Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 17
Immunization Safety Review:
Vaccinations and Sudden Unexpected
Death in Infancy
Immunization to protect children and adults from many infectious diseases is
one of the greatest achievements of public health. Immunization is not without
risks, however. It is well established, for example, that the oral polio vaccine can
on rare occasion cause paralytic polio, that some influenza vaccines have been
associated with a risk of Guillain-Barre syndrome, and that vaccines sometimes
produce anaphylactic shock. Given the widespread use of vaccines, state man-
dates requiring vaccination of children for entry into school, college, or day care,
and the importance of ensuring that trust in immunization programs is justified, it
is essential that safety concerns receive assiduous attention.
The Immunization Safety Review Committee was established by the Insti-
tute of Medicine (IOM) to evaluate the evidence on possible causal associations
between immunizations and certain adverse outcomes, and then to present con-
clusions and recommendations. The committee's mandate also includes assess-
ing the broader significance for society of these immunization safety issues.
In this sixth report in a series, the committee examines the hypothesis that
infant vaccination is associated with an increased risk of sudden unexpected
death during the first year of life.
THE CHARGE TO THE COMMITTEE
Challenges to the safety of immunizations are prominent in public and scien-
tific debate. Given these persistent and growing concerns about immunization
safety, the Centers for Disease Control and Prevention (CDC) and the National
Institutes of Health (NIH) recognized the need for an independent, expert group
17
OCR for page 18
18
IMMUNIZATION SAFFI Y REVIEW
to address immunization safety in a timely and objective manner. The IOM has
been involved in such issues since the 1970s. (A brief chronology can be found in
Appendix C.) In 1999, because of IOM's previous work and its access to inde-
pendent scientific experts, CDC and NIH began a year of discussions with IOM
to develop the Immunization Safety Review project, which would address both
emerging and existing vaccine safety issues.
The Immunization Safety Review Committee is responsible for examining a
broad variety of immunization safety concerns. Committee members have exper-
tise in pediatrics, neurology, immunology, internal medicine, infectious diseases,
genetics, epidemiology, biostatistics, risk perception and communication, deci-
sion analysis, public health, nursing, and ethics. While all the committee mem-
bers share the view that immunization is generally beneficial, none of them has a
vested interest in the specific immunization safety issues that come before the
group. Additional discussion of the committee composition can be found in the
Foreword written by Dr. Harvey Fineberg, President of the IOM.
The committee is charged with examining three immunization safety hy-
potheses each year during the three-year study period (2001-2003~. These hy-
potheses are selected by the Interagency Vaccine Group (IAVG), whose mem-
bers represent several units of the Department of Health and Human Services: the
National Vaccine Program Office, the National Immunization Program, and the
National Center for Infectious Diseases at CDC; the National Institute for Allergy
and Infectious Diseases at NIH; the Food and Drug Administration; the National
Vaccine Injury Compensation Program at the Health Resources and Services
Administration; and the Centers for Medicare and Medicaid Services (formerly
the Health Care Financing Administration). The IAVG includes representation
from the Department of Defense and the Agency for International Development
as well.
For each topic, the Immunization Safety Review Committee reviews rel-
evant literature and submissions by interested parties, holds an open scientific
meeting, and directly follows the open meeting with a 1- to 2-day closed meeting
to formulate its conclusions and recommendations. The committee's findings are
released to the public in a brief consensus report 60 to 90 days after its meeting.
The committee is charged with assessing both the scientific evidence regard-
ing the hypotheses under review and the significance of the issues for society.
· The scientific assessment has two components: (1) an examination of the
epidemiologic and clinical evidence regarding a possible causal relationship
between exposure to the vaccine and the adverse event; and (2) an examination of
theoretical, experimental, and observational evidence from in vitro, animal, or
human studies regarding biological mechanisms that might be relevant to the
hypothesis.
· The significance assessment addresses such considerations as the burden
of the health risks associated both with the vaccine-preventable disease and the
OCR for page 19
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
19
adverse event. Other considerations may include the perceived intensity of public
or professional concern, or the feasibility of additional research to help resolve
scientific uncertainty regarding causality.
The findings of the scientific and significance assessments provide the basis
for the committee's recommendations regarding the public health response to the
issue. In particular, the committee addresses needs for a review of immunization
policy, for current and future research, and for effective communication strate-
gies. See Figure 1 for a schematic representation of the committee's charge.
THE STUDY PROCESS
The committee held an initial organizational meeting in January 2001. CDC
and NIH presented the committee's charge at the meeting, and the committee
then conducted a general review of immunization safety concerns. At this initial
meeting, the committee also determined the basic methodology to be used for
assessing causality in the hypotheses to be considered at subsequent meetings. A
website (www.iom.edu/imsafety) and a listserv were created to provide public
access to information about the committee's work and to facilitate communica-
tion with the committee. The conclusions and recommendations of the
committee's reports thus far (see Box 1) are summarized in Appendix A.
For its evaluation of the potential role of vaccination in sudden unexpected
death in infancy, the committee held an open scientific meeting in October 2002
(see Appendix B) to hear presentations on issues germane to the topic. These
presentations are available in electronic form (audio files and slides) on the
project website (www.iom.edu/imsafety). In addition, the committee reviewed an
extensive collection of material, primarily from the published, peer-reviewed
scientific and medical literature. A list of the materials reviewed by the commit-
OCR for page 20
20
.......................
~ ~3
fit .
,
En
..........................
-
,
~7
i= ~ 03
O U ~ ~
_s
._
X ~
. ~ ~
1-
1.o
~ \
._
E cat
,~
_ ~
- 1 i=
~ ,~Q ~
,oo
_r
r
a, ~
m ~ In
._
3
a
a,
Do,
_ _
40
CO
hi,
.o
_ 9
/
f
/
f
~ ~ ,o
o
C:)
o
a.>
/—\
a}
JO
o
CO
_ ~
C: C
Q
A_ ~
~ .~
~ Eo_
. . Co a,
e _ ~ ~~ tip
~ 75 I_
tv c} ~
~ -a='>
~ \ ~
_'
In
o
to
5:
^1'm-
~ ~ C
I_.
o
X
OCR for page 21
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
21
tee, including many items not cited in this report, can be found on the project's
website.
