Overview

Sudden infant death syndrome (SIDS) is a term used to refer to the unexpected death of a healthy infant in the absence of any medical, physical, or clinical history. SIDS is still a prominent contributor to infant mortality in the United Kingdom (UK). While there are no certain diagnostic criteria that determine SIDS, it is usually diagnosed by exclusion when there is no known cause of death. Sometimes, however, after case investigation, a certain cause of death may be found suggesting natural or unnatural aetiology such as metabolic disorders, suffocation, infection, trauma, cardiac health concerns, and others.^1–3

SIDS occurs during sleep or in the transition between sleep and waking. Currently, there are ongoing awareness campaigns that support promoting better sleep environments, as studies have shown that the majority of sudden infant deaths are due to low-safety environments in the UK. 

Pathophysiology

The pathophysiology of sleep-related deaths in infancy is complicated and could be multifactorial. According to research, the proposed approach for SIDS is that the infant has impaired cardio-respiratory functions, genetic, and/or autonomic responses that undergo exogenous triggers such as unsafe environmental changes during a vital growth stage. On the other hand, systematic reviews of case series have demonstrated variable extrinsic impacts. Thus, identification of a single cause of sleep-related deaths is challenging.¹

Prevalence

Racial disparities

Sleep-related death rates in infants showed a link to ethnicity and race. People of American Indian/Alaskan and non-Hispanic Black heritage have higher rates of SIDS. The differences in sleep habits and practices among these ethnic groups could be one of the main factors contributing to sleep-related deaths in infants. Besides, low socio-economic status, domestic violence, housing instability, and unemployment, correlated with race/ethnicity are linked to a higher risk of SIDS.

UK rates

SIDS is a leading and significant cause of infant mortality in the UK. In 2014, there were about 247 cases of children below 2 years of age without a clear reason for their death, 230 of these were classified as unexplained infant deaths, while 17 unexplained deaths were between 12 and 24 months. Several strategies to reduce SIDS began in the 1970 and 1980’s, aiming to overcome SIDS-linked smoking during pregnancy, overwrapping, and sleeping positions. Educational campaigns were highly implemented for parents resulting in a notable decline in mortality rates over the last 25 years.³

Diagnosis

Diagnosis of SIDS by elimination process

There are no specific diagnostic criteria for SIDS, and thus diagnosis relies on the elimination process after excluding all possible causes of sudden infant death. However, not all cases that were identified as SIDS have the same characteristics, which makes this following strategy seem to be general, with a wide window of interpretation as to how and when the term SIDS should be used. In the past, many cases were identified as SIDS without fulfilling the required process to confirm the diagnosis by exclusion, as SIDS term should be used in infants younger than 1 year of age after performing a full investigation that includes a review of medical and clinical history, a full autopsy, and a death scene investigation.2

The preliminary investigation should combine the expertise of both medical settings and law enforcement. This would be a full documentary via photographic and video evidence using a similar size dull to the infant which includes a recording of the sleep environment, the position in which the infant was placed to sleep and the position in which they were found. Besides, other correlated factors should be mentioned like room temperature details of household activities before death, details regarding clothing and bedding, and any uncommon traits. 

In addition to the full death scene investigation, a routine autopsy should be conducted including histological analysis, toxicology analysis, evaluation of the presence of infectious agents, and genetic testing.

Also, a complete medical assessment is to be performed before and after birth including details about the mother's medical history and complications during delivery, way of feeding, and immunisation status. Moreover, family history should be reviewed, such as the presence of any history of illness in siblings of the infant, and if there are any previous deaths or serious inherited disorders. 

Diagnostic challenges in the UK

In the UK, the term SUDI which refers to Sudden Unexpected Death in Infancy is used when there are no identified specific reasons within 24 hours prior to the event of infant death. About one-third of SUDI cases in the UK are later found to have a medical concern anticipating death.

According to the San Diego definition, SIDS applies to those who remain without any explained evidence of death after a complete scene investigation and medical assessment, but often they are defined as “ascertained”. In the UK, coroners who are responsible for issuing cause-of-death certificates may debate whether to use the SIDS term in cases that show risk factors of accidental asphyxia.

