Targeting Sudden Infant Death

Syndrome (SIDS): A Strategic Plan

FROM CELLS TO SELVES

National Institute of Child Health and Human Development
Contents

The NICHD Mission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

The Strategic Planning Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5

Etiology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Prognostics and Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Preventive Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

Health Disparities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7

The Concept of “Risk” in SIDS Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8

Etiology and Pathogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

The Brain and Homeostatic Control . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Autonomic Development and Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12

Infant Care and the Sleep Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14

Infectious Disease and Immunity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16

Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17

Sudden and Unexpected Death in Childhood . . . . . . . . . . . . . . . . . . . . . . . . . 19

Infrastructure: DNA and Tissue Banks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20

Prognostics and Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Preventive Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

Infrastructure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Health Disparities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36

Infrastructure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Appendix—Roster of Advisors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39

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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan
FROM CELLS TO SELVES

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

Programs at the NICHD are based on the concepts that

adult health and well-being are determined in large

part by episodes early in life, sometimes before birth;

that human development is continuous throughout life;

and that optimal outcomes of development are

important not only to the individual but to society.

NICHD research is also directed toward restoring or

maximizing individual potential and functional capacity

when disease, injury, or a chronic disorder intervenes

in the developmental process. Thus, the NICHD mission

truly spans the life cycle, and much of the health and

well-being of our population depends on the success of

the Institute’s research.

The NICHD Mission

1

The National Institute of Child Health and Human

Development (NICHD) seeks to ensure that every

individual is born healthy, is born wanted, and has the

opportunity to fulfill his or her potential for a productive

life unhampered by disease or disability. The Institute

further strives to help parents have the children they

want, at the times they want them, and to ensure that

every mother experiences a pregnancy free of adverse

complications, and that persons with physical or mental

disabilities receive the maximum benefit of rehabilitation

to allow them to function as fully as possible in society.

Key to the success of this mission is answering the

fundamental questions of how a single fertilized cell

eventually develops into a fully functional adult human

being and how a multitude of genetic and environmental

factors influence that process for good or ill.
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3

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

During 1998 and 1999, the NICHD staff engaged the

scientific community in jointly developing a strategic

plan to facilitate achieving its mission.

The initial framework document for this plan, From Cells

to Selves, highlighted four areas for immediate strategic

development and described a series of scientific goals

under each area. These four areas were as follows:

• Genetics and Fetal Antecedents of Disease

Susceptibility includes the interaction of the genotype

with socioeconomic, environmental, and

psychological factors in the fetal and postnatal

environment that contribute to health or the

pathophysiology of diseases.

• Reproductive Health for the 21st Century comprises

the biological and behavioral factors that allow

couples to have healthy children when they want

them and the reproduction-related conditions that

may affect women during and after their 

reproductive years.

• Developmental Biology: Understanding Normal and

Abnormal Development consists of the basic

biological science necessary to understand early

development in utero and through the time when

many organ systems form.

• Biobehavioral Development includes research to better

understand the developmental processes involved in

forming cognitive, learning, emotional, social, and

physical behaviors, and the biological and

environmental factors that make infants, children, and

adolescents more susceptible to behavioral disorders

or to adopting risk-taking and violent behaviors.

Health Disparities: Bridging the Gap, a fifth strategic 

plan, was developed to better understand how natural

biological and behavioral forces interact with a variety

of social, community, and economic factors to produce

health disparities, and how to intervene to enhance the

health and well-being of these minority and

underserved populations.

In addition, at the request of the United States Congress,

the NICHD produced strategic plans in 1989 and 1995

that summarized advances in Sudden Infant Death

Syndrome (SIDS) research and made recommendations

identifying the most promising avenues of research to be

pursued over subsequent 5-year periods. In 1999,

Congress recommended that the Institute develop a third

5-year plan. Since the NICHD has been engaged in

strategic planning from 1998 to 2001, the planning

process for the SIDS program was integrated with the

development of other research agendas.

To formulate the new SIDS strategic plan, the NICHD

convened a working group comprising distinguished

scientists and health care professionals from around

the country. (See Appendix.) In collaboration with

NICHD staff, the working group identified and

prioritized research goals and suggested strategies to

meet those goals. The working group drew upon

ongoing planning efforts, previous emphasis areas,

recent forums, workshops, conferences, and research

findings to develop a draft of the strategic plan for a

SIDS research and public health agenda that would

guide the Institute for the next 5 years.

The Strategic Planning Process
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

4

The draft plan was posted on the NICHD Web site to

allow members of advocacy groups, nonprofit

organizations, the scientific community, and the general

public to comment. In addition, the Institute shared the

plan with members of the National Advisory Child

Health and Human Development Council and with the

Friends of the NICHD, a coalition of more than 100

professional and patient organizations committed to the

Institute’s scientific mission. After consolidating and

reviewing all comments, the NICHD revised and

finalized the plan. This document is intended as a

targeted, but flexible, blueprint that can be modified as

new scientific findings, research opportunities, or

resources become available.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

SIDS occurs worldwide. In the United States alone,

approximately 3,000 infants die each year from SIDS.

The majority of SIDS deaths occur before infants reach 

6 months of age. These deaths, although associated with

a sleep period, are sudden and unpredictable. In most

cases, infants appear healthy before succumbing to SIDS.

No explanation for these deaths can be found, even

when a complete postmortem is performed, including an

autopsy, an examination of the death scene, and a

review of the infant’s clinical and family history. In the

absence of an identifiable cause of death, these infants’

deaths are, by standard definition, labeled SIDS.

SIDS exacts a devastating emotional toll on affected

families and caregivers. In 1974, landmark

legislation—the Sudden Infant Death Syndrome Act 

(P.L. 93-270)—gave the NICHD the statutory

responsibility to oversee SIDS research. The Institute’s

ultimate goal is to eliminate SIDS. To reach this aim, it is

important to understand the underlying causes and

mechanisms of the syndrome, to develop strategies to

identify infants at high risk for sudden death, and to

develop and implement preventive strategies that can

effectively reduce the incidence of SIDS across diverse

populations.

Great progress has been achieved in understanding SIDS

and reducing the number of deaths caused by this tragic

disorder since the formulation of the first 5-year plan.

The plans served to organize the efforts of researchers,

clinicians, and Federal agencies. The decade’s most

significant accomplishments are as follows:

• Establishment of the Back to Sleep coalition 

and campaign;

• Revision of the SIDS definition and the development

of death investigation guidelines to improve the

scope and quality of information used to establish

the diagnosis;

• Formation of tissue banks to facilitate studies of

etiology and pathogenesis;

• Elucidation of the role of inborn errors of metabolism

in sudden infant death and the incorporation of

screening for disorders of fatty acid metabolism as a

diagnostic tool at autopsy;

• Establishment of a system to monitor infant care

practices and health outcomes associated with SIDS

risk reduction interventions;

• Identification of unsafe bedding practices in the infant

sleep environment;

• Delineation of the patterns of risk factors that

contribute to the increased incidence of SIDS in

specific minority populations;

• Assessment of current methods of cardiorespiratory

monitoring to identify useful physiologic markers of

SIDS risk; and

• Discovery of the neurologic abnormalities unique to

SIDS infants and exploration of how they may place

an infant at risk.

The specific advances in knowledge are described in the

background sections located throughout the plan.

Less than a decade ago, almost twice as many

American infants were dying of SIDS than is the case

today. By the early 1990s, the practice of placing

Introduction
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

6

infants to sleep on their stomachs had been identified 

as a significant risk factor. The subsequent

recommendation by the American Academy of

Pediatrics to place healthy babies on their backs to sleep

(side as an alternate position) and the success of the

NICHD-led national Back to Sleep campaign are

associated with a large decrease in the number of

infants placed to sleep on their stomachs and a 

40-percent reduction in SIDS rates between 1992 and

1998. As a result, about 2,000 fewer babies now die

each year than was the case in 1992. However, SIDS

still remains the leading cause of death in infants

between 1 month and 1 year of age in the United

States. Moreover, significant disparities in SIDS

prevalence rates still exist among various racial and

ethnic groups.

The purpose of this strategic plan is to build on past

successes and forge new paths of discovery. The

recommendations go beyond deaths labeled as SIDS by

medical examiners and coroners to include all sudden

deaths occurring from late fetal life through infancy and

early childhood. The plan defines strategies aimed at

improving maternal as well as infant health. It

encompasses both basic infant care practices and

research based on the latest molecular genetic

technologies. This framework will provide researchers

with the knowledge and resources needed to illuminate

the etiology of SIDS and, ultimately, to eliminate these

needless deaths.

The plan is divided into four sections: Etiology and

Pathogenesis, Prognostics and Diagnostics, Preventive

Strategies, and Health Disparities. Each section contains

a statement of the problem, background information,

and specific recommendations designed to address gaps

in our current state of knowledge or intervention

activities and to correct deficiencies in our basic

scientific infrastructure.

Etiology and

Pathogenesis

Knowledge acquired during the past decade supports

the general hypothesis that infants who die from SIDS

have abnormalities at birth that render them vulnerable

to potentially life-threatening challenges during infancy.

The recommendations in this section are targeted toward

understanding the following circumstances:

• How the neural abnormalities observable in SIDS

infants develop;

• How these neural abnormalities affect infant health

and development before and after birth;

• Whether there are genetic factors that predispose

infants to sudden death; and

• How specific characteristics of the fetal and postnatal

environment either contribute to the pathologic

process or serve to protect infants.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

We know that SIDS is a developmental disorder: it

originates during fetal development and occurs within a

distinct developmental window. Ongoing research into

the basic mechanisms governing normal development,

utilizing the latest technologies, will provide us with an

essential basis for understanding how developmental

processes go awry in SIDS infants. This approach is

founded on the basic principle that understanding

normal developmental processes is an essential

prerequisite for understanding derangements in

development, a principle which is strongly emphasized

in another of the Institute’s strategic plans, Developmental

Biology: Understanding Normal and Abnormal

Development. We also know that the health of the fetus

determines the health of the infant—another

fundamental principle reiterated in several current

NICHD strategic plans, most notably Genetics and Fetal

Antecedents of Disease Susceptibility and Biobehavioral

Development. The biological continuum linking fetal and

infant health or disease are carefully explored

throughout this SIDS strategic plan.