THE FRAMEWORK FOR SCIENTIFIC ASSESSMENT
Causality
The Immunization Safety Review Committee has adopted the framework for
assessing causality developed by previous IOM committees (IOM, 1991;
1994a,b), convened under the congressional mandate of P.L. 99-660 to address
questions of immunization safety. The categories of causal conclusions used by
the committee are as follows:
1. No evidence
2. Evidence is inadequate to accept or reject a causal relationship
3. Evidence favors rejection of a causal relationship
4. Evidence favors acceptance of a causal relationship
5. Evidence establishes a causal relationship.
Assessments begin from a position of neutrality regarding the specific vac-
cine safety hypothesis under review. That is, there is no presumption that a
specific vaccine (or vaccine component) does or does not cause the adverse event
in question. The weight of the available clinical and epidemiologic evidence
determines whether it is possible to shift from that neutral position to a finding for
causality ("the evidence favors acceptance of a causal relationship") or against
causality ("the evidence favors rejection of a causal relationship"~. The commit-
tee does not conclude that the vaccine does not cause the adverse event merely if
the evidence is inadequate to support causality. Instead, it maintains a neutral
position, concluding that the "evidence is inadequate to accept or reject a causal
relationship."
Although no firm rules establish the amount of evidence or the quality of the
evidence required to support a specific category of causality conclusion, the
committee uses standard epidemiologic criteria to guide its decisions. The most
definitive category is "establishes causality," which is reserved for those relation-
ships in which the causal link is unequivocal, as with the oral polio vaccine and
vaccine-associated paralytic polio or with anaphylactic reactions to vaccine ad-
ministration (IOM, 1991; 1994a). The next category, "favors acceptance" of a
causal relationship, reflects evidence that is strong and generally convincing,
although not firm enough to be described as unequivocal or established. "Favors
rejection" is the strongest category in the negative direction. (The category of
"establishes no causal relationship" is not used because it is virtually impossible
to prove the absence of a relationship with the same surety that is possible in
establishing the presence of one.)
OCR for page 22
22
IMMUNIZATION SAFFI Y REVIEW
If the evidence is not reasonably convincing either in support of or against
causality, the category "inadequate to accept or reject a causal relationship" is
used. Evidence that is sparse, conflicting, of weak quality, or merely sugges-
tive whether toward or away from causality falls into this category. Under
these circumstances, some authors of similar assessments use phrases such as
"the evidence does not presently support a causal association." The committee
believes, however, that such language does not make the important distinction
between evidence indicating that a relationship does not exist (category 3) and
evidence that is indeterminate with regard to causality (category 2~.
The category of "no evidence" is reserved for those cases in which there is
a complete absence of clinical or epidemiologic evidence.
The sources of evidence considered by the committee in its scientific assess-
ment of causality include epidemiologic and clinical studies directly addressing
the question at hand. That is, the data are specifically related to the effects of the
vaccines under review and the adverse health outcomes) under review in this
report, the effects of vaccination on the risk for sudden unexpected death in
infancy.
Epidemiologic studies carry the most weight in a causality assessment. These
studies measure health-related exposures and outcomes in a defined set of sub-
jects and then make inferences about the nature and strength of associations
between exposures and outcomes in the overall population from which the study
sample was drawn. Epidemiologic studies can be categorized as observational or
experimental (clinical trial), and as uncontrolled (descriptive) or controlled (ana-
lytic). Among the various study designs, experimental studies generally have the
advantage of random assignment to exposures and are therefore the most influen-
tial in assessing causality. Uncontrolled observational studies are important but
are generally considered less definitive than controlled studies. In uncontrolled
observational studies, where observations are made over time, confounding fac-
tors such as changing case definitions or improving case detection may affect the
apparent incidence and prevalence of the adverse outcomes studied.
Case reports and case series are generally inadequate by themselves to estab-
lish causality. Despite the limitations of case reports, the causality argument for
at least one vaccine-related adverse event (the relationship between vaccines
containing tetanus toxoid and Guillain-Barre syndrome) was strengthened most
by a single, well-documented case report on recurrence of the adverse event
following re-administration of the vaccine, a situation referred to as a
"rechallenge" (IOM, 1994a).
Biological Mechanisms
The committee's causality assessments must be guided by an understanding
of relevant biological processes. Evidence considered in the scientific assessment
OCR for page 23
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
23
of biological mechanisms] includes human, animal, and in vitro studies related
to biological or pathophysiological processes by which immunizations could
cause an adverse event.
When convincing statistical or clinical evidence of causality is available,
biological data add support. But this committee is often faced with circumstances
in which the epidemiologic evidence is judged inadequate to accept or reject a
causal association between a vaccine exposure and an adverse event of concern.
It is then left with the task of examining proposed or conceivable biological
mechanisms that might be operating if an epidemiologically sound association
could be shown between a vaccine exposure and an adverse event. The biological
data alone cannot be invoked as proof of causality, however.
The committee has established three general categories of evidence on bio-
ogical mechanisms:
1. Theoretical. A reasonable mechanism can be hypothesized that is com-
mensurate with scientific knowledge and does not contradict known physical and
biological principles, but has not been demonstrated in whole or in part in hu-
mans or in animal models. Postulated mechanisms by which a vaccine might
cause a specific adverse event but for which no coherent theory exists would not
qualify for this category. Thus, "theoretical" is not a default category, but one that
requires thoughtful and biologically meaningful suppositions.
2. Experimental. A mechanism can be shown to operate in in vitro systems,
animals, or humans. But, experimental evidence often describes mechanisms that
represent only a portion of the pathological process required for expression of
disease. Showing that multiple portions of a process operate in reasonable experi-
mental models strengthens the case that the mechanisms could possibly result in
disease in humans.
Some experimental evidence is derived under highly contrived conditions.
For example, achieving the results of interest may require extensive manipulation
of the genetics of an animal system, or in vivo or in vitro exposures to vaccine
antigen that are extreme in terms of dose, route, or duration. Other experimental
evidence is derived under less contrived conditions. For example, a compelling
animal or in vitro model might demonstrate a pathologic process analogous to
human disease when a vaccine antigen is administered under conditions similar
to human use. Experimental evidence can also come from studies in humans. In
any case, biological evidence is distinct from the epidemiologic evidence ob-
tained from randomized controlled trials and other population-based studies that
are the basis for the causality assessment.
3. Evidence that the mechanism results in known disease in humans. For
example, the wild-type infection causes the adverse health outcome associated
1For a discussion of the evolution of the terminology concerning biological mechanisms, see the
committee's earlier reports (TOM, 2001 a,b; 2002a,b,c).
OCR for page 24
24
IMMUNIZATION SAFFI Y REVIEW
with the vaccine, or another vaccine has been demonstrated to cause the same
adverse outcome by the same or a similar mechanism. Data from population-
based studies of the risk of adverse outcomes following vaccination constitute
evidence regarding causality, not biological mechanisms.
