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http://jama.ama-assn.org/cgi/content/full/301/21/2252
. 2009;301(21):2252-2259 (doi:10.1001/jama.2009.754) JAMA
Jack P. Shonkoff; W. Thomas Boyce; Bruce S. McEwen
for Health Promotion and Disease Prevention
Roots of Health Disparities: Building a New Framework
Neuroscience, Molecular Biology, and the Childhood
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SPECIAL COMMUNICATION
Neuroscience, Molecular Biology, and the
Childhood Roots of Health Disparities
Building a New Framework for Health Promotion
and Disease Prevention
Jack P. Shonkoff, MD
W. Thomas Boyce, MD
Bruce S. McEwen, PhD
ADVANCES IN DEVELOPMENTAL
biology are building an increas-
ingly persuasive case for a new
way of thinking about health
promotion and disease prevention that
focuses on the origins of persistent dis-
parities in morbidity and mortality in the
early years of life. Central to this frame-
work is an increasing interest in the
extent to which early experiences and
exposures are biologically embedded and
have lifelong consequences.
The following example illustrates
how the translation of this evolving sci-
ence base into innovative policy can
generate new approaches to reducing
the burden of preventable disease.
In 2008, the American Academy of Pe-
diatrics issued a report to address a “new
urgency given the current epidemic of
childhood obesity with the subsequent
increasing risk of type 2 diabetes melli-
tus, hypertension, and cardiovascular dis-
ease in older children and adults.”1The
report underscored the need for a more
proactive approach in childhood to the
prevention of cardiovascular disease
through enhanced adherence to dietary
guidelines, increasing physical activity,
and consideration of pharmacologic
treatment of dyslipidemia beginning as
early as age 8 years. What the report did
not consider is the idea, based on grow-
ing evidence of the cardiovascular se-
quelae of early life adversity, that new in-
terventions to reduce significant stress
in early childhood may be a more ap-
propriate strategy for preventing adult
heart disease than the off-label admin-
istration of statins to school-aged chil-
dren. In this article, we explore the sci-
entific validity of the proposition that
reducing significant disadvantage early
in life may be a powerful strategy for re-
ducing the population-level burden of
chronic morbidity and premature death.
Emergence of a New Scientific
Approach for Health Policy
Differences in health outcomes related
to social class and other markers of dis-
advantage have been well documented
across a broad range of cultures, as well
as in societies with a variety of health care
systems.2-4 Despite the unassailable re-
liability of this robust association, the elu-
cidation of precise causal mechanisms
linking adversity to health status re-
mains elusive, and effective policy rem-
edies are not readily apparent.5
Notwithstanding the fundamental im-
portance of high-quality medical care for
those who are ill, the limited capacity of
high-quality care to reduce socioeco-
nomic and racial disparities in health out-
comes is clear. Central to this under-
standing is the persistence of social class
gradients in disease prevalence and mor-
tality rates in nations that provide uni-
versal access to health care services.6
Some critics have responded by suggest-
ing greater focus on inequalities in ser-
vice utilization and differential treat-
ment by the health care system. Others
have called for greater attention to the
role of broader social and economic in-
fluences on health, although the task of
translating this perspective into con-
crete policy initiatives has generated
more rhetoric than action. While clini-
cians apply advances in the biomedical
Author Affiliations: Center on the Developing Child at
Harvard University, Cambridge, Massachusetts (Dr Shon-
koff ); College for Interdisciplinary Studies and Faculty
of Medicine, University of British Columbia, Vancou-
ver, Canada (Dr Boyce); and Harold and Margaret Mil-
liken Hatch Laboratory of Neuroendocrinology, Rock-
efeller University, New York, New York (Dr McEwen).
Corresponding Author: Jack P. Shonkoff, MD, Cen-
ter on the Developing Child, Harvard University,
50 Church St, Fourth Floor, Cambridge, MA 02138
(jack_shonkoff@harvard.edu).
