Sudden infant death syndrome: Risk factors and risk reduction strategies

INTRODUCTION — Sudden infant death syndrome (SIDS), also previously called crib or cot death, is the leading cause of infant mortality between one month and one year of age in the United States [1]. Since the 1990s, however, new studies in pathology and epidemiology have provided the basis for an important evolution in the understanding of SIDS.

The risk factors for and measures to reduce the risk of SIDS are discussed in this topic review. Clinical management for the family of an infant who has succumbed to SIDS and alternate diagnostic considerations are discussed separately. (See "Sudden unexpected infant death including SIDS: Initial management".)

DEFINITION — SIDS is defined as the sudden death of an infant younger than 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 [2,3].

This definition emphasizes the necessity of autopsy, death scene investigation, and review of the clinical history when making the diagnosis of SIDS, to exclude other explanations for the sudden unexpected infant death (SUID) that can mimic SIDS (table 1). The evaluation of an infant who has died of suspected SIDS and alternate diagnostic considerations are discussed separately. (See "Sudden unexpected infant death including SIDS: Initial management".)

TERMINOLOGY — Due in part to potential inconsistencies in the diagnosis of SIDS, the term "sudden unexpected infant death" (SUID) is often used to describe all unexpected infant deaths. The SUID designation can then be subdivided into explained SUID and unexplained SUID. Unexplained SUID generally includes those cases considered SIDS by the medical examiner, as well as some cases that are not considered SIDS but lack a clear explanation due to uncertain circumstances. Some reports in the literature use the term "unexplained SUID" instead of "SIDS" to avoid inconsistencies between medical examiners in reporting SIDS as a cause of death. The National Association of Medical Examiners has recommended that death certifiers use the term "unexplained sudden death," including for cases that meet the current definition of SIDS, and specify whether intrinsic and extrinsic factors were identified [4].

Reported risk factors discussed in this topic are similar across the spectrum of SUIDs, including those that are unexplained (whether or not categorized as SIDS) and other sleep-related infant deaths, including those attributed to suffocation, asphyxia, and entrapment. Therefore, these risk factors are addressed together in recommendations for a safe infant sleeping environment [5]. In the absence of formal adoption of the terminology for unexplained infant deaths that was recommended by the National Association of Medical Examiners, in this topic review, we will continue to use the term "SIDS," but much of the discussion about risk factors and preventative measures applies to other sleep-related infant deaths.

EPIDEMIOLOGY — SIDS is the leading cause of infant mortality between one month and one year of age in the United States [1]. The risk of SIDS in the United States is <1 per 1000 live births [6-8]. Higher rates (two to three times the national average) are found in Black and Native American/Alaska Native children [1,9]. A disproportionately high rate (15 to 20 percent) of SIDS cases occurs in childcare settings [10,11]. The risk of SIDS is slightly increased in boys (multivariate odds ratio [OR] 1.49 [95% CI 1.14-1.83] in one large European case-control study) [12]. Although SIDS is uncommon, it is important to note that the risk of a child dying from SIDS during the first year of life is more than 20-fold higher than the risk of death during any of the subsequent 17 years of life due to any other cause, including motor vehicle traffic accidents, firearms, drugs and overdose, and suicide [13].

The incidence of SIDS has declined dramatically in countries that have adopted policies encouraging non-prone sleeping ("Back to Sleep" campaigns). The initial campaigns were in Europe, Australia, and New Zealand [14]. In the United States, the incidence of SIDS has declined by more than 50 percent since the mid-1980s, and the greatest reduction occurred after 1992, when the American Academy of Pediatrics (AAP) issued a recommendation to reduce the risk of SIDS by placing infants in a supine position for sleep [14-16]. Between 1992 and 2001, the SIDS rate in the United States fell from 1.2 to 0.56 per 1000 live births, while the proportion of infants sleeping in the supine position increased from 13 to 72 percent [17,18]. The rate of sudden unexpected infant death (SUID) then remained approximately constant between 2001 and 2015 [19,20]. Similar declines have occurred in other countries after campaigns to encourage non-prone sleeping [21,22]. In modern datasets, a higher proportion of cases are associated with unsafe sleeping conditions and a higher proportion are attributed to accidental asphyxia rather than SIDS [19,23-25].

Data from the National Institute of Child Health and Human Development (NICHD) Collaborative SIDS Study have helped to define the epidemiologic features of SIDS (table 2) [26]. This landmark study was a multicenter, population-based, case-controlled project that included 10 percent of the live births in the United States; the study was published in 1988, prior to the widespread use of supine sleep positioning. The pathologic diagnoses were confirmed by an independent panel of forensic pathologists.

In the NICHD study, the median age for SIDS deaths was 11 weeks, the peak incidence was between two and four months, and 90 percent occurred before six months of age [26]. This unique age distribution has been confirmed in other datasets [13] and strongly suggests that critical stages of development or maturation affect the risk of SIDS. Approximately 1.6 percent of sudden unexpected deaths resembling SIDS occur within the first 24 hours of life [27-30], 3 to 4 percent occur during the first week and 12 percent within the first month of life [24], and 2 percent of cases occur after nine months of age [31]. SUID during the first week of life appears to have different mechanisms from later-occurring cases, as suggested by differing risk factors [30]. Moreover, the rate of SUID in the early perinatal period has not declined since the mid-1980s. These statistics vary among datasets, in part because they depend on how an unexplained death is categorized, which has changed over time and is particularly variable for deaths during the first day of life.

RISK FACTORS — Numerous risk factors for SIDS have been identified in observational and case-control studies (table 2). Those that are consistently identified as independent risk factors include:

●Maternal factors:

•Young maternal age

•Maternal smoking during pregnancy

•Late or no prenatal care

●Infant and environmental factors:

•Preterm birth and/or low birth weight

•Prone sleeping position

•Sleeping on a soft surface and/or with bedding accessories such as loose blankets and pillows

•Bed-sharing (eg, sleeping in parents' bed)

•Overheating

More than 95 percent of SIDS cases are associated with one or more risk factors, and in many cases, the risk factors are modifiable (usually sleeping position, sleep environment, or parental smoking) [32]. Risk factors for SIDS are discussed below. Those that can be modified to decrease the risk of SIDS are also discussed in the section on prevention. (See 'Prevention' below.)

