Sudden Infant Death Syndrome: Comparison
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Sudden infant death syndrome (SIDS) is defined as “the sudden death of an infant under 1 year of age which remains unexplained after thorough investigation including a complete autopsy, death scene investigation, and detailed clinical and pathological review”. 

  • Sudden Infant Death Syndrome

1. Introduction

Sudden infant death syndrome (SIDS) is defined as “the sudden death of an infant under 1 year of age which remains unexplained after thorough investigation including a complete autopsy, death scene investigation, and detailed clinical and pathological review”

[1][2]

. SIDS is characterized by an unexpected death during the sleeping period and it typically occurs in the first 12 months of age in a previously healthy infant. Most events take place in the child’s home; the out-of-home deaths are most frequent at a relative’s home or a child-care setting, especially if the child sleeps in prone position and in a stroller and/or car seat

[3]

. SIDS is a subcategory of Sudden Unexpected Infant Deaths (SUID) and represents nearly half of these cases; SUID includes SIDS of unknown cause and also events of strangulation in bed or accidental suffocation

[4]

. The peak of incidence of SIDS is around two to four months of age and 90% of cases occur before six months of age; prevalence of SIDS is higher in boys than girls, at a 3:2 ratio

[5]

.

In the late 1980s prone sleep has been documented as a major risk factor for SIDS, leading in the 1990s to “back-to-sleep” campaigns which have had a great impact on reduction of SIDS rates

[6]

. SIDS infant mortality has decreased well over 50% for most countries, especially in the first few years after the beginning of national campaigns

[7]

. Alongside the SIDS prevention recommendations, perinatal care has experienced numerous other improvements, so it’s difficult to attribute the SIDS incidence drop to only the supine sleep practice

[6]

. Furthermore, the increasing rates of other causes of death such as strangulation in bed and accidental suffocation may represent another explanation of the decline in SIDS rates

[8]

. Over the first decade of this century, infant mortality from SIDS has experienced a continuous drop in some countries such as Australia, Canada, England and Wales, Germany, Japan and the Netherlands, while it has remained stationary in others, notably the USA and New Zealand

[9]

. Despite continuous public health efforts concentrating on the improvement of sleep conditions with a special focus on the high-risk groups

[10][11]

, incidence of SIDS still continues to be high. In fact, SIDS still represents a prominent cause of infant death, occurring at a rate of 27/100,000 live births in the United Kingdom and 38/100,000 the United States

[12][13]

. In Italy incidence is about 1 out of 1000 live births

[14]

. Therefore, continuous research on the cause and prevention of SIDS is needed.

2. Pathogenesis and Risk Factors

The most recent evidence suggests that SIDS pathogenesis is a multifactorial condition that comprehends genetic, environmental and sociocultural factors

[8]

. The Triple-Risk Model, first described in 1994, affirms that SIDS occurs in infants with latent biological vulnerability (brainstem abnormality or genetic pattern), who is exposed to a trigger event or extrinsic risk factor (prone sleeping, airway obstruction) during a critical phase of development

[15]

. The combination of intrinsic and extrinsic factors which overlap during a period of respiratory, autonomic and cardiac development, usually occurring between two to four months of age, leads to a life-threatening event during a period of sleep. Failure of protective mechanisms during these episodes finally concludes with unexpected death. On the contrary, SIDS is less likely to occur with the removal of one of these factors

[16][17]

.

Multiple extrinsic risk factors for SIDS in the sleep environment of the infants have been examined. Prone sleeping appears to be the most significant risk factor for SIDS. In fact, it is likely to be associated with re-breathing expired gases, suffocation, overheating and decreased arousal

[18]

. Infants in side lying position are also at high risk to roll into prone position while sleeping

[19]

. Other factors related to the sleeping environment involve soft bedding, sleeping with blankets, pillows, soft objects, bumper pads, head or face covered during sleep, bedsharing (especially co-sleeping on a couch or sofa) and room or infant overheating

[20]

. Maternal smoking during pregnancy is associated with a fivefold increase in SIDS events, and postnatal smoking exposure further increases the risk