If the committee identifies evidence of biological mechanisms that could be
operating, it will offer a summary judgment of that body of evidence as weak,
moderate, or strong. Although the committee tends to judge biological evidence
in humans as "stronger" than biological evidence from highly contrived animal
models or in vitro systems, the summary judgment of the strength of the evidence
also depends on the quantity (e.g., number of studies or number of subjects in a
study) and quality (e.g., the nature of the experimental system or study design) of
the evidence. Obviously, the conclusions drawn from this review depend both on
the specific data and scientific judgment. To ensure that its own summary judg-
ment is defensible, the committee intends to be as explicit as possible regarding
the strengths and limitations of the biological data.
The committee's examination of biological mechanisms reflects their opin-
ion that available information on possible biological explanations for a relation-
ship between immunization and an adverse event should influence the design of
epidemiologic studies and analyses. Similarly, the essential consideration of con-
founders and effect modifiers in epidemiologic studies depends on an under-
standing of the biological phenomena that could underlie or explain the observed
statistical relationship. The identification of sound biological mechanisms can
also guide the development of an appropriate research agenda and aid
policymakers, who frequently must make decisions without having definitive
information regarding causality.
In addition, investigating and understanding possible biological mechanisms
is often of value even if the available epidemiologic evidence suggests the ab-
sence of a causal association. A review of biological data could give support to
the negative causality assessment, for example, or it could prompt a reconsidera-
tion or further investigation of the epidemiologic findings. If new epidemiologic
studies were to question the existing causality assessment, the biological data
could gain prominence in the new assessments.
Published and Unpublished Data
Published reports carry the most weight in the committee's assessment be-
cause their methods and findings are laid out in enough detail to be assessed.
Furthermore, those published works that undergo a rigorous peer review are
subject to comment and criticism by the entire scientific community. In general,
the committee cannot rely heavily on unpublished data in making its scientific
assessments (regarding either causality or biological mechanisms) because they
usually lack the comment and criticism provided by peer review and must there-
OCR for page 25
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
25
fore be interpreted with caution. The committee also relies on editorial and peer-
review procedures to ensure the disclosure of potential conflicts of interest that
might be related to the source of funding for the research study. The committee
does not investigate the source of funding of the published research reports it
reviews, nor does the funding source influence the committee's interpretation of
the evidence.
Unpublished data and other reports that have not undergone peer review do
have value, however, and are often considered by the committee. They might be
used, for example, in support of a body of published, peer-reviewed literature
with similar findings. If the committee concluded that the unpublished data were
well described, had been obtained using sound methodology, and presented very
clear results, the committee could report, with sufficient caveats in the discus-
sion, how the unpublished data fit with the entire body of published literature.
Only in extraordinary circumstances, however, could an unpublished study refute
a body of published literature.
The Immunization Safety Review Committee's scope of work includes con-
sideration of clinical topics for which high-quality experimental studies are rarely
available. Many other panels making clinical recommendations using evidence-
based methods are able to require that randomized trials be available to reach
strong conclusions, but, the IOM committee was convened specifically to assess
topics that are of immediate concern yet for which data of any kind may just be
emerging. Given the unique nature of this project, therefore, the committee
deemed it important to review and consider as much information as possible,
including unpublished reports. The committee does not perform primary or sec-
ondary analyses of unpublished data, however. In reviewing unpublished mate-
rial, the committee applies generally accepted standards for assessing the quality
of scientific evidence, as described above. (All unpublished data reviewed by the
committee and cited in this report are available in the form reviewed by the
committee through the public access files of the National Academies. Informa-
tion about the public access files is available at 202-334-3543 or www.national-
academies . org/publicacces s . ~
UNDER REVIEW:
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
Infant Mortality: Rates and Causes of Death
Infant mortality refers to deaths that occur between birth and 1 year of age. In
2000, there were approximately 28,000 infant deaths in the United States, and the
infant mortality rate was 6.9 deaths per 1,000 live births (Mining et al., 2002~.
This rate in 2000 is the lowest ever recorded in the United States and is 25 percent
lower than the rate of 9.2 in 1990. The decline in the infant mortality rate during
the 1990s is attributed in part to the use of surfactants and other medical interven-
OCR for page 26
26
IMMUNIZATION SAFFI Y REVIEW
lions that improved the survival of premature and low-birth-weight infants, and,
in part to reductions in sudden infant death syndrome (SIDS) that resulted from
the spreading adoption of recommendations that prone positions be avoided for
infant sleep.
Various characteristics of infants or their mothers are associated with differ-
ences in the infant mortality rate (Mathews et al., 2002~. The rate is higher for
male infants (7.2) than for female infants (6.0~. Low birth weight and premature
birth are associated with especially high rates of infant mortality; in 2000, the
mortality rate for infants born weighing less than 1,500 grams was 244.3 per
1,000 births, compared with 2.5 for infants who weighed 2,500 grams or more at
birth. Low birth weight and prematurity contribute to an even higher mortality
rate in multiple births (Branum, 2002~. Higher infant mortality rates are also
associated with lack of prenatal care, births to teenage mothers, and maternal
smoking during pregnancy.
Among racial and ethnic groups in 2000, the lowest infant mortality rate was
3.5, seen for children born to mothers of Chinese origin. For children of non-
Hispanic white mothers, the rate was 5.7. The overall rate for infants born to
Hispanic mothers was 5.6, but within the Hispanic population it was highest for
children of Puerto Rican mothers (8.2~. For children born to American Indian
mothers, the rate was 8.3. Infant mortality was highest for the non-Hispanic black
population, with 13.6 deaths per 1,000 live births (Branum, 2002; Mathews et al.,
2002~. Some of the difference among racial and ethnic groups is accounted for by
their differences in rates of low birth weight.
About two-thirds of infant deaths occur within 27 days of birth, a period
designated as neonatal. In 2000, approximately 80 percent of neonatal deaths
occurred within the early part of the neonatal period the first 6 days of life and
most early neonatal deaths occurred less than 24 hours after birth (Branum, 2002;
Mathews et al., 2002~. For 2000, the neonatal mortality rate was 4.6 deaths per
1000 births (Mathews et al., 2002~. The postneonatal mortality rate deaths at
ages 28 days to 1 year was 2.3.
Most deaths occurring during the neonatal period are related to problems
arising during gestation or delivery. The five leading causes of neonatal mortality
in 2000 were (1) disorders related to short gestation and low birth weight, (2)
congenital anomalies, (3) effects of maternal complications of pregnancy, (4)
effects of pregnancy complications related to the cord or placenta, and (5) respi-
ratory distress (Branum, 2002~.