A scientific consensus is emerging that the origins of adult disease are of-
ten found among developmental and biological disruptions occurring dur-
ing the early years of life. These early experiences can affect adult health in
2 ways—either by cumulative damage over time or by the biological em-
bedding of adversities during sensitive developmental periods. In both cases,
there can be a lag of many years, even decades, before early adverse expe-
riences are expressed in the form of disease. From both basic research and
policy perspectives, confronting the origins of disparities in physical and men-
tal health early in life may produce greater effects than attempting to modify
health-related behaviors or improve access to health care in adulthood.
JAMA. 2009;301(21):2252-2259 www.jama.com
2252 JAMA, June 3, 2009—Vol 301, No. 21 (Reprinted) ©2009 American Medical Association. All rights reserved.
at University of Calgary on June 16, 2009 www.jama.comDownloaded from
sciences to transform their capacity to
treat patients who are sick, policy mak-
ers who are interested in population
health would be well served by a deeper
understanding of the underlying biol-
ogy of early adversity.
For much of the 20th century, adult
conditions such as coronary heart dis-
ease, stroke, diabetes, and cancer were
regarded solely as products of adult be-
havior and lifestyles.7By the century’s
end, however, an extensive body of evi-
dence linked adult chronic disease to
processes and experiences occurring de-
cades before, in some cases as early as in-
trauterine life, across a wide range of im-
pairments. Longitudinal studies have
demonstrated that pulmonary disease in
adulthood is commonly associated with
a history of respiratory illnesses in child-
hood.8Intrauterine exposure to dieth-
ylstilbestrol was discovered to underlie
vaginal and cervical cancers in young
women.9Prenatal processes have been
associated with the later manifestations
of schizophrenia10,11 and autism,12,13 and
early social environments have been
shown to play formative roles in cogni-
tive and socioemotional develop-
ment.14 Researchers have also found that
cardiovascular disease in later life can be
linked to nutritional deficits and growth
impairments in the prenatal period.15-18
Although full elucidation of the
causal mechanisms that account for
these associations awaits further inves-
tigation, the relation between early life
conditions and long-term health out-
comes remains robust. A comprehen-
sive review of that evidence base and
detailed analysis of its policy implica-
tions are beyond the scope of a single
report. The purpose of this article is to
propose a framework for increased col-
laborative work in this area, based on
the assertion that the promotion of
health and prevention of disease in
adults begins in the early years of life.
Investigators have postulated that
early experience can affect adult health
in at least 2 ways—by accumulating
damage over time or by the biological
embedding of adversities during sen-
sitive developmental periods.7,19 In both
cases, there can be a lag of many years,
even decades, before early adverse ex-
periences are expressed in the form of
illness. If the damage occurs through
a cumulative process, chronic dis-
eases can be seen as the products of re-
peated encounters with both psycho-
logically and physically stressful
experiences. When exposures occur
during sensitive periods of develop-
ment, their effects can become perma-
nently incorporated into regulatory
physiological processes, and subse-
quent adult disease may be viewed as
the latent outcome of critical events that
occurred during early periods of spe-
cial susceptibility.