Maternal risk factors — There are two major maternal risk factors for SIDS that are independent of birth weight [12,26]:

●Maternal smoking

●Age of the mother under 20 years

These factors increased the risk of SIDS two to fourfold in the National Institute of Child Health and Human Development (NICHD) Collaborative SIDS Study [26].

Maternal smoking is an important modifiable risk factor for SIDS. SIDS rates increase with the amount smoked [33,34] and decrease if the mother quits or reduces smoking during the pregnancy [35]. The strongest effect is from smoking during pregnancy, but exposure of an infant to secondhand smoke is an additional independent risk factor [36,37]. Smoking prevention/intervention programs have the potential to substantially lower SIDS rates [33,38]. Several studies have shown abnormal cardiovascular responses to stimuli (eg, head-up tilt, hypoxemia, or carbon dioxide exposure) and impaired arousal to stimuli in infants born to mothers who smoked during pregnancy, suggesting a possible mechanism for this association [39-44]. (See "Secondhand smoke exposure: Effects in children", section on 'Sudden infant death syndrome' and "Cigarette and tobacco products in pregnancy: Impact on pregnancy and the neonate", section on 'Postnatal'.)

Maternal drug abuse and all of its associated phenomena are also associated with an excessive number of SIDS deaths [45,46]. In one report, a fivefold increase in SIDS risk was reported for infants of substance-abusing mothers in the Los Angeles area [47]. It is not known if this association is related primarily to the biologic effect of drugs in utero, an increased risk of prematurity and low birth weight, and/or other postnatal conditions (socioeconomic, environmental, or parenting behavior). One study found an association between a report of infant maltreatment and subsequent sudden unexpected infant death (SUID), after adjustment for several known SIDS risk factors (hazard ratio 3.22, 95% CI 2.66-3.89) [48]. It is possible that the observed association is attributable to common risk factors that were not captured in the analysis, including maternal smoking or substance use, or infant sleep position. Alternatively, some of the association may be attributable to unrecognized child maltreatment (intentional or neglect).

Maternal alcohol use is an important risk factor for SIDS in some populations [49]. In a population-based case-control study among Northern Plains American Indians, SIDS was significantly associated with periconceptional maternal alcohol use (adjusted odds ratio [OR] 6.2, 95% CI 1.6-23.3) and first-trimester binge drinking (adjusted OR 8.2, 95% CI 1.9-35.3) [50].

Pregnancy complications associated with an increased risk of SIDS include placenta previa, abruptio placenta, premature rupture of membranes, and elevated maternal alpha-fetoprotein [8,51-53]. The increased risk associated with these complications appears to be independent of their relationship with preterm birth.

Infant risk factors

●Prematurity – Preterm infants should be placed supine for sleep as soon as possible, at least from the postmenstrual age of 32 weeks onward, as recommended by the American Academy of Pediatrics (AAP) [5,54,55]. Preterm infants are at a higher risk for SIDS than term infants, with significant disparities between different race and ethnic groups even after adjustment for other risk factors [9,56-58]. Among low and very low birth weight infants, the SIDS rate has consistently been three- to fourfold higher than in term infants [59]. The gestational age of peak vulnerability for SIDS appears to occur four to six weeks earlier among preterm than term infants [56]. It is unclear whether the population of low birth weight infants is experiencing a decline in the rate of SIDS similar to that in the general population. A decline in SIDS rates among preterm infants was noted in New Zealand [57] but not in Sweden [60]. Preterm infants are subject to the same risk factors for SIDS as term infants, as discussed in greater detail below [57,61,62].

Supine positioning for sleep substantially reduces the risk for SIDS among premature infants. Traditionally, there were some concerns that supine positioning of premature infants may reduce oxygenation in premature infants, as measured by peripheral pulse oximetry. However, two small studies have suggested that this may not be the case, at least among infants who are older than 32 weeks postmenstrual age (ie, gestational age measured from the last menstrual period) and not in the acute phase of a respiratory illness [63,64]. Moreover, another study that included infants as young as 26 weeks gestational age found that cerebral oxygenation was improved in the supine compared with prone sleep position, with the maximal effect of sleep position at two to three months chronologic age [65]. A direct connection between cerebral oxygenation and arousal response or SIDS risk has not been established. If the risk/benefits balance favors prone positioning in the setting of a neonatal intensive care unit (NICU), infants should be transitioned to supine positioning prior to discharge. (See "Discharge planning for high-risk newborns", section on 'Medical readiness'.)

The importance of supine sleep position for premature infants was demonstrated in a population-based case-control study in England, in which the parents of 325 SIDS cases and 1300 age-matched control infants were interviewed [61]. In multivariate analysis, infants who were small at birth (<37 weeks and/or <2500 g) were five times more likely to die of SIDS than infants who were born at term or >2500 g. However, when infants who were small at birth were placed to sleep on their side or prone, they were 15 and 24 times more likely, respectively, to die of SIDS than infants who were not small at birth who were placed on their backs to sleep.

●Low birth weight – Infants born small for gestational age have an increased risk for SIDS [8,61,66]. Low birth weight has a weak but significant association with SIDS risk, even after adjustment for gestational age and several other factors known to be associated with low birth weight, including maternal pregnancy-induced hypertension and tobacco use.

●Sibling of a SIDS victim – Siblings of SIDS victims have a five- to sixfold increase in risk for SIDS [67-70]. However, assuming a SIDS rate of 0.56 per 1000 live births (0.06 percent) [17,18], the risk in subsequent siblings for most families remains less than 1 percent.

The small but increased risk of SIDS in siblings of SIDS victims is probably due to a combination of biologic and/or epidemiologic factors. However, it has not been possible to identify the relative importance of these factors, because many of the risk factors for SIDS are the same as those for other causes of infant mortality [67]. In some cases, for example, deaths from inborn errors of metabolism may have been mistaken for SIDS. In other cases, the deaths may have resulted from child abuse or were in some way related to severe deprivation and poverty [71]. (See "Sudden unexpected infant death including SIDS: Initial management", section on 'Differential diagnosis'.)