In contrast to the neonatal period, the leading causes of infant death during
the postneonatal period reflect the impact of social and environmental factors, as
well as biological ones. The five leading causes of postneonatal infant mortality
in 2000 were (1) SIDS, (2) congenital anomalies, (3) unintentional injuries, (4)
diseases of the circulatory system, and (5) assault (Branum, 2002~.
OCR for page 27
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
Sudden Unexpected Death in Infancy
27
A death that occurs suddenly and unexpectedly in the first year of life,
whether or not there is an underlying disorder that predisposes the infant to death,
has been referred to collectively by the term "sudden unexpected death in in-
fancy" (SUDI). It includes deaths that can be attributed to an identifiable cause as
well as deaths for which the cause remains uncertain. SIDS is the diagnosis most
commonly given to the deaths of uncertain cause.
No generally accepted list of causes of death has been established to define
SUDI. As a result, it is difficult to assess the national rate of SUDI in the popula-
tion from vital statistics data. However, special investigations examining deaths
in infants less than a year old in Quebec (Cote et al., 1999) and in several regions
in the United Kingdom (Leach et al., 1999) found that about 80% of the SUDI
cases in the study sample could be attributed to SIDS.
The committee acknowledges that vaccines protect against diseases that con-
tribute to infant mortality. The committee's charge, however, was to examine
sudden unexpected infant death, not all-causes of death. For purposes of this
report, the committee looked widely for all possible associations with SUDI but
focused particularly on three distinct contributors to sudden unexpected death in
infants SIDS, inborn errors of metabolism, and anaphylaxis in considering
possible links to immunization.
Sudden Infant Death Syndrome
SIDS is defined as "the sudden death of an infant under 1 year of age, which
remains unexplained after a thorough case investigation, including performance
of a complete autopsy, examination of the death scene, and review of the clinical
history" (Willinger et al., l991~. Although this definition calls for an autopsy and
other investigation of the death before a diagnosis of SIDS is made, Sullivan and
Barlow (2001) note that autopsy rates and protocols for investigation of infant
deaths vary among countries and among regions within countries.
In the United States in 2000, the 2,523 deaths from SIDS accounted for 9
percent of all infant deaths (Anderson, 2002~. Of those deaths, 2,319 occurred in
the postneonatal period, representing 25 percent of all postneonatal deaths. SIDS
deaths have been observed to peak at 2 to 4 months of age and to be somewhat
higher in the colder fall and winter months than in spring and summer (Adams et
al., 1998; Sullivan and Barlow, 2001~. Also characteristic of SIDS is higher
mortality rates for male infants than for female infants. In 2000, the postneonatal
SIDS mortality rate in the United States was 67.6 per 100,000 live births for
males and 46.2 for females.
SIDS deaths occur among all socioeconomic and racial and ethnic groups,
but the rates vary widely. For non-Hispanic African-American infants in 2000,
the postneonatal mortality rate from SIDS was 122.9 per 100,000 births, com-
OCR for page 74
74
IMMUNIZATION SAFFI Y REVIEW
The committee makes its recommendation for further research recognizing
that it has no basis for judging whether the results of such research will alter the
balance of evidence that led to the committee's conclusions in this report. Never-
theless, any research that helps to elucidate the mechanisms underlying SIDS
would inform future investigations of the potential association between sudden
unexpected infant death and vaccines, or any other hypothesized trigger.
Postmortem evaluation of infants varies widely across the country and the
depth of the investigation is often related to the evaluation site, the diagnostic
resources available, and the availability of specialists such as pediatric or neona-
tal pathologists (AAP, 1999~. The committee recommends that a comprehen-
sive postmortem workup, including a metabolic analysis, be done on all
infants who die suddenly and unexpectedly. In SIDS cases for which metabolic
analyses (such as those done using the tandem mass spectrometry method dis-
cussed above) were not done at birth, it may useful to conduct such analyses
using samples obtained at autopsy or, if available, stored blood samples
(bloodspots) originally obtained for newborn screening tests.
Basic and clinical research, surveillance and epidemiologic studies, and post-
mortem investigations would all be strengthened by use of standard definitions of
SIDS and SUDI. The committee's efforts to reach conclusions regarding causal-
ity were hampered by inconsistencies in the epidemiologic reports in the use of
these terms.
The committee notes the development of various resources in the United
States and internationally to aid in standardizing approaches to the diagnosis of
SIDS. In the United States, the accepted definition of SIDS specifies "the sudden
death of an infant under 1 year of age which remains unexplained after a thorough
case investigation, including performance of a complete autopsy, examination of
the death scene, and review of the clinical history" (Willinger et al., 1991~. The
definition agreed to at more recent international consensus conferences does not
restrict SIDS to infants under 1 year of age (Byard et al., 1996; Sullivan and
Barlow, 2001~.
Guidance from CDC (1996a) and the AAP (1999; 2001) emphasizes the
importance of postmortem examinations and thorough investigation of death
scenes to rule out other causes, especially child abuse, before deaths are attrib-
uted to SIDS. Also available is an international standardized protocol for autop-
sies in cases of sudden unexpected infant death (Krous, 1996~. In the United
States, however, requirements for investigation of unexpected infant deaths are
officially established by state and local statutes (CDC, 1996a). The committee
encourages efforts by CDC, AAP, and others to promote the development
and consistent use throughout the United States of national guidelines for
investigation, diagnosis, and reporting of SIDS cases.
SUDI, unlike SIDS, is not a single, officially recognized cause of death. It
can include deaths that are attributed to many different causes but that are linked
OCR for page 75
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
75
by being sudden and unexpected. Despite the heterogeneity of SUDI, it is a useful
concept for research on infant deaths following vaccination. The committee
recommends the development of standard definitions and guidance for diag-
nosis and reporting of SUDI for research purposes.
Consistent application of the criteria related to SIDS and SUDI will aid
interpretation of reports of vaccine-related deaths and enhance the comparability
of results from surveillance, epidemiologic, and biological investigations.