Cumulative Exposures to Stressful
Experiences. Strong associations have
been shown between retrospective adult
reports of increasing numbers of trau-
matic childhood events with greater
prevalence of a wide array of health im-
pairments, including coronary artery
disease, chronic pulmonary disease,
cancer, alcoholism, depression, and
drug abuse,20,21 as well as overlapping
mental health problems,22 teen preg-
nancies,23 and cardiovascular risk fac-
tors such as obesity, physical inactiv-
ity, and smoking.24 Other longitudinal
studies have found similar link-
ages.25-28 Recent prospective data have
reinforced this association, including
evidence that depressed adults with a
documented history of maltreatment in
childhood are twice as likely to have
clinically relevant elevations of high-
sensitivity C-reactive protein levels
compared with controls, whereas in-
dividuals with depression and no his-
tory of maltreatment showed nonsig-
nificant increases in this biomarker of
greater risk of cardiovascular disease.29
Another body of research has sug-
gested that “weathering” of the body
under persistent adversity (ie, the
increased wear and tear induced by stress-
ful experiences that overuse and dys-
regulate pathways normally used for
adaptation to threat) reflects an accel-
eration of normal aging processes.30-32
African Americans, for example, expe-
rience earlier deteriorations of health in
a cumulative fashion, leading to progres-
sively larger health disparities with age
and a life expectancy that is 4 to 6 years
less than for whites.33 One hypoth-
esized causal mechanism is the persis-
tence of stress associated with discrimi-
nation that accelerates the aging process.34
Cumulative-exposure explanations of
chronic adult disease are consistent with
research that addresses the breakdown
of physiological steady state under
conditions of chronic challenge—a
phenomenon referred to as “allostatic
load.”35 Under such circumstances, acti-
vation of stress management systems in
the brain results in a highly integrated
repertoire of responses involving secre-
tion of stress hormones, increases in
heart rate and blood pressure, protec-
tive mobilization of nutrients, redirec-
tion of blood perfusion to the brain, and
induction of vigilance and fear.36 These
neurobiological responses are essential
and generally protective, but when acti-
vated persistently under circumstances
of chronic or overwhelming adversity,
they can become pathogenic.37,38 Within
this context, extensive documentation
of the disproportionate exposure of low-
income children to environmental stress-
ors, traumatic experiences, and family
chaos39-41 takes on a greater sense of
urgency. This threat is underscored even
further by recent evidence of higher lev-
els of physiological and emotional dys-
regulation in this high-risk group.42
Latent Effects of Adversity During
Sensitive Periods. A considerable body
of research also suggests that adult dis-
ease and risk factors for poor health can
be embedded biologically during sensi-
tive periods in which the developing brain
is more receptive to a variety of environ-
mental signals, whether positive or
negative.43 For example, poor living con-
ditions early in life (eg, inadequate nutri-
tion, other constraints on fetal and infant
growth, and recurrent infections) are
associated with increased rates of
cardiovascular, respiratory, and psychi-
atric diseases in adulthood.15,44-48 Inves-
tigators have also documented an asso-
ciation between lower birth weight and
several risk factors for heart disease,
including hypertension, central body fat
distribution, insulin resistance, meta-
bolic syndrome, and type 2 diabetes.15
CHILDHOOD ROOTS OF HEALTH DISPARITIES
©2009 American Medical Association. All rights reserved. (Reprinted) JAMA, June 3, 2009—Vol 301, No. 21 2253
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These findings are supported by evi-
dence from both animal and human
studies. For example, lower birth weight
due to intrauterine growth restriction in
rats has been associated with higher
blood pressure,49 and studies of human
infants have linked poor intrauterine
growth to deficits in neural control of the
heart50 and hypertension.51 Early expe-
riences of child maltreatment and pov-
erty have been associated with height-
ened immune responses in adulthood
that are known risk factors for the de-
velopment of cardiovascular disease, dia-
betes, asthma, and chronic lung dis-
ease.52,53 So-called natural experiments
have provided additional, corroborat-
ing support for this association. Indi-
viduals exposed to severe nutritional defi-
cits in utero during the Dutch famine of
1944, for example, showed a higher
prevalence of coronary heart disease
when evaluated 50 years later.46 Simi-
larly, children in a Helsinki birth co-
hort evacuated to temporary foster care
during World War II have shown higher
rates of both cardiovascular morbidity
and symptoms of depression compared
with their nonevacuated peers.54,55
The Central Role of the Brain. As the
primary organ of stress and adapta-
tion, the brain is both vulnerable and
adaptable. It interprets and regulates be-
havioral, neuroendocrine, autonomic,
and immunological responses to ad-
verse events, serves as a target of acute
and chronic psychosocial and physi-
cal stress, and changes both structur-
ally and functionally as a result of sig-
nificant adversity.35,56 Animal models
have provided considerable insights
into differential responsivity to stress
among different brain regions, includ-
ing the hippocampus, amygdala, and
prefrontal cortex. Studies have shown
both adaptive and maladaptive effects
of stress hormones throughout the life
course, with early life events influenc-
ing lifelong patterns of emotionality and
stress responsiveness as well as alter-
ing the rate of brain and body aging.