●Twins – In cohort studies, linking data from birth and death records, the crude risk of SIDS among twins is approximately twice that of singletons [6,7,72]. The increased risk is in part attributable to the higher proportion of twins that are preterm and/or of low birth weight [6,7]. However, in subset analyses of some studies, the risk of SIDS among twins born at ≥37 weeks gestation [72] or with birth weight ≥3000 g [7] remained increased compared with singletons as described below:

•37 to 38 weeks – Relative risk (RR) 1.31

•39 to 40 weeks – RR 1.47

•≥41 weeks – RR 2.09

•Birth weight ≥3000 g – RR 2.98

●History of apnea – Apnea or otherwise impaired respiratory function likely falls within the final common pathway of many of the proposed mechanisms for SIDS. However, a history of apnea, apparent life-threatening event (now called brief resolved unexplained event [BRUE]), or other abnormalities in breathing patterns are not clinically useful predictors of SIDS risk, and monitoring for apnea using standard cardiorespiratory monitors does not appear to reduce SIDS risk [5]. (See "Use of home cardiorespiratory monitors in infants" and "Acute events in infancy including brief resolved unexplained event (BRUE)", section on 'Prognosis'.)

This was illustrated by the following studies:

•In case-control studies, a history of apnea or cyanosis is not specifically increased in SIDS victims [26]. Approximately 5 percent of parents whose infant died of SIDS recall cyanotic episodes during the months before death, but this not substantially different from parent recall of cyanotic episodes in control infants and may be influenced by recall bias.

•Prospective studies have failed to identify respiratory abnormalities that correlate with known SIDS risk factors: In a large series of infants followed longitudinally with cardiorespiratory monitors, neither "conventional" (apnea 20 to 30 seconds) nor "extreme" events (apnea >30 seconds) correlated with the primary epidemiologic risk factors for SIDS, including the time at which the apnea occurred and the infant's age [73]. (See "Management of apnea of prematurity".)

Sleep position — The prone sleeping position is the strongest modifiable risk factor for SIDS. In case-control studies, ORs for the risk of prone sleeping or non-supine sleeping range between 2.3 and 13.1 [12,20]. Additional support for this association comes from the decreased rate of SIDS in various countries following recommendations to place infants on their back or side to sleep [15,17,18,74-76]. Supine positioning also is beneficial for infants born prematurely, as discussed above. (See 'Infant risk factors' above.)

Avoidance of side positioning is also important, perhaps because the probability of rolling from the side to the prone position is greater than that of rolling from the supine to the prone position (see 'Epidemiology' above) [77-80]. As the proportion of infants placed to sleep in the prone position has decreased, the relative contribution of side-sleeping to SIDS risk has increased [61,77,81-84], as suggested by the following studies:

●In a population-based case-control study, the risk of SIDS was increased for infants placed on the side and found in the prone position (adjusted OR 8.7) [82]. In the same study, the risk of SIDS was also increased among infants who were usually placed supine but were placed on their sides or prone for the last sleep (OR 6.9 and 8.2, respectively).

●Other case-control studies have demonstrated an increased risk of SIDS when infants unaccustomed to the prone position are placed in the prone position [85,86].

●A population-based study noted decreases in SIDS mortality associated with non-prone sleep positioning and documented further decreases associated with specifically supine positioning of infants for sleep [87].

●Use of infant "sleep positioners" to position infants on their side has also been associated with several cases of infant deaths, as reported in a safety alert by the US Food and Drug Administration [88]. Between 1997 and 2011, the deaths of 13 infants in the United States were linked to use of infant sleep positioners [89]. Most of the infants had been placed on their sides in the positioner to sleep and were found prone or with the positioner against their faces.

The increased risk among infants unaccustomed to the side or prone position highlights the importance of supine positioning for every sleep [5].

Sleep environment — Various aspects of the sleep environment, including the sleep surface, sleepwear, bedding, room temperature, and whether or not the bed or room is shared with parents also appear to affect the risk of SIDS, as illustrated below.

●Soft sleeping surface – Use of a soft sleeping surface is a consistent risk factor for SIDS in several case-control studies, especially in association with prone positioning [90,91]. In one study, soft bedding increased the risk of SIDS fivefold and the combination of prone positioning and soft bedding increased the risk 21-fold (95% CI 7.8-56.2) [92]. Other forms of soft bedding (eg, sofa or recliner chair, polystyrene beads, air mattresses, or natural fiber mattresses) also have been associated with an increased risk of SIDS [93-97]. Sheepskin bedding has been associated with an increased risk for SIDS when infants are placed in the prone position [98,99]. Sleep surfaces marketed commercially with claims that they reduce SIDS risk have not been adequately tested for either safety or benefit [5].

●Loose bedding accessories – Loose bedding accessories such as blankets, quilts, pillows, stuffed toys, and sheepskins also increase the risk of SIDS by as much as fivefold, independent of sleeping position [91,100,101]. The association appears to be mediated by the soft objects covering the head or otherwise obstructing airflow [102,103]. These are particularly important risk factors in older infants because they can roll onto the soft objects [5,104].

●Crib bumper pads – In particular, crib bumper pads have been associated with infant deaths by "suffocation," including at least 48 infant deaths in the United States over a seven-year period from 2006 to 2012 [105,106]. This rate appears to be increasing, despite recommendations against the use of bumper pads by the AAP, Canadian Paediatric Society (CPS), and others [5,107].

●Bed-sharing – A variety of studies report an association between SIDS risk and infants sharing a bed with their parents [80,91,108-113]. In a meta-analysis, the combined OR for bed-sharing versus non-bed-sharing infants was 2.89 (95% CI 1.99-4.18) [110]. The risk of bed-sharing was greatest for infants younger than three months of age (OR 10.37, 95% CI 4.44-24.21) or for infants of mothers who smoke (OR 6.27, 95% CI 3.94-9.99). Similar findings were reported in a large meta-analysis that included 1472 cases of SIDS and 4679 controls from the United Kingdom, Europe, and Australasia [114]. Although overall SIDS rates were low, bed-sharing significantly increased SIDS risk in young infants even with no other SIDS risk factors. For infants younger than three months of age, the adjusted OR for bed-sharing was 5.1 (95% CI 2.3-11.4). The risk attributable to bed-sharing was increased up to 15-fold in infants with additional SIDS risk factors, including bottle-feeding and parental smoking and drinking. In addition, there is a consistent association between increased risk of SIDS and sharing a couch or sofa with parents during sleep [21,92,108,109,115]. Other factors that increase the risk of bed-sharing include soft sleeping surfaces, additional bedding such as pillows and blankets, the presence of multiple bed-sharers, and consumption of alcohol by the bed-sharing adult [5].

