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Duncan JR, Byard RW, editors. SIDS Sudden Infant and Early Childhood Death: The Past, the Present and the Future. Adelaide (AU): University of Adelaide Press; 2018 May.

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SIDS Sudden Infant and Early Childhood Death: The Past, the Present and the Future.

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Chapter 10Risk Factors and Theories

, MD and , MD, MS.

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Introduction

Identification of factors that increase risk of, or are protective against, sudden infant death syndrome (SIDS) has largely been accomplished through epidemiological case-control studies. Risk factors include side and prone positioning, prenatal and postnatal tobacco smoke exposure, sleeping on soft or cushioned surfaces (particularly sofas, couches, and armchairs), bed sharing, soft bedding, head covering and overheating, and prematurity. Protective factors include breastfeeding, pacifier use, and room sharing. In this chapter, we will discuss the evidence for these risk and protective factors. We will also review the leading theories for SIDS causation including the Triple Risk Hypothesis, rebreathing theory, and deficient arousal and autonomic regulation, and how these theories create a plausible explanation for the risk and protective factors for SIDS identified in case-control studies.

Risk Factors

Side and prone sleep position

The prone sleep position was noted in multiple case-control studies to be associated with SIDS (1-6), beginning in 1965 in the United Kingdom (UK) (7). Even before this, in 1944, Abramson reported that prone positioning was found in 68% of young infants who died of accidental mechanical suffocation in New York City (8). Public health campaigns, which first promoted non-prone positioning in the 1980s and then supine placement, only beginning in the 1990s in many Western countries, have all been associated with a decline in SIDS rates. Subsequent studies have confirmed the association of prone sleep positioning and an increased SIDS risk (adjusted odds ratio [aOR] 2.3-13.1) (9-11). Physiologic studies have demonstrated an association of prone positioning with an increased risk of hypercapnia and hypoxia (12-14), overheating (15), diminished cerebral oxygenation (16), altered autonomic control (17), and increased arousal thresholds (18).

Subsequent studies have identified that the risk of side sleep positioning is similar to that of prone positioning (aOR 2.0 and 2.6 respectively) (10). Side positioning also has a higher population-attributable risk than prone positioning (11), likely because many infants who are placed on their side are found prone (10). Placement in, or rolling to, the prone position, particularly when infants are unaccustomed to that position, places infants at extremely high risk of SIDS (aOR 8.7-45.4) (10, 19). Thus all caregivers, including childcare providers, family members, and friends, should place the infant in the supine position for every sleep.

Prenatal and postnatal tobacco smoke, alcohol, and illicit drug exposure

Multiple studies have found that both in utero and environmental tobacco smoke exposure increase the risk of SIDS (20-24) in a dose-dependent manner (25-27). The strongest risk occurs with maternal smoking; there is a small independent risk when fathers smoke after the infant’s birth (23, 28).

While it is difficult to separate out the effects of in utero and environmental smoke exposure, in utero exposure reduces lung compliance and volume, impairs arousal mechanisms, and decreases heart rate variability in response to stress (29, 30), all factors which may negatively impact an infant’s ability to respond appropriately to the environment. Researchers have estimated that one-third of SIDS deaths could be prevented if in utero smoke exposure were eliminated (31, 32).

Substance abuse often involves more than one substance, and it is difficult to separate each effect from the others or to separate it from smoking. In addition, there are few studies that have examined the association between substance use and SIDS. In one study of Northern Plains American Indians, periconceptual maternal alcohol consumption was associated with a sixfold increased risk of SIDS, and binge drinking during the first trimester of pregnancy was associated with an eightfold increase (33). In another study, a maternal alcoholism diagnosis was associated with a sevenfold increased risk (34). Maternal drinking postnatally has also been found to be associated with increased SIDS risk (34, 35), especially when it occurs within the 24 hours prior to the infant’s death. Additionally, although the data for maternal drug use and SIDS are conflicting, overall, maternal prenatal drug use, especially of opiates, is associated with a 2- to 15-fold increased risk of SIDS (36-38). Thus parents should not smoke during pregnancy, and there should be no smoking around the infant. In addition, alcohol and illicit drugs should not be consumed during pregnancy. There is also a substantial risk when smoking or consumption of alcohol or illicit drugs occurs in the context of infant-adult bed sharing (11, 39, 40).

