and also suggested that the problem was larger than previously acknowledged—1, cases annually in England and Wales, equating to over 20 per cent of postneonatal infant mortality.

Banks' committee conducted the enquiry under three broad headings, examining microbiological, pathological and social factors.

A perspective on SIDS pathogenesis. The hypotheses: plausibility and evidence

The investigation was concentrated in Cambridgeshire, where previous investigation had taken place, and the London County Council area. Part one of the form recorded post-mortem findings, including results of histological and bacteriological tests. This covered prior signs of illness or symptoms, the location and position in which the body was found and any other findings relevant to evaluating suffocation as the likely cause of death. In , the interim report of the committee identified trends in the 81 cases investigated.

The report underlined the need for more detailed pathological investigation. While naked eye pathological appearances might suggest mechanical asphyxia, some thought histological findings indicated acute respiratory infection. It continued in Cambridge, although a further 50 cases also produced negative findings. In three other cases the presence of a virus could not be ruled out. Only nine cases were recorded as occurring when the infant was in bed with a parent and there was little evidence for other causes of accidental suffocation.

Although recognising that the social investigation was important, the report concluded that the intensification of virus investigation was the crux. The MRC review had been undertaken by four referees. In , a team of researchers from Cambridge and London published research demonstrating that inhalation of cow's milk could produce a severe immunological reaction leading to sudden death in sensitised guinea pigs.

Mavis Gunther had been investigating the effects of bottle feeding on infants, and, combining this with Robin Coombs' work in immunology, a collaborative project was devised to assess whether an overwhelming immunological reaction might result from regurgitated milk getting into the respiratory tract or lungs of the infant. First, immunological work became the major focus of British research into sudden infant deaths.

Sudden unexpected infant death syndrome in Ribeirão Preto, Brazil

Prior to departing for Washington to attend the first international symposium on the causes of sudden death in infants, in July Coombs wrote a letter urging the MRC to set up a small working party or conference to discuss cot deaths. He felt that an independent evaluation of the research was necessary before developing it further with Gunther, who had a funding application pending at the MRC. Although their experimental findings had yet to produce convincing evidence in support of the anaphylactic shock hypothesis, there were still promising leads.

Evidently they were struggling to prove that a modified anaphylactic reaction, triggered by the regurgitation of cows' milk into the respiratory tract or lungs of a sensitised sleeping infant, was a likely cause of cot death. While there was some evidence for this hypothesis in results of their tests in anaesthetised guinea pigs, it was no more than circumstantial. Nonetheless, even without solid proof that anaphylaxis resulting from hypersensitivity to cows' milk was definitely the cause of some cases of cot death, they might still assist in reducing the risk of such deaths.

Their strategy focused on infant feeding, in particular the risks associated with the use of dried milk powders specially treated to render the soluble proteins insoluble in the stomach. If ways could be found to reduce the likelihood of infants regurgitating artificial feeds, then the risk of cot death resulting from anaphylactic shock might be correspondingly reduced regardless of the fact that the specific mechanism or aetiology had not been experimentally proven.

The MRC extended Gunther's funding and this research later informed the recommendations on breastfeeding and research on artificial feeds arising out of the Steering Committee's final report. Evidently he was not inspired by the current work of the Steering Committee. While there was Ministry of Health support for an MRC sponsored meeting, this was delayed until publication of the final report of the Steering Committee. The Steering Committee issued its final findings in autumn Following the recommendation of its interim report, exhaustive virological examination had been undertaken on specimens from a further 51 cases but results remained negative.

Consequently, this aspect of the work was suspended in in order to concentrate on analysis of sociological and immunological factors. Investigation of social factors was refined, omitting questions that prior analysis had shown to be irrelevant and adding more detailed questions about bedding, the clinical history of cases and the use of medicines.

The former included cases in which either a definite or a possible cause of death had been identified. Both the bacteriological and viral investigations echoed the negative findings of the interim report. The analysis of social circumstances drew on reports of cases, of which remained unexplained. There was increased recollection of symptoms of respiratory illness from the parents of sudden death cases when compared to the control group—68 per cent compared to 31 per cent.

Echoing the interim findings, these were often very trivial—snuffles or a slight head cold—and had not given cause for anxiety at the time.

Clearly then, while cases of sudden infant death were found across the socioeconomic spectrum, the risk factors identified for sudden infant death echoed earlier concerns surrounding overlaying—highlighting poor families, living in bad housing, and illegitimacy as major factors. The immunological research had focused on establishing evidence that hypersensitivity to cows' milk might provoke fatal anaphylactic shock. Studies of lung tissue were largely inconclusive. Although a large number of deaths remained unexplained after detailed investigation, the report concluded by highlighting what appeared to be statistically significant risk factors: early bottle-feeding, the use of a soft pillow, and, at least in some cases, recent infection.

