SUDDEN INFANT

DEATH SYNDROME
Michael Klufas, MS III
INTRODUCTION
 Sudden Infant Death Syndrome (SIDS) continues
to be the most common cause of postneonatal
infant death
 25% of all deaths between 1 month and 1 year of age
 SIDS is a complex, multifactorial disorder of
which the cause is not fully understood
 Some environmental risk factors are modifiable
 Reducing exposure to modifiable risk factors has
lowered the incidence of SIDS
 New research indicates genetic risk factors
 Actual risk of SIDS may depend on interaction of
environmental and genetic risk factors
DEFINTION
 Sudden death of an infant under 1 year old
that is unexpected by history and unexplained
after a thorough postmortem examination

 Investigation includes:
 Complete autopsy
 Investigation of the scene of death
 Review of medical history
EPIDEMIOLOGY

 SIDS rate in United States

 1990 – 1.3 per 1000 live births
 2002 – 0.6 per 1000 live births
 ~ 3000 SIDS deaths/yr

 Changes in classification of sudden unexpected

deaths in infants from SIDS to categories of
asphyxia and “unknown” has occurred in recent
years
 May be falsely reducing SIDS rates while overall
death rate from unexpected infant deaths remains
the same
DEMOGRAPHICS
 less frequently in 1st month of life
 Peaks 2-4 month of age
 90% in first 6 months of life
 Boys 30-50% more likely to be affected than girls
 Racial and ethnic disparities
 2-3x risk for African American, Native American or
Alaska Native (irrespective of socioeconomic status)
 African Americans twice as likely to place infants
prone to for sleep & twice as likely to bedshare
 High rates of smoke exposure and bedsharing among
Native Americans and Alaskan Natives
 Asian, South Pacific, Hispanic infants lowest
incidence
 Winter seasonal predominance has declined or
disappeared
PATHOPHYSIOLOGY
 Multifactorial in origin

 Triple Risk Hypothesis

 Vulnerable infant
 Critical developmental period in
homeostatic control
 Exogenous stressors

 Final pathway believed to involve

immature cardiorespiratory and
autonomic control along with
failure of arousal responsiveness
from sleep
AUTONOMIC CONTROL
AND AROUSAL
 SIDS infants higher baseline heart rates, lower heart rate
variability, prolonged QT indexes, lower parasympathetic tone
and/or high sympathovagal balance
 Abnormalities of arousal
 Kato and colleagues report infants who died of SIDS had fewer
spontaneous arousals from sleep and immature sleep patterns
 Prone sleeping
 Increases total time infants spend asleep particularly time
spent in quiet sleep, a state of reduced arousability
 Also decreased spontaneous arousability, induced arousability
and fewer full cortical arousals
 Associated with altered autonomic control manifest by raised
heart rates, decreased heart rate variability and increased
sympathetic tone
 Infants exposed to smoking in utero have decreased spontaneous
and stimulus-induced arousal from sleep
AUTOPSY FINDINGS
 No pathognomonic findings
 Common findings:
 Petechial hemorrhages of thymus gland, visceral pleura in 68-
95%
 Pulmonary congestion (89%) and edema (63%) indicative of
terminal left ventricular failure
 Oronasal secretions that are typically frothy, mucoid and pink
or bloody
 2/3 structural evidence of pre-existing, chronic low-grade
asphyxia
 Study identified increased VEGF in CSF of SIDS infants, 308

versus 85 pg/dL in controls

 Hypoxia frequently precedes death in SIDS

 One study of 20 SIDS infants found 50% had levels of IL-6 in CSF
equivalent to those found in infants who died of infectious
diseases
 Staphylococcus aureus may have role in infection as 56% of
healthy infants and 86% of SIDS infants had these bacteria in
the respiratory tract
 NEUROANATOMICAL FINDINGS

 Structural and neurotransmitter alterations in

brainstem consistent with autonomic dysregulation
 Increase in dendritic spines (marker of delayed
neuronal maturation) and delayed maturation of
synapes in medullary respiratory centers
 Decreased tyrosine hydroxylase immunoreactivity in
catecholaminergic neurons
 Increased number and density of 5-HT neurons with
decreased serotonin 1A and 2A receptor
 Serotonin affects various autonomic functions

including cardiorespiratory and circadian rhythms

NEUROANATOMICAL FINDINGS
 60% SIDS cases hypoplasia of arcuate nucleus
 Vital area of autonomic control and integration
 Receptor abnormalities relevant to autonomic control
 Decreases in binding to kainate, muscarinic cholinergic and
5-HT receptors
 Lavezzi showed alterations of the cerebellum
 62% of SIDS compared to 10% controls showed
neuronal immaturity, altered apoptotic programs,
negative expression somatostatin and EN2 gene,
intense c-fos expression and astrogliosis in cortex and
dentate nucleus
 Water reported increased neuronal apoptosis in
hippocampus and brainstem
 Neuronal loss in regions sensitive to hypoxia and
regions associated with sensation in the face
RISK FACTORS
 PREGNANCY
SOCIAL RELATED
FACTORS FACTORS
 Increased risk with:  Mothers of SIDS infants:
 Lower socioeconomic  Less prenatal care
status  Care initiated later in
 Younger maternal age pregnancy
 Lower maternal  Low birth weight
education  Preterm birth
 Single marital status  IUGR
 Shorter intervals between
pregnancies (< 18 mo)
 More often 2nd or higher
order birth child
SUBSTANCE USE