Soft or cushioned sleep surfaces (including sofas, couches, armchairs)

A firm sleep surface, such as a tight-fitting mattress in an infant cot (known in some countries as “cribs”), bassinet, play yard, or portable crib, is the safest sleep surface. Sofas, couches, and armchairs are particularly dangerous sleep surfaces; compared with a crib mattress, these surfaces confer up to 67 times higher risk of infant death (41-43). A recent study in the United States (US) found that deaths on sofas comprised 12.9% of all infant sleep-related deaths in 2004-12, including SIDS, accidental suffocation, and ill-defined deaths (44). Parents should be counseled about the risk of placing the infant for sleep, or falling asleep with an infant, on a sofa, couch, or similarly cushioned surface.

Infants are also often placed to sleep in car seats, strollers, swings, infant carriers, and slings, often because the infant will fall asleep more quickly or because of the belief that sleeping in a sitting position will alleviate gastroesophageal reflux. However, sitting in a car seat or similar sitting device exacerbates gastroesophageal reflux (45) and is thus not recommended for that purpose. Additionally, young infants may not have adequate head control to support their airway when sleeping in such sitting devices, and sleeping in these devices may lead to accidental death (46). Slings are of particular concern in this regard, and infants who are carried in slings should have their heads visible and outside of the sling to minimize the risk of suffocation (47).

Bed sharing

Bed sharing is defined as the infant sleeping on the same surface as another person. The practice of bed sharing is common in many cultures and facilitates breastfeeding (48, 49), which is known to be a protective factor against SIDS (50). However, in case-control studies, bed sharing has been associated with an increased risk of SIDS (39, 41), and it is believed that soft mattresses, other soft bedding, the risk of overheating, and the risk of overlay contribute to this increased risk.

It is clear that there is increased risk of infant death when bed sharing occurs when one or both parents are smokers (even if they do not smoke in the bed), when there was maternal smoking during pregnancy, when the adult bed sharer has drunk alcohol or taken arousal-altering medications or drugs, when the bed sharing takes place on a couch or sofa, when there is soft bedding, when bed sharing lasts for the entire night, and when the infant is <11 weeks of age (11, 39, 40). Indeed, bed sharing was found in one US analysis of infant deaths to be the most important risk factor for death for infants <4 months of age (51).

However, there is controversy about bed sharing for infants who are breastfed and whose parents are non-smokers and have not consumed alcohol, medications, or illicit drugs. Case-control studies have had conflicting conclusions. An individual-level analysis of 19 studies from nine datasets in the UK, Europe, Australia, and New Zealand, with 1,472 SIDS cases and 4,679 controls, found that bed sharing for these low-risk infants was associated with a fivefold increased risk of SIDS in the first three months of life (aOR 5.1, 95% CI: 2.3-11.4) and an eightfold increased risk in the first two weeks of life (aOR 8.3, 95% CI: 3.7-18.6) (52). In this study, there was no increased risk of SIDS if the bed-sharing infant was >3 months old. However, this study has been criticized for the large amount of imputed missing data on parental alcohol and drug use (53). Another analysis of data from two English studies, with 400 SIDS infants and 1,386 controls, found that, although bed sharing with a smoker or an adult who had recently consumed >2 units of alcohol was associated with an increased risk of SIDS, infants younger than 98 days of age who bed shared with an adult who was a non-smoker and did not recently consume alcohol were not at increased risk for SIDS (OR 1.6, 95%: CI 0.96-2.7) (43). Both of these studies are limited by small sample size in the subanalyses (54).

Recommendations regarding bed sharing differ. In the Netherlands, parents are advised not to bed share if the infant is <3 months old. In the US, parents are advised to avoid bed sharing for the first year but instead to have the infant sleep on a separate sleep surface close to the parents’ bed (55). Because there is no increased SIDS risk if bed sharing does not last the entire night (11), parents are encouraged to bring the infant to the bed for feeding and comforting, and then to return the infant to his/her own sleep space when the parent is ready to go to sleep. Other countries, including Australia and the UK, recommend against bed sharing, particularly when the parent is a smoker or has consumed alcohol, drugs, or arousal-altering medication (56, 57).

