Sudden infant death syndrome

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Sudden infant death syndrome Rachel Y Moon, Rosemary S C Horne, Fern R Hauck Lancet 2007; 370: 1578–87 Goldberg Center for Community Pediatric Health, Children’s National Medical Center and George Washington University School of Medicine and Health Sciences, Washington, DC, USA (R Y Moon MD); Ritchie Centre for Baby Health Research, Monash Institute for Medical Research, Monash University, Melbourne, Australia (R S C Horne PhD); and Departments of Family Medicine and Public Health Sciences, University of Virginia School of Medicine Charlottesville, Virginia, USA (F R Hauck MD) Correspondence to: Rachel Y Moon, Children’s National Medical Center, Michigan Avenue NW, Washington, DC 20010, USA [email protected]

Despite declines in prevalence during the past two decades, sudden infant death syndrome (SIDS) continues to be the leading cause of death for infants aged between 1 month and 1 year in developed countries. Behavioural risk factors identified in epidemiological studies include prone and side positions for infant sleep, smoke exposure, soft bedding and sleep surfaces, and overheating. Evidence also suggests that pacifier use at sleep time and room sharing without bed sharing are associated with decreased risk of SIDS. Although the cause of SIDS is unknown, immature cardiorespiratory autonomic control and failure of arousal responsiveness from sleep are important factors. Gene polymorphisms relating to serotonin transport and autonomic nervous system development might make affected infants more vulnerable to SIDS. Campaigns for risk reduction have helped to reduce SIDS incidence by 50–90%. However, to reduce the incidence even further, greater strides must be made in reducing prenatal smoke exposure and implementing other recommended infant care practices. Continued research is needed to identify the pathophysiological basis of SIDS.

Introduction Sudden infant death syndrome, or SIDS, is defined as “the sudden death of an infant under one year of age, which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene, and review of the clinical history”.1 Despite declines in SIDS rates following risk reduction campaigns, SIDS continues to be the leading cause of death for infants aged between 1 month and 1 year in developed countries. Currently, Japan and the Netherlands have the lowest reported SIDS rates, at 0·09 and 0·1 per 1000 livebirths, respectively,2,3 whereas New Zealand has the highest reported SIDS rate in developed countries, at 0·8 per 1000 livebirths.4 The USA and the UK have intermediate SIDS rates of 0·57 and 0·41 per 1000 livebirths, respectively.5,6 In this Seminar, we focus on newer epidemiological and pathophysiological findings, risk reduction recommendations, and controversies related to some of these recommendations.

Epidemiology In the 1980s and 1990s, after epidemiological studies showed a decreased incidence of SIDS in infants who slept supine, many countries implemented public-health campaigns to encourage families to place infants on their back for sleep. In most of these countries, the rate

Search strategy and selection criteria We used the PubMed database to search for publications, using the search terms “SIDS,” “crib death,” “infant death,” and “sudden infant death syndrome.” Additionally, we reviewed listings of articles received through various mailing lists to identify publications that were not yet in PubMed. Citations were selected from articles published in English. We mostly selected publications from the past 5 years but did not exclude commonly referenced and highly regarded older publications. Reference lists in key textbook chapters and review articles were also checked for relevant publications and references.

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of placing infants prone for sleep has decreased 50–90%, and the rate of SIDS has similarly decreased 50–90%. As prone sleeping has become a less common risk factor, new epidemiological risk factors have emerged. We will discuss the epidemiology of SIDS both before and after the decrease in prone sleeping.