The issue of bed-sharing has been controversial. This is in part because the risk of bed-sharing may be relatively low if none of the additional risk factors outlined above are present and because of potential beneficial effects of bed-sharing on breastfeeding or parental sleep [116-119]. In addition, bed-sharing is a common practice in many cultures: in one study from the United States, 13.5 percent of families with young infants reported bed-sharing as a usual practice in 2010, up from 6.5 percent in 1993 [120]. Nonetheless, we agree with the AAP recommendation against bed-sharing, although room-sharing is encouraged [5]. This is because bed-sharing usually means that the infant sleeps on a surface that is designed for adults and because some of the other factors that contribute to the risk of bed-sharing cannot be predicted or controlled. Moreover, breastfeeding and parental sleep can still be supported by room-sharing. For convenience, the infant's bed or bassinet can be placed in close proximity to the parents' bed. There is no evidence to suggest that the risk of bed-sharing can be reduced by the use of "co-sleeper" devices that are placed within the parents' bed [20].

Guidelines in the United States and Australia suggest that twins and higher-order multiples also not sleep in the same crib, although this is a common practice [5,121,122]. This suggestion is based on a lack of evidence for either the safety or benefits of bed-sharing by twins and because these infants are likely to have other risk factors for SIDS, such as low birth weight and/or prematurity.

●Car safety seats and other sitting or inclined rocking devices – Use of a car safety seat or other sitting device (stroller, swing, or infant carrier) for sleep has been associated with some sleep-related infant deaths [20,123]. This may be because the sitting position may reduce oxygenation in young infants [124-126]. In addition, some cases have been reported in which an infant suffered suffocation after a car seat accidentally overturned when placed on a soft bed or couch [127]. Other deaths have been associated with the use of sling carriers (adult-worn soft infant carriers) for young infants [128,129]. In addition, infant deaths have been associated with inclined or rocking sleeper devices (Fisher-Price Rock 'n Play Sleeper, Kids II Inclined Sleepers, and others), which have been recalled and removed from the market [130].

Use of a car seat for car travel has safety benefits that clearly outweigh the small risk of SIDS associated with sleep in these devices. Therefore, the AAP recommends against routine use of car seats for sleep outside of a car [5] but continues to strongly recommend their use for car travel [131].

●Overheating – The risk of SIDS increases with the amount of clothing or blankets on an infant and with room temperature, but it is not clear whether these risks are mediated by head-covering and rebreathing or by overheating [5]. In a population-based case-control study among Northern Plains American Indians, SIDS was significantly associated with two or more layers of clothing on the infant (adjusted OR 6.2, 95% CI 1.4-26.5) [50]. Another study noted an increased risk with swaddling or in heated rooms [94].

●Swaddling – Swaddling appears to increase the risk for SIDS, especially for older infants and those who are not placed in a supine position for sleep. In a meta-analysis, based on limited data, the risk of placing an infant on their side or prone for sleep doubled when the infants were swaddled and the added risk from swaddling increased with age [132]. This may be because older infants may attempt to turn over and swaddling prevents an infant from moving out of an unsafe sleeping position. Swaddled infants are less likely to be aroused by external stimuli, but this effect is not seen in infants who are routinely swaddled, and it is unclear if this is clinically relevant in infants who are in the supine position [133,134].

Protective factors — The following factors are somewhat protective against SIDS. However, these effects are generally weak and are outweighed by the modifiable risk factors described above.

●Breastfeeding – Breastfeeding appears to have an independent protective effect against SIDS [135]. In a meta-analysis of eight case-control studies with individual-level data, any breastfeeding for at least two months nearly halved the risk for SIDS, after controlling for potential confounders, such as sleep position, bed-sharing, smoke exposure, and sociodemographic factors [136]. Protection increased with greater duration of breastfeeding; however, exclusive breastfeeding did not confer additional benefits over partial breastfeeding with regards to SIDS reduction. In a separate study of more than 3 million births in the United States, any breastfeeding was associated with a 15 percent reduction in SUIDs including SIDS during the post-perinatal period (28 to 364 days) [137]. (See "Infant benefits of breastfeeding", section on 'Mortality and hospitalization'.)

Of note, lower rates of breastfeeding explain only a very small component of the increased SIDS risk experienced by non-Hispanic Black and American Indian/Alaskan Native groups in the United States [138]. Instead, the disparity in SIDS risk is more likely to be related to other social/structural determinants of health.

●Room-sharing – Room-sharing, without bed-sharing, between parents and infants appears to reduce the risk of SIDS [12,92,108,109,115]. As an example, a case-control study from a large administrative database reported that infants who did not share a room with their parent/caregiver were more likely to die of SIDS (adjusted odds ratio [aOR] 7.6, 95% CI 4.7-12.2) or sleep-related suffocation (aOR 18.7, 95% CI 6.8-51.3) than infants who did share a room with their parent/caregiver [139]. The analysis adjusted for other variables, including sleep practices such as sharing a sleep surface, to assess the independent effect of room-sharing.

This was also illustrated by a case-control study from New Zealand in which 393 infants who died from SIDS were compared with 1592 controls, and the relative risk associated with sleeping in the prone position was reduced by approximately 80 percent if the infant slept in the same room as an adult [140]. A similar reduction in the risk of SIDS was not seen if the infant shared a room with another child.

The mechanisms by which room-sharing with a parent/caregiver may protect an infant from SIDS are unclear. However, having the infant sleep in close proximity to the mother (but on separate surfaces) supports breastfeeding. The optimal age to transition an infant to sleep outside the parents' room has not been established. (See 'Sleep position and environment' below.)

●Pacifier use – Use of a pacifier ("dummy," "soother") during sleep appears to reduce the risk of SIDS. This was shown in a meta-analysis of seven studies, in which the pooled OR was 0.71 (95% CI 0.59-0.85) for usual pacifier use and 0.39 (95% CI 0.31-0.50) for pacifier use during last sleep [141]. The mechanism for this association is unclear; studies conflict as to whether there is a lowered arousal threshold during pacifier use [142-145] (see 'Pathogenesis' below).