Soft bedding

The presence of soft bedding, including pillows, blankets, sheepskins, bumper pads, and positioners, in the infant sleep environment has been shown to increase the risk for infant death fivefold, independent of the sleep position, and 21-fold when the infant is in the prone sleep position (9). In addition, the US Consumer Product Safety Commission has reported an increased risk of accidental suffocation and asphyxial deaths associated with soft bedding use (58). Soft bedding increases the risk of overheating and head covering, both of which have been associated with increased SIDS risk. Finally, in an analysis of US child deaths, the presence of soft bedding in the infant sleep environment was reported to be the most important risk factor for sudden and unexpected death in infants 4 months and older (51).

Infants are safest when they do not sleep with blankets (53, 59). If parents are concerned that their infant will become cold, an infant sleeping bag, sleeping sack, or wearable blanket is recommended as an alternative to blankets. A safe infant sleeping bag is one in which the infant cannot slip inside the bag and the head cannot become covered. One Dutch study found that the odds ratio for a sleeping bag was 0.30 (95% CI: 0.13-0.67); however, when adjusted for confounders, the odds ratio was no longer statistically significant (aOR 0.73 (95% CI: 0.29-6.43)) (60). Cot bumpers and similar products that attach to the cot sides are not recommended because of the risk of entrapment between the mattress or cot and the bumper, the risk of suffocation against the bumper, and the risk of strangulation with bumper pad ties (61, 62).

Head covering and overheating

In one case-control study, 24.6% of SIDS victims had their heads covered by bedding, compared with 3.2% of control infants during last sleep (63). Duvets, blankets, and quilts should be avoided in the infant sleep environment, as they may cover the infant’s head or face and obstruct breathing (11, 63).

Prematurity

Infants who are born preterm or with low birth weight are at fourfold risk of SIDS, compared to full term, normal birth weight infants (64, 65). Despite overall declines in SIDS rates, the rates among infants born preterm or with low birth weight still remain higher (66). Much of this may be due to an immature autonomic system, with impaired arousal mechanisms and an increased risk for hypercarbia. The increased SIDS risk does not appear to be related to apnea of prematurity, as there is no evidence that these episodes of apnea precede SIDS deaths (67). The increased risk of SIDS, however, may also be related to prone sleep positioning. Preterm infants are at equal or increased SIDS risk when placed prone (68). Further, they are more likely to be placed prone after hospital discharge, presumably because they were placed prone in the neonatal intensive care unit as a means to improve ventilatory status while requiring mechanical ventilation (69). It is therefore recommended that preterm infants be placed supine as soon as they are clinically stable, so that they and their parents can become accustomed to the supine position before the infant is discharged to home. The American Academy of Pediatrics recommends that this transition to the supine position occur by 32 weeks post-menstrual age (70).

Protective Factors

Breastfeeding

Multiple studies have demonstrated that breastfeeding provides protection against SIDS (50). Studies do not distinguish between direct breastfeeding and feeding with expressed breast milk. A meta-analysis of 18 case-control studies found that any breastfeeding was protective, but that the protective effect increased with increased duration and exclusivity of breastfeeding (50). A recent individual-level analysis of eight case-control studies in the US, Europe, Australia, and New Zealand found that two months of breastfeeding was required before a protective effect against SIDS was seen, and that this protective effect is seen with any amount of breastfeeding, regardless of exclusivity (70). Parents are encouraged to feed the infant with breast milk as much and for as long as possible.

Dummy (pacifier) use

Several case-control studies and meta-analyses have found a strong protective effect with dummy (also known as pacifier) use (71-73). Although the mechanism of protection is yet unclear, proposed mechanisms include increased arousability and improved autonomic control (74). Others note that non-nutritive sucking of the pacifier may alter the upper airway diameter (75). However, it should be noted that the protective effect of dummy use is seen if the dummy is used when the infant is falling asleep, even though the dummy often falls out of the mouth soon after the onset of sleep (76, 77). Because the mechanism by which dummy use confers protection is still unclear, some experts are reluctant to recommend dummy use as a SIDS risk reduction strategy. However, in some countries, such as the US, dummy use is promoted as a risk reduction strategy. Because there is some concern that dummy use may interfere with breastfeeding initiation, introduction of a dummy for infants who are directly breastfed should be delayed until breastfeeding has been well established. In infants who are fed with formula or expressed breast milk, a dummy can be introduced at any time. If the dummy is not accepted by the infant, it should not be forced.