Demographic factors SIDS occurs less frequently in the first month of life, peaks between 2 and 4 months of age, and decreases thereafter. Around 90% of SIDS deaths happen in the first 6 months of life. Boys are more likely to die than girls, at a ratio of 60:40. Despite the overall decline in SIDS worldwide, there are still racial and ethnic disparities. In the USA, infants who are African American, Native American, or Alaska Native have SIDS rates that are two to three times the national average, irrespective of socioeconomic status.7,8 Maoris in New Zealand9 and Aboriginal Australians10–12 are also at higher risk for SIDS. Maoris are six times more likely to die of SIDS than non-Maori New Zealanders.13 Although biological differences (such as racial differences in tobacco metabolism14) might partially explain the disparity, behavioural factors also have an effect on the disparity. For instance, African Americans are twice as likely to place infants prone for sleep15 and twice as likely to bedshare than white people.16 Although the supine sleep position is the norm for infants who are Native American, Alaska Native, Aboriginal Australian, and New Zealand Maori, there are also high rates of smoke exposure17 and bedsharing in these groups, which place these infants at higher risk of SIDS.11,18

Maternal smoking and smoke exposure Maternal smoking during pregnancy is a major risk factor in almost every epidemiological study of SIDS.19–21 Postnatal exposure to tobacco smoke has emerged as a separate risk factor in a few studies,21,22 although this variable is difficult to separate from maternal smoking prenatally. Prenatal smoke exposure results in decreased lung volume and compliance,23 and decreased heart rate variability to stress.24 Additionally, nicotine has neuroteratogenic effects, www.thelancet.com Vol 370 November 3, 2007

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resulting in alterations in autonomic pathways, including decreased arousal to hypoxia and other stimuli.25–30 All of these effects could directly affect SIDS risk. If in-utero smoke exposure was eliminated, a third of SIDS deaths could possibly be prevented.31

Sleep practices and environment Since the introduction of international Back to Sleep campaigns and the subsequent large decrease in the proportion of infants placed prone to sleep, the contribution of the side sleep position to SIDS risk has increased, such that the risk of side and prone placement are similar.9,32–35 The side sleep position is unstable, and many infants placed this way will roll to prone,36,37 placing them at high risk for SIDS.34,35,38 Infants usually placed supine are sometimes placed prone by secondary caregivers (grandparents, babysitters, child care providers, or other relatives). Soft bedding and soft surfaces, including pillows, quilts, comforters, sheepskins, and porous mattresses, have been shown to be important risk factors.39–45 In particular, a strong interaction has been found between prone sleep position and soft bedding surface.45 Soft bedding is also a likely factor contributing to infant deaths occurring on adult beds.46–48 Warmer room temperatures and multiple layers of clothing or blankets on the infant have also been associated with an increased SIDS risk.43,49,50 This increased risk of overheating is particularly evident when infants are sleeping in the prone position and heat loss from the face is reduced;43 the risk is less clear when infants are supine. Bed sharing between an infant and adult facilitates breastfeeding and enhances parent-infant interactions.51,52 However, epidemiological studies have shown that this practice can be hazardous, especially when there are multiple bedsharers,45 when the infant is younger than 11 weeks,53,54 and when bed sharing occurs for the entire night.55,56 The risk for infant death might also be increased when the person sharing the bed has consumed alcohol or is overtired.53,56 Bed sharing is particularly hazardous with mothers who smoke,55,56 but sharing with non-smoking mothers is also a risk factor among infants younger than 11 weeks.53,54 Bed sharing on a couch or sofa is particularly dangerous and should always be avoided.45,54,57,58 There is growing evidence that room sharing without bed sharing is associated with a reduced risk of SIDS.53–55 The USA, UK, Canada, Australia, and several other countries currently recommend that infants sleep in a crib or bassinet next to the parents’ bed. Published case-control studies have shown a significantly reduced risk of SIDS when a pacifier is used at sleep time,45,53,58–63 and two meta-analyses have reported a strong protective effect.64,65 Several mechanisms have been postulated to explain this protective effect. Franco and colleagues66 found a lower arousal threshold in infants who frequently used a pacifier than those who www.thelancet.com Vol 370 November 3, 2007

