Sudden Infant Death Syndrome

1
SUDDEN INFANT DEATH SYNDROME
Michael Klufas, MS III
2
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

3
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

4
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

5
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

6
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

7
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

8
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

9
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

10
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

11
RISK FACTORS
12
PREGNANCY RELATED FACTORS
SOCIAL FACTORS

• Increased risk with
• Lower socioeconomic status
• Younger maternal age
• Lower maternal education
• Single marital status

• Mothers of SIDS infants
• Less prenatal care
• Care initiated later in pregnancy
• Low birth weight
• Preterm birth
• IUGR
• Shorter intervals between pregnancies (lt 18 mo)
• More often 2nd or higher order birth child

13
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

14
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 parents bedroom
  in separate crib

15
(No Transcript)
16
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

17
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

18
(No Transcript)
19
GENE ENVIRONMENT INTERACTIONS
20
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)?

21
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

22
AAP SIDS RISK REDUCTION RECOMMENDATIONS 2005
23
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

24
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

25
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

26
REFERENCES

• Hunt CE, Hauck FR. Sudden infant death syndrome.
  Cmaj. Jun 20 2006174(13)1861-1869.
• Moon RY, Horne RS, Hauck FR. Sudden infant death
  syndrome. Lancet. Nov 3 2007370(9598)1578-1587.
• Weese-Mayer DE, Ackerman MJ, Marazita ML,
  Berry-Kravis EM. Sudden Infant Death Syndrome
  review of implicated genetic factors. Am J Med
  Genet A. Apr 15 2007143A(8)771-788.
• Gurbutt D, Gurbutt R. Risk reduction and sudden
  infant death syndrome. Community Pract. Jan
  200780(1)24-27.
• Fleming P, Blair PS. Sudden Infant Death Syndrome
  and parental smoking. Early Hum Dev. Nov
  200783(11)721-725.
• Damato EG. Safe sleep can pacifiers reduce SIDS
  risk? Nurs Womens Health. Feb 200711(1)72-76.
• Haycock G. Recent research in sudden infant death
  syndrome. J Fam Health Care. 200717(5)149-151.