Room sharing

The safest place in which an infant can sleep is in the parental bedroom, on a separate sleep surface; this reduces the risk of SIDS by as much as 50% (39, 41, 42, 78, 79). Infants who have died of SIDS while sleeping in a separate room are more likely to have been found with their heads covered by bedding and to have rolled into the prone position if they had been placed on their sides for sleep (80). It is recommended that the infant sleep surface be placed close to the parents’ bed, to allow for easy monitoring and feeding. Room sharing, without bed sharing, is recommended for the first 6-12 months of life (55, 56, 57, 81, 82).

Theories

There have been multiple theories over the years regarding the etiology and mechanisms of SIDS. This may be partly because the successes in reducing the SIDS rates have come from epidemiological studies. Thus there has been considerable research into the underlying mechanisms that may underpin the risk factors identified in these epidemiological studies.

For many years, it was believed that apneic events, including apparent life-threatening events, were precursors to SIDS. Home apnea monitors were often prescribed for these infants as a means to prevent SIDS. However, subsequent research found that apparent life-threatening events and apnea did not predict SIDS. Indeed, the increase in the use of apnea monitors beginning in the 1970s did not correlate with a decline in the SIDS rate (67).

Because many deaths occurred in cribs, much attention has been paid to sleep surfaces. One theory has attributed SIDS to toxic gases and has proposed that gases such as antimony, arsenic, or phosphorus can be released from infant mattresses (in particular, old mattresses) and cause toxicity when inhaled. However, no data support this theory. In addition, case-control studies have found no benefit to wrapping mattresses in plastic to reduce toxic gas emission (83, 84).

Another theory that focuses on the infant sleep environment proposed that, in specific situations, infants may rebreathe exhaled carbon dioxide. Relevant situations include when the infant is prone and/or when the infant’s face is close to bedding. It is theorized that, in these conditions, a “pocket” of exhaled carbon dioxide collects around the infant’s face, and the infant, rather than inhaling oxygen, inhales the exhaled carbon dioxide. The infant thus becomes increasingly hypercarbic and eventually succumbs to death if there is no stimulus that interrupts the rebreathing (85, 86). It has been suggested that the rebreathing theory could explain some of the risk posed by soft bedding and prone sleeping. However, there are no physiologic data from infants who died for which evidence supporting rebreathing has been documented.

In recent years, there has been growing consensus among scientists that SIDS is multifactorial in origin. The Triple Risk Hypothesis (87) (Figure 10.1) proposes that when a vulnerable infant, such as one born preterm or one exposed to maternal smoking, is at a critical but unstable developmental period in homeostatic control and is exposed to an exogenous stressor, such as being placed prone to sleep, then SIDS may occur. The model proposes that infants will die of SIDS only if all three factors are present, and that the vulnerability lies dormant until they enter the critical developmental period and are exposed to an exogenous stressor. SIDS usually occurs during sleep, and the peak incidence is between 2-4 months of age, when sleep patterns are rapidly maturing. The final pathway to SIDS is widely believed to involve immature cardiorespiratory control, in conjunction with a failure of arousal from sleep (86, 88, 89). Support for this hypothesis comes from numerous physiological studies showing that the major risk factors for SIDS (prone sleeping, maternal smoking, prematurity, head covering) have significant effects on blood pressure, heart rate, and their control (90), and also impair arousal from sleep (91).

Figure 10.1:. Triple Risk Hypothesis. (Adapted by the National Institutes of Health with permission from (87).).

Figure 10.1:

Triple Risk Hypothesis. (Adapted by the National Institutes of Health with permission from (87).).

Conclusions

Epidemiological case-control studies have been critical in identifying factors that are associated with an increased or decreased risk of SIDS. As such, great strides have been made in our understanding of the risk and protective factors for SIDS based on epidemiologic research, leading to educational interventions that have resulted in dramatic declines in SIDS rates. Theories regarding the pathophysiology of SIDS are myriad, but they all rely upon understanding the mechanisms by which these factors increase or decrease SIDS risk. However, further research — especially on the physiological mechanisms that contribute to or cause SIDS — is essential to achieving the reduction of SIDS rates to lowest levels possible.

Acknowledgements

The authors thank their families for their continuous support.

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