did not during sleep, perhaps allowing increased responsiveness to a life-threatening challenge, such as obstructive apnoea, cardiac arrhythmia, or external conditions leading to hypoxia and asphyxia. Other theories include an improved ability to breathe through the mouth if the nasal airway becomes obstructed61,67,68 and decreased likelihood of oropharyngeal obstruction by bringing the tongue forward.66,67 Use of a pacifier might also reduce SIDS risk by affecting sleep position.59,61,68 Even when pacifiers become dislodged from the mouth after an infant falls asleep, which generally occurs soon after sleep onset,66,69 the protective effect still persists. Displacement of the pacifier might contribute to increased sleep disruption and greater arousability of the infant.70 Infants in child care settings (ie, cared for by a nonparental caregiver, including babysitters and child care providers) make up around 20% of SIDS deaths.71–73 Why these infants are at higher risk is unclear, since there is less exposure to environmental risk factors, such as smoke exposure, soft bedding, prone sleep position, and bed sharing.71,73 Furthermore, a large proportion of these deaths take place during the first week of child care.72 Stress and sleep disruption during the transition to child care could be contributing factors.71,73

Infant medical conditions Infants who are born prematurely or who have low birthweight have up to four times the risk of SIDS than those infants born at term, and this risk increases with decreasing gestational age or birthweight.74–76 Apnoea of prematurity and other complications of prematurity do not explain this increased risk.74 Infants born preterm who are placed prone are at equally high risk for SIDS as infants born at term.77 However, infants born preterm are often placed prone in the intensive care setting to enhance respiratory mechanics.78,79 The results of one study showed that before neonatal unit discharge, infants born prematurely slept longer, had fewer arousals from sleep, and more central apnoeas when sleeping prone.80 Thus, premature infants should be placed supine as soon as is medically safe, and well before hospital discharge, to ensure and assure that the infant and parents are accustomed to supine placement. Although apnoea was for many years thought to be the predecessor of SIDS, results of studies such as the Collaborative Home Infant Monitoring Evaluation have shown that it does not precede or predict SIDS.81 Apnoea monitors might be useful in selected patients who have had apparent life-threatening events, but there is no evidence that they are useful for reducing the occurrence of SIDS.82 Evidence of a recent infection has been a common finding of SIDS autopsies. Upper respiratory tract infections within 4 weeks of death have been reported in 53% of SIDS cases, compared with 38% of controls.83 The same study also reported that fewer SIDS cases (33%) 1579

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than controls (68%) had received age-adequate pertussis immunisation.83 There is no evidence that immunisations increase the risk for SIDS.84,85

Breastfeeding Epidemiological studies have produced inconsistent findings on the protective effects of breastfeeding for SIDS. Results of some studies have shown a protective effect,86–88 whereas others, after adjustment for socioeconomic status, did not show such an effect.89–92 Studies in Germany have found breastfeeding initiation to be associated with a reduced risk of SIDS.93,94 Chen and Rogan95 reported that postneonatal death in general, but not SIDS, is decreased in breastfed infants. Physiological studies have shown that breastfed infants arouse more readily at 2–3 months of age than do formula-fed infants,96 and post-mortem studies have shown that formula-fed infants who died of SIDS have significantly lower concentrations of docosahexaenoic acid in the frontal lobes of their brains than do breastfed infants.97 This long chain fatty acid is concentrated in neural tissue and has been reported as a predictor of developmental indices at 1 year of age in preterm infants.98 It has also been associated with more mature infant sleep patterns.99

Recurrence of SIDS in siblings Siblings of SIDS victims are at increased risk for SIDS. However, the exact extent of the increase in risk is as yet unclear. Metabolic or genetic disorders, such as fatty acid oxidation disorders or prolonged QT syndrome, might go unrecognised and subsequent deaths attributed to SIDS. Although homicide should be considered as a possibility, a sudden infant death in a subsequent sibling is six times more likely to be SIDS than homicide.100 If a family has more than one infant death or if more than one infant dies while in the care of the same caregiver, a careful and complete autopsy, death scene investigation, and review of medical history are especially imperative so that causes other than SIDS can be ruled out.101

Pathophysiology SIDS is regarded to be multifactorial in origin. The so-called triple risk hypothesis is a useful model to organise current knowledge. It proposes that SIDS results when three factors coincide: a vulnerable infant; a critical developmental period in homoeostatic control; and an exogenous stressor, such as being placed for sleep in the prone position.102 The triple risk hypothesis posits that infants will die of SIDS only if they possess all three factors, and that the vulnerability lies latent until they enter the crucial developmental period and are exposed to an exogenous stressor. The final pathway to SIDS is widely believed to involve immature cardiorespiratory autonomic control, together with a failure of arousal responsiveness from sleep. 1580