Prognostics and

Diagnostics

The development of fetal and neonatal screening tools to

identify fetuses and infants at high risk of sudden death

depends upon knowing—or at least having a strong

indication of—the functional abnormalities that are

responsible for death. Such knowledge is also

necessary for the development of effective therapies for

at-risk infants. Advances in the realm of prognostics

and diagnostics are likely to create new opportunities for

refining ongoing investigations into the etiology and

pathogenesis of SIDS. Although a slow process, as one

knowledge base grows so does the other. The

recommendations in this section address the assessment

of neural maturity and the development and predictive

value of screening tools.

Preventive Strategies

As often happens in public health, it is possible to

intervene successfully in the disease pathway and to

reduce morbidity or mortality without a full

understanding of the pathologic mechanism(s) involved.

During the next 5 years, we wish not only to bolster the

success of the Back to Sleep campaign but also to

diminish the prevalence of other SIDS risk factors.

The recommendations in this section emphasize the 

need for

• Strong community partnerships;

• Knowledge of cultural variations;

• Rigorous evaluations of interventions and feedback

from the lay community; 

• Comprehensive and consistent assessments of fetal

and infant deaths; and

• An understanding of how multiple risk factors 

may interact.

The need to build and maintain viable collaborative

partnerships with communities is a central theme of

another of the Institute’s strategic plans, Health

Disparities: Bridging the Gap. A recognition of the

essential value of collaborations among all the

stakeholder communities informs not only this section of

the SIDS strategic plan but also the following section.

Health Disparities

Although SIDS rates have declined in all populations

throughout the United States during the last decade,

disparities in SIDS rates and in the prevalence of risk

factors remain evident in certain groups. On a national

level, SIDS rates are highest among American Indians,

Alaskan Natives, and African Americans, and lowest

among Asians, Pacific Islanders, and Hispanics.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

8

However, prevalence rates vary within these groups

based on socioeconomic factors. The recommendations

in this section emphasize the following factors:

• The creation and maintenance of strong community

resources for research and intervention; 

• The investigation of both protective and adverse

forces operating within and across populations;

• The investigation of both macro (e.g., equity of care)

and micro (e.g., genetic predisposition) forces

operating within and across populations.

The Concept of “Risk”

in SIDS Research

The principal aims of this strategic plan are to focus

research resources and effort into scientifically

identifying risk factors for SIDS and to develop

intervention strategies that reduce the occurrence of

these tragic deaths. Many people have trouble

understanding the concept of “risk.” As it is defined by

epidemiologists, risk refers to the probability that an

outcome will occur given the presence of a particular

factor or set of factors.

Risk factors are identified through specific associations

with the outcome, and their contribution is expressed as

either decreasing or increasing the probability that the

outcome will occur. Scientifically identified associations

between risk factors (e.g., socioeconomic characteristics,

behaviors, or environmental exposures) and outcomes,

such as SIDS, do not necessarily denote causality. Other

explanations for the association must be considered, and

the mechanisms underlying the risk factor need to be

delineated. Furthermore, as discussed in this report, the

best current working model of SIDS suggests that more

than one scenario of pre-existing conditions and

initiating events may lead to SIDS.

Therefore, when a SIDS death occurs, it is important to

focus on all of the risk factors that may be involved.

Our goal is to develop knowledge that helps families

and caregivers provide the best supportive environment

for their children. We also wish to help families who

have experienced a SIDS death better understand what

has happened and why. We hope that this knowledge

will help SIDS families heal.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

Although deaths from SIDS still occur in this country

every day and we do not yet know its cause or causes,

we begin the millennium with tremendous excitement

about the great strides that have been made in SIDS

research over the past three decades. Almost three

decades ago, Congress passed landmark legislation that

gave the NICHD responsibility for SIDS research. Since

then, Institute-supported multidisciplinary teams of

medical and scientific investigators have focused on five

major areas in SIDS research: (1) the brain and

homeostatic control, (2) autonomic development and

function, (3) infant care and the sleep environment, 

(4) infection and immunity, and (5) genetics.

As we have acquired more knowledge, it has become

clear that these five broad areas of research are even

more relevant to a full understanding of the etiology

(cause) and pathogenesis (development of the disease

process) of SIDS than was suspected at the beginning of

these decades-long research efforts. What we now know

about the relationships between each of these research

areas and SIDS is detailed in the background material

introducing each of the following subsections. One major

goal of the 2001 Strategic Five-Year Plan is to eradicate

all SIDS deaths through understanding the etiology and

pathogenesis of the syndrome. Moreover, focusing the

five major areas of research on possible cause(s) of SIDS

is likely to result in the development of more specific—and

hence, more effective—prognostic, diagnostic, and

preventive strategies than are now available.

An overall “driving” hypothesis guiding SIDS research—

now commonly referred to as the “triple-risk

hypothesis”—has emerged during the past 30 years of

investigations into the syndrome’s etiology and

pathogenesis. This hypothesis, resulting from a synthesis

of the knowledge gained from separate investigations,

has been advanced in different ways and gradually

refined by many different researchers.

According to the triple-risk hypothesis, SIDS occurs when

three events impinge upon an infant simultaneously: 

(1) an underlying vulnerability in homeostatic control, 

(2) a critical developmental period in state-related

homeostatic control, and (3) an exogenous stressor(s)

that exacerbates the infant’s underlying vulnerability.

Homeostasis includes the vital functions of blood

pressure control, heart rate, respiration, chemoreception,

upper airway reflexes, and thermoregulatory control, as

well as the return of these functions to normal after stress

has occurred. The underlying vulnerability puts an

infant at risk for sudden death when he/she passes

through the critical developmental period and

encounters an exogenous stressor (e.g., stomach

sleeping position). The triple-risk hypothesis explains,

for example, why all infants do not die when placed in

the stomach sleeping position (i.e., they do not have the

underlying vulnerability), and why an exogenous

stressor (e.g., stomach sleeping position) can be

eliminated and thereby reduce mortality without our

understanding the cause of the underlying vulnerability

(etiology and pathogenesis). While most investigators

perceive an underlying vulnerability in the infant, some

investigators contend that healthy infants also are at risk

during the unstable, rapidly changing developmental

period in homeostatic control and when faced with a

life-threatening stress.

Etiology and Pathogenesis

Statement of the Problem
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

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The past 30 years of research have been particularly

exciting because different investigations have provided

compelling evidence in support of the triple-risk

hypothesis. We have learned that (1) the underlying

vulnerability most likely resides within the nervous

system, which regulates homeostatic control, (2) the

critical period likely relates to the development of the

nervous system, and its interactions with other

physiological systems, e.g., immunologic,

cardiovascular, and respiratory systems, and 

(3) exogenous risk factors most likely interact with neural

mechanisms that protect the infant from life-threatening

events. Moreover, there may be a continuum of sudden

death in early life that encompasses the last weeks of

gestation (stillbirths) and the first year of life (SIDS).

Epidemiologic studies have shown that the underlying

vulnerability may result from an adverse fetal exposure

to cigarette smoke. Neuropathological studies indicate

that the vulnerability may be due to a deficiency in a

serotonergic network of the brainstem in many SIDS

infants, thereby affecting regions of the brain involved in

homeostatic control. Developmental behaviorists have

identified clinical markers of autonomic function,

arousal, and behavioral maturity in infants. Laboratory

physiologists have demonstrated that the first 6 months

of life, the major risk period for SIDS, are a critical

period for the development of homeostatic mechanisms

and learned protective behaviors in all infants.

Epidemiologists and laboratory physiologists point to

exogenous stressors in the risk for SIDS, e.g., asphyxia

from the face-down sleeping position, soft bedding,

infection, and hyperthermia. A very important but stillunanswered question is the role of genetic factors in the

etiology of SIDS, particularly possible interaction(s)

between genetic and environmental factors.

We have learned that SIDS is an extraordinarily complex

problem, and eliminating SIDS requires a multidisciplinary

approach involving the efforts of pediatricians,

epidemiologists, pathologists, neuroscientists, geneticists,

infectious disease experts, nurses, and investigators in the

behavioral and social sciences, as well as other

disciplines. We have learned that daily infant-care

practices play a critical role. In addition, we have made

extraordinary technical advances in all fields, including,

for example, infectious diseases, with molecular screening

for microbial agents; genetics, with the human genome

project; and neuroscience, with modern techniques for

application directly to the human brain. Thus, the

groundwork is laid for major progress during the next 

5 years of SIDS research.

The Brain and

Homeostatic Control

Background

• SIDS brains may look “normal” with conventional

neuropathological techniques at autopsy. Powerful

research tools in quantitative neuroanatomy and

neurochemistry, however, have uncovered important

abnormalities within and above the brainstem in

SIDS brains.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

• These include deficits in serotonin receptors in the

medullary raphe, the arcuate nucleus, and related

regions of the brainstem, along with structural and

developmental delays in the cerebellum. All of these

regions have a common embryonic origin in fetal life.

• Other brain abnormalities reported in SIDS babies

include heavy brain weight, white matter injury and

developmental delay, and structural and

neurochemical abnormalities in the hypoglossal

nucleus, a region involved in the control of the

airway during waking and sleeping.

• It is unclear how all these findings relate to each other

because they have not all been studied in the same

brains. However, many of these findings are in

regions related to homeostatic control, and their

discovery in SIDS brains represents a critical first step.

• Brainstem regions in animals that are likely

homologous with the human arcuate (ventral medulla)

and raphe regions are known to be involved in the

development and control of breathing and blood

pressure, thermoregulation, sleep and arousal, and

the modulation of sensory and motor activity.

• Abnormal respiratory reflexes may explain the

greater susceptibility to SIDS when infants are

sleeping on their stomachs. Rebreathing of exhaled

gas rich in carbon dioxide and poor in oxygen may

fail to arouse and stimulate an infant with deficient

chemoreception. Laryngeal receptors that cause

apnea are more likely stimulated by reflux when the

infant is in the prone position, an undesirable effect

that may be exaggerated by brainstem abnormalities

in the control system.

• Abnormal thermoregulation and sleep architecture

may also contribute to risk because infants who sleep

on their stomachs lose heat less effectively and

experience fewer arousals.