●Fan use – In a population-based case-control study performed in California, use of a fan was associated with a 72 percent reduction in SIDS risk (adjusted OR 0.28, 95% CI 0.10-0.77) [146]. The effect was greater for infants with other environmental SIDS risk factors, including prone or side sleeping, bed-sharing, and warmer room temperature. The study was limited by low participation rates and recall bias and needs confirmation by prospective studies.

●Immunizations – SIDS is not associated with diphtheria-tetanus-pertussis (DTP) vaccine or other vaccines [147-149]. In fact, immunization may lower the risk of SIDS [150-153].

PATHOGENESIS — A triple-risk model for SIDS has been proposed, suggesting that SIDS occurs in infants with underlying vulnerability (eg, genetic pattern, brainstem abnormality) who experience a trigger event (eg, airflow obstruction, maternal smoking, or infection) at a vulnerable developmental stage of the central nervous or immune system [154,155]. In one study, 95 percent of the infants dying of SIDS had one or more additional risk factors for SIDS (eg, prone position, intercurrent illness before death, male sex, or prematurity) and 88 percent had two or more risk factors [156]. These observations underscore the notion that SIDS results from the simultaneous occurrence of multiple events.

Underlying vulnerability

Brain abnormalities — Emerging evidence suggests that a brainstem abnormality or maturational delay related to neuroregulation of cardiorespiratory control is a critical contributor to the pathogenesis of SIDS. This hypothesis is suggested by the following findings:

●Maternal and antenatal risk factors indicating a less than optimal intrauterine environment have been described for infants who later died of SIDS [26,157,158]. These observations suggest that the presumed brain disorder may originate before birth. (See 'Maternal risk factors' above.)

●Subtle abnormalities in the regulation of cardiac, respiratory, and sleep arousal patterns have been observed in infants who subsequently succumbed to SIDS [159,160].

Abnormalities in serotonin (5-hydroxytryptamine [5-HT]) signaling in the brain have been implicated as a mechanism. Several studies of infants who succumbed to SIDS have demonstrated subtle alterations or "delayed maturation" in the arcuate nucleus and other regions of the brain that participate in ventilatory and blood pressure responses to hypoxia and hypercarbia [161-165]. Furthermore, specific abnormalities of serotonin signaling have been shown, including decreased 5-HT(1A) receptor binding in the medullary areas [156,166,167]. Male infants had particularly low binding, consistent with the clinical observation of a male predominance in SIDS cases [167]. Affected infants appear to have a deficiency in serotonin and its key biosynthetic enzyme, tryptophan hydroxylase, in the medulla [156]. Because serotonin signaling in the medulla is known to influence a broad range of autonomic processes, these findings are consistent with the hypothesis that SIDS is related to serotonin-mediated dysregulation of the autonomic nervous system. Furthermore, serotonin signaling is altered by exposure to nicotine [166,168], providing a potential explanation for the association between maternal smoking and SIDS risk.

Genetic factors — The role that genetic factors play in susceptibility to SIDS is not clear. On the one hand, the overall low rate of SIDS in siblings, the lack of concordance in twins, and the finding that like-sex twins are at no greater risk than unlike-sex twins [6,7] suggest that SIDS is not a genetic disorder. On the other hand, the identification of gene polymorphisms in SIDS victims suggests that specific genetic polymorphisms may interact with specific environmental risk factors to increase the susceptibility to SIDS in critical situations [169,170]. Specific genetic polymorphisms in the following genes have been proposed to play a role in SIDS [169,170]:

●Genes encoding cardiac ion channels, such as SCN5A, KCNQ1, KCNH2, or RYR2 [171-177], or proteins involved in myocardial conduction [178] – These account for less than 5 percent of SIDS cases [177] (see "Congenital long QT syndrome: Epidemiology and clinical manifestations").

●Genes encoding skeletal muscle sodium channels, such as SCN4A [179].

●Serotonin transporter gene [180-184], or monoamine oxidase A (MAOA) gene, which affects serotonergic and noradrenergic transmission [185,186].

●Genes involved in the development of the autonomic nervous system [187,188].

●Partial deletions of complement component C4 [189].

●Interleukin-10 promoter gene [190-192].

●Testis-specific Y-like gene [193], which is expressed in the fetal brain [194].

●Genes encoding heat shock proteins [182,195].

Environmental triggers — Little is known about the mechanism of death in SIDS. One report described heart rate and respiratory effort wave form data recorded by memory monitors in three children who died while being monitored and whose autopsies reported SIDS as the cause of death [196]. Bradycardia, not apnea, was the predominant feature in these infants' deaths. One major caveat to interpreting this report is that the home monitors could not have detected obstructive apnea and did not record oxyhemoglobin saturation data.

●Prone position – The mechanism for the increase in SIDS risk with the prone position is not known. Some studies have suggested that the prone position predisposes to suffocation, precipitated by decreased arousal [197-200], the type of bedding, and overheating [77,90,93,94,201,202].

Decreased arousal in the prone position was suggested by a study of Belgian infants, in which prone sleep position was associated with longer duration of sleep, longer obstructive events, decreased behavioral arousal, longer interval between obstruction and arousal, and overall decreased reaction (arousal or sigh) to obstructive events [197]. In another study, arousal thresholds during both active and quiet sleep were higher in infants younger than five to six months of age [198]. Measures of cerebral oxygenation are lower in the prone compared with supine position, particularly in preterm infants [65], but an association between cerebral oxygenation and arousal threshold has not been established.

Accidental suffocation in the prone position was suggested by a study of 25 infant deaths that occurred during sleep in the prone position on cushions filled with polystyrene beads; accidental suffocation by rebreathing was found to be the most likely cause of death in most of the infants [93]. The cushion was thought to allow limited movement of the infant's head to obtain fresh air, and the estimated amount of subsequent rebreathing was lethal in a rabbit model. Similarly, in a study of 393 cases of SIDS in New Zealand, infants who were found in the prone position with their face down were more likely to be younger, have a low birth weight, and to have used sheepskin bedding or pillows as compared with infants with SIDS found in other positions (prone with face to side, supine, or side) [203]. This finding suggests that infants dying of SIDS in the face down prone position represent a distinct subgroup and that the mechanism of SIDS may differ depending on specific circumstances related to the infant's sleeping position.

