Current Pediatric Reviews - Volume 6, Issue 1, 2010

The sudden unexpected death of an infant (SUDI) is one of the most tragic events that can occur to their families. The infant is seemingly healthy, probably asleep, and is then found dead. For these families the next hours and days can only be described as a nightmare. The police may investigate the case as a homicide, which causes further anguish. The families have to deal with the pathologist and coronial system (and/or medical examiner in the United States). They have to deal with their partner and the infant's brothers and sisters, who have their own needs, and with the extended family. To compound the problem many deaths are unexplained, and families are left with the unanswered question “Why did my baby die?” Their grief is overwhelming and there is guilt. It can be compounded by fear that tragedy could strike again making subsequent pregnancies and the experience of parenting fraught with anxiety. Sadly many marriages (partnerships) cannot handle these stresses, so separation and divorce is added to the trauma. Fortunately much has changed. The dramatic decline in mortality from sudden infant death syndrome (SIDS) and in total infant mortality is one of the most successful public health interventions in child health. We need to remember the pioneering work of people in the 1970s, people like Bruce Beckwith (US), John Emery (UK), Bob Carpenter (UK), Susan Beal (Australia) and Shirley Tonkin (NZ), who highlighted the problem of cot (crib) death, as it was commonly called, a problem not really recognised by hospital based paediatricians. Furthermore they made many astute clinical observations, which have been confirmed in more formal studies. The breakthrough came in the 1980s when SIDS case control studies were set up with a focus on infant care practices. The strong association with prone sleeping position was clearly seen in a number of independent studies. This led to the recommendation to avoid placing the infant to sleep in the prone position. The rest is history. Mortality declined rapidly, although some countries were late in implementing the advice and their rates remained high until they too implemented their prevention campaign. Despite the reduction in the number of babies dying, there are still many infants dying suddenly and unexpectedly. Those who die now are more likely to be from disadvantaged families, some living in poverty and chaos. These were probably always there but now are more visible because the socioeconomically advantaged families have heeded the prevention advice. This has led to deaths being labelled by pathologists as positional asphyxia, unascertained and undetermined etc. In this series we start with a discussion of the definition of SUDI and SIDS [1, 2]. We then discuss the investigation of a death with contributors describing the multidisciplinary team approach in the UK [3] and Norway [4], the role of the pathologist [5] and the death scene investigation [6]. These are best practice models of care and should be the norm. The next papers address altered physiological control during sleep [7] and potential mechanisms [8]. This is probably the hardest area of research as it is of course impossible to study living cases. One of the more exciting developments is the studying the genetics of SUDI. A small number of deaths are due to long QT syndrome [9], but many more are likely to be a combination of genetic predisposition and environmental influences [10]. We are still waiting for the first genome wide association studies (GWAS). This series (issue) has not focussed on the epidemiology of SIDS (and SUDI), as specific aspects have been reported previously. We refer readers specifically to: • Smoking [11] • Pacifiers [12, 13] • Head covering [14] • Immunisations [15] • Breastfeeding [16] One of the more contentious areas relates to the increased risk of SUDI with bed sharing. The arguments that this is a valued traditional practice and that it increases breastfeeding is balanced by the increased risk in infant death in certain circumstances....

Sudden unexpected death in infancy (SUDI) is an umbrella label that some employ to encompass all sudden unexpected infant deaths, whether or not explained, while others restrict its use to cases in which the cause of death is uncertain, but possibly due to asphyxia as may occur, for example, with sleeping prone, face down on a soft sleep surface, and/or being found with the head covered. Since sudden infant death syndrome (SIDS) is a diagnosis of exclusion, there is an inevitable interface between it and those cases whose deaths are potentially caused by unsafe sleep environments. This interface is especially blurred given the lack of definitive, easily identifiable postmortem marker(s) for SIDS. Therefore, present SIDS definitions are imprecise and its diagnosis remains one of exclusion. Improved death scene investigation has resulted in a diagnostic shift away from SIDS towards other causes of death such as positional asphyxia or undetermined. Unfortunately incomplete death scene investigation has hampered evaluation of the real circumstances of death in too many of the cases further contributing to confusion. In this report, the purposes for and primary definitions of SIDS are delineated. Subsequent discussion focuses on the increasing challenge to incorporate risk factors and the underlying pathology germane to the pathophysiology of SIDS into future definitions. This challenge is matched by the need to develop affordable and widely available testing that will identify pathology relevant to medical examiners and others charged with certifying the cause and manner of death.