Thus, combining SIDS and unascertained terms results in a more accurate definition regarding cases without any single explained death evidence. Knowing that, the UK demonstrated lower rates of accidental asphyxia in SUDI compared to other countries, this could be due to the competitive diagnostic criteria in diagnosing asphyxial deaths.³

Risk factors for SIDS

In 1994, Filiano and colleagues proposed a triple risk model for SIDS which illustrates intrinsic, extrinsic, and additional risk factors for SIDS as shown in figure 1.²

Developmental period

Although sudden death can occur at any period during infancy after the age of 1 without any explained reason, SIDS is a term used for those confirmed cases by elimination process who are younger than 1 year old. SIDS can occur at any time during the first year, however, 90% of deaths occur within the first 6 months of life. 

Intrinsic risk factors

Sex, prematurity, and low birth weight

Vulnerability was demonstrated to be higher in males than females recording higher incidence rates with a ratio of 60 to 40 respectively. However, it is not clear why it is higher in males, this might be because male infants are more exposed to infections and illnesses than females. Prematurity and low birth weight are 4 times more likely to contribute to SIDS.

Genetic polymorphisms

Unlike some genetic disorders which can be detected through genetic testing due to a certain mutation or DNA abnormalities, SIDS has no single alteration in a gene that detects SIDS aetiology to date. However, this does not exclude the fact that some infants may carry undetected genetic variations or unknown polymorphisms that interact with the extrinsic and environmental factors triggering the occurrence of SIDS.

A recent sequencing study of 161 SIDS cases in 2017 revealed a combination of metabolic, cardiologic, and other disorders due to genetic variants linked to these disorders specifically and not SIDS, thus scientists didn’t focus on certain genetic defects that are only associated with SIDS itself. There are two issues in analysing SIDS aetiology.

First, is that there are no multiple SIDS deaths in a family which limits the ability to study the inherited genetic abnormalities (familial). Second, researchers found among groups of SIDS death cases differences in one single gene or several genes exhibiting nonspecific heterogeneous functions. 

Prenatal exposure to drugs and maternal cigarette smoking

maternal cigarette smoking showed up to a fivefold increase in the relative risk for SIDS. Despite the harmful outcomes the cigarette causes to the pregnancy, about 13% of women continue to smoke during the gestational period.

Moreover, alcohol and drug use including alcohol, also elevates the risk of premature and low birth weight, research indicates an increased risk of SIDS in individuals who are on such drugs and alcohol consumption. In addition, infants born to mothers of drug use history may develop impaired physiological functions as the alteration in heart rhythms and body movements. 

Extrinsic risk factors

Sleep position

SIDS is the sudden death of infants with unexplained cause, regardless of the time of day. This often related to the position of the infant which was placed in during sleep, particularly placing infants on their stomach (prone position), and on their sides during sleep, increased the risk of developing SIDS up to 14 times.

The proposed outcomes of such positions include poor oxygen supply, low blood flow, and carbon dioxide rebreathing. However, suffocation remains the common outcome. Although safety sleep campaigns have arisen advising about the correct sleep position for a better sleeping environment, still some healthcare workers advocate wrong sleep positions, knowing that other contributing factors have been suggested. 

Sharing a sleep surface

Shared sleep environments in beds, sofas, and coaches have demonstrated an increased risk of SIDS from 12% to 50% over 20 years in the UK.

Unsuitable sleep surfaces and soft bedding

Soft bedding in particular, is linked to a higher risk of SIDS independent of sleep position, however, placing the infant in a prone position enhances the possibility of SIDS to occur. Soft surfaces such as mattresses cause the surface to be depressed under the weight of the infant, thus the infant may not be able to free themselves, posing a risk of suffocation, overheating, or asphyxia. 

Geographic location and climate

Geographic location plays a significant role in affecting infant death rates. In cold countries, SIDS cases are at higher rates, especially during the cold months. However, its incidence has decreased with the support of educational campaigns, keeping in mind that the variations in the diagnostic protocols and childcare practices contribute to differences in these rates. 