SUMMARY
With current recommendations calling for infants to receive multiple doses
of vaccines during their first year of life and with suddent infant death syndrom
(SIDS) the most frequent cause of death during the postneonatal period, it is
important to respond to concerns that vaccination might play a role in sudden
unexpected infant death. A death that occurs suddenly and unexpectedly in the
first year of life, whether or not there is an underlying disorder that predisposes to
death, has been referred to by the term "sudden unexpected death in infancy"
(SUDI). SUDI includes deaths that can be attributed to identifiable causes and
deaths for which the causes remain uncertain. SIDS is the diagnosis most com-
monly given to the deaths of uncertain cause. The committee reviewed epidemio-
logic evidence focusing on three outcomes: SIDS, all SUDI, and neonatal death
(infant death, whether sudden or not, during the first 4 weeks of life). Based on
this review, the committee concluded that the evidence favors rejection of a
causal relationship between some vaccines and SIDS; and that the evidence is
inadequate to accept or reject a causal relationship between other vaccines and
SIDS, SUDI, or neonatal death. The evidence regarding biological mechanisms is
essentially theoretical, reflecting in large measure the lack of knowledge con-
cerning the pathogenesis of SIDS. Anaphylaxis related to vaccination has been
discussed in detail in previous IOM reports and is reexamined in the report; the
committee observed that anaphylaxis is known to be a rare but causally related
adverse event following the administration of some vaccines. Fatal anaphylaxis
in infants is extraordinarily rare. The committee found no basis for a review of
current immunization policies, but saw a clear need for continued research on
adverse event following vaccination and on the biological basis for sudden unex-
pected infant deaths. See Box 2 for a summary of all conclusions and recommen-
dations.
OCR for page 76
76
IMMUNIZATION SAFFI Y REVIEW
OCR for page 77
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
77
OCR for page 78
78
IMMUNIZATION SAFETY REVIEW
REFERENCES
AAP (American Academy of Pediatrics). 1999. Committee on Child Abuse and Neglect and Com-
mittee on Community Health Services. Investigation and Review of Unexpected Infant and
Child Deaths (RE9921) Policy Review. Pediatrics. 104(5):1158-60.
AAP. 2000. Changing concepts of sudden infant death syndrome: implications for infant sleeping
environment and sleep position. American Academy of Pediatrics. Task Force on Infant Sleep
Position and Sudden Infant Death Syndrome. Pediatrics 105(3 Pt 1):650-6.
AAP. 2001. Committee on Child Abuse and Neglect. Distinguishing Sudden Infant Death Syndrome
from Child Abuse Fatalities (RE0036) Policy Statement. Pediatrics 107(2):437-441.
Ackerman MJ, Siu BL, Sturner WQ, Tester DJ, Valdivia CR, Makielski JC, Towbin JA. 2001.
Postmortem molecular analysis of SCN5A defects in sudden infant death syndrome. JAMA
286(18):2264-9.
Adams EJ, Chavez OF, Steen D, Shah R. Iyasu S. Krous HF. 1998. Changes in the epidemiologic
profile of sudden infant death syndrome as rates decline among California infants: 1990-1995.
Pediatrics 102(6):1445-51.
Anderson R. 2002. Deaths: Leading Causes for 2000. National Vital Statistics Report 50(No. 16).
Bennett MJ, Powell S. 1994. Metabolic disease and sudden, unexpected death in infancy. Hum
Pathol 25(8):742-6.
Black SB, Shinefield HR, Ray P. Lewis EM, Fireman B. Hiatt R. Madore DV, Johnson CL, Hackell
JO. 1993. Safety of combined oligosaccharide conjugate Haemophilus influence type b
(HbOC) and whole cell diphtheria-tetanus toxoids-pertussis vaccine in infancy. The Kaiser
Permanente Pediatric Vaccine Study Group. Pediatr Infect Dis J 12(12):981-5.
Blood-Siegfried J. Nyska A, Lieder H. Joe M, Vega L, Patterson R. Germolec D. 2002. Synergistic
effect of influenza A virus on endotoxin-induced mortality in rat pups: A potential model for
sudden infant death syndrome. Pediatr Res 52(4):481-90.
Boles RG, Buck EA, Blitzer MG, Platt MS, Cowan TM, Martin SK, Yoon H. Madsen JA, Reyes-
Mugica M, Rinaldo P. 1998. Retrospective biochemical screening of fatty acid oxidation disor-
ders in postmortem livers of 418 cases of sudden death in the first year of life. J Pediatr
132(6):924-33.
Branum A. 2002. Infant Mortality in the US: An Introductory Exploration. Presentation to Immun
zation Safety Review Committee: Irvine, CA.
Braun MM, Terracciano G. Salive ME, Blumberg DA, Vermeer-de Bondt PE, Heijbel H. Evans G.
Patriarca PA, Ellenberg SS. 1998. Report of a US public health service workshop on hypo-
tonic-hyporesponsive episode (HHE) after pertussis immunization. Pediatrics 102(5):E52.
Braun MM, Mootrey GT, Salive ME, Chen RT, Ellenberg SS. 2000. Infant immunization with
acellular pertussis vaccines in the United States: Assessment of the first two years' data from
the Vaccine Adverse Event Reporting System (VAERS). Pediatrics 106(4):E51.
Buckley MG, Variend S. Walls AF. 2001. Elevated serum concentrations of beta-tryptase, but not
alpha-tryptase, in sudden infant death syndrome (SIDS). An investigation of anaphylactic
mechanisms. Clin Exp Allergy 31 (11): 1696-704.
Busse WW, Lemanske RF Jr. 2001. Asthma. N Engl J Med 344(5):350-62.
Byard RW, Becker LE, Berry PJ, Campbell PE, Fitzgerald K, Hilton JM, Krous HF, Rognum TO.
1996. The pathological approach to sudden infant death-consensus or confusion? Recommen-
dations from the Second SIDS Global Strategy Meeting, Stavangar, Norway, August 1994, and
the Third Australasian SIDS Global Strategy Meeting, Gold Coast, Australia, May 1995. Am J
Forensic Med Pathol 17(2): 103-5.
CDC (Centers for Disease Control and Prevention).1996a. Guidelines for Death Scene Investigation
of Sudden, Unexplained Infant Deaths: Recommendations of the Interagency Panel on Sudden
Infant Death Syndrome. MMWR 45(RR-10):1-6.
OCR for page 79
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
79
CDC. 1996b. Update: Vaccine Side Effects, Adverse Reactions, Contraindications, and Precautions:
Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR
45(RR-12):8, 25.
CDC. 1997. Pertussis Vaccination: Use of Acellular Pertussis Vaccines Among Infants and Young
Children: Recommendations of the Advisory Committee on Immunization Practices
(ACIP).MMWR 46(RR-7):1-25.
C:DC:. 1999. Achievements in Public Health, 1900-1999 Impact of Vaccines Universally Recom-
mended for Children-United States, 1900-1998. MMWR 48(12):243-48.
CESDI SUDI (Confidential Enquiry into Stillbirths and Sudden Unexpected Deaths in Infancy).
2000. The CESDI SUDI Studies 1993-1996. Fleming P. Blair P. Bacon L, Berry J. Eds. Lon-
don: The Stationery Office.
Chace D, Naylor E. 2002. Screening for Inborn Errors of Metabolism. Presentation made to Immun
zation Safety Review Committee: Irvine, CA.