Therefore, the report recommended that certain precautions be taken. If a pillow was used for sleeping, it should be hard rather than soft. All babies should be exclusively breastfed for the first two weeks of life. In order to minimise any risk of fatal anaphylactic shock resulting from inhalation of cow's milk, a means of treating cows' milk should be found to ensure that all the proteins coagulated in the infant's stomach, thereby minimising the risk of regurgitated food proteins provoking an overwhelming immunological response. Having taken the Steering Group's investigations as far as he felt possible, Banks suggested to Sir George Godber that the MRC should determine if further investigation was necessary.

Echoing his previous comments to the MRC in , Coombs' presentation noted the strengths and weaknesses of attempts to produce firm evidence for the theory. In the ensuing debate, the participants expressed reservations, pointing to the circumstantial, unconvincing nature of the evidence produced to support the hypothesis, highlighting in particular the problem of using anaesthesia to mimic sleep conditions in guinea pigs.

In summing up, Miles felt that no clear programme of further investigation had emerged from the meeting. There was consensus of opinion that, despite equivocal evidence for the anaphylaxis hypothesis, some further work should be undertaken—a conclusion driven more by a general interest in further research on infant immunology than any clear belief that it was likely to reveal the aetiology of unexplained infant deaths. More generally, there was little evidence of desire to undertake significant further research on this aspect.

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Coombs received a small grant, but when the MRC approached other researchers there was reluctance to develop work on the anaphylaxis hypothesis. She cited the need to concentrate on writing a book on infant feeding which had been set aside whilst working on cot death research: the ending of my grant should be seen quite apart from the need for a structure of some sort to consider further work on cot death. The events have been like a game of chess with a sequence of moves. The Council took over formally from the Ministry's Steering Committee and then by limiting all future consideration to aspects of milk allergy and then finding no means of tackling milk allergy, have cornered the subject into absolute immobility.

Gunther urged the MRC to set up a new committee to consider various lines of enquiry, including the virology of intrauterine and neonatal infections; further study of the peculiarities of the immune state in the first six months of life; more detailed post-mortem histology of cot death; and further statistical analysis of the registration of cases. She enclosed a copy of an article she had recently written, which postulated that exposure to viruses, such as rubella, could result in intrauterine or neonatal infection and the development of antibodies.

As an alternative to the artificial feeding hypothesis, Gunther suggested that a severe antibody-antigen reaction may be another possible cause of anaphylactic shock resulting in cot death. Replying the following month, the MRC indicated that a new committee was unlikely. The letter stressed that they had not taken over investigation of sudden infant deaths from the Ministry of Health, but rather, in discussion they had come to the view that further examination of the hypersensitivity hypothesis would be a productive next step.

However, they had been unable to stimulate interest in undertaking new work in the field. To this end, the MRC gauged expert opinion on the merits of Gunther's idea. The respondents were in favour of investigations into the role of viruses in cot death, in light of recent advances in knowledge of respiratory viral infections, although they recognised a potential difficulty in obtaining suitable material for study. Dudgeon, who already had MRC funding for research on rubella, suggested he could follow this up as an aspect of his current work.

He indicated that his colleague, Dr Soothill, an immunologist, might also be interested in undertaking some investigation. Whilst acknowledging British support for the anaphylactic shock hypothesis linked with hypersensitivity to cow's milk, Valdes-Dapena noted that attempts to evidence the theory had been unsuccessful.

Valdes-Dapena's presentation was followed by a discussion of terminology, led by Bergman and Beckwith, which resulted in the decision to use Sudden Infant Death Syndrome. This highlights a further factor in the historicity of SIDS: the medicalisation of such deaths required an ontological model of disease. In his introductory chapter to Framing Disease , Charles Rosenberg highlights that the physical manifestation and perception of symptoms is the starting point of defining disease.

The patient's narrative case history, prominent in eighteenth-century medicine, was gradually absorbed into models of disease based on standardised understandings of pathological anatomy, supplemented by germ theory and the growing importance of laboratory based analysis. Increasingly, the patient's awareness and experience of disease and the scientifically defined existence of disease could be separated.

The latter understood disease as a localised and standardised entity which could be more easily theorised and analysed apart from its presence in specific patients. The ontological idea of disease as specific entity was connected with the rise of scientific and laboratory analysis as the basis of diagnostic medicine over the course of the nineteenth and twentieth centuries.

Writing in the s, when SIDS was becoming established as an internationally recognised diagnosis, Stanley Reiser argued that medicine increasingly prioritised the importance of objective evidence provided by scientific laboratory tests and technological investigation of the body, over patients' subjective accounts of their symptoms or doctors' unaided observations. A SIDS diagnosis could only be retrospectively applied to the deceased following autopsy. The growth of the ontological concept of disease allowed for analysis in isolation from patient experience.

This gave greater scope for the medicalisation of sudden infant deaths as SIDS, a disease diagnosis, in the second half of the twentieth century. However, it was still a jump to get from a more amenable context for the recognition of sudden infant death as a medical problem, to the acceptance of SIDS as an official diagnosis.