[21][22][23]

. In fact, it’s been demonstrated that smoking during pregnancy contributes to the risk due to the disruption of arousal patterns in the sleeping baby along with impairment of autonomic system and cardiovascular response: uterine exposure reduces lung compliance and volume, alters arousal mechanisms and decreases heart rate variability in response to stress, all factors that can negatively affect a baby’s ability to respond appropriately to the environment

[24][25]

. A recent study showed a linear correlation between number of cigarettes smoked daily during pregnancy and the risk of a SUID event. Furthermore, quitting smoking over the three trimesters is strongly associated with great reduction of SUID risk but also diminution of cigarettes smoked daily contributes to a small decrease in risk

[26]

. Additional risk factors include maternal alcohol use, young maternal age (under 20 years) and poor prenatal care

[27]

. The combined exposure of alcohol and tobacco beyond the first trimester of pregnancy appears to have a synergistic effect on the risk for SIDS events

[28]

. Co-sleeping associated with recent use of alcohol or drugs by the parents also increases the risk significantly

[29]

. The strong association between smoking, alcohol consumption and drugs utilization may also explain, in part, the interaction described between co-sleeping and smoking

[29][30][31][32]

. Bottle-feeding is associated with increased risk, while the use of a pacifier and breastfeeding appear to be protective factors

[27][33][34]

. Some studies suggest that a significant part of SIDS cases may be closely related to sub-clinical infection processes

[35][36]

. In a study conducted by Goldwater et al. in 2020, significantly heavier thymus and brain were found in SIDS victims compared to non-SIDS controls. This finding is related to immune responses in the brain and thymus associated with possible subclinical infections

[37]

.

Intrinsic risk factors are male gender, population subgroups such as non-Hispanic black infants, American Indian or Alaska Native infants

[8][38]

and prematurity. Preterm birth or low birth weight increases the risk of SIDS events three to four times, suggesting that altered intrauterine environment may contribute to the pathogenesis

[39]

. Additionally, smoking during pregnancy increases the risk of premature delivery

[40]

. Furthermore, research suggests that disorders of homeostasis, neuroregulation and cardiorespiratory function associated with brain and brainstem anomalies play an important role in SIDS

[16]

. In particular, serotonin brainstem abnormalities have been identified in up to 70% of infants who have died of SIDS

[16]

. Since the serotonin system is associated with several homeostatic functions, these anomalies may possibly lead to a network dysfunction that affects arousal and cardiorespiratory functions

[41][42]

. In addition to brain vulnerabilities, research has focused on identifying genetic variants related to defects involving autonomic and metabolic functions, neurotransmission and cardiac repolarization, suggested to contribute to SIDS infant’s “underlying vulnerability”

[2][43][44]

. Thus, certain infants may have a genetic predisposition to SIDS or an underlying abnormality in the brainstem, which becomes manifest when the infant experiences environmental challenges (hypoxia, asphyxia, hypercarbia, overheating) during sleep and differentiates a SIDS infant from a healthy infant. In fact, infants without the underlying conditions present an efficient protective brainstem response to homeostatic challenges which promptly manage to avoid SIDS occurrence

[2]

. The combination of multiple extrinsic and intrinsic factors leads to asphyxia. Vulnerable infants are not able to respond with arousal that prevents re-breathing or apnea. Consequently, asphyxia leads to bradycardia and insufficient gasping breathing, which eventually terminate with death

[45]

.

Most of these life-threatening events occur during the sleep period. In fact, sleep is associated with a reduction of blood pressure, heart rate, respiratory rate and muscle tone, especially in the upper airways. During sleep phases protective reflexes to hypoxia and hypercapnia are also depressed. Blood pressure, cerebral oxygenation and cerebral vascular homeostasis are decreased in the prone position

[46][47]

. In fact, term infants between two to four months of age show a depressed baroreflex response and decreased arousal in the prone position

[48][49]

. In premature babies these characteristics in prone position are mostly marked

[50][51]

. These considerations highlight, indeed, the increased risk of SIDS occurring during sleeping, mainly in the prone position during specific infant development windows.

References

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