Goals and Objectives

Goal: Elucidate the origin and range of brain

abnormalities in SIDS and other forms of sudden death

and reveal how these abnormalities are interrelated.

• Objective: Investigate the development of human

brain regions involved in homeostatic control during

gestation and early infancy, using neuroanatomic,

neurochemical, cellular, and molecular techniques.

• Objective: Investigate the development of regions

involved in homeostatic control in SIDS brains

compared with postconceptionally age-matched

control brains, including regions that have not been

adequately tested with research tools—e.g., the

hypothalamus, arousal systems, and the cerebellum—

using neuroanatomic, neurochemical, cellular, and

molecular techniques. Compare lesions [collected

and studied] before and after the beginning of the

Back to Sleep campaign.

• Objective: Study cerebral white matter

abnormalities indepth in SIDS infants, including

subtle gliosis, periventricular leukomalacia, lipidladen macrophages, and hypomyelination. Attempt

to correlate resultant findings with known biochemical

deficiencies and histories of perinatal hypoxia 

and ischemia.

• Objective: Assess the effects of environmental

insults known to put infants at risk for SIDS on 

human fetal brain development. These environmental

insults include prenatal exposures to tobacco smoke

and alcohol.

• Objective: Analyze the neuropathology of known

diseases of autonomic function—e.g., Prader-Willi,

Congenital Central Hypoventilation Syndrome

(CCHS)—for clues to guide the further analysis of SIDS

brains. Clues derived from these known autonomic

disorders will come from functional brain imaging.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

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• Objective: Investigate the neuropathology of

unexplained antepartum stillbirths in order to

understand the relationship between such stillbirths

and SIDS.

Goal: Understand the neurobiology of homeostatic

processes, especially during different states of arousal

and during development.

• Objective: Evaluate the functions of the ventral

medulla and the medullary raphe in homeostatic

regulation during various stages of development,

beginning in fetal life. The degree of abnormal

serotonin receptor binding and exclusivity to a

substantial subset of SIDS victims provides a valuable

clue; however, our current knowledge of the basic

neurobiological role of the medullary raphe in a

variety of homeostatic processes is incomplete.

• Objective: Evaluate the role of homeostatic

processes in nervous system development.

Genetically engineered or mutant animal models will

prove useful for this endeavor.

• Objective: Investigate the functional maturation of

sleep and arousal and how the arousal state

influences homeostatic physiologic control.

• Objective: Investigate the interactions among

homeostatic control systems because SIDS and

related types of sudden death are likely to result from

the inadequate function of more than one

neurobiological process.

• Objective: Model and study lethal scenarios and

protective reflexes, such as the laryngeal

chemoreflex, during development. Investigate the

possibility that presumably homeostatic processes or

protective responses, if exaggerated by the

malfunction of modulatory neurons or initiated at an

inopportune time, may become maladaptive.

• Objective: Further define the central nervous

system sites of physiologic dysfunction by integrating

postmortem findings with physiologic studies in both

humans and animals.

Autonomic

Development and

Function

Background

• The autonomic nervous system (ANS) regulates many

of the rescue responses to potentially life-threatening

events, including responses to respiratory, cardiac,

thermal, and blood pressure challenges. These

cardiorespiratory challenges frequently occur during

sleep and during transitions between sleep states.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

• ANS dysfunction and/or an altered trajectory in the

development of this system are features found in

many infants who have subsequently succumbed to

SIDS. This ANS dysfunction appears to arise before

birth owing to a compromised fetal environment.

• The peak incidence of SIDS occurs during a period of

major reorganization of the autonomic nervous system.

Measures of autonomic control show dramatic changes

and instability during this transition period.

• An infant’s defensive behaviors to respiratory

challenges, such as rebreathing expired air, are

compromised in the facedown position or when

covered by loose bedding. Vulnerable infants 

also may have altered responses to changes in

oxygen levels associated with sleeping under these

risk conditions.

• Several physiologic responses mediated by the ANS

are depressed when infants sleep on their stomachs.

These include reactivity to noise, sudden decreases in

blood pressure, and tactile stimulation. There is also

a reduction in heart rate control in the prone

position, as well as decreased movement, less

wakening, longer periods of deep sleep, and higher

arousal thresholds.

• The heart rate response following postural adjustment

(tilt) is a reliable measure of the competence of

neural mechanisms to process and respond to sudden

changes in blood pressure. During the vulnerable

period for SIDS, infants have diminished responses to

this challenge.

• Epidemiologic studies have reaffirmed a strong

relationship between amounts of cigarette smoking

during pregnancy and SIDS. The development of

neural substrates for autonomic control is susceptible

to the known toxic effects of exposure to alcohol and

smoking during gestation. Basic research has

pointed to a relationship between nicotine exposure

and autonomic function during the fetal period.

Smoking has also been shown to lead to low

birthweight, alterations in baseline heart rate and

blood pressure, and blunted responses to hypoxia,

which are characteristics of many SIDS victims.

• Recent psychobiological research findings suggest

that important continuities exist in fetal and infant

neurobehavior. Individual differences in patterns of

fetal heart rate, movement, and sleep-state

organization predict similar patterns in newborns

and older infants.

Goals and Objectives

Goal: Elucidate the role of the continuity of fetal and

infant autonomic development and dysfunction in the

etiology of sudden unexplained deaths.

• Objective: Study the longitudinal development of

fetal-to-infant cardiorespiratory and cardiovascular

control. In addition to illuminating the origin and

nature of the pathogenic process, these studies may

help to identify the most vulnerable infants before

they enter the period of greatest risk.

• Objective: Investigate the role of prenatal

environmental factors (e.g., smoking, nutrition, 

toxins) that function to degrade or improve the

capability of the ANS to respond to potentially lifethreatening challenges.

• Objective: Initiate multidisciplinary approaches to

investigate interactive effects of smoking with other

prenatal risk factors, such as alcohol, stress, and 

fetal nutrition.

• Objective: Extend investigations of developmental

neurobehavioral deficits to other clinical entities, 

such as fetal demise, stillbirth, or childhood syncope

(fainting), which may share similar risk profiles as

well as central nervous system (CNS) deficits 

with SIDS.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

14

• Objective: Investigate the contribution of preterm

birth to autonomic dysfunction and SIDS pathogenesis.

Goal: Investigate the repertoire of responses to lifethreatening challenges in the infant’s environment.

• Objective: Continue to study the developmental

changes in control of breathing as well as the

compensatory behavioral changes required under

conditions of reduced oxygen and increased carbon

dioxide (rebreathing of expired air).

• Objective: Evaluate mechanisms required to

mount adequate cardiovascular responses to

hypotensive challenges during the vulnerable period

for SIDS.

• Objective: Understand the mechanisms underlying

a possible shock-like response leading to sudden

death in infants. Include studies of related autonomic

disorders, such as Congenital Central Hypoventilation

Syndrome, which is characterized by a number of

physiologic deficits similar to those of infants who

later succumb to SIDS, including lower heart rate

variability and cardiorespiratory responses to blood

pressure challenges.

• Objective: Investigate the long-term effects of

postnatal environmental factors (e.g., sleep position,

thermal stress) on the development and function of

the ANS.

Infant Care and the

Sleep Environment

Background

• Depending on the study, between 10 and 60 percent

of SIDS infants are found with their face, head, or

entire body covered by a blanket, comforter, pillow, or

other form of bedding. Between 25 and 50 percent

are found dead facedown in the bedding. Laboratory

studies have shown that these situations can cause fatal

asphyxia and/or dangerous overheating; these are

presumed to be the lethal mechanisms underlying the

increased risk of sudden death that is associated with

a prone sleeping position.

• Epidemiologic studies have shown that soft bedding,

such as sheep skins, pillows, quilts, or soft mattresses

of several types, are risk factors for SIDS, particularly

in infants who sleep prone.

• “Accidental suffocation” is a preventable cause of

death in infancy that occurs somewhat less frequently

than SIDS: 0.1-0.5/1,000 live births affected by

accidental suffocation versus 0.7/1,000 live births

affected by SIDS. Accidental suffocation is difficult to

distinguish from SIDS because postmortem findings

may be similar and the age of peak risk overlaps

between the two. The diagnosis often depends on an

estimation of whether an infant would have been

physically capable of escaping entrapment. Since

this is often a subjective assessment, such judgments

tend to further obscure differences between SIDS and

accidental suffocation cases.

• Use of adult furniture, such as sofas or adult beds, is

a risk factor for both SIDS and accidental suffocation.

The potential for entrapment created by crevices in

bedding, the presence of bed partners, and the lack

of protective barriers may, in part, underlie this risk.

• Infants who are unaccustomed to sleeping on their

stomachs are at risk for SIDS when they are put

down prone or turn onto their stomachs

spontaneously. A high percentage of such infants

are found facedown at death. Studies suggest that

head turning to avoid airway obstruction or

rebreathing is a learned behavior.
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15

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

• Some studies have shown that if an infant is sleeping

in the same room with the mother but in a separate

bed space (crib or bassinet), the risk for SIDS is lower

in comparison with putting the infant to sleep in a

separate room.

• Mothers and infants sleeping together on a shared

surface (e.g. bed, mat, floor) is widely practiced

throughout the world. Factors that increase the risk

for SIDS or accidental suffocation under bed-sharing

conditions include characteristics of the bed or

bedding that create a potential for falling to the floor

or entrapment, maternal cigarette smoking, maternal

use of alcohol in moderate to large amounts,

excessive maternal fatigue, and bed-sharing with

individuals other than the mother.

• Intentional suffocation is often impossible to

distinguish from SIDS and may be the true diagnosis

in no more than 5 percent of SIDS cases.

Goals and Objectives

Goal: Elucidate the infant’s neural capacity to avoid

risky sleeping situations.

• Objective: Develop reliable examination

techniques to determine an infant’s capacity to

arouse, and avoid facedown or other potentially

asphyxiating situations.

• Objective: Investigate thermal control in infants

and potential thermal stressors.

• Objective: Consider collaborations with other

Federal agencies to develop practical standards for

assessing bedding softness, rebreathing, and thermal

insulation characteristics (togs) that can be

interpreted readily by industry and infant caregivers.

• Objective: Determine whether “tummy time” or

other types of experience improve an infant’s ability

to avoid potentially asphyxiating situations (e.g.,

lying facedown with the head covered).