Stress-induced remodeling of neuro-
nal structure and connectivity in these
regions alters behavioral and physi-
ological responses, including anxiety,
aggression, mental flexibility, memory,
and other cognitive processes.56
New imaging techniques are driv-
ing rapid advances in knowledge about
how the human brain changes with ex-
perience. Recent findings include the
association of reduced hippocampal
volume with prolonged perceived
stress57 as well as with diagnosed con-
ditions such as diabetes, major depres-
sion, Cushing disease, and posttrau-
matic stress disorder.58,59 In contrast,
physical activity and fitness in elderly
individuals is associated with in-
creased hippocampal volume and bet-
ter memory function,60 as well as greater
activation of prefrontal cortical activ-
ity and enhanced executive function.61,62
The prefrontal cortex, which is in-
volved in executive functions such as
working memory and behavioral inhi-
bition, as well as top-down control of
autonomic nervous system balance, has
been found to be smaller in individu-
als with major depression63 and in in-
dividuals who self-report lower socio-
economic status.64 In addition, the
prefrontal cortex has been shown to be
impaired transiently by increased lev-
els of perceived stress in medical stu-
dents studying for a board examina-
tion.65 Functional activation of the
prefrontal cortex is also associated with
blood pressure responses,66 whereas
greater functional activation of the
amygdala is associated with the devel-
opment of atherosclerosis.66
The Complexity of Heterogeneous
Response. Although evidence contin-
ues to accumulate supporting both cu-
mulative and latent effect models of
how early adversities may amplify long-
term disease risks, studies also reveal
compelling individual differences in the
magnitude or even direction of such ef-
fects. One investigation, for example,
found that 61% of individuals report-
ing significant emotional abuse in child-
hood developed major depression as
adults (compared with 18.5% of those
reporting no emotional abuse), yet
nearly 2 of 5 emotionally abused indi-
viduals had no such impairment.67
Similarly, although the risk of coro-
nary heart disease is nearly 4 times more
frequent among adults with birth weights
less than 2500 g (15%) compared with
individuals with birth weights greater
than 4000 g (4%), these risk ratios tend
to obscure the counterobservation that
85% of low-birth-weight infants did
not develop later heart disease.68 Such
marked heterogeneity in the longitudi-
nal consequences of early life experi-
ences suggests underlying differences in
vulnerability that may moderate these as-
sociations.56,69,70 Evidence for such effect
modification has been derived from stud-
ies of gene-environment interaction in
which allelic variations in neuroregula-
tory and transcription factor−encoding
genes are associated with greater risks re-
lated to early stressors71-74 as well as from
studies showing that individual differ-
ences in neurobiological sensitivity to so-
cial environments can bias outcomes
both positively and negatively, depend-
ing on the protective vs injurious na-
ture of early exposures.37,72,75-77
Biological Embedding. The epige-
netic pathways by which adversity is
transmuted into lasting alterations in dis-
ease risk are an example of the broader
adaptive processes through which early
influences affect the regulation of bio-
logical systems.78 These adaptations are
evolved mechanisms that monitor the
environment, beginning during the pre-
natal period, to adjust set points within
important brain circuits. For example, a
fetus in an intrauterine environment
characterized by poor nutrition may
undergo energy-sparing, metabolic
changes that are designed to be adap-
tive in a postnatal environment of food
scarcity. While these metabolic changes
may be beneficial in the short run, later
problems can arise when the adaptive
prediction turns out to be wrong, and the
early childhood environment is charac-
terized by energy abundance, a carbo-
hydrate-rich diet, and a sedentary life-
style.79 In such circumstances, according
to some theorists, the risk of later obe-
sity and other metabolic disorders can
begin very early in life.80
Children from families and commu-
nities with low income and low educa-
tion levels may be especially vