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Sudden infant death syndrome (SIDS) is the unexpected
death of infants <1 year old for which no pathologic cause can
be determined by a thorough history, physical examination, postmortem
examination, and environmental investigation. SIDS is a diagnosis
of exclusion. The syndrome has been a leading cause of death
of infants between 1 month and 1 year of age. In the past, between
5000 and 10,000 infants (1 to 2 per 1000 live births) succumbed
yearly to SIDS. With recent changes in infant sleep position, the
number of deaths has decreased to about 3000, or 0.8 deaths per
1000 infants. In addition, the recognition of other risk factors,
such as bed-sharing and parental smoking, have altered the way sudden
unexpected deaths during infancy are categorized, and the number
of SIDS cases may be, in part, related to this change in diagnostic
criteria.1 Another term that is applicable to these
infants is sudden unexplained infant death, which
includes cases of SIDS.
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The etiology and pathophysiology of SIDS remain unclear in spite
of continued investigation. Over the years, >70 different theories
have been proposed to explain SIDS, including suffocation from sleeping
with a parent (overlaying), milk allergy, and thymic enlargement.
Because most SIDS victims are found dead in their cribs, early theories
emphasized the role of apnea and ventilatory control, as well as
possible cardiac etiologies. Although cardiac dysfunction related
to prolonged QT interval or Wolff-Parkinson-White syndrome have
been reported,2 prospective studies monitoring
infants failed to show antecedent dysrhythmia in infants who subsequently
succumbed to SIDS. More recent studies on the brains of infants
who have died from SIDS demonstrate the presence of medullary serotonergic
(5-hydroxytryptamine) pathology, including abnormal firing, synthesis,
release, and clearance.3,4 Currently, emphasis
is placed on the interplay between developmental factors related
to autoregulation, arousal, and environmental stressors. The triple-risk
model for SIDS3 hypothesizes a “perfect
storm” of underlying vulnerability, a critical period of
development, and exogenous stressors. The underlying vulnerability
can include genetic factors, male gender, race, poverty, or prenatal
exposure to cigarettes, alcohol, and illicit drugs. Although no single
genetic locus for SIDS has been identified, the 10-fold increased risk
among the siblings of SIDS victims suggests a genetic component. Recently,
polymorphism in the interleukin-10 gene promoter has been associated
with SIDS and sudden unexpected death associated with infection. The
first 6 months of life represents a unique critical period of vulnerability.
Potential external stressors include prone sleeping, soft or adult
bedding, bed sharing, and minor infection, often with respiratory syncytial
virus (RSV).
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Autopsies of some SIDS victims have shown pathologic changes,
including smooth muscle thickening in small pulmonary arteries,
right ventricular hypertrophy, hematopoiesis in the liver, increase
in periadrenal brown fat, adrenal medullary hyperplasia, and abnormalities
of the carotid body. Other markers reported with some regularity
include brainstem gliosis and increased neuronal apoptosis in the
brainstem and hippocampus. These were thought to be indicative of
long-standing hypoxemia and, in the early 1990s, attention focused
on an association between SIDS and sleeping in the prone position.5,6 Epidemiologic ...