• Objective: Perform studies of infant behaviors and

neurologic development predisposing to entrapment

and to the ability to evade or escape entrapment in

order to improve the design of safe child furnishings.

Goal: Elucidate traditional and new methods of child

care and the use of bedding with the potential to reduce

the risk of sudden death.

• Objective: Investigate types of bedding that

provide adequate insulation without rebreathing or

thermal-stress risks.

• Objective: Investigate methods of child care that

might minimize the risk of infants spontaneously

turning to the prone position, covering their heads, or

suffering from “wedging” deaths during sleep.

Examples include the use of the Dutch sleeping sack,

Polynesian hammocks, modern car seats, and Native

American cradle boards.

Goal: Elucidate differences between SIDS and

accidental suffocation.

• Objective: Develop new forensic tools that will

assist in distinguishing SIDS from accidental and/or

intentional suffocation.

• Objective: Perform forensic studies to clarify 

and standardize the diagnoses of SIDS, 

accidental suffocation, positional asphyxia,

intentional suffocation, overlaying, and cause of

death undetermined.

• Objective: Perform epidemiologic studies of SIDS,

accidental suffocation, and cause of death

undetermined with particular emphasis on child care

practices (e.g., room sharing, bed sharing).
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

16

Goal: Elucidate the role of child care practices

prevalent in day care in relationship to SIDS.

• Objective: Study sudden unexpected deaths that

occur while infants are being cared for by day-care

providers (licensed and unlicensed) in order to

identify specific risk factors that might be increased in

these settings. A case-controlled setting might

uncover novel risk factors, such as the timing or

frequency of infant observation.

Infectious Disease 

and Immunity

Background

• Several factors suggest a role for infection in the

pathogenesis of SIDS: (1) the increased occurrence

of SIDS in winter and spring when increased

infectious respiratory and gastrointestinal diseases

are seen in infants, (2) the peak occurrence of SIDS

with the waning occurrence of maternal immunity

and first exposures to many pathogens, and (3) the

association of SIDS deaths with recent upperrespiratory-tract and gastrointestinal infections.

• A role for infection in SIDS is also suggested by

autopsy findings of mild inflammatory changes at a

variety of levels of the respiratory tract and elevations

of specific inflammatory cytokines, chemokines,

and/or pathogen- or toxin-specific antibodies in a

variety of body fluids or tissues in SIDS babies.

• The increased risk for SIDS associated with lower

socioeconomic status may relate to an increased

exposure to infectious agents at a younger age.

• The decreased risk for SIDS associated with

breastfeeding may relate to immune factors 

passed to the infant through breast milk.

• Over the past 30 years, multiple attempts have been

made to directly link pathogens (such as respiratory

syncitial virus, enteroviruses, Staphylococcus aureus,

and Clostridia species) to SIDS, but numerous

methodological and technical problems have

characterized these studies, and they all remain

inconclusive. Their weaknesses include small sample

size and the lack of appropriate controls. Many of

the infectious agents are ubiquitous, with only loose

associations with SIDS. No single pathogen has

been proven to cause SIDS or a subset of SIDS.

• Proposed potential mechanisms for the role of

infection in SIDS include partial airway obstruction

by respiratory tract infection, which may lead to

disorders of sleep arousal, sleep deprivation stress,

or apnea, and complex theories of inflammation

(i.e., cytokine-induced changes affecting the central

nervous system). The studies performed to date often

attempt to implicate infectious agents working in

conjunction with other cofactors, such as prenatal

nicotine exposure and sleep position. Direct

evidence for these theories is lacking.

Goals and Objectives

Goal: Elucidate immunologic/inflammatory responses

influenced by a variety of infectious agents and their

interactions with the host, the developing infant.

• Objective: Determine the common pathways of the

inflammatory response incited by a wide variety of

infectious agents, and the mechanisms that may

affect other known developmental physiological

factors, such as sleep patterns and arousal.
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17

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

• Objective: Determine developmental aspects of the

immune system that may alter the inflammatory

response in the SIDS age range.

• Objective: Determine novel pathophysiologic

mechanisms of particular pathogenic agents that

involve one or more homeostatic systems and result in

sudden death in infancy.

Goal: Examine the contribution of infectious agents

in the context of carefully designed large-scale,

prospective epidemiologic (case control) studies of SIDS.

• Objective: Analyze a wide variety of infectious

agents, looking for common pathways and

interactions with known SIDS risk factors and current

etiologic hypotheses. Avoid bias towards identifying

a role for a specific pathogen unless a particularly

unique mechanism can be elucidated.

• Objective: Delineate the natural history (rates of

infection and colonization) of potentially contributing

infectious agents in the infant population, and their

interactions with the host immune system

(inflammatory response).

Genetics

Background

• Studies to determine whether SIDS is hereditary show

that SIDS does not behave like a classical genetic

disease with a 25- to 50-percent risk of occurrence

among siblings. There is controversy over whether

SIDS recurs in families, but if it does, the risk for

subsequent siblings is probably less than 0.5 percent.

• Since SIDS is a syndrome, genetic factors will likely

be of variable importance, playing a small role in

some cases and being of major importance in others.

As environmental risk factors, such as sleep position,

are identified and minimized through public

education campaigns, genetic causes of SIDS may

play an increasingly more decisive role in the

remaining cases.

• Known genetic disorders of metabolism likely account

for up to 5 percent of SIDS cases. Other genetic

diseases, such as prolonged QT syndrome, may

contribute to SIDS in a small percentage of cases.

• Increasing knowledge of SIDS-associated

abnormalities, such as developmental brainstem

anomalies or association with upper respiratory

infections, is suggesting possible genetic risk factors

(i.e., “susceptibility genes”) that may predispose an

infant to SIDS.

• Genetic factors or their interactions with

environmental factors may account in part for the

variations in SIDS incidence observed across

subgroups of the population. The incidence of SIDS

varies widely among racial and ethnic groups in the

United States, yet it is not clear to what extent genetic

factors may contribute to this variation.

• The successful completion of a complete DNA

sequence of the human genome is providing research

opportunities to identify genes that may influence an

infant’s risk for SIDS.

• Knowledge of the structure and sequence of all

human genes has made it possible to screen 

rapidly and easily any potential SIDS-related gene

for mutations.

• The development of rapid and efficient methods for

identifying natural variations in the human genome is

making genomewide searches for SIDS-susceptibility

genes possible.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

18

• Identification of the complete repertoire of human

genes and the development of high-throughput

microarray-based methods to measure gene

expression have made it possible to examine the

complete pattern of gene expression in the tissues of

SIDS victims.

Goals and Objectives

Goal: Elucidate the role of gene-environment

interactions in SIDS and related disorders.

• Objective: Conduct genetic epidemiologic studies

to characterize the distribution of genetic traits and

outcomes related to SIDS in populations or families 

to include disorders of fetal development, autonomic

disorders, stillbirths, and other infant and 

childhood deaths.

• Objective: Conduct epidemiologic studies to

characterize the determinants of the distribution of

genetic traits and their relation to disease in

populations or families.

Goal: Evaluate potential “SIDS genes” through

mutation searches and association studies of potential

candidate genes to be selected based on their known

relationships to physiologic processes relevant to SIDS.

• Objective: Evaluate the incidence of known

genetic disorders, such as metabolic diseases of fatty

acid metabolism or inherited cardiac arrhythmias,

including long-QT syndrome, among cases of SIDS.

Encourage multidisciplinary studies that utilize

genetic, biochemical, and pathologic approaches to

identify and characterize SIDS cases attributable to

single-gene disorders.

• Objective: Identify and evaluate potential

associations between genotypic polymorphisms in

candidate SIDS-susceptibility genes and SIDS.

Candidates will be chosen based on knowledge of

SIDS epidemiologic risk factors, such as recent

infection (e.g., cytokines, complement genes) and

overheating (e.g., heat shock genes) as well as

neuropathologic studies implicating abnormal

brainstem development and cranial dysmorphism

(e.g., homeobox and other developmental genes).

Goal: Identify SIDS-susceptibility genes through

large-scale genomewide association studies in clearly

defined high- and low-risk populations.

• Objective: Collaborate with other Institutes to

encourage the development of methods for highthroughput genotyping methods for the analysis of

functional genetic polymorphisms and silent single

nucleotide polymorphisms (SNPs).
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19

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

• Objective: Support one or several large-scale

genetic association studies using high-density maps

of functional and nonfunctional SNPs to identify

genes and regions associated with increased

susceptibility to SIDS.

• Objective: Conduct followup studies to determine

the role(s) played by these genes in normal

development and/or homeostasis, and identify

particular environmental risk cofactors that may act

in concert with each susceptibility gene.

Goal: Understand the “vulnerable” physiologic state

of dysfunctional tissues associated with SIDS and related

deaths in order to elucidate interactions with known

environmental risk factors.

• Objective: Support research utilizing the latest

advances in microarray-based gene expression

studies to characterize global patterns of gene

expression in the tissues of SIDS victims and normal

controls. Anatomic areas to be examined will be

selected on the basis of current anatomic studies

implicating abnormal development of specific regions.

• Objective: Support second-generation proteomic

studies of SIDS and control tissues to confirm and

extend the results of the gene expression studies.

• Objective: Facilitate multidisciplinary

collaborations to correlate patterns of gene and

protein expression with epidemiologic, clinical,

physiologic, and pathologic data for a more

complete understanding of the role of gene

expression in the disease process.

Sudden and

Unexpected Death 

in Childhood

Background

• About 175 children between the ages of 1 and 4 

die in the United States each year from unknown

causes, a substantial fraction of these are sudden

and unexpected.

• Sudden and unexpected death in childhood, although

rare, is devastating.

Goals and Objectives

Goal: Understand the underlying causes and

mechanisms of sudden unexpected death in children

between 1 and 4 years and their relationship to SIDS.

• Objective: Evaluate trends in the incidence of

sudden and unexpected childhood deaths in the

United States and abroad from 1985 to the present.

• Objective: Evaluate the relationship between these

deaths and SIDS by investigating the epidemiology,

genetics, and pathology of these cases.