Autonomic control and arousal More than 20 years ago, autonomic dysfunction or impairment was suggested as a possible cause of SIDS.103 Infants who had been studied and subsequently died from SIDS, compared with surviving infants, had higher baseline heart rates,104 lower heart rate variability,105 prolonged QT indexes,106 and low parasympathetic tone, high sympathovagal balance, or both.107,108 Arousal from sleep is an important survival response to a life-threatening event, such as hypotension or prolonged apnoea.109 Arousal from sleep can occur spontaneously in response to internal physiological changes, and can also be induced by external environmental factors. Arousal involves both autonomic and behavioural components. During arousal from sleep, heart rate, arterial pressure, and ventilation are increased,110 and importantly, a behavioural response is evoked, allowing body movements aimed at avoiding the life-threatening stimulus.109 The cardiorespiratory responses at arousal are similar to fight-or-flight reactions, which also increase arterial pressure, heart rate, and ventilation.110 These responses are relayed and integrated in specific regions of the hypothalamus and the brainstem. The underlying neuronal activity that elicits cortical activation also involves specific neurotransmitter-modulated discharge patterns of thalamocortical neurons. The defence-alerting responses range from mild cardiorespiratory activation (eg, a sigh), through awakening, and finally to redistribution of blood flow and gasping during asphyxia. The carotid bodies are believed to play a major part in the mediation of the arousal response to arterial hypoxaemia, as surgical denervation of the carotid body chemoreceptors produces a delayed or incomplete hypoxic arousal.111 Similarly, the arterial baroreceptors are vital for arousal responses to hypotension and hypertension.112,113 Abnormalities of arousal are now believed to be involved in the final SIDS pathway. Prospective studies of infants who subsequently died from SIDS have identified fewer spontaneous arousals from sleep and immature sleep patterns, compared with those infants who survived.114–116 The most compelling evidence was provided by Kato and colleagues117 in a study of more than 20 000 infants, which found both reduced numbers of spontaneously occurring arousals and a pattern of arousals suggestive of an impaired arousal pathway in infants who subsequently died from SIDS. Multiple studies of sleep and arousal responses in healthy infants exposed to major risk factors for SIDS have shown that these risk factors alter sleep patterns and physiology and impair infant arousal responses to both internal and external stimuli. Prone sleeping has been shown to increase the total amount of time infants spend asleep80,118,119 and, in particular, the time spent in quiet sleep, a state of reduced arousability.80,118–121 Additionally, infants sleeping in this position have decreased spontaneous arousability,80,118,122 diminished www.thelancet.com Vol 370 November 3, 2007

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induced arousability,120,121,123–125 and fewer full cortical arousals,126 than those sleeping in the supine position. Prone sleeping has also been associated with altered autonomic control, manifest by raised heart rates,118,121,127–133 decreased heart rate variability,120,123,124,128,133,134 and increased sympathetic tone.120,128,135 Similarly, infants exposed in utero to maternal smoking have been shown to have both decreased spontaneous arousal from sleep29,136–138 and diminished stimulus-induced arousal responses.25,28,137,139 The results of other studies also suggest that autonomic control is altered in these infants.24,27,140 These findings provide further support for the theory that autonomic control and arousal responsiveness are implicated in SIDS causation.

Autopsy findings Although there are no pathognomonic autopsy findings for SIDS, there are several common findings. Petechial haemorrhages of the thymus gland, visceral pleura, and epicardium occur in 68–95% of SIDS deaths and are generally more extensive than in non-SIDS deaths.100 Additionally, pulmonary congestion and oedema indicative of terminal left ventricular failure are more common in SIDS cases.100 Oronasal secretions, which are typically frothy, mucoid, and pink or bloody, are also more common in SIDS cases.141