Chen RT. 2000. Special methodological issues in pharmacoepidemiology studies of vaccine safety.
Strom B. Ed. Pharmacoepidemiology. Third ed. West Susses, England: John Wiley & Sons,
Ltd. Pp. 707-732.
Chen RT, DeStefano F. Davis RL, Jackson LA, Thompson RS, Mullooly JP, Black SB, Shinefield
HR, Va&eim CM, Ward JI, Marcy SM. 2000. The Vaccine Safety Datalink: Immunization
research in health maintenance organizations in the USA. Bull World Health Organ 78(2): 186-
94.
Cochran-Black DL, Cowan LD, Neas BR. 2001. The relation between newborn hemoglobin F frac-
tions and risk factors for sudden infant death syndrome. Arch Pathol Lab Med 125(2):211-17.
Cote A, Russo P. Michaud J. 1999. Sudden unexpected deaths in infancy: What are the causes? J
Pediatr 135(4):437-43.
Decker MD, Edwards KM. 1996. The multicenter acellular pertussis trial: An overview. J Infect Dis
174 (Suppl 3):S270-5.
Decker MD, Edwards KM, Steinhoff MC, Rennels MB, Pichichero ME, Englund JA, Anderson EL,
Deloria MA, Reed GF. 1995. Comparison of 13 acellular pertussis vaccines: Adverse reactions.
Pediatrics 96(3 Pt 2):557-66.
DuVernoy TS, Braun MM. 2000. Hypotonic-hyporesponsive episodes reported to the Vaccine Ad-
verse Event Reporting System (VAERS), 1996-1998. Pediatrics 106(4):E52.
Edston E, Gidlund E, Wickman M, Ribbing H. Van Hage-Hamsten M. 1999. Increased mast cell
tryptase in sudden infant death anaphylaxis, hypoxia, or artifact? Clin Exp Allergy
29(12): 1648-54.
Ehrengut W. Staak M. 1973. [Anaphlylactic reaction following injection of tetanus immunization]
Anaphylaktische reaktionen nach Tetanustoxoid-Injektion. Deutsche Medizinische
Wochenschrift 98:517.
Ellenberg S. Chen R. 1997. The complicated task of monitoring vaccine safety. Publ Health Re
112:10-20.
Essery SD, Raza MW, Zorgani A, MacKenzie DA, James VS, Weir DM, Busuttil A, Hallam N.
Blackwell C. 1999. The protective effect of immunisation against diphtheria, pertussis and
tetanus (DPT) in relation to sudden infant death syndrome. FEMS Immunol Med Microbiol
25(1-2): 183-92.
Fagan DG, Walker A. 1992. Haemoglobin F levels in sudden infant deaths. Br J. Haematol 82(2):422-
30.
Filiano JJ, Kinney HC. 1994. A perspective on neuropathologic findings in victims of the sudden
infant death syndrome: The triple-risk model. Biol Neonate 65(3-4):194-7.
Filiano JJ, Bellimer SG, Kunz PL. 2002. Tandem mass spectrometry and newborn screening: Pilot
data and review. Pediatr Neurol 26(3):201-4.
Fleming PJ, Blair PS, Platt MW, Tripp J. Smith IJ, Golding J. 2001. The UK accelerated
immunisation programme and sudden unexpected death in infancy: Case-control study. BMJ
322(7290):822.
OCR for page 80
80
IMMUNIZATION SAFETY REVIEW
Forsyth KD. 1999. Immune and inflammatory responses in sudden infant death syndrome. FEMS
Immunol Med. Microbiol 25(1-2):79-83.
Freudenberg MA, Salomao R. Sing A, Mitov I, Galanos C. 1998. Reconciling the concepts of
endotoxin sensitization and tolerance. Prog Clin Biol Res 397:261-8.
Galanos C, Freudenberg MA. 1993. Mechanisms of endotoxin shock and endotoxin hypersensitivity.
Immunobiology 187(3-5):346-56.
Gilbert-Barness E, Hegstrand L, Chandra S. Emery JL, Barness LA, Franciosi R. Huntington R.
1991. Hazards of mattresses, beds and bedding in deaths of infants. Am J. Forensic Med. Pathol
12(1):27-32.
Gilbert-Barness E, Kenison K, Carver J. 1993. Fetal hemoglobin and sudden infant death syndrome.
Arch Pathol Lab Med 117(2): 177-9.
Gold MS. 2002. Hypotonic-hyporesponsive episodes following pertussis vaccination: A cause for
concern? Drug Saf 25(2):85-90.
Goodman, S. 2002. Research Strategies for Investigating Inborn Errors of Metabolism. Presentation
to Immunization Safety Review Committee: Irvine, CA
Greco D, Salmaso S. Mastrantonio P. Giuliano M, Tozzi AK, Anemona A, Ciofi degli Atti ML,
Giammanco A, Panei P. Blackwelder WC, Klein DL, Wassilak SG. 1996. A controlled trial of
two acellular vaccines and one whole-cell vaccine against pertussis. Progetto Pertosse Working
Group. N Engl J. Med 334(6):341-8.
Gumenscheimer M, Mitov I, Galanos C, Freudenberg MA. 2002. Beneficial or deleterious effects of
a preexisting hypersensitivity to bacterial components on the course and outcome of infection.
Infect Immun 70(10):5596-603.
Guntheroth WG, Spiers PS. 2002. The triple risk hypotheses in sudden infant death syndrome.
Pediatrics 110(5):e64.
Harper R. 2002. Neuroregulation and Sudden Infant Death. Presentation to Immunization Safety
Review Committee: Irvine, CA.
Harper RM. 2000. Sudden infant death syndrome: A failure of compensatory cerebellar mecha-
nisms? Pediatr Res 48(2): 140-2.
Harper RM. 2001. Autonomic control during sleep and risk for sudden death in infancy. Arch Ital
Biol 139(3):185-94.
Harper RM, Kinney HC, Fleming PJ, Thach BT. 2000. Sleep influences on homeostatic functions:
Implications for sudden infant death syndrome. RespirPhysiol 119(2-3):123-32.
Heijbel H. Ciofi degli Atti MC, Harzer E, Liese J. Preziosi MP, Rasmussen F. Schmitt HJ, Storsaeter
J. Taranger J. Uberall M, Tozzi AK. 1997. Hypotonic hyporesponsive episodes in eight pertus-
sis vaccine studies. Dev Biol Stand 89:101-3.