• Objective: Evaluate the contribution of inborn

errors of metabolism and cardiac arrhythmias to the

cause of death in these cases.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

20

Infrastructure: 

DNA and Tissue Banks

Background

• Developmental banks provide an opportunity for

investigators to obtain samples from victims of rare

disorders and deceased normal controls, which are

equally rare.

• Establishing banks permits adequate sample sizes to

be collected more quickly than any individual

researcher is capable of doing alone.

• Banks follow standard clinical, pathologic, and

biochemical protocols, which facilitate uniformity in

the quality of the research material and ensure the

collection of necessary case information.

Goals and Objectives

Goal: Continue the NICHD-sponsored “Brain and

Tissue Banks for Developmental Disorders” program,

which banks samples of normal and diseased brain

tissues from fetal life through adolescence. These brain

banks make clinicopathologic data available for

correlation with brain findings and have proven to be

useful for SIDS research.

• Objective: These banks should have provisions to

permit different investigators working on different

parts of the same brain to compare their findings;

similarly, they should facilitate the correlation of

investigators’ systemic findings in different organ

systems of the body. In this way, all the findings

relating to one case could be integrated, and a more

complete clinicopathologic picture would emerge.

• Objective: Encourage the collection and

annotation of pathologic specimens for biochemical

studies of gene and protein expression, and

infectious agents. Support the development of a

centralized database listing availability and clinical

and pathologic characteristics of specimens from

critical tissues of SIDS victims, such as the brainstem,

liver, bone marrow, and blood.

Goal: Facilitate future genetic studies of SIDS

through the development of DNA and tissue banks for

specimens from SIDS victims and relatives, including full

and half-siblings.

• Objective: Support the development of a

comprehensive DNA bank to include specimens from

SIDS victims, their parents, and siblings. DNA

samples should be linked to phenotypic data

collected through new and existing NICHD-supported

clinical studies. Coded DNA samples should be

made available to qualified investigators for genetic

studies of candidate SIDS-related genes and

genomewide searches for genetic risk factors for

SIDS. Prospective informed consent will allow

recontact of families for appropriate followup studies.

• Objective: Consider utilizing nontraditional

sources for the collection of biologic specimens, such

as banked blood spots, or specimens banked from

past or ongoing epidemiologic studies of pregnant

women and their offspring.
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21

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

Despite our knowledge of selected SIDS risk factors, no

population characteristics have been identified that

provide sufficient predictive value to permit the

prospective identification of an individual infant at risk

for SIDS. Although geographic and socioeconomic

disparities exist, most infants who die from SIDS do not

fall into any well-defined risk group. Although the

majority of SIDS deaths may be associated with a single

underlying mechanism, infants currently considered to

have died from SIDS include deaths from a number of

distinct causes. Therefore, the sensitivity of any

screening test based on one mechanism of death would

be limited since it would not be expected to identify

infants at risk of death from alternative causes. In

addition, the specificity of screening may be limited

since it is likely that only a fraction of those infants who

have an underlying vulnerability for a particular cause

of SIDS will go on to die.

Based on the studies available to date, it may be

unrealistic to expect an individual screening test to have

a sensitivity surpassing 50 percent or a specificity

greater than 97 percent. If such a screening test were

implemented, based on the current SIDS rate in the

United States of 0.7 per 1,000, the proportion of SIDS

deaths even among infants testing positive would be

approximately 1 percent. The low rate of occurrence of

SIDS makes it particularly difficult to perform the

prospective studies needed to validate screening tools.

However, the development of methods of identifying

infants at higher risk of SIDS would greatly enhance

research efforts. Following an initial screening, which

would have to test large numbers of infants efficiently in

order to be useful, those with a high risk of SIDS 

(e.g., 1 percent or greater) would then become

candidates for more intensive study.

Without a means of identifying infants or groups of

infants at high risk for SIDS, studies that are invasive,

expensive, and/or time consuming are not practical.

For example, studies that have used home

cardiorespiratory monitoring have been able to shed

light only on the nature of the cardiorespiratory events

experienced. Home monitoring as currently performed

is not a practical approach for the study of a population

Prognostics and Diagnostics

Statement of the Problem
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

22

sufficiently large enough to draw meaningful conclusions

with regard to SIDS. However, data gathered from

infants who succumbed while on monitors have helped

shape investigations into certain physiologic deficits that

may lead to SIDS. 

It is likely that continued research into the basic

mechanisms underlying SIDS will nourish developments

in prognostics and diagnostics. For example,

neuropathologic studies of SIDS victims point to likely

candidates for markers of autonomic deficits. In

addition, investigations of possible genetic contributions

may ultimately lead to prenatal and neonatal screening

procedures for diseases and disorders associated 

with SIDS.

Continued epidemiologic investigation of genetic and

environmental factors, in concert with investigations of

developmental physiology and neuropathology

associated with SIDS, will provide far greater specificity

than possible today to define risk groups. Studying

infants from high-risk groups may then offer an

opportunity to identify potential markers or profiles that

may be associated with an individual’s vulnerability for

SIDS. Preventative or therapeutic strategies could then

be designed based on rigorous diagnostic criteria and

could be targeted at the specific underlying deficits

found in high-risk populations or individuals.

Background

• Prospective studies of large numbers of infants have

identified characteristics that are more common in

newborns who subsequently died of SIDS compared

with living newborns, including higher heart rates,

reduced heart rate variability associated with

respiration, increased variability of breathing during

quiet sleep, abnormalities in the beat-to-beat

dynamics of cardiac control, prolonged QT intervals,

and abnormal acoustical cry characteristics.

• Prospective studies replicating these findings and

evaluating the relationship of each of these variables

to one another have not been done.

• Alternative linear and nonlinear methods of

measuring heart rate variability have been proposed

as markers of autonomic instability. Among linear

analyses, time and frequency domain approaches

are used to exploit heart rate rhythms as a means of

assessing maturation of cardiac and ANS control

during the fetal and early infant period. Since

decreased heart rate variability under different

conditions—e.g., during deep sleep or in the prone

position—may be a sign of autonomic impairment,

this measure may provide a means of very early

assessment of risk for autonomic dysfunction during

the late fetal and neonatal periods.

• Nonlinear analyses of instantaneous heart interval

have been useful in identifying adults with cardiac

disease who are at imminent risk of heart attack.

These alternative approaches for evaluating heart

rate variability may provide an opportunity to better

quantify disturbances in heart rate variability that

have been found using more conventional

approaches to study SIDS.

• The heart rate response following postural adjustment

(tilt) is a reliable measure of the competence of

neural mechanisms to process and respond to sudden

changes in blood pressure. The degree of

vasoconstriction in response to tilt is also emerging as

a promising measure of ANS development. During

the vulnerable period for SIDS, infants have

diminished responses to this type of challenge.

• Studies that have utilized home monitoring have 

been able to shed light only on the nature of

cardiorespiratory events experienced. Home

monitoring as currently performed is not a 
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23

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

practical approach for the study of a sufficiently large

population to draw meaningful conclusions with

regard to SIDS.

Goals and Objectives

Goal: Develop technology for assessing SIDS risk

factors in large populations.

• Objective: Utilizing advances in technology,

including digital storage capacity and signal

processing techniques, develop systems capable of

efficiently processing physiologic and other signals

that have been or may be described as associated

with increased risk for SIDS, including heart rate and

blood pressure coherence and variability, QT

interval, breathing rate variability, and cry acoustics.

Goal: Identify screening tests for SIDS capable of

identifying infants at high risk of SIDS in whom indepth

prospective studies would be feasible.

• Objective: Encourage and support research 

that would utilize experimental designs, such as

randomized clinical or community trials, to evaluate

screening tools empirically. This would include, but

not be limited to, measurement issues such as

sensitivity, specificity, and predictive value of existing

or promising new screening tools. Trials that are

sensitive and responsive to the characteristics of 

the target population (such as racial/ethnic and

sociocultural factors) should be especially encouraged.

• Objective: Based on existing data sets and new

studies, assess developmental patterns in

characteristics that have been reported as associated

with increased risk for SIDS.

• Objective: Assess the interrater reliability and

validity of proposed infant assessments, and

develop and disseminate guidelines for the

appropriate performance of proposed infant

assessment techniques.

Goal: Develop assessments derived from the

integration of postmortem findings with physiologic

studies.

• Objective: Support research for the development

of noninvasive probes of function known to be

associated with deficits in brainstem areas, e.g.,

thermoregulation, sensory and motor activity, 

control of breathing, sleep arousal, and

cardiovascular reactivity.

Goal: Encourage methodologies for assessments of

developmental neurobehavioral deficits of clinical entities

possibly related to SIDS, such as fetal demise and

childhood syncope (fainting), which may share similar

risk profiles as well as central nervous system deficits.

• Objective: Support research for the development

of tools to assess the competencies required to mount

adequate cardiovascular responses to hypotensive

challenges during the vulnerable period for SIDS.

• Objective: Quantify continuities in fetal-to-infant

cardiorespiratory control in order to identify the most

vulnerable infants before they enter the period of

greatest risk.

• Objective: Develop noninvasive techniques to

assess the maturation of compensatory mechanisms

in high-risk groups, including gasping ability, the

ability to arouse to a safer state, and somatomotor

adjustments needed to respond to challenges during

the vulnerable period.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

24

• Objective: Perform studies to elucidate underlying

physiologic vulnerabilities in infants of mothers who

smoked during pregnancy and in low-birthweight

infants, both of which are at increased risk of SIDS

according to epidemiologic studies.

Goal: Evaluate prenatal and neonatal screening

procedures for diseases and disorders associated 

with SIDS.

• Objective: Development of improved methods for

the early detection of fatty acid oxidation disorders is

needed to allow for interventions to prevent metabolic

crises that can lead to sudden infant deaths.

— Encourage development and evaluation of highthroughput, high-sensitivity screening tests, e.g.,

tandem mass spectroscopy, to detect fatty acid

oxidation disorders as a group.

— Support development and evaluation of efficient

and sensitive genetic mutation detection methods

for each of the fatty acid oxidation pathway

genes associated with SIDS.

• Objective: Evaluate the contribution of prolonged

QT syndrome and associated genotypes to sudden

deaths in infancy.
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25

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

When we think of preventing disease, the classic

example is infectious disease. In this case, vaccination

and public health strategies to reduce the exposure to an

infectious agent protect individuals from contracting the

infection. However, most human diseases and disorders

result from multiple interacting factors that include

individuals’ genetic makeup, their lifestyles, and the

physical and cultural environment in which they live.