Other pathological findings Sustained and intermittent hypoxia promotes the formation of vascular endothelial growth factor, which is an endothelial cell-specific mitogen that increases peripheral oxygen delivery by stimulating angiogenesis. Even small changes in tissue oxygenation can substantially alter expression of vascular endothelial growth factor.142 In one study, concentrations of this growth factor in cerebrospinal fluid were significantly higher in 51 infants who died from SIDS than in 33 control infants who died from known causes, suggesting that hypoxia frequently precedes death from SIDS.143 Infants who died from SIDS have also been found to have structural and neurotransmitter alterations in the brainstem in areas associated with autonomic control, control of respiration, sleep, and arousal. Kinney and colleagues144 have reported that the serotonin or 5-hydroxytryptamine (5-HT) system is abnormal in at least 50% of SIDS cases. Serotonin is a neurotransmitter that affects various autonomic functions, including cardiorespiratory and circadian regulation. Recently, the same group reported that infants who died from SIDS had a significantly higher number and density of 5-HT neurons, a significantly lower density of 5-HT1A receptor binding sites in regions of the medulla involved in homoeostatic function, and a lower ratio of 5-HTT binding density to 5-HT neuron count in the medulla than infants who died of known cases.145 These findings suggest that the deficiencies in the medullary 5-HT system are quite extensive and involve abnormal 5-HT www.thelancet.com Vol 370 November 3, 2007

neuron firing, synthesis, release, and clearance. Importantly, this study also identified decreased 5-HT1A receptor binding in male infants who died of SIDS compared with female infants, which could explain the increased incidence of SIDS in male infants.145 Recent studies by Lavezzi and colleagues146 show that the cerebellum, a structure not normally associated with respiratory and cardiovascular control, might have an important role in compensatory responses to hypoxic insults. The investigators reported that, compared with 10% of controls, 62% of sudden perinatal and infant deaths showed alterations, such as neuronal immaturity, altered apoptotic programmes, negative expression of somatostatin and the EN2 gene, intense c-fos expression positivity, and astrogliosis in the cortex and dentate nucleus. There was also a strong correlation between these findings and a history of maternal smoking, further supporting the strong link between maternal smoking and SIDS. Other neuropathological defects and abnormalities found in the brains of infants who died of SIDS include increased numbers of neuronal dendritic spines, which are thought to be indicative of delayed neuronal maturation.141 Waters and colleagues147 have reported increased neuronal apoptosis in the hippocampus and brainstem, which might lead to functional loss in regions sensitive to hypoxia and regions associated with sensation in the face and position of the head, suggestive of an hypoxic insult before death. These findings could explain why infants whose faces have been covered by bedding, as is commonly noted in SIDS deaths, do not simply turn or lift their heads to avoid asphyxia. Inflammatory changes have been reported in several systems including the respiratory tract, digestive tract, nervous system, and blood. SIDS could be due to a rapid, uncontrolled release of inflammatory mediators in response to an infectious agents or their toxins.148 In support of this idea, one study reported that 10 of 20 (50%) infants with SIDS had levels of interleukin-6 (IL-6) in their cerebrospinal fluid equivalent to those found in infants who died of infectious diseases.149 The common bacterium Staphylococcus aureus might have a role in this infection, since despite being isolated in 56% of healthy infants, 86% of SIDS infants had these bacteria in the respiratory tract.150 Some of the risk factors for SIDS, such as smoke exposure and lower socioeconomic status, parallel the risk for serious infection, particularly respiratory tract infections in infants. In summary, the pathological findings from research protocols support the theory that SIDS is associated with abnormalities or immaturity of the autonomic nervous system, immune system, and arousal pathways.

Genetic factors Currently, there are no specific genotypic differences in infants who died of SIDS that can be linked to specific clinically defined phenotypes. However, several dif1581

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Environmental risk factors

Genetic risk factors

Smoking

5-HTT polymorphism

Soft bedding

ANS polymorphism Impaired autonomic regulation and arousal Cardiac ion channel polymorphism