●Cardiac dysfunction – Some studies have suggested that the control of cardiac function may be abnormal in infants at risk for SIDS, but results have been inconsistent. One large prospective study found mildly increased heart rates in infants who subsequently died of SIDS [204]. Others have described prolonged QT intervals on electrocardiographic analysis [205] or sodium channel mutations associated with long QT syndrome in postmortem tissues [206,207]. However, given the limitations of small sample sizes in cross-sectional studies of rare conditions, the incidence and role of cardiac abnormalities in SIDS remain controversial. Based on a study of the prevalence of functionally significant genetic variants associated with long QT syndrome, such abnormalities appear to be present in fewer than 10 percent of SIDS cases. (See "Congenital long QT syndrome: Epidemiology and clinical manifestations", section on 'Sudden infant death syndrome'.)

●Infection – Infection is clearly the cause in a subgroup of explained sudden unexpected deaths in infancy, but its role in SIDS remains unclear [208]. Autopsy findings in infants dying from SIDS have some similarities with those of infants dying of toxemic shock, although there may be minimal inflammatory tissue reaction. This raises the possibility that some cases of SIDS may have an infectious trigger, leading to a toxic shock-like event [209,210]. Implicated organisms include enteric bacteria (enterotoxigenic Staphylococcus aureus and Escherichia coli) and mild viral infections [209-211]. Variations in the innate immune system, including polymorphisms that result in an exaggerated proinflammatory response, have been found in a higher proportion of SIDS cases than in controls [190,192,209]. (See 'Genetic factors' above.)

Distinguishing between autopsy findings that represent perimortem contamination and those that suggest infection as a trigger for SIDS is challenging and controversial. More than 70 percent of postmortem bacteriologic samples grow organisms when cultured, but this is not sufficient to attribute infection as a cause or trigger for death. However, one well-conducted study found that infants dying of SIDS were more likely to harbor organisms that are potentially pathogenic as compared with infants dying from clearly noninfectious causes (eg, accidents or congenital heart disease) [212]. The bacterial colonization documented in this study could also be explained as an epiphenomenon, caused by another established epidemiologic risk factor for SIDS such as prone sleeping, but not directly implicated as a cause of death.

Developmental timing — SIDS usually occurs between the second and fourth months of life, a period of remarkable developmental changes in cardiac, ventilatory, and sleep-wake patterns in otherwise normal infants. This coincidence of timing suggests that infants are vulnerable to sudden death during a critical period of autonomic maturation [213].

PREVENTION — All parents and caregivers of infants should be advised about how to minimize risk for SIDS, especially regarding safe sleeping position and environment [214-216].

The approach outlined in the following sections is generally consistent with the recommendations of the American Academy of Pediatrics (AAP) [5], the Canadian Paediatric Society (CPS) [215], and/or the United Kingdom Department of Health and Social Care [216-218]. The recommendations apply to infants up to one year of age. (See 'Society guideline links' below.)

The evidence supporting these recommendations are primarily case-control studies, as described above. (See 'Risk factors' above.)

Prenatal measures — (See 'Maternal risk factors' above.)

●Smoking and other substances – Mothers should avoid use of tobacco, alcohol, and illicit drugs during pregnancy, as well as after birth.

●Prenatal care – Pregnant women should receive regular prenatal care.

Sleep position and environment — Clinicians should give anticipatory guidance to all caregivers of young infants about each of the following practices for safe infant sleep (figure 1). Unfortunately, receipt of such counseling appears to be inconsistent, especially for aspects other than supine sleep position [219], and unsafe sleep practices remain common. (See 'Limited adherence to safe sleep guidance' below.)

●Supine sleep position – All infants, including infants with a history of prematurity, should be placed to sleep on their backs (supine) for every sleep, even if they are able to roll from their backs to the prone position [216,220]. Side sleeping is not recommended. (See 'Sleep position' above.)

•The recommendation for supine sleeping also applies to infants with gastroesophageal reflux because normal infants effectively protect their airway after an episode of reflux. A rare exception is an infant with impaired swallowing mechanisms due to neurologic dysfunction. The head of the mattress should not be elevated, because this is not effective for reducing reflux. (See "Gastroesophageal reflux in infants", section on 'Additional options for infants with problematic GER'.)

•Sitting devices, including car seats, infant carriers, strollers, and swings, should not be used for routine sleep. (See 'Sleep environment' above.)

•Infant "sleep positioners" (wedges and other positioning devices) should not be used, as described in an US Food and Drug Administration Safety Alert [88].

•If swaddling is used, it should be discontinued as soon as the infant is old enough to attempt to roll over. It is particularly important to avoid non-supine sleep for swaddled infants [132].

•Infants should be placed supine for sleep throughout the first year of life. After six months of age, the risk of SIDS decreases substantially but is not eliminated (see 'Epidemiology' above). Once the infant can roll from supine to prone and from prone to supine, the infant can be allowed to remain in the assumed sleep position [5]. However, especially when infants first start to roll over, there is a concern that those who roll prone may not be able to roll back, particularly if there is soft bedding present [104]. Therefore, it remains important to avoid having soft or loose bedding in the infant's sleep environment to prevent suffocation or entrapment if the infant rolls. For the same reason, the parent should not use bedding, pillows, or devices to try to keep the infant in a particular sleep position.

●Firm sleep surface – Infants should always be placed to sleep in a crib or bassinet on a firm, flat, noninclined surface that is certified for use as infant bedding.

The following sleep surfaces are unsafe for infant sleep and should be avoided (see 'Sleep environment' above):

•Any bed designed for older children and adults, including those with bed rails. Similarly, an air mattress or air bed is not safe for infant sleep, even when "firm" (or fully inflated) [96,97].

•Soft sleep surfaces, including sofas, polystyrene-filled cushions, and sheepskin bedding.

•Sleep surfaces with inclines of >10 degrees, as they can cause wedging or entrapment.