Holgate ST, Walters C, Walls AF, Lawrence S. Shell DJ, Variend S. Fleming PJ, Berry PJ, Gilbert
RE, Robinson C. 1994. The anaphylaxis hypothesis of sudden infant death syndrome (SIDS):
Mast cell degranulation in cot death revealed by elevated concentrations of tryptase in serum.
Clin Exp Allergy 24(12): 1115-22.
Howat WJ, Moore IE, Judd M, Roche WR. 1994. Pulmonary immunopathology of sudden infant
death syndrome. Lancet 343(8910):1390-2.
IOM (Institute of Medicine). 1991. Adverse Events Following Pertussis and Rubella Vaccines. Wash-
ington, DC: National Academy Press.
IOM 1994a. Adverse Events Associated With Childhood Vaccines: Evidence Bearing on Causality.
Washington, DC: National Academy Press.
IOM. 1994b. DPT Vaccine and Chronic Nervous System Dysfunction: A New Analysis. Washington,
DC: National Academy Press.
IOM. 2001a. Immunization Safety Review: Measles-Mumps-Rubella Vaccine and Autism. Washing-
ton, DC: National Academy Press.
IOM. 2001b. Immunization Safety Review: Thimerosal-Containing Vaccines and Neurodevelopmental
Disorders. Washington, DC: National Academy Press.
OCR for page 81
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
81
IOM. 2002a. Immunization Safety Review: Hepatitis B Vaccine and Demyelinating Neurological
Disorders. Washington, DC: National Academy Press.
IOM. 2002b. Immunization Safety Review: Multiple Immunizations and Immune Dysfunction. Wash-
ington, DC: National Academy Press.
IOM. 2002c. Immunization Safety Review: SV40 Contamination of Polio Vaccine and Cancer. Wash-
ington, DC: National Academy Press.
Jonville-Bera AP, Autret E, Laugier J. 1995. Sudden infant death syndrome and diphtheria-tetanus-
pertussis-poliomyelitis vaccination status. Fundam Clin Pharmacol 9(3):263-70.
Jonville-Bera AP, Autret-Leca E, Barbeillon F. Paris-Llado J. 2001. Sudden unexpected death in
infants under 3 months of age and vaccination status a case-control study. Br J Clin
Pharmacol 51(3):271-6.
Kaback M. 2002. Personal communication with representatives from Toronto, NYC/Sinai, Boston
Children's Hospital, UCLA, UCSF, and UCSD.
Keens TO, Ward SL, Gates EP, Andree DI, Hart LD. 1985. Ventilatory pattern following diphtheria-
tetanus-pertussis immunization in infants at risk for sudden infant death syndrome. Am J Dis
Child 139(10):991-4.
Kemp SF, Lockey RF. 2002. Anaphylaxis: A review of causes and mechanisms. J Allergy Clin
Immunol 110(3):341-8.
Kinney HC, Filiano JJ, White WF. 2001. Medullary serotonergic network deficiency in the sudden
infant death syndrome: Review of a 15-year study of a single dataset. J Neuropathol Exp
Neurol 60(3):228-47.
Krous H. 1996. Instruction and reference manual for the international standardized autopsy protocol
for sudden unexpected infant death. J Sudden Infant Death Syndrome Infant Mortal 1 :203-46.
Krueger JM, Majde JA. 1995. Cytokines and sleep. Int Arch Allergy Immunol 106(2):97-100.
Krueger JM, Obal FJ, Fang J. Kubota T. Taishi P. 2001. The role of cytokines in physiological sleep
regulation. Ann NYAcad Sci 933:211-21.
Leach CE, Blair PS, Fleming PJ, Smith IJ, Platt MW, Berry PJ, Golding J. 1999. Epidemiology of
SIDS and explained sudden infant deaths. CESDI SUDI Research Group. Pediatrics 104(4):e43.
Loy CS, Horne RS, Read PA, Cranage SM, Chau B. Adamson TM. 1998. Immunization has no
effect on arousal from sleep in the newborn infant. J Paediatr Child Health 34(4):349-54.
Mathews TJ, Menacker F. MacDorman MF. 2002. Infant Mortality Statistics from the 2000 Period
Linked Birth/Infant Death Data Set. CDC: National Vital Statistics Report 50(12).
Mathur A, Sims HF, Gopalakrishnan D, Gibson B. Rinaldo P. Vockley J. Hug G. Strauss AW. 1999.
Molecular heterogeneity in very-long-chain acyl-CoA dehydrogenase deficiency causing pedi-
atric cardiomyopathy and sudden death. Circulation 99(10):1337-43.
McInnes RR, Clarke JTR. 2002. Chapter 9: Metabolic Disorders. Rudolph CD, Lister G. Hostetter
MK, ed. Rudolph's Pediatrics 21st Edition. Appleton and Lange.
Minino AM, Arias E, Kochanek KD, Murphy SL, Smith BL. 2002. Deaths: Final data for 2000.
National Vital Statistics Report 50(15).
Mitchell EA, Milerad J. 1999. Smoking and sudden infant death syndrome. International Consulta-
tion on Environmental Tobacco Smoke (ETS) and Child Health. Geneva: World Health Organi-
zation: 105-129.
Mitchell EA, Stewart AW, Clements M. 1995. Immunisation and the sudden infant death syndrome.
New Zealand Cot Death Study Group. Arch Dis Child 73(6):498-501.
Naylor EW, Chace DH. 1999. Automated tandem mass spectrometry for mass newborn screening for
disorders in fatty acid, organic acid, and amino acid metabolism. J Child Neurol 14 (Suppl
1):S4-8.
NICHD (National Institute of Child Health and Human Development). 2001. Targeting Sudden
Infant Death Syndrome (SIDS): A Strategic Plan. Washington, DC.
Niu MT, Salive ME, Ellenberg SS. 1999. Neonatal deaths after hepatitis B vaccine: The Vaccine
Adverse Event Reporting System, 1991-1998. Arch PediatrAdolesc Med 153(12):1279-82.
OCR for page 82
82
IMMUNIZATION SAFETY REVIEW
Overpeck MD, Brenner RA, Cosgrove C, Trumble AC, Kochanek K, MacDorman M. 2002. National
underascertainment of sudden unexpected infant deaths associated with deaths of unknown
cause. Pediatrics 109(2):274-83.
Parham P. 2000. Elements of the immune system and their roles in defense. The Immune System.
First ed. New York: Garland Publishing. Pp. 1-30.
Perry GW, Vargas-Cuba R. Vertes RP. 1997. Fetal hemoglobin levels in sudden infant death syn-
drome. Arch Pathol Lab Med 121(10):1048-54.