Ethnicity

Ethnicity is linked to SIDS, the higher rates are recorded in African-American and Indigenous populations, and the lower rates were in individuals of Asian heritage. However, this may change when considering maternal history, socioeconomic status, and risk factors. 

Sleep patterns

Infants who die from SIDS may experience impaired sleep patterns and stress reactions during sleep. Research has demonstrated variations in rapid eye movement (REM) periods, waking time, and the organisation of sleep compared to controls. Additionally, changes in sleep behaviours including self-recovery and waking up during sleep are also noticed, especially if their moms have a smoking history during pregnancy, resulting in an increased risk of SIDS. 

Sibling deaths

The correlation between SIDS among siblings is debated. Few reports suggested increased risk, especially in families with multiple sibling deaths, however, maternal and environmental factors require consideration in this situation. The overall risk of recurrence is small for 92% of families.

Parental characteristics

Young parents of age less than 20 years are considered to be at higher risk for SIDS. Although, this is less likely to occur in the firstborn child of young parents. Moreover, complications during pregnancy, admission for psychiatric treatment (particularly drug-related), single maternal marital status, few prenatal examinations, and multiple births, are also contributed to the aetiology of SIDS.

Recommendations to reduce the risk of sleep-related infant deaths

Two main charities in the UK support educational programs by following effective strategies to reduce the risk factors contributing to SIDS among families. These are The Lullaby Trust in England and Wales and the Scottish Cot Death Trust in Scotland. The following list is produced by The Lullaby Trust.³

• During pregnancy and after birth provide a smoke-free environment for your baby
• Place your baby on their back during sleep, and avoid prone and side positions
• For the first 6 months, place your baby to sleep in a separate cot or Moses basket in the same room as you
• If possible breastfeed your baby
• Never sleep in an armchair or on a sofa with your baby
• Use a flat, comfortable, firm, waterproof mattress
• Avoid anything that lets your baby get too hot
• Don’t cover your baby's head or face while sleeping
• Don’t use loose bedding
• Don’t sleep in the same bed as your baby in case you take drugs, drink, smoke, or are extremely tired, or if your baby is born premature or low birth weight

Summary

• Sudden infant death syndrome (SIDS) is a term used for an expected sudden death without any clear explanation in infants younger than 1 year of age
• SIDS should be confirmed by exclusion after applying a complete scene investigation, full medical assessment, and clinical history
• SIDS occurs during sleep or in the transition phase between sleeping and waking
• The pathophysiology of SIDS is complicated due to the lack of a direct single aetiology that relates SIDS with death. However, some research linked SIDS to intrinsic factors such as impaired autonomic functions which are triggered by extrinsic factors such as unsafe sleep environments
• People of American Indian/Alaskan and Non-Hispanic Black heritage are at greater risk of SIDS
• There are no specific diagnostic criteria for SIDS, and thus it relies on the elimination process after excluding all possible causes of sudden infant death
• In the UK, the term SUDI which refers to Sudden Unexpected Death in Infancy is used when there are no identified specific reasons within 24 hours before the event of infant death
• The UK demonstrated lower rates of accidental asphyxia in SUDI compared to other countries, this could be due to the competitive diagnostic criteria in diagnosing asphyxial deaths
• The risk factors for SIDS are intrinsic, extrinsic, and additional risk factors. Intrinsic factors such as gender, genetic polymorphism, and prenatal exposure to drugs and smoking. While extrinsic risk factors such as sleeping position, geographic location, sibling deaths, sleep patterns, and ethnicity
• There is a list that was produced by The Lullaby Trust in England to support educational programs to reduce the risk factors for SIDS. These lists include recommendations about avoiding placing the baby in a prone position during sleep, keeping the baby in a safe environment free of smoking, placing the baby on a waterproof flat mattress, not sleeping with the baby on the same bed if the parent is tired, smoking or taking drugs, and encouraging breastfeeding and other