●Room-sharing without bed-sharing – For young infants, the lowest risk sleep environment is sleeping in the parents' room in a crib, bassinet, or other sleep surface designed for infants (not the parents' bed) (figure 2). We encourage room sharing for the first six months after birth, though the optimal duration has not been established [221]. Infants should NOT sleep in or share the parents' bed or on a sofa, recliner, armchair, or other type of cushioned chair.

In a study in infants four to nine months of age, longer duration of room-sharing was associated with shorter total sleep time and longest single sleep period, as well as a higher rate of bed-sharing [222]. These findings suggest a need for research to better understand consequences of room-sharing on parental and infant sleep and other potential unintended consequences of this recommendation aimed at minimizing the risk of SIDS. (See 'Protective factors' above.)

●Avoid soft objects and bumper pads in the bed – Soft bedding accessories such as pillows, stuffed toys, sheepskins, and blankets should be kept out of the crib, bassinet, or cradle. Bumper pads appear to be particularly dangerous and should not be used. The infant's head should remain uncovered. Avoiding use of these accessories is particularly important after three months of age because rolling onto soft bedding is an important risk factor in older infants [20]. Infant sleep clothing ("sleeper" or "sleep sack") is a safe alternative to a blanket, provided that the sleep clothing is appropriately sized and selected to avoid overheating. (See 'Sleep environment' above.)

●Avoid overheating – Overheating should be avoided; the infant should be lightly clothed for sleep, and the bedroom temperature should be comfortable for a lightly clothed adult. If the infant is dressed in a sleeper, a blanket should not be necessary. Infants should not sleep next to a radiator or heater or in direct sunshine. (See 'Sleep environment' above.)

●Pacifier use – We suggest offering a pacifier at sleep initiation because of some evidence that this is protective against SIDS, even if the pacifier subsequently falls out of the infant's mouth. (See 'Protective factors' above.)

The pacifier should not be attached to a strap or cord, because this can present a strangulation risk. It should be used when placing the infant to sleep but not reinserted once the infant is asleep. The AAP suggests delaying the introduction of the pacifier in breastfed infants to ensure that breastfeeding is firmly established [223]. There is some concern that pacifier use may increase the risk of acute otitis media [224]. However, the incidence of acute otitis media is relatively low during the first six months of life, when the risk of SIDS is greatest. (See "Breastfeeding: Parental education and support" and "Acute otitis media in children: Epidemiology, microbiology, and complications", section on 'Risk and protective factors'.)

Limited adherence to safe sleep guidance — Unfortunately, unsafe infant sleep practices remain common in some populations, despite public education campaigns [120,219,225-231]. As an example, in a population from central Pennsylvania, non-supine sleeping positions were used for 14 percent of one-month-old infants, rising to 18 percent at three months and 33 percent at six months [226]. Moreover, potentially hazardous items were noted on the sleep surface in approximately 90 percent of the observed infants in each age group. In the United States, parent-reported adherence to the supine sleeping position recommendation gradually improved between 1991 and 2015 to approximately 80 percent (with significant disparity among races) but has not reached target levels [228-231]. Moreover, fewer than one-half of caregivers "always" place their infant in a supine sleeping position, demonstrating poor consistency in using supine sleep position in the United States [228]. Efforts to change other risk factors such as bed-sharing and soft bedding use have been less effective [120,225]. In 2015, more than one-half of respondents reported sharing their bed with their infant at eight weeks postpartum [229]. A large survey in the United States found that most parents recalled receiving advice from their clinician regarding the back sleep position (93 percent) but were less likely to recall advice about avoiding soft objects in the bed (85 percent), safe sleep surfaces (84 percent), or room-sharing without bed-sharing (50 percent) [219].

These observations underscore the need for effective educational interventions that reach a range of populations, including consistent counseling by clinicians about safe sleep practices. Available educational resources include training videos for families, childcare providers, and medical professionals, available from the National Center for Education in Maternal and Child Health (NCEMCH) [232]. Added benefits of using targeted electronic messaging to deliver SIDS-related education was shown in a large cluster-randomized trial, in which a series of health messages and short educational videos were delivered to parents of young infants by text message or email [233]. The intervention significantly increased self-reported adherence to supine sleep (89 versus 80 percent) as well as room-sharing without bed-sharing, no soft bedding use, and pacifier use. This randomized study also demonstrated that the improved adherence to supine sleep and room-sharing without bed-sharing was mediated by changing maternal attitudes and perception of social norms [234].

Hospital setting

●Perinatal care and precautions – Immediately after birth, the infant should be given to the mother for skin-to-skin contact [235]. Professional staff should instruct and observe closely during skin-to-skin contact and breastfeeding to ensure that the infant's face is clear, the airway is not obstructed, and the mother remains alert [5]. Thereafter, infants should be placed supine in a bassinet. Side positioning does not reduce aspiration risk and is not recommended. These measures serve to promote breastfeeding while minimizing risks for SIDS and suffocation. Sudden unexpected deaths in the perinatal period are rare but have been reported [24,27]. Moreover, safe sleeping practices in the newborn nursery are important because appropriate role modeling by nursery staff increases maternal adherence to recommendations [236]. (See "Initiation of breastfeeding".)

●Other hospital care – Hospitals should develop specific policies on safe infant sleeping conditions, including maintaining a flat and completely empty sleeping surface, appropriate supine positioning, and avoidance of excessive bundling. One study in a general pediatrics ward reported that most infants were exposed to unsafe sleeping conditions during the hospital stay [237]. A quality-improvement intervention resulted in substantial improvement in the practices but did not significantly change adherence to safe sleeping practices after discharge.

Other measures

●Smoking and other substances – Mothers should avoid smoking, alcohol, and illicit drug use after birth as well as during pregnancy. Postnatal exposure of infants to tobacco smoke should be avoided; providers should encourage the parents to quit smoking and to set a firm rule against smoking in the house or car. (See 'Maternal risk factors' above and "Secondhand smoke exposure: Effects in children", section on 'Sudden infant death syndrome' and "Control of secondhand smoke exposure", section on 'The home environment'.)

●Breastfeeding – Breastfeeding is recommended for possible effects on reducing the risk of SIDS, in addition to other benefits. (See 'Protective factors' above and "Infant benefits of breastfeeding".)