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Experience of the investigation of unexpected infant deaths in several countries has identified recurring instances of two types of error in such investigations — both equally destructive and undesirable — 1) inadequate investigation failing to identify child neglect or abuse, or 2) innocent parents being wrongly accused of harming their child. Studies of the use of multiagency investigation of unexpected infant deaths have shown that the needs of bereaved parents for help and support and the need for statutory agencies to investigate unexpected infant deaths need not be seen as conflicting or incompatible. The implementation in England of a co-ordinated multiagency approach to the investigation of unexpected deaths in infancy has led both to improved care and support of families and to higher standards in the investigation of such deaths, making optimal use of all available forensic, clinical and epidemiological skills and evidence. This chapter describes the rationale behind the English approach and the preliminary effects of its implementation over the past few years.

To use the diagnosis SIDS, investigation of the death scene is a prerequisite. In some countries death scene investigation is performed by ordinary police, in some states in the US it is performed by the medical examiner, but in many countries no death scene investigation is done at all. There is general agreement in the SIDS community that the death scene should be investigated by a specialist team including medical and forensic experts. This requirement has been a challenge for the legislators and legal experts who claim that entering homes without consent is violation of human rights. This challenge has been overcome in the UK where after a new law was passed on April 1, 2008, professor PJ Fleming and his co-workers successfully have developed a multi-agency approach which may be a model for other countries.

The involvement of a pathologist with forensic and pediatric training in all stages of the assessment of sudden and unexpected infant death (SUDI) is crucial as pathologists are among a limited group of medical practitioners who have been trained in evaluating the interaction of injuries, disease processes, and post-mortem changes. However problems exist, with variations in the quality of pediatric autopsy practice and in diagnostic categories that are applied. While the development of standard definitions and protocols has improved this situation, use of the term SUDI as an umbrella term has also assisted in evaluating trends and reducing the impact of diagnostic shift. The following paper reviews the contributions that may be made by pathologists in cases of SUDI, from an initial evaluation of a death scene, through the autopsy process, discussions with families, research and participation in multidisciplinary death review committees.

The death-scene investigation is an important and increasingly recognized step in the process of diagnosing Sudden Infant Death Syndrome (SIDS). According to current definitions, information from death-scene investigations is required when SIDS diagnoses are made. Due to differences in national jurisdictions, however, there are differences in the methods used and the professions involved in routinely performed death-scene investigations. Therefore any international comparability of death-scene data is limited. Only a few epidemiological studies have used thorough death-scene investigations in a systematic way, including a standardized, objective observation of the scene in cases and reference data from the general population. These studies gave close insights into the circumstances of infant death, but their complex protocols are mostly not feasible for routine use. For that purpose, manageable death-scene investigation protocols need to be distilled from the ones used in complex studies, taking into account their results. Whilst protocols for post-mortem examinations and definitions for SIDS have been largely standardized and agreed internationally, this step is still missing for death-scene investigations. If routinely obtained death-scene data were standardized and, thus, comparable, this would have a potential of generating new hypotheses that eventually lead to a better understanding of the underlying mechanisms and to more effective measures of prevention.

A failure of cardiorespiratory control mechanisms, together with an impaired arousal from sleep response, is believed to play an important role in the final event of the Sudden Infant Death Syndrome (SIDS). The ‘Triple Risk Model’ describes SIDS as an event that results from the intersection of three overlapping factors: [1] a vulnerable infant, [2] a critical developmental period in homeostatic control, and [3] an exogenous stressor. In an attempt to understand how the Triple Risk Hypothesis is related to infant cardiorespiratory physiology many researchers have examined how the known risk factors for SIDS alter infant physiology and arousal particularly during sleep. This review discusses the association between the three components of the Triple Risk Hypothesis, the major risk factors for SIDS (prone sleeping and maternal smoking), together with three “protective” factors (breastfeeding, pacifiers and swaddling), and cardiovascular control and arousability from sleep in infants, and discusses their potential involvement in SIDS.

Current evidence suggests that multiple neural mechanisms contribute to the fatal lethal event in SIDS. The processes may develop from a range of otherwise seemingly-innocuous circumstances, such as unintended external airway obstruction or accidental extreme flexion of the head of an already-compromised structure of the infant upper airway. The fatal event may occur in a sleep state which can suppress muscle tone essential to restore airway patency or exert muscle action to overcome a profound loss of blood pressure. Neural processes that could overcome those transient events with reflexive compensation appear to be impaired in SIDS infants. The evidence ranges from subtle physiological signs that appear very early in life, to autopsy findings of altered neurotransmitter, including serotonergic, systems that have extensive roles in breathing, cardiovascular regulation, and thermal control. Determination of the fundamental basis of SIDS is critical to provide biologic plausibility to SIDS risk reduction messages and to develop specific prevention strategies.