Thus, when we are concerned with prevention strategies,

we must understand the extent to which particular

factors in the population increase or decrease the

probability of disease development. Those factors

deemed to most strongly influence the degree of risk are

targeted for intervention.

In the section on Etiology and Pathogenesis, we

presented a triple-risk model for SIDS. According to this

model, if we can eliminate prenatal factors that increase

the risk of developmental abnormalities in the fetus, we

may reduce the likelihood of a SIDS death. If we can

positively alter the developmental trajectory during the

critical period, we may also reduce the likelihood of a

SIDS event. Removing environmental risk factors in the

critical period that are hazardous to the infant may also

be effective in reducing risk. Placing an infant on the

back to sleep is an excellent example of reducing a

major environmental risk factor.

The more we know about how risk factors contribute to

SIDS pathogenesis, the more confident we can be that

an infant will not succumb to SIDS. SIDS occurs during

the early months of an infant’s life, when he or she is

extremely dependent on the caregiver. It is a time of

adjustment and learning for the infant and the 

caregiver, as each gets to know the other and the baby

becomes familiar with the extrauterine environment. 

The early months are also a time of rapid growth 

and development, with changing nutritional and 

sleep requirements.

To prepare for these changes, the baby needs a healthy

start during the prenatal period. What are the

requirements for normal development? What factors

increase the likelihood that the developmental process

will go awry? How can we reduce the risk that they

might? Our knowledge of human development in fetal

life and early infancy is still quite limited. Although

research on SIDS risk factors has identified prenatal and

postnatal environmental characteristics and care

practices that are critical to healthy outcomes, more

research is needed.

Historically, women are the primary decision-makers for

family health care and the major caregivers for infants,

children, and elderly relatives. In modern times,

additional demands and stresses occur as more and

more women work outside the home as well as within it.

Furthermore, the proportion of single-parent households

headed by women continues to increase. Therefore,

preventive strategies targeting SIDS must, of necessity,

also address issues of women’s health. Women’s health

during the periconceptional, prenatal, and postnatal

periods profoundly influences the health of the

developing fetus and the newborn.

Since we cannot presently identify those individual

infants who are predisposed to SIDS, any intervention

aimed at reducing the risk of SIDS must be designed for

Preventive Strategies

Statement of the Problem
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

26

the entire population of babies and/or pregnant women.

In the United States, our society is heterogeneous.

Subpopulations can be defined by many criteria, such

as geography, race, ethnicity, or socioeconomic

characteristics. We have learned that the definition of a

population will influence the development of the risk

profile, the nature of the intervention, and the way in

which an intervention is implemented. During the next 

5 years, efforts to improve the effectiveness of SIDS riskreduction interventions will need to harness the strengths

that lie within communities and cultures.

Research

Background

• Case-control studies have identified the following

maternal characteristics as increasing the risk for

SIDS: maternal age under 20 at first pregnancy, a

short interval between pregnancies, late or no

prenatal care, placental abnormalities, and urinary

tract infection during pregnancy.

• Maternal cigarette smoking during pregnancy

increases the risk of SIDS about threefold,

independent of the birthweight of the baby. The risk

increases with the number of cigarettes smoked 

per day.

• Some studies have shown that cigarette smoke in the

baby’s environment after birth also increases SIDS

risk. The risk has been shown to increase with either

the number of cigarettes smoked by the parents or

the number of hours the infant spends in the

presence of smokers. However, it is difficult to

separate the contribution of prenatal and postnatal

smoke exposure.

• Maternal drug abuse during pregnancy increases the

risk for SIDS, and preliminary findings suggest that

maternal binge drinking also increases risk.

• Low birthweight and prematurity increase the risk of

SIDS; the risk increases with decreasing birthweight

and gestational age.

• If an infant is placed to sleep in the prone position,

the risk for SIDS is increased threefold to ninefold.

Most studies have found that infants placed to sleep

on their sides are at twofold increased risk compared

with those placed on their backs.
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27

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

• If an infant is placed to sleep on soft bedding,

including blankets, pillows, sofas, and adult bed

mattresses, the risk for SIDS increases. The use of a

quilt increases the risk of SIDS for infants placed to

sleep on their backs. Many SIDS infants are found

dead with the head or face covered with bedding.

• The presence of recent viral, respiratory, or

gastrointestinal illnesses enhances the risk for an infant

placed to sleep on the stomach or for an infant who is

over bundled (i.e., covered by more clothes and

blankets than necessary for the room temperature).

• Although sharing a room with the parents may be

protective, sharing a bed appears to increase risk

under certain conditions. These include maternal

smoking, recent maternal alcohol consumption, and

parental fatigue, as well as the use of a quilt to cover

the infant and the infant sleeping with individuals

other than parents.

• Some studies have found that infants who are

breastfed are less likely to die from SIDS. However,

other studies have failed to find a protective effect

after other factors have been taken into account.

Infants who are bottle-fed are not at increased risk

for SIDS.

• Several studies have shown that infants who use

pacifiers are at decreased risk of SIDS.

• Preliminary results from a study of infant mortality

among Northern Plains Indians demonstrate that

home visits by public health nursing personnel have a

strong protective effect on infants at risk of SIDS.

Goals and Objectives

Goal: Continue to elucidate environmental risk

factors and the timing of exposures that are amenable to

public health action.

• Objective: Foster multidisciplinary research

focusing on known risk factors for SIDS (e.g., smaller

birth size, earlier maternal age, multiple births) and

relatively unstudied environmental agents, including

chemicals (e.g., pesticides, heavy metals, persistent

organochlorines) and physical agents (e.g.,

temperature, air particulate matter) in order to

delineate the role of each in the pathophysiology of

SIDS. Certain environmental agents have been

linked to reduced birth size and developmental

delays in infants, both of which are associated with

an increased risk of SIDS.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

28

• Objective: Support research to determine the

period of fetal or infant vulnerability or susceptibility

to environmental agents. Research designs that

support the use of statistical techniques to assess

methodological issues such as the timing and

duration of exposures (before, during, and after

pregnancy) are needed.

Goal: Continue to examine the role of maternal

health before and after birth in influencing SIDS risk and

the risk for unexplained stillbirths.

• Objective: Foster multidisciplinary research to

investigate the role of abnormal placental function in

SIDS risk prospectively.

• Objective: Further investigate the association of

genitourinary tract infections with increased SIDS risk

by examining the pathogens, timing of infection, and

relationship of infection to preterm births, potential

placental or fetal pathologies, and maternal age.

• Objective: Examine the role of maternal chronic

diseases such as asthma and diabetes in influencing

SIDS risk.

• Objective: Investigate the contribution of health

programs designed to improve maternal and infant

health—e.g., home visits by public health nurses

before and after birth—to decreases in SIDS risk.

• Objective: Further investigate the effects of

prenatal and postnatal cigarette smoke exposure 

on SIDS risk in order to understand the pathogenic

mechanisms involved and to refine public health

messages.

• Objective: Support multidisciplinary studies

elucidating the contribution of prenatal and postnatal

alcohol consumption to SIDS risk, including the timing

and pattern of alcohol use, as well as determinants of

maternal drinking behaviors.

Goal: Encourage research that simultaneously

addresses a multitude of risk factors for SIDS and 

related outcomes in order to determine the nature and

magnitude of known (e.g., sleep position and bed

sharing) and potential interactions and to develop a rank

ordering of risk factors amenable to public health

intervention. This avenue of research should consider

genetic, lifestyle, behavioral, and environmental factors in

order to model infants’ postnatal lives more accurately.

• Objective: Further examine the interactions among

characteristics of the sleep environment, including

sleep position, bedding, environmental temperature,

infant clothing, bed sharing, and room sharing.

• Objective: Describe patterns of bed sharing and

elucidate the risk of SIDS and accidental suffocation

under a variety of environmental conditions,

including phenomena such as overlay.

— Investigate the role of infant characteristics (e.g.,

age, arousal characteristics, and protective

behaviors) and maternal characteristics (e.g.,

postnatal smoking and alcohol consumption) 

in determining the levels of risk associated with

bed sharing.

• Objective: Determine the role of pacifiers in

reducing SIDS risk and assess the risks versus benefits

in order to formulate recommendations regarding

pacifier use.

• Objective: Continue to monitor the influence of

prevention messages on health outcomes in order 

to identify unintended consequences, both positive

and negative.
FROM CELLS TO SELVES

29

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

Interventions

Background

• In 1992, the American Academy of Pediatrics (AAP)

released a recommendation that healthy infants

should be placed to sleep on their sides or backs to

reduce the risk of SIDS.

• In 1994, the national public education campaign,

Back to Sleep, was launched by a coalition consisting

of the U.S. Public Health Service, the AAP, the SIDS

Alliance, and the Association of SIDS and Infant

Mortality Programs. The campaign recommended

that infants be placed on their backs or sides to sleep

to reduce SIDS risk.

• The campaign also recommended that babies should

be placed to sleep on a firm mattress. Blankets and

comforters should not be placed under the baby, 

and pillows and stuffed toys should not be placed in

the crib.

• Secondary campaign messages included maintaining

a “smoke-free” zone around the baby before and

after birth, and regular prenatal and well-baby care.

• The campaign disseminated information to hospital

nurseries, physicians, and licensed day care centers

and initiated public media campaigns nationwide.

• In 1996, the AAP and the Back to Sleep campaign

revised the basic recommendation to state that the

back is the preferred sleeping position and safer than

sleeping on the side.

• In 1999, in collaboration with the Consumer Product

Safety Commission, a safety alert was released to

remove all soft bedding, including quilts and

comforters, from cribs.

• Between 1992 and 1998, the proportion of infants

placed to sleep on their stomachs declined from

about 70 percent to about 17 percent.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

30

• About one-third of caregivers who placed infants on

their sides or backs at 1 month of age switched to

placing infants on their stomachs by 3 months of age.

• By 1998, almost 95 percent of the survey population

reported receiving a recommendation encouraging

back or side position. Of those who placed their

babies on their stomachs, 86 percent had only

received a recommendation for back or side sleeping

positions. The majority said the reason for choosing

the riskier position was that the baby liked it better or

slept better that way.

