Unexpected infant death: Occult cardiac disease and sudden infant death syndrome

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SIDS

Sudden infant death syndrome

See related article, p 336.

The impact of the sudden death of an infant or young child on families and communities is significant and lasting. The responsibility placed on medical and police investigators to accurately determine the precise cause of death and clarify the surrounding circumstances is considerable. Unfortunately, cases in the past have all too often been attributed to sudden infant death syndrome (SIDS) without proper examination and analysis.¹ Although it is well recognized that a wide variety of diseases may cause sudden deaths in infancy and early childhood,² Dancea et al, in the current issue of The Journal, confirm the importance of autopsy examination in such cases by showing that a significant percentage of these deaths may be the result of cardiac disease.³

The authors performed a retrospective review of all autopsy cases of sudden death in infants (and young children) between the ages of 1 week and 2 years, who died in Québec, Canada, during the period between 1987 and 1999. They found 82 of 848 cases (9.7%) in which death had been associated with cardiac disease. In 69 cases (84%) death was attributed to the cardiac condition. In some cases, the condition had been recognized and treated before death. Conditions included myocarditis, cardiomyopathy, tumors, septal defects, left ventricular hypoplasia, outflow obstruction, cyanotic heart disease, and vascular abnormalities. Cases of sudden death with cardiac pathology accounted for 12% of the total number of deaths due to cardiac disease in this age group. One third of the infants and young children who had structural cardiac defects died while awake, and a significant number of cases (60%) had not had a diagnosis established before autopsy.

The study by Dancea et al³ clearly demonstrates problems that arise in the epidemiologic evaluation of unexpected infant and early childhood death. The authors note that only two thirds of their cases were examined in a tertiary pediatric hospital by pediatric pathologists. Because it appears that the remaining autopsies may have been performed by pathologists without specific pediatric training, it is possible that there was under-recognition of subtle, or not so subtle, cardiovascular disease. If these cases occurred in isolated rural communities, the incidence of heritable cardiac disorders may have been even higher than was documented.

It should be emphasized that this is not a problem limited to Québec; for example, in certain European countries autopsy rates for infants found suddenly dead were reported in the early years of the study, with percentages ranging from 50% to 60% to <25%.² In more recent times in Australia, cases have also been attributed to SIDS without either death scene examinations or autopsies having been conducted. In parts of Australia and New Zealand, infant autopsies in cases of sudden death may have been performed by nonpathologists.⁴ The investigation of infant deaths in the United Kingdom has been found to be “often scanty and inexpert,”⁵ with autopsies sometimes excluding elements as basic as histologic examination of the lungs.⁶ This has resulted in calls for the introduction of standard autopsy and death scene protocols.^7,8 Without the benefit of an autopsy, conclusions on possible causes of death in cases of unexpected infant death in the community must be considered suspect. As well, the validity of the autopsy assessment by a nonspecialist regarding the presence or absence of rare and subtle cardiovascular, or other, defects must also be questioned. Dancea et al have pointed out the usefulness of reviewing the circumstances surrounding the fatal episode, with death occurring while awake in one third of infants with underlying congenital cardiac disease.³

Whereas there is no doubt that a number of cases of infant death with definable cases have been misdiagnosed as SIDS, resulting in Emery's suggestion that SIDS represented a “diagnostic dustbin,”⁹ the situation is improving. Scene examinations with comprehensive autopsies in all cases of infants found dead in their cribs have resulted in significant numbers having a diagnosis made other than SIDS,^10,11 confirming that not all deaths in cots are “cot deaths.” This raises the question as to how many cases that are being attributed to SIDS are actually the result of definable diseases. This really cannot be answered accurately because autopsy practices are extremely variable and there are a number of rare disorders, such as inborn errors of metabolism and cardiac conduction tract defects, that are not routinely evaluated. Although the number of alternative causes of death that were diagnosed before the recent dramatic fall in numbers of SIDS deaths was under 10%, the percentage has increased to 25%¹² when the clinical history has been reviewed, and full death scene and autopsy investigations have been undertaken according to an accepted standard definition.¹³ This figure will increase as other conditions, such as prolonged QT interval are identified with the use of molecular techniques.¹⁴ It appears likely, however, that rare causes of sudden infant death probably individually account for 2%.^15,16

Despite the great success of the “Back to Sleep” campaigns in reducing the number of deaths, and our ability to identify disorders and circumstances that would previously have been confused with SIDS, there remains, however, a group of infants who die fulfilling the criteria for the designation of SIDS. Although no specific pathologic findings are found at autopsy, there is evidence that certain of these infants may have subtle brainstem neurotransmitter and receptor abnormalities.¹⁷ The “triple risk” theory, which describes susceptible infants being subjected to environmental stresses at particularly vulnerable periods of their lives, provides an elegant model to explain the persistence of these deaths.¹⁸ Thus, although there have been calls for the abandonment of the term “SIDS,”^1,19 this would not appear to be either a warranted or useful step.

There are also other implications that will arise from an improvement in diagnostic accuracy. Epidemiologic studies will be more precise and the validity of research based on data and tissues derived from individual, or series of, cases will be strengthened. Most importantly, parents will be given information that they can rely on and that may have considerable effect on future family planning. Striking developments in pediatric cardiovascular disease have occurred in recent years with the demonstration of specific genetic defects for a range of disorders, including several of the cardiomyopathies, various aortic disorders, ventricular dysplasia, and conduction defects.^20-22 Genetic linkages may be extremely complex, for example familial hypertrophic cardiomyopathy has been mapped to chromosomes 1q3, 3p21.2-3p21.3, 7q3, 11p11.2, 12q23-q24.3, 14q11.2-q12, 15q2, 15q14, and 19p13.2-q13.2; arrhythmogenic ventricular dysplasia has been mapped to chromosomes 1q42, 2q35, 3p23, 10p12-14, 14q24 and 14q12-22.²²

Although the clinical significance of this genetic heterogeneity is not completely understood, the role of diagnostic accuracy at autopsy is obvious. If these disorders are not correctly identified, molecular studies may not be undertaken and genetic counseling of families may not occur. Not only could this lead to a second afflicted child in the family, but a second death could cause the family to be subjected to an extremely rigorous police investigation in an effort to exclude, or prove, homicide.

The interpretation of the significance of postmortem findings is not necessarily easy, and in an era where we have seen considerable criticism in the media leveled at pathologists who perform pediatric autopsies, there is an increasing need for specialist training in this area. Not only are dissections in infants and young children technically difficult, but they require an extensive knowledge of normal development and growth. Disease which may have contributed to, or caused, death must be correctly identified, while recognizing that infants may have significant underlying conditions that may be completely unrelated to the lethal event. Four such cases were found by Dancea et al,³ and in 16% of their cases, the relationship of the underlying cardiac problem to the lethal episode remained uncertain. Coincidence must not be confused with cause, and undue significance must not be placed on minor abnormalities and normal histologic findings if a plausible mechanism of death cannot be established.²³

The challenge that we have is to take pediatric mortality seriously by taking steps to ensure that the investigation of cases is optimized and that diagnoses are as accurate as possible. Dancea et al³ have shown that a significant number of unexpected deaths in the young are the result of cardiovascular diseases, some of which are heritable. Given the recent criticisms of infant death investigations, both in the media and in the literature, there are many reasons why we have an obligation to get it right.

References

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1. Meadow R. Unnatural sudden infant death. Arch Dis Child 1999;80:7-14.