After more than 30 years of research into the hypothesis that long QT syndrome (LQTS) might be a cause of arrhythmic sudden infant death, we are now at the point where we can state with certainty that some sudden unexplained deaths in infancy, about 10%, are indeed due to long QT syndrome. The evidence for this lies in large population ECG screening programmes, post-mortem molecular genetic testing of sudden infant death victims, and some informative case reports. The cardiac sodium channel gene SCN5A (LQTS type 3) is the most common culprit, but LQTS types 1,2, 6, 9 and 12 have also been found. There is also new evidence that other arrhythmic syndromes sometimes cause SUDI, in particular short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia (CPVT). These conditions are also due to disordered cardiac ion channel function like LQTS, and are usually inherited in an autosomal dominant fashion. There remain, however, many unanswered questions, most particularly whether all populations are affected equally, and what should clinicians do with this knowledge? Should newborn ECG screening become mandatory? How should we best investigate SUDI at post mortem in order to diagnose LQTS? This review summarises the evidence to date and addresses these questions.

Sequencing of the human genome has expanded our understanding of the molecular basis of many diseases and the complexity of genotype-phenotype relationships. Knowing the genotype does not define the clinical characteristics or phenotype, however, since phenotype is also influenced by gene-gene and gene-environment interactions. Studies in SIDS infants have now identified polymorphisms in 25 genes that are present in increased frequency compared to controls. These include polymorphisms in 8 cardiac channelopathy genes, 3 genes related to serotonin (5-HT), 7 genes related to autonomic nervous system development, 6 genes related to inflammation, and 1 gene related to energy production. The polymorphisms related to cardiac channelopathies and 5-HT have been confirmed in several reports. Confirmation is less robust, however, for the polymorphisms in other genes, in particular as related to energy production. We still know very little about the associated clinical phenotypes and the environmental perturbations required to unmask antemortem phenotypes having increased risk for sudden unexpected death in infants (SUDI). The recent identification of multiple genetic risk factors for SIDS and enhanced understanding of gene-environment interactions are contributing to our knowledge related to SUDI. The challenge now is to capitalize on these hypothesis-generating studies to identify opportunities for effective assessment and intervention in infants who will otherwise die suddenly and unexpectedly. This review summarizes current knowledge regarding gene and gene-environment risk factors that interact to yield phenotypes susceptible to SUDI.

Bed sharing is a major risk factor for sudden infant death syndrome. This risk is increased when the mother smokes or smoked in pregnancy, or when the parent has drunk alcohol or taken drugs. This risk is further increased in younger infants. The mechanism of sudden infant death with bed sharing is unknown, but airway obstruction, thermal stress and head covering have all been suggested. The benefit from bed sharing has only been established for breastfeeding, although other benefits are claimed. There is a small group of infants that has been shown to be at no increased risk of SIDS with bed sharing, namely infants of mothers who do not smoke, who are aged 3 months or more, and whose mothers have not taken alcohol or drugs and do not co-sleep on a sofa. Recommendations on how to bed share safely are not evidence based. Without this knowledge parents cannot make an informed choice on whether or not to bed share. Parents should be advised to place the baby to sleep in its own cot next to the parents' bed for the first six months.

The successful and dramatic reduction in cot deaths has come about not so much because of a better understanding of causal mechanisms of sudden death but rather from identifying risk factors in the infant sleeping environment; in particular placing young infants on their front to sleep. More recently bed-sharing has been identified as a potential risk factor and similar efforts are being made in some countries to advise against this care practice. However prone sleeping is not a culturally widespread behaviour; introduced in the 20th century partly based on observations showing how premature infants thrived (and still do) when placed in this position in incubators. If we are going to advise against a behaviour such as bed-sharing that is common to many cultures over many thousands of years we need to address some basic questions. This review asks i) Is there any benefit to bedsharing? ii) Is bed-sharing in itself a 'risk-factor' for SIDS? and iii) By advising against bed-sharing will we do any harm?