Prone or side sleeping

SIDS Prematurity

Complement or interleukin polymorphism

Figure: Gene-environment interactions Adapted from Hunt.153

ferences in gene polymorphisms between infants with SIDS and control infants have been identified. These include polymorphisms in sodium channel (SCN5A) and potassium channel genes that are associated with prolonged QT syndrome;151,152 ion channel defects are thought to be associated with up to 5–10% of SIDS cases.153,154 Polymorphisms have also been identified in a serotonin transporter (5-HTT) gene that increases serotonin transporter activity, in turn reducing serotonin concentrations at nerve endings.155,156 Other polymorphisms have been identified in genes that affect autonomic nervous system development (PHOX2a, RET, ECE1, TLX3, EN1).157 Additionally, deletions in genes associated with infection have been reported. In a casecontrol study, infants who died from SIDS who had a mild upper respiratory tract infection before death were more likely to have deletion of the complement C4A or C4B gene than control infants.17 In SIDS infants, polymorphisms in the promoter region of the anti-inflammatory cytokine interleukin 10 (IL10) could lead to decreases in antibody production or alternatively to increases in inflammatory cytokine production.158 All of these findings are consistent with post mortem and physiological findings of abnormalities in the control of cardiorespiratory and immune function and arousal. The triple risk model suggests that these and possibly other gene polymorphisms might make certain infants more vulnerable to SIDS; this vulnerability then manifests when there is an environmental challenge, such as prone positioning or tobacco exposure, at a critical age (figure). The interaction between genetic and environmental factors is thus an emerging area of research that needs to be further explored.

Diagnosis By definition, SIDS is a diagnosis of exclusion. Protocols for standardised autopsies and death scene investigations in sudden unexpected infant deaths have been published.159–161 However, there is wide variability in both 1582

the content and frequency with which these protocols are implemented across jurisdictions, both within countries and across different countries. For example, autopsy rates in the Netherlands61 and Japan70 are lower than in most other developed countries. Differences could be a result of political, cultural, religious, and economic factors. Although autopsies are crucial in identifying the cause of death in many kinds of sudden infant death, such as infections, congenital anomalies, and trauma, deaths from suffocation are often difficult to diagnose from the autopsy alone. Thus, examination of the circumstances present immediately before death, including detailed description of the infant’s sleep environment, has become increasingly emphasised in recent years. Greater attention has also been paid to establishing the critical elements of these investigations and how to interpret the data collected. Analyses of trends in causes of sudden unexpected deaths in infancy indicate that a diagnostic shift might be taking place. Malloy and colleagues162 showed that during the period 1999–2001, the US postneonatal SIDS rate declined slightly, but the total postneonatal mortality rate did not change, and that the decrease in SIDS rate was largely accounted for by an increase in deaths due to suffocation and cause unknown or unspecified. Similar findings were reported by Shapiro-Mendoza and colleagues163 for all infants from birth to 1 year of age, for the years 1989–2001. In a South Australian investigation, the number of SIDS deaths declined from 1989–93 to 1994–98, and the number of suffocations in bed and cause undetermined deaths increased.164 A survey of medical examiners and coroners representing six US jurisdictions reported that “…almost all of the pathologists reflected on their experiences with the changing SIDS diagnostic criteria and protocols from when they first began practicing in the 1980s and discussed how much more complicated, confusing, and timeconsuming SIDS cases have become. Most of them also noted that they used to label many more infant death cases as SIDS than they do now.”159 Part of the uncertainty in diagnosing SIDS seems to be the growing trend of confusing risk factors for the syndrome with causes of sudden unexpected infant deaths. For example, some pathologists might code the cause of death as positional asphyxia when an infant is found unresponsive in the face-down position, although this is a well-established risk factor for SIDS. Other pathologists might not code a death as SIDS if the infant had been sleeping with another person (bed sharing) at the presumed time of death.159 Several classification schemes for sudden unexpected infant death have been developed as a way to standardise the assignment of cause of death on the basis of autopsy, scene investigation, and clinical information.165–67 Reaching consensus internationally on a classification scheme is essential to accurately monitor trends in sudden infant death and to make appropriate use of data obtained through the autopsy and death scene investigation. www.thelancet.com Vol 370 November 3, 2007