• Between 1992 and 1998, the SIDS rate declined by

about 40 percent, from 1.2/1,000 live births to

0.72/1,000 live births.

• The prevalence of soft bedding being placed under

the baby has not decreased since 1992.

Goals and Objectives

Goal: Actively work with communities to obtain

information on cultural variances with regard to the

Back to Sleep campaign messages. Obtain feedback

and advice from communities on ways to address

cultural variances effectively and to identify ways to

refine campaign messages in light of cultural differences.

• Objective: Conduct research to identify social,

cultural, and behavioral factors that influence SIDS

risk reduction.

• Objective: Target barriers that may exist in various

communities. Design interventions and education

programs about safe sleep practices for infants that

take into account the influence of such barriers.

• Objective: Develop materials with tailored

messages to address specific actions in order to

reduce the risk of SIDS. Such messages should

include concrete statistical information describing

relative degrees of risk and ensure clarity in

conveying information on SIDS. Conduct focus

groups to test whether messages are appropriate for

specific populations and subpopulations.

Goal: Promote research to broaden the

understanding of cultural variations existing among

communities with high rates of infant deaths. Such

variations should also be studied among communities

where risk-reduction messages may not have penetrated,

such as the child-care provider community.

• Objective: Encourage studies aimed at identifying

relationships between risk factors and existing

cultural practices. Research should include strategies

to enhance our understanding of how the reception

of risk-reduction messages is influenced by different

cultural practices.

• Objective: Foster studies to explore methods for

effectively crafting culturally appropriate messages.
FROM CELLS TO SELVES

31

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

Measures should be studied to disseminate culturally

appropriate messages that identify effective processes

to tailor communications that target diverse groups.

• Objective: Encourage research to study long-term

effects of risk-reduction messages on populations in

the context of varying cultural practices.

• Objective: Assure methods are implemented to

evaluate risk-reduction communications and their

effects on cultural groups.

Goal: Ensure that the Back to Sleep campaign

messages are sustained and remain consistent

throughout all outreach activities and initiatives. Actively

seek out other agencies and organizations and

collaborate with them to assist with continued campaign

efforts.

• Objective: Ensure that the Back to Sleep campaign

messages are updated to reflect current SIDS

research. Keep campaign partners informed of SIDS

research and changes in campaign messages.

• Objective: Conduct process evaluation to assess

efficacy of ongoing campaign activities. Share

information and findings with the collaborative

partners to maintain the campaign’s cohesiveness.

• Objective: Enhance the NICHD’s partnerships with

agencies, community leaders, and organizations to

communicate Back to Sleep messages in the

communities these entities serve.

• Objective: Develop and implement strategies with

partner organizations and the Consumer Product

Safety Commission to decrease the use of soft

bedding in the infant sleep environment.

Goal: Develop and implement interventions that are

favorable to women’s health.

• Objective: Education and prevention activities and

services should be offered to people where their daily

activities take place, such as Women’s Wellness

clinics, well-child clinics, and school prevention

programs. The staff providing such services should

work closely with school nurses, where available.

Often, mobile clinics and flexible clinic hours are

necessary to accommodate working mothers and

their families. Human and financial resources need

to be identified and coordinated to improve the

health status of women and their families.

• Objective: Collaborate with other programs inside

and outside the Institute to promote smoking cessation

before and after birth.

Infrastructure

Background

• Perinatal infant mortality review is not conducted

consistently throughout the country. Some local

jurisdictions lack review teams.

• Perinatal infant mortality review under uniform

conditions provides information on trends and

patterns of fetal and child deaths; when coupled with

standardized data collection, it can inform about

public health policy and guide research and

prevention activities.

• Perinatal infant mortality review provides a forum 

for the uniform diagnosis of unexpected and/or

preventable deaths, and the expedited follow-up 

of cases.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

32

Goals and Objectives

Goal: Improve the diagnosis and surveillance of

sudden unexpected fetal and infant deaths to optimize

the development and monitoring of prevention efforts.

• Objective: Work with other agencies at the

national and local levels to provide uniform

guidelines and training for perinatal infant mortality

review personnel that take the limited resources of

many small or rural communities into account.

— Educate health professionals and involved

community members in the conduct of the reviews,

with guidelines describing methods of data

collection, analysis, review, and follow-up.

Emphasize multiagency efforts that include infant

and toddler health as well as high-risk pregnancies.

— Develop expanded information systems to

facilitate comprehensive reviews.

• Objective: Continue to work with other agencies

and nongovernmental organizations to improve the

diagnosis of sudden unexpected infant deaths

through coroner mentoring programs and healthprofessional education.

• Objective: Review the knowledge accrued over the

next 5 years to determine whether the standard 

SIDS definition should be revised to increase the

specificity of diagnosis, including possibly changing

the age range.

Goal: Continue to strengthen the Back to Sleep

Coalition.
FROM CELLS TO SELVES

33

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

Eliminating the disparities in SIDS rates among minority

communities is one of the most important and

challenging problems facing SIDS researchers in the new

millennium. The NICHD defines health disparities as

differences in health and developmental outcomes,

particularly between and among racial and ethnic

groups. The facts: despite a 40-percent overall decline

in SIDS deaths, the rate among American Indians

(1.5/1,000) and African Americans (1.4/1,000)

remains more than twice that of Whites (0.6/1,000). 

In addition, many of the risk factors for SIDS are more

prevalent among American Indians and African

Americans than Whites. In contrast, infants born to

Hispanic and Asian or Pacific Islander mothers have

among the lowest SIDS rates (0.4/1,000) of any racial

or ethnic group in the United States. Moreover, overall

rates vary within racial and ethnic groups. The Indian

Health Service reports, for example, that the SIDS rate is

3.5/1,000 in the Aberdeen area of North and South

Dakota, Iowa, and Nebraska, 1.6/1,000 in the Phoenix

area, and 0.78/1,000 among the Navajo.

Research and intervention into this complex problem

require new ways of thinking and multidisciplinary

approaches. The overall goal guiding research into

health disparities is to understand the mechanisms

through which racial and ethnic differences occur due to

complex interactions between basic biological processes

and factors such as poverty, education, and

“community” with its distinct geographic, environmental,

and cultural realities. Disparities between American

Indians and Whites and between African Americans

and Whites in regard to SIDS have, in part, been

attributed to the higher level of poverty in these minority

populations. The poverty rate, for example, among

African Americans is more than twice that among

Whites. For American Indians residing on a

reservation, the poverty rate is 2.4 times that of the

general U.S. figure of 13.1 percent. Aberdeen, Navajo,

Billings, Albuquerque, and Phoenix all have poverty

rates exceeding 40.0 percent. More specifically, 13.4

percent of American Indian women age 16 and older

are unemployed, in contrast with 6.2 percent of women

of all races nationwide.

Health Disparities

Statement of the Problem
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

34

Epidemiologic studies of SIDS prevalence rates have

demonstrated the relevance of the following risk factors

for SIDS: low family income; low parental educational

levels; young (teenage) maternal age; maternal single

marital status; few and often late prenatal healthcare

visits; maternal illicit drug, alcohol, and/or cigarette

intake during pregnancy; the presence of sexually

transmitted diseases in mothers; and the absence of a

telephone in the home. These risk factors are more

common in impoverished communities than in the

general population as a whole. Another major risk

factor for SIDS is low birth weight. Disparities among

different racial and ethnic groups likewise occur here:

African American infants are more than twice as likely

to be born with a low birthweight (<2500g) and more

than 3 times as likely to be born with a very low

birthweight (<1500g) than are white neonates. Of note,

the higher incidence of low birthweight rate among

African American infants cannot be explained by

socioeconomic factors alone.

The remoteness of many American Indian reservations

and other types of rural communities frequently affects

access to preconceptional, prenatal, and postnatal

health care. It likewise affects the coroner’s system and

the correct diagnosis of SIDS, since it magnifies the

difficulties in performing a proper death scene

investigation. In addition, the inequity of care evident in

the coroner’s system on the reservation is exacerbated

by improper, and in some instances a complete lack of,

training of the coroner and other personnel responsible

for examining sudden infant deaths. Inconsistencies in

death scene investigations also often result from the

frequent turnover of coroners in rural areas.

Lack of access to care, inequities in the quality of care,

and other barriers are more common in minority

communities. It is not known to what extent these factors

contribute to disparities in SIDS risk and prevalence

rates. Such factors need to be examined through further

research. Moreover, it is unclear whether perceptions of

racial discrimination or reported incidences of

discrimination affect the maternal-fetal environment.

Given the complexity of our social systems and the

potential negative effects these factors may have on the

lives of infants and their families, it is imperative that we

continue to support efforts exploring these issues.

Little is also known about the protective factors that

operate within certain poor minority communities to

decrease SIDS risk. Why do Hispanics and some

American Indian populations have low SIDS rates,

despite adverse socioeconomic circumstances?

Differences in SIDS rates among racial and ethnic

groups cannot be explained by social or economic

inequalities alone. For example, when epidemiologists

correct for socioeconomic factors, an excess risk for

SIDS remains in the African American and American

Indian populations. This observation suggests that

biological factors—e.g., susceptibility genes—may play

important roles in the pathogenesis of SIDS in specific

racial and ethnic groups; certain genes predisposing

infants to premature birth or sudden death may prove to

be more prevalent in some populations than in others.

Such susceptibility genes may interact with

environmental factors to trigger a cascade of intrinsic

biological events that lead to sudden death. It has been

reported, for example, that nicotine from tobacco smoke

is metabolized more slowly in African American

populations. This putative genetic variation suggests that

toxic levels of nicotine may accumulate more rapidly in

African American fetuses exposed to maternal cigarette

smoking during pregnancy, thereby having a more

deleterious effect on their growth and development.

Thus, maternal cigarette smoking during pregnancy may

make a greater contribution to the risk of SIDS among

African Americans than it does among whites. It is also

well recognized that SIDS is a syndrome and that there

may be more than one mechanism of sudden death.
FROM CELLS TO SELVES

35

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

Thus, there may be factors unique to the pathogenesis 

of SIDS in individual racial or ethnic groups that 

must be considered in order to elucidate pathogenic

mechanisms and the development of preventive

strategies.