For, as Canguilhem notes, the development of a standardised model of disease, potentially allowing it to be diagnosed even before symptoms have become manifest to the patient, is typically a result of the recording and investigation of previous cases.

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An alternative option was to use epidemiology to seek an objective understanding of the disease derived from analysis of population level statistics rather than the symptoms or signs from individual patients. As Figure 1 demonstrates, in the decade prior to the definition of SIDS, overall infant mortality was decreasing, primarily as a result of falling neonatal mortality. Although numerically smaller, postneonatal mortality was relatively static over the period. As the Department of Health and Social Security's enquiry made clear, the comparative trends made postneonatal mortality a significant cause for concern, provoking further investigation.

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However, when considered at the level of population statistics, these deaths posed problems for epidemiologists. Peter Froggatt identified three difficulties: definition, post-mortem diagnosis and controls. However, there were grey areas in classifications and inconsistency in registration practice. Echoing findings of earlier studies, Froggatt noted that the registered cause of death could be influenced by the socioeconomic circumstances of cases.

In more affluent areas, doctors might register a clear cause, even in the absence of evidence, in order to ease the upset and avert any stigma of suspicion. Cases of sudden infant death shared characteristics with respiratory deaths—a point evidenced by the subsequent diagnostic transfer from respiratory infection to SIDS in the s and s—and the former were often registered as the latter despite the absence of any evidence of respiratory infection. Inconsistent registration inhibited the development of longitudinal trends in sudden infant death, affecting comparisons of incidence across geographical regions.

Arguably, SIDS was adopted as a diagnosis because it would facilitate better registration statistics. Given his reservations about the lack of positive diagnostic criteria, Emery favoured SIDS being entered as secondary information after whatever the pathologist considered was the most likely primary cause. Between and the postneonatal mortality rate in England and Wales dropped from 5.

Between and , there was sharp decline in all forms of postneonatal mortality, including SIDS. Froggatt's second and third problems were the fact that SIDS was solely a post-mortem diagnosis and it was difficult to identify suitable controls for comparative study. This limited the range of potential investigations and made it difficult to determine whether risk factors identified for the SIDS group were characteristic of SIDS in particular.

The resultant study population will be biased toward factors known to be associated with infant mortality in general—that is, in all probability, toward bigger and poorer families, a preponderance of males and of winter deaths, a lower birth weight, and so on. We note, of course, that these are the very factors incriminated in sudden unexpected death. While epidemiological research highlighted sudden infant deaths as an area of concern, this was only a tentative step towards identification of a disease.

Progress required the development of causal explanations demonstrating the mechanism s by which the risk factors resulted in sudden death, followed by experimental testing of the hypotheses. However, as Dally's account of medical interest in Status Lymphaticus underlines, there were significant risks in attempting this using healthy infants; and the work of Coombs et al. Emery's publications highlight the importance of statistics to the rise of medical interest in SIDS, but without symptoms, signs or pathology, it is obvious why he suggested SIDS appeared to be a diagnostic dustbin.

However, the validity of this provocative label is dependent on regarding diagnoses purely in terms of symptoms, signs and pathology. Rosenberg notes that the act of diagnosis not only structures medical practice but also confers social approval on particular sickness roles and legitimises bureaucratic relationships. In cases of SIDS, the diagnosis provided a medical model of understanding that presented the first step towards an explanation, helping to counter legal suspicions of intentional harm that often surrounded the parents of SIDS victims. Many publications open with personal accounts of cases, paying tribute to the role that the families of SIDS victims have played in promoting medical interest and research.

Having been pronounced healthy at a check-up two weeks beforehand, Mark's sudden death left his parents seeking an explanation. Unable to identify a suitable foundation or research project, in the Roes decided to set one up using the substantial insurance policy Mark's grandfather had taken out at his birth.

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Change was wrought by a small band of parents who had lost babies to SIDS, aided by a few good-hearted physicians by means of an organised political campaign. In Britain, the Foundation for the Study of Infant Deaths was established in at a symposium, held in Cambridge, which arose out of a grandmother's attempts to find an explanation for her infant grandson's unexpected death.

The incident has profound psychological and social concomitants. Thus recognition and understanding both of the biology and the sociology of the syndrome, and hopefully in the future the prevention of the deaths has importance that goes far beyond the immediate death of the single infant—it reflects on the whole well-being of a family. Only by recognition and understanding of both these facts—the occurrence of the syndrome and the prevalence of the family reactions—can the physician assist properly in his chosen role.

As scientists we may be more comfortable in discussing and studying the biological process; but we are negligent if we disregard the psychological and social implications of this disease. Where typically a medical diagnosis was of great significance to the patient diagnosed, in the case of SIDS there were no patients. Rao, Doody's Book Reviews, May, Toggle navigation.

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