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Risk reduction interventions and their effect Campaigns to reduce the risk of SIDS were initiated in the Netherlands in 1987; in the UK, New Zealand, and Australia in 1991, in the Scandinavian countries 1990–92, and in the USA in 1994.168 These campaigns largely focused on reducing prone sleeping. Initially, recommendations stressed side or back placement, but after new research identified an increased risk with the side position compared with supine, subsequent recommendations include supine placement only.84 Some campaigns have also included messages about other behaviours and practices to reduce risk, such as reducing smoking during pregnancy and increasing breastfeeding, but there have been no significant changes seen in these behaviours, and thus reduced SIDS rates have been attributed mainly to avoidance of prone sleeping.169–171 Although there have been barriers to changing parental practices about infant sleep position, the prevalence of supine sleeping now approaches 100% in many countries or in subgroups within countries or regions.172 Individual behaviours, such as maternal smoking during pregnancy, are more difficult to change. Research continues to seek factors associated with increased and decreased risk of SIDS to expand the effectiveness of risk reduction campaigns and to overcome the levelling in SIDS rates in many countries.173 Such efforts are particularly salient for population groups disproportionately affected by SIDS, such as African Americans in the USA,174 Aboriginal Australians,10 and Maoris in New Zealand.9 In its most recent SIDS policy statement, the American Academy of Pediatrics reiterated some previous recommendations, revised others, and added new recommendations to potentially further reduce SIDS risk (panel),84 such as offering a pacifier to infants at bedtime and discouraging bed sharing while encouraging room sharing during infant sleep periods. These recommendations have met with resistance, mainly from breastfeeding advocates who worry that these measures will reduce breastfeeding frequency and duration and prevent families from enjoying the experience and benefits of bed sharing.175 The controversy is likely to continue for some time, until new research specifically targeted to these issues is done. Monitoring is needed of the adoption patterns of these recommendations among parents and health personnel and the effect they have on the SIDS rate and on other important outcomes, such as breastfeeding. We should also not lose sight of the more established and proven risk reduction measures, such as supine sleeping for all infants including those born preterm and avoidance of smoke exposure in utero, and to continually reinforce these measures to new generations of health providers, parents, and others who care for young children.

Management and support The loss of an infant is devastating for everyone concerned. However, in addition to the loss of their infant, families whose infant has died of SIDS could face police investigation, a long wait for autopsy results, and www.thelancet.com Vol 370 November 3, 2007

Panel: American Academy of Pediatrics SIDS risk reduction recommendations, 200584 • Back to Sleep: infants should be placed for sleep in a supine position for every sleep. Side sleeping is not as safe as supine sleeping and is not advised • Use a firm sleep surface • Keep soft objects and loose bedding out of the crib • Do not smoke during pregnancy • A separate but proximate sleeping environment is recommended: the infant’s crib or bassinet should be placed in the parents’ bedroom, which, when placed close to their bed, will allow for convenient breastfeeding and contact • Consider offering a pacifier at nap time and bedtime: the pacifier should be used when placing the infant down for sleep and not be reinserted once the infant falls asleep. If the infant refuses the pacifier, he or she should not be forced to take it. For breastfed infants, delay pacifier introduction until 1 month of age to ensure that breastfeeding is firmly established • Avoid overheating • Avoid commercial devices marketed to reduce the risk of SIDS • Do not use home monitors as a strategy to reduce the risk of SIDS • Avoid development of positional plagiocephaly: encourage “tummy time” when the infant is awake and observed. This will also enhance motor development. Avoid having the infant spend excessive time in car-seat carriers and “bouncers,” in which pressure is applied to the occiput. Upright “cuddle time” should be encouraged • Continue the Back to Sleep campaign

continued uncertainty, leading to prolonged emotional distress, all of which complicate the grieving process. The physician can play an active part by advocating for an autopsy in all cases of sudden unexpected death, discussing the results of the autopsy with the family, and providing emotional support. Surviving siblings and other family members also need age-appropriate support. If appropriate, the family should be referred for genetic counselling, metabolic testing, or both. Additionally, the family should be directed to local counselling and support groups, which are available in most communities.