Differences in SIDS rates between racial and ethnic

groups need not relate to socioeconomic and/or genetic

factors alone. They may involve community traditions

and cultural practices as well, particularly those

involving methods of child care. For the message of the

Back to Sleep campaign to be heard and acted upon,

those delivering the message must be community-based

and culturally sensitive.

Given the complexity of the problem of health disparities

in regard to SIDS, multidisciplinary approaches to

research into relevant social, economic, environmental,

genetic, and cultural factors are essential.

Multidisciplinary teams are needed to investigate both

the protective and adverse factors operating within and

across populations. For ultimate success, the

multidisciplinary research approach must be linked to

community involvement at all levels.

Research

Background

• Despite 40-percent declines in SIDS rates across all

populations over the period of the Back to Sleep

campaign, the rate of SIDS among African

Americans and American Indians is still at least twice

that of whites.

• Some risk factors for SIDS are more common among

the economically disadvantaged, who are

disproportionately represented among racial and

ethnic minorities. These factors include maternal and

paternal education of less than 12 years, late or no

prenatal care, maternal age below 20 at the time of

the first pregnancy, and maternal single marital status.

• The rates of low birthweight and preterm birth are

twice as high among African Americans as among

Whites. These factors increase the risk for SIDS

threefold.

• Bed sharing is more common among minority

populations. Bed sharing has been shown to

increase the risk for SIDS under the following

conditions: when the mother smokes, when she has

recently consumed alcohol, when the infant is

covered by a quilt, and when parents are fatigued.

• Preliminary results from a study of SIDS among

Northern Plains Indians demonstrate strong

associations between prenatal binge drinking and

SIDS and between the use of multiple layers of

clothing and SIDS.

• Even after adjusting for socioeconomic factors and

cigarette smoking, African Americans, American

Indians, and Alaskan Natives are at increased risk 

for SIDS.

Goals and Objectives

Goal: Identify the mechanisms underlying racial and

ethnic disparities in SIDS rates.

• Objective: Support research that focuses on

environmental, biological, and cultural factors related

to SIDS within specific minority populations and

develop partnerships with these populations. The

analysis of data can be approached in at least two

different ways: (1) within the context of the minority

population itself and (2) in comparison with other

racial and ethnic populations. Design studies to

address the potential role of race and/or ethnicity as

an independent risk factor for SIDS, as a modifier of
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

36

other known risk factors, and as a confounder or

intervening event in the natural history of SIDS.

• Objective: Support research that delineates the

contribution of genetic and environmental factors that

influence the risk of SIDS, including potential geneenvironment interactions.

• Objective: Investigate the role of inequities in

prenatal and postnatal health care that are

contributing to the disparate SIDS rates evident in

various racial and ethnic groups.

• Objective: Investigate the role of culturally specific

patterns of infant care practices in disparate SIDS

rates among racial and ethnic groups. Such care

practices include infant sleep position, bed sharing,

and types of bedding. 

Interventions

Background

• Between 1992 and 1998, the proportion of infants

placed to sleep on their stomachs declined from 70

percent to 17 percent. Among African Americans in

the survey population, however, the decline was

significantly less: from 82 percent to 32 percent.

• After adjusting for socioeconomic factors, and for

whether they received a recommendation to place

infants on their backs to sleep, African Americans

were twice as likely to place infants on their stomachs

and half as likely to place infants on their backs as

compared with Whites.

• Between 1992 and 1998, the SIDS rate among

African Americans decreased by almost 40 percent,

a magnitude similar to that observed in the White

population. Nonetheless, the SIDS rate among

African Americans remained twice that of whites.

• Within the Hispanic and American Indian

populations, there are subpopulations based on

country of origin or tribe that are more likely to 

place babies on their stomachs to sleep rather than

on their backs.

• Sleeping on soft bedding is a significant SIDS risk

factor among all minority populations. The use of

soft bedding has not changed appreciably since the

initiation of the Back to Sleep campaign and the

release of recommendations from the AAP and CPSC

to remove soft bedding from the crib.

• In 1999, the Back to Sleep campaign initiated an

outreach component aimed at the African American

community. It formed a partnership with the National

Black Child Development Institute and other African

American leadership organizations to develop a

community-linked campaign.

• In 2000, a “Resource Kit for Reducing the Risk of

SIDS in African American Communities” was

produced and a plan for national and local training

programs was developed. In 2001, training activities

through the affiliate organizations began.

Goals and Objectives

Goal: Improve the dissemination and adoption of the

Back to Sleep campaign recommendations among

minority populations in the United States.

• Objective: Integrate knowledge of cultural

practices and beliefs into approaches formulated to

reach specific minority populations.
FROM CELLS TO SELVES

37

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

• Objective: Continue to develop strategies for

community input into the development and

implementation of campaign activities.

— Conduct training workshops and educational

sessions with health professionals, community

leaders, outreach workers, and individuals to

develop methods for working locally in SIDS riskreduction activities.

— Work on existing health promotion projects within

organizations that will enhance their scope and

infrastructure by incorporating SIDS risk

reduction strategies.

— Among American Indian communities, involve

tribal programs and services provided by the

Indian Health Service. Tribal educators are often

the keys to communication with local communities.

Universities, colleges and tribal community

colleges can also offer important resources.

• Objective: Evaluate the process of information

dissemination, behavioral change, and health

outcomes at the national and local levels among

minority populations.

— Provide this information to community

organizations to stimulate the adoption and

revision of SIDS risk-reduction strategies.

Goal: Reduce disparities in SIDS rates that may be

related to risks not targeted by the Back to Sleep

campaign.

• Objective: Develop a dialogue with partnership

organizations to identify potential sources of risk

within specific communities. Disseminate research

data relevant to specific communities in order to

support existing health promotion programs or to

develop interventions. An example is the reduction

of prenatal alcohol exposure among some American

Indian tribal communities.

Infrastructure

Background

• The infrastructure necessary to perform research in

health disparities in SIDS rates is complex and

involves novel multidisciplinary approaches.

• Innovative programs currently exist that provide

models for community partnerships aimed at

reducing disparities in SIDS rates: e.g., the

interrelationship among the Women’s Health Program

of the Aberdeen Area, Healthy Start, Indian Health

Service hospitals and clinics, and the Maternal and

Child Health Division of the state of South Dakota.

• The NICHD has already established two national

“Brain and Tissue Banks for Developmental

Disorders” that include specimens taken from infants

who died of SIDS. These banks should be expanded

to permit genetic analyses of tissues within and

between different racial and ethnic groups.

• Innovative methods exist for developing mentoring

programs to encourage minority middle school, high

school, college, and graduate students to enter the

health professions, and conduct health-related

research focused on their communities: e.g., the Four

Directions Program for American Indian college

students at Harvard Medical School.

Goals and Objectives

Goal: Develop and sustain community partnerships

for research and intervention in an effort to reduce

disparate SIDS rates in minority populations.

• Objective: Support partnerships between

academic institutions and community organizations

for research, the training of minority investigators,

and the dissemination of research findings in

minority communities.
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Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

38

• Objective: Develop partnerships with

organizations and other significant community

leaders at the national, regional, state, and

community levels to collaborate in the design of

materials and initiatives in their geographic areas.

• Objective: Provide leadership to partner

organizations in coordinating regional summits and

in enlisting the resources of community organizations,

faith-based groups, public health officials, and

service organizations to reduce the risk of SIDS.

Goal: Facilitate the definition of risk profiles for 

SIDS in different racial and ethnic groups by conducting

large-scale epidemiologic studies within and 

across populations.

• Objective: Develop web-based data management

strategies for conducting research. This technology

permits simultaneously-conducted studies and

employs standardized methods, while allowing

investigators continual access to all aspects of an

ongoing study.

• Objective: Investigate promising new medical

informatics technologies to identify critical data or

research gaps.

• Objective: Foster the use of new research designs

and analytic tools well suited to the identification of

triggers for SIDS or the possible repetition of adverse

pregnancy outcomes in families. Case crossover

designs, for example, might prove useful in

identifying factors that increase SIDS risk.

Goal: Recruit minority researchers in basic health

sciences and applied clinical care, as well as in the social

and behavioral disciplines, to conduct SIDS research.

• Objective: Develop mentoring programs at the

middle school and high school levels for minority

students in the relevant health and social science

disciplines.

• Objective: Develop targeted mentoring programs

in SIDS research at the graduate and postdoctoral

level for minority students already trained in the

relevant health and social science disciplines.
FROM CELLS TO SELVES

39

Targeting Sudden Infant Death Syndrome (SIDS): A Strategic Plan

Hannah C. Kinney, M.D., Co-Chair

Children’s Hospital of Boston

Harvard University

LTC Martin G. Ottolini, USAF, MC, Co-Chair

Uniformed Services University of the Health Sciences

Alan H. Beggs, Ph.D.

Children’s Hospital Boston

Harvard University

Germaine Buck, Ph.D.

Epidemiology Branch

National Institute of Child Health and 

Human Development

Michael Corwin, M.D.

Boston Medical Center

Dawn Dailey, R.N., M.S.N.

Association of SIDS and Infant Mortality Programs

Mary Lynn Eaglestaff, R.N., M.S.

Women’s Health Program

Indian Health Service

William P. Fifer, Ph.D.

NY State Psychiatric Institute

Columbia University

Judith Jacobson

Sudden Infant Death Syndrome (SIDS) Alliance

Eugene Nattie, M.D.

Dartmouth Medical School

Bradley Thach, M.D.

Washington University St. Louis

Appendix—Roster of Advisors

Although this document has benefited from the input of many scientists within and outside the NICHD, and from 

the general public, we wish to particularly note the advice of the following members of the SIDS strategic plan

working group:

The NICHD would like to acknowledge The Noah Fund and The Considering Alexander SIDS Foundation

for supporting workshops that contributed to the development of the NICHD SIDS Strategic Plan.
For additional copies of this strategic plan, or for more information on contacts or related issues,

please contact the NICHD Clearinghouse at

P.O. Box 3006

Rockville, MD 20847

Phone: (800) 370-2943

Fax: (301) 496-7101

Web: http://www.nichd.nih.gov/publications/

For additional information about other NICHD strategic plans and research, please visit our Web site at

http://www.nichd.nih.gov/