Creating public health messages regarding how mothers should sleep close and safely with their babies is tricky and complex. It requires an appreciation of what exactly the term “sleeping with baby” and “co-sleeping” can mean. It also requires sensitivity to what parents will or can do if told emphatically “never sleep with your baby.” In the United States, well-intentioned public health messages from prominent government agencies about safe infant sleep have increasingly used language that equates “safe infant sleep” with the absence of the mother. Many messages seemingly imply that all forms of “co-sleeping” are dangerous and that those parents that practice it are acting irresponsibly. Messages such as “babies sleep safest alone” conflict with both laboratory and epidemiological findings as well as with recommendations from most medical organizations, including the American Academy of Pediatrics, who state that mothers and babies should sleep on separate surfaces close together in the same room. Moreover, studies reveal that breastfeeding and forms of co-sleeping, including both roomsharing and bedsharing, are functionally interdependent and that many mothers worldwide find that they can manage their own and their infant's needs more easily by adopting at least intermittent bedsharing. Hence, simple, unqualified recommendations against ever bedsharing are not likely to be followed. According to recent studies the most effective public health recommendations are likely to be those that educate parents and facilitate parents in implementing bedsharing safeguards alongside their own choices. This approach does not exclude informing parents of what we know can be dangerous about some bedsharing practices, nor where and when it should be avoided altogether. Rather, it acknowledges that while separate surface co-sleeping in the form of roomsharing should always be recommended, nonetheless, many parents will appreciate and benefit from the opportunity to learn how to reduce the risks associated with bedsharing.

Almost 20 years ago prone sleeping position was established as a risk factor for sudden infant death syndrome (SIDS) and with risk reduction campaigns which largely focused on this one factor, the incidence of SIDS has declined by 50-80% in most of the countries where campaigns were conducted. However, the pathophysiological cause or causes of SIDS are not yet known, although many theories have been proposed. This paper examines several of the more controversial theories for SIDS causation. In 1997 a link between Helicobacter pylori and SIDS was proposed. Initial positive results were not confirmed. More recently there is new evidence that H. pylori may play a role in some cases but these results need to be confirmed by others. Anaphylaxis caused by milk is an older theory, which has its merits, but needs to be verified with new methods. The toxic gas theory was interesting but had flaws. “Toxic gases” have not been produced in an environment remotely resembling that found in a cot. Proponents of the theory have recommended wrapping the cot mattress in polythene to prevent the postulated gases reaching the baby, but there is no evidence that this has had any effect. The proponents have been very vocal in the lay media despite evidence that disproves this theory. No further evidence is needed for the final rejection of this theory. The harm and benefits of immunisations are a controversial topic in the lay press, although seldom in the scientific literature. As the age of infants dying from SIDS is similar to that when immunisation is given, it has been postulated that there is a causal link. Several large case-control studies have shown that immunisations are not a risk factor for SIDS and recent a Meta analysis in fact reported that immunisation halve the risk for SIDS compared with infants who had not been immunized. In conclusion, while the cause or causes of SIDS remains unknown new theories will be proposed and this is to be welcomed. These theories should be first discussed within the scientific community. Debating theories and preliminary findings in the lay media risks confusing parents of young infants and takes attention away from established risk factors and recommendations.

Voluntary organisations, working closely with scientists and doctors in some 15 countries, play a key role in promoting research into Sudden Infant Death, providing support for bereaved families, disseminating infant care messages to help prevent deaths and improving investigations when a baby dies. This paper provides an overview of the role of voluntary organisations including giving examples of innovative projects and programmes to tackle the problems of sudden infant death.

We know how to protect babies from sudden infant death syndrome (SIDS) and have had considerable success in doing so. Yet babies continue to die in non-supine positions, unsafe sleeping environments and exposed to smoking. Why? Understanding what underpins the success to date is essential to the design of strategies for the final stage of prevention. This paper reviews influences on changing SIDS mortality, describes the practice of creating change as it relates to protecting babies from sudden infant death, and presents three principles that emerge from the success to date to focus the design of research and intervention programmes for ending the SIDS story.

Purpose: The aim of this paper is to compare international trends in sudden infant death syndrome (SIDS) and postneonatal mortality (PNM) since the introduction of SIDS risk reduction and safe sleep campaigns, offer possible explanations for differences, and to provide recommendations to improve consistency in classifying and reporting sudden unexpected deaths in infancy (SUDI) internationally. Methods: SIDS and postneonatal mortality rates were obtained for 15 countries from 1990 through the year for which most recent data were available. Results: SIDS rates have declined in all countries, with reductions well over 50% for most countries. These declines are attributed to SIDS risk reduction campaigns, which achieved success primarily in reducing rates of prone sleeping among infants. The largest declines generally occurred in the first few years after initiation of national campaigns, and there are concerning indications that these rates have reached plateaus in many countries. Conclusions and Recommendations: Diagnostic accuracy is essential to monitor and compare trends in SIDS and other sudden unexpected infant deaths. This requires establishing sudden infant death definitions and diagnostic categories that are agreed upon widely. National and local campaigns need to be reenergized to continue the early successes made in reducing SIDS incidence. Finally, data collection needs to be easy to access and this would best be accomplished by national vital statistics agencies posting data in a uniform way on their websites.