Pless R. Casey C, Chen R. 2002. Clinical immunization safety assessment centers: Improving the
evaluation, management and understanding of adverse events possibly related to immuniza-
tion. [Online] Available: http://www.partnersforimmunization.org/cisa.pdf [accessed Decem-
ber 9, 2002].
Regamey RH. 1965. Die Tetanus-Schutzimpfung. Herrlick A, Ed. Handbuch Der Schutzimpfungen.
Berlin-Heidelberg-New York: Springer.
Ridgway D. 1998. Disputed claims for pertussis vaccine injuries under the National Vaccine Injury
Compensation Program. J Investig Med 46(4): 168-74.
Rinaldo P. Yoon HR, Yu C, Raymond K, Tiozzo C, Giordano G. 1999. Sudden and unexpected
neonatal death: A protocol for the postmortem diagnosis of fatty acid oxidation disorders.
Semin Perinatol 23(2):204-10.
Rinaldo P. Studinski AL, Matern D. 2001. Prenatal diagnosis of disorders of fatty acid transport and
mitochondrial oxidation. Prenat Diagn 21(1):52-4.
Rognum TO, Saugstad OD. 1993. Biochemical and immunological studies in SIDS victims. Clues to
understanding the death mechanism. Acta Paediatr Suppl 82 Suppl 389:82-5.
Schmitt HJ, Schuind A, Knuf M, Beutel K, Schulte-Wissermann H. Gahr M, Schult R. Folkens J.
Rauh W. Bogaerts H. Bork HL, Clemens R. 1996. Clinical experience of a tricomponent acel-
lular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in
22,505 infants. JPediatr 129(5):695-701.
Schoen EJ, Baker JC, Colby CJ, To TT. 2002. Cost-benefit analysis of universal tandem mass
spectrometry for newborn screening. Pediatrics 110(4):781-6.
Schwartz HJ, Yunginger JW, Schwartz LB. 1995. Is unrecognized anaphylaxis a cause of sudden
unexpected death? Clin Exp Allergy 25(9):866-70.
Schwartz PJ, Stramba-Badiale M, Segantini A, Austoni P. Bosi G. Giorgetti R. Grancini F. Marni
ED, Perticone F. Rosti D, Salice P. 1998. Prolongation of the QT interval and the sudden infant
death syndrome. NEngl JMed 338(24):1709-14.
Schwartz PJ, Priori SG, Dumaine R. Napolitano C, Antzelevitch C, Stramba-Badiale M, Richard TA,
Berti MR, Bloise R. 2000. A molecular link between the sudden infant death syndrome and the
long-QT syndrome. N Engl J Med 343(4):262-7.
Silvers LE, Ellenberg SS, Wise RP, Varricchio FE, Mootrey GT, Salive ME. 2001. The epidemiol-
ogy of fatalities reported to the Vaccine Adverse Event Reporting System 1990-1997.
Pharmacoepidemiol Drug Saf 10(4):279-85.
Spiess H. Staak E. 1973. [Anaphlylactic reaction following active tetanus immunization]
Anaphylaktische reaktionen nach aktiver Tetanus-Immunisierung. Deutsche Medizinische
Wochenschrift 98:682.
Staak M, Wirth E. 1973. [Anaphylactic reactions following active tetanus immunization] Zur
problematik anaphylaktischer reaktionen nach aktiver Tetanus-Immunisierung. Deutsche
Medizinische Wochenschrift 98:110-111.
Steinschneider A, Freed G. Rhetta-Smith A, Santos VR. 1991. Effect of diphtheria-tetanus-pertussis
immunization on prolonged apnea or bradycardia in siblings of sudden infant death syndrome
victims. J Pediatr 119(3):411-4.
Strauss AW, Powell CK, Hale DE, Anderson MM, Ahuja A, Brackett JC, Sims HF. 1995. Molecular
basis of human mitochondrial very-long-chain acyl-CoA dehydrogenase deficiency causing
cardiomyopathy and sudden death in chil&ood. Proc Natl Acad Sci USA 92(23): 10496-500.
OCR for page 83
VACCINATIONS AND SUDDEN UNEXPECTED DEATH IN INFANCY
83
Sullivan FM, Barlow SM. 2001. Review of risk factors for sudden infant death syndrome. Paediatr
PerinatEpidemiol 15(2):144-200.
Vege A, Rognum TO. 1999. Inflammatory responses in sudden infant death syndrome past and
present views. FEMS Immunol Med. Microbiol 25(1-2):67-78.
Vege A, Rognum TO, Scott H. Aasen AO, Saugstad OD. 1995. SIDS cases have increased levels of
interleukin-6 in cerebrospinal fluid. Acta Paediatr 84(2):193-6.
Ward J. 2002. Analysis of Mortality Risk Following Vaccination. Presentation to Immunization
Safety Review Committee: Irvine, CA.
Wattigney WA, Mootrey GT, Braun MM, Chen RT. 2001. Surveillance for poliovirus vaccine ad-
verse events, 1991 to 1998: Impact of a sequential vaccination schedule of inactivated poliovi-
rus vaccine followed by oral poliovirus vaccine. Pediatrics 107(5):E83.
Wedgewood RJ. 1972. Review of USA Experience. Camps FE, Carpente RG, Eds. Sudden and
Unexpected Death in Infancy (Cot Deaths). Bristol, England: Wright. P. 28.
Werne J. Garrow I. 1946. Fatal Anaphylactic Shock: Occurrence in identical twins following second
injection of diphtheria toxoid and pertussis antigen. JAMA 730-35.
Wilcox RL, Nelson CC, Stenzel P. Steiner RD. 2002. Postmortem screening for fatty acid oxidation
disorders by analysis of Guthrie cards with tandem mass spectrometry in sudden unexpected
death in infancy. J Ped iatr 141 (6): 833-6.
Willinger M, James LS, Catz C. 1991. Defining the sudden infant death syndrome (SIDS): Delibera-
tions of an expert panel convened by the National Institute of Child Health and Human Devel-
opment. Pediatr Pathol 11(5):677-84.
OCR for page 84
84
NIH- National Institutes of Health
NIP - National Immunization Program
NVPO - National Vaccine Program Office
OPV - oral polio vaccine
OR- Odds Ratio
PCV - pneumococcus vaccine
SIDS - Sudden Infant Death Syndrome
SUDI - Sudden Unexpected Death in Infancy
TNF - Tumor Necrosis Factor
VAERS - Vaccine Adverse Events Reporting System
VLCAD- Very Long Chain acyl-CoA dehydrogenase
VSD - Vaccine Safety Datalink
.,
IMMUNIZE TION SAFETYREVIEW
UNEDITED, UNCORRECTED PROOFS
Representative terms from entire chapter:
unexpected death