●"Tummy time" – Prone positioning is encouraged when the infant is awake and observed to facilitate the development of shoulder girdle strength and avoidance of occipital plagiocephaly [116]. (See "Overview of craniosynostosis".)

No benefit from home monitors — The available evidence does not support the use of home cardiorespiratory (CR) monitors in SIDS prevention, and the AAP recommends against prescribing home monitors for this purpose [5]. In addition, there is no role for use of direct-to-consumer heart rate and pulse oximetry monitoring devices, including wearable devices, as a strategy for preventing sleep-related infant deaths. There is concern that use of such devices could lead to complacency and decreased adherence to safe sleep practices.

Hypotheses proposed during the 1970s suggested that infants with a history of apnea or an apparent life-threatening event (now called brief resolved unexplained event [BRUE]) are at risk for SIDS, even if they are otherwise asymptomatic, and that death could be prevented by CR monitoring. However, studies done over the past decade have failed to confirm the relationship between SIDS and apnea. Moreover, studies of infants with a history of BRUE and others considered to be at risk for SIDS (such as siblings of SIDS victims) have shown that CR monitors have high rates of false alarms and they do not appear to prevent SIDS deaths. These issues are discussed in detail separately. (See "Use of home cardiorespiratory monitors in infants" and "Acute events in infancy including brief resolved unexplained event (BRUE)", section on 'Prognosis'.)

Counseling parents of asymptomatic infants with risk factors for SIDS who request a home monitor may be challenging. If parents are concerned about SIDS and request a monitor, we suggest that the clinician engage them in a focused conversation about the potential benefits and risks of using a home monitor before making the decision. (See "Use of home cardiorespiratory monitors in infants", section on 'Asymptomatic infants with risk factors for sudden infant death syndrome'.)

A new class of smartphone-integrated infant physiologic monitors are being marketed directly to consumers; these have sensors built into socks, clothing, or diaper clips [238]. There is no evidence that these devices have any benefit for prevention of SIDS or any other risk. A trial of two of these commercial devices in hospitalized infants revealed poor correlation with standard pulse oximeter readings, resulting in many false-positive and false-negative readings for both oxygen desaturation and bradycardia [239]. Device manufacturers avoid making direct statements about disease prevention, so the devices are not subject to regulation as medical devices in the United States.

Use of home CR monitors (whether it be a medical device or direct-to-consumer product) has several downsides:

●First, marketing strategies may make parents unnecessarily fearful of SIDS risk.

●Second, parents might feel falsely reassured by the use of such devices and be less likely to adhere to safe sleep practices.

●Third, false-positive alarms in healthy infants can lead to anxiety, over-diagnosis, and unnecessary testing.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sudden unexpected infant death including SIDS".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Sudden infant death syndrome (SIDS) (The Basics)")

●Beyond the Basics topics (see "Patient education: Sudden infant death syndrome (SIDS) (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Definition – Sudden infant death syndrome (SIDS) is defined as the sudden death of an infant less than 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. (See 'Definition' above.)

●Epidemiology – SIDS is the leading cause of infant mortality between one month and one year of age in the United States. The rate of SIDS peaks between two and four months of age, and 90 percent of cases occur before six months of age. Approximately 12 percent of sudden unexpected infant deaths (SUIDs) occur during the neonatal period and 4 percent during the first week of life. (See 'Epidemiology' above.)

●Mechanism – The mechanism of sudden death is unknown. The most compelling hypothesis involves a brainstem abnormality or maturational delay related to neuroregulation or cardiorespiratory control, combined with a trigger event such as airflow obstruction. The mechanism most likely involves abnormalities of serotonin (5-hydroxytryptamine [5-HT]) signaling. (See 'Pathogenesis' above.)

●Risk factors – Identified risk factors for SIDS include (table 2) (see 'Risk factors' above):

•Exposure to cigarette smoke

•Maternal age <20 years

•Prematurity (apnea of prematurity is not an independent risk factor)

•Prone sleeping position

•Soft bedding

•Overheating

●Practices to minimize risk of SIDS – Clinicians should give anticipatory guidance to all caregivers of newborns and young infants about safe sleep practices for infants to minimize the risk for SIDS. Unfortunately, receipt of such counseling appears to be inconsistent, especially for aspects other than supine sleep position, and unsafe sleep practices remain common. (See 'Limited adherence to safe sleep guidance' above.)

Appropriate counseling includes each of the following measures (see 'Sleep position and environment' above):

•Supine sleeping – We recommend that all infants be placed on their backs (supine) for every sleep (Grade 1B). Side sleeping is not recommended. These recommendations apply to term infants and preterm infants starting at 32 weeks postmenstrual age or earlier. (See 'Sleep position' above.)

•Safe sleep environment – Additional safe sleep practices include (figure 1) (see 'Sleep environment' above and 'Sleep position and environment' above):

-Infants should sleep on a firm sleep surface designed specifically for infants (crib, cradle, or bassinet)

-Do not place pillows, stuffed toys, or other soft objects in the crib

-Do not use crib bumper pads, blankets, loose bedding, excessive clothing, or sleep positioners

-Infants should not sleep on an air mattress/air bed, even if it is fully inflated

-Bed-sharing should be discouraged; however, room-sharing (sleeping in the parents' room but not in the parents' bed (figure 2)) may reduce the risk of SIDS

•Parental smoking cessation – Expectant mothers should avoid smoking during pregnancy because of effects on SIDS risk, in addition to other adverse effects of smoking. Exposure of an infant to secondhand smoke after delivery also probably increases SIDS risk. Maternal smoking cessation is discussed separately. (See 'Maternal risk factors' above and 'Other measures' above and "Tobacco and nicotine use in pregnancy: Cessation strategies and treatment options".)

•Breastfeeding – Breastfeeding should be encouraged for its beneficial effect on reducing SIDS risk and for its other established benefits, as discussed separately. (See "Infant benefits of breastfeeding".)

●No benefit from home monitors – The use of home cardiorespiratory (CR) monitors is not an effective strategy for reducing the risk of SIDS. CR monitors have high rates of false alarms and they do not appear to reduce the incidence of SIDS. These issues are discussed separately. (See "Use of home cardiorespiratory monitors in infants".)