 Major association between intrauterine exposure to

cigarette smoking and risk of SIDS
 Risk of death is progressively greater with increased
smoking
 May be small independent effect of paternal smoking
 An independent effect of postnatal exposure to
tobacco smoke has been found in a small number of
studies as well as dose-response effect with number
of household smokers
 Evidence linking prenatal illegal drug is conflicting
 Opiates increase risk of SIDS 2-15 fold
 Alcohol not clearly linked, but siblings of infants with
FAS 20 fold increased risk of SIDS compared to
controls
INFANT SLEEP PRACTICES &
ENVIRONMENT
 Prone sleeping consistently shown to increase risk of SIDS
 Highest risk when usually placed in another sleeping
position but were placed on stomach for last sleep,
“unaccustomed prone”, more likely to occur outside the
home such as day care centers
 Also risk of choking highest in prone position
 Placing infant on side still places risk twice as likely to die
of SIDS compared to sleeping supine
 Exceptions may be made with certain medical conditions
 Soft sleeping surfaces 2 to 3 fold increase risk of SIDS
 Prone sleeping + soft bedding  20 fold increase
 Overheating with increased room temperature, high body
temperature, sweating or excessive clothing increase incidence
 No increase with high external environment temperature
 No protective effect from bed sharing
 Advocates of this practice typically promoters of breast
feeding
 1/3 reduction with sleeping in parent’s bedroom in separate
crib
 INFANT FEEDING PRACTICES &
EXPOSURES
 Association between breast-feeding and SIDS inconclusive
 Recent study showed breast-feeding associated with decreased risk
of postneonatal deaths overall but not decreased risk of SIDS

 Decreased risk with pacifier use

 Not known whether direct effect or
associated infant or parental behaviors
 Pacifier use and dislodgement may
enhance arousability
 No association between pacifier use and
breast-feeding duration
 Small increased in otitis media,
respiratory tract and GI tract illnesses
 Must use consistently, one study showed
increased risk of SIDS if pacifier was not
used before last sleep
 AAP recommends pacifier use once
breast-feeding has been established
OTHER CONCERNS
 Upper respiratory tract infection has not been
found to be independent risk factor for SIDS
 However, these and other minor infections may play
a role in the pathogenesis if SIDS
 For instance, if in prone position, heavily wrapped or head
covered during sleep there was increased risk of SIDS with
infection

 Parents should be reassured that

immunization does not present a risk for
SIDS
 No temporal relation between vaccine administration
and death

 Not caused by vomiting or choking

GENE ENVIRONMENT
INTERACTIONS
GENETIC RISK FACTORS
 Sodium (SCN5A) and Potassium channel polymorphisms
associated with long QT syndrome
 5-10% of SIDS cases associated with defective cardiac ion
channel with increased potential for lethal arrhythmia
 Polymorphisms in serotonin transporter (5-HTT) gene
 Increased in transporter activity, reducing 5-HT concentrations at
nerve endings
 Autonomic nervous system development genes (PHOX2A,
RET, ECE1, TLX3, EN1)
 Polymorphisms in promoter of anti-inflammatory cytokine
IL-10  decreased antibody production and increased
inflammatory cytokines
 SIDS infants w/mild respiratory infections before death were
more likely than SIDS infants without infection and controls
to have deficient complement C4 gene (C4A, C4B)
DIAGNOSIS
 By definition, SIDS is a diagnosis of exclusion
 Protocols for standardized autopsies and death scene investigations
have been published
 However, wide variability in protocols in both content and
frequency with which they are implemented across jurisdictions,
within countries and across different countries
 Cause of death can be difficult to diagnose from autopsy alone
 Examination of circumstances present immediately before death
including detailed description of sleep environment have been
increasingly emphasized in recent years
 Surveys of medical examiners and coroners have reflected how much
more complicated, confusing and time consuming SIDS case
have become
 Most also noted they used to label many more infant death cases
as SIDS than they do now
 This may be an effect of confusing risk factors for SIDS
 Reaching consensus internationally on a classification scheme is
essential to accurately monitor trends and direct future research
AAP SIDS RISK REDUCTION
RECOMMENDATIONS 2005
RISK REDUCTION
 Campaign to reduce risk of SIDS began
in 1994 in the United States
 Largely focused on reducing prone
sleeping and promoting supine
positioning
 Some campaigns also included messages to
reduce smoking during pregnancy
 No significant changes in these behaviors and
reduced SIDS rates mostly attributed to
avoidance of prone sleeping
 Breast-feeding advocates have opposed
discouraging bed sharing as they worry
these measures will reduce breast-
feeding frequency and duration and
prevent families from enjoying the
experience and benefits of bed sharing
MANAGEMENT AND SUPPORT
 Loss of infant is devastating for everyone concerned
 In addition to loss of infant, families face could face
police investigation, long wait for autopsy results and
continued uncertainty leading to prolonged
emotional distress consequently affecting the
grieving process
 Physician can play active role by advocating for
an autopsy, discussing autopsy results with the
family and providing emotional support
 Surviving siblings and other family members need
age appropriate emotional support
 If appropriate refer family for genetic counseling
and/or metabolic testing
 Direct family to local counseling and support groups
which are available in most communities
FUTURE DIRECTIONS
 Despite decrease in prevalence of SIDS, more work is needed
 Elucidation of risk and protective factors with appropriately
targeted and implemented interventions leading to increased
adoption by families
 Unlikely disorder is completely eliminated or reduced to
lowest possible rates until specific causative mechanisms are
more fully understood
 Need studies with larger sample sizes and infants from
highest risk groups
 Investigations of still births and sudden unexplained
deaths in children over 1 year of age might provide
additional insights
 Surveillance of trends in rates of SIDS comparisons across
jurisdictions and internationally according to a universal,
standardized classification protocol
 Will require multidisciplinary and collaborative effort to
understand more
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