Future directions Despite declines in prevalence of SIDS, work still needs to be done on many fronts. Further refinement in elucidation of the risk and protective factors, with appropriately targeted and implemented interventions leading to increased adoption by families, could bring the number of SIDS deaths to lower and lower levels. However, the disorder is unlikely to be completely eliminated or reduced to the lowest possible rates until the specific causative mechanisms are understood more fully. Continued research to identify the pathophysiology and genetics of SIDS must therefore be supported and expanded to include larger sample sizes of both affected and control infants, and infants from the highest risk groups.176 Additionally, systematic investigations of stillbirths and sudden unexplained deaths in those over 1 year of age are equally important and might provide additional insight into the pathogenesis of SIDS. New investigators, both in the basic and epidemiological sciences, need to be funded, mentored, and encouraged to enter the field of SIDS research. 1583

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Surveillance of trends in rates of SIDS and other sudden unexpected infant deaths is crucial. Comparisons across jurisdictions within countries and across countries would be made more meaningful with standardised classification guidelines. The international community needs to work together to either accept previously recommended approaches or develop a new one to achieve standardisation. Ideally, these changes would be incorporated into a new revision of the International Classification of Diseases and thus reflected on death certificates, the major way we have to establish trends in the causes of infant death internationally. In conclusion, the multifactorial, complex, and changing knowledge base and approach to SIDS requires a multidisciplinary and collaborative effort that engages health professionals and policymakers, researchers, medical examiners and coroners, grief counsellors and agencies that provide support to families, and above all, families and communities, especially those at highest risk. Continued research, surveillance, risk reduction campaigns, and standardisation of autopsy and scene investigation protocols and classification of deaths are all essential pieces to illuminating the SIDS puzzle and reaching our shared goal of eliminating it as a cause of infant death. Conflict of interest statement RYM has received research grants to undertake studies of SIDS epidemiology and risk reduction interventions from the National Institutes of Health and the Gerber Foundation. RSCH’s salary is currently funded by a National Health and Medical Research Council of Australia Senior Research Fellowship. Funding for research has been awarded by the National Health and Medical Research Council of Australia, the Sudden Infant Death Research Foundation of South Australia and the National SIDS Council of Australia. FRH is currently funded by the National Institute of Child Health and Human Development and the University of Virginia Children’s Hospital. Both RYM and FRH have received speaker’s fees from various SIDS organisations. References 1 Willinger M, James LS, Catz C. Defining the sudden infant death syndrome (SIDS): deliberations of an expert panel convened by the National Institute of Child Health and Human Development. Pediatr Pathol 1991; 11: 677–84. 2 Maternal and Child Health Statistics of Japan: Boshi Eisei Kenkyuu Kai, 2006. 3 Central Bureau of Statistics, Netherlands, 2006. http://www.cbs.nl/enGB (accessed July 5, 2007). 4 New Zealand Health Information Service, 2003. http://www.nzhis. govt.nz (accessed July 5, 2007). 5 Hoyert DL, Mathews TJ, Menacker F, Strobino DM, Guyer B. Annual summary of vital statistics: 2004. Pediatrics 2006; 117: 168–83. 6 Report: Unexplained Deaths in Infancy, 2005. Health Stat Q 2006: 82–86. 7 Hoyert DL, Arias E, Smith BL, Murphy SL, Kochanek KD. Deaths: final data for 1999. Natl Vital Stat Rep 2001; 49: 1–113. 8 Mathews TJ, Menacker F, MacDorman MF. Infant mortality statistics from the 2002 period: linked birth/infant death data set. Natl Vital Stat Rep 2004; 53: 1–29. 9 Mitchell EA, Tuohy PG, Brunt JM, et al. Risk factors for sudden infant death syndrome following the prevention campaign in New Zealand: a prospective study. Pediatrics 1997; 100: 835–40. 10 Freemantle CJ, Read AW, de Klerk NH, McAullay D, Anderson IP, Stanley FJ. Sudden infant death syndrome and unascertainable deaths: trends and disparities among Aboriginal and non-Aboriginal infants born in Western Australia from 1980 to 2001 inclusive. J Paediatr Child Health 2006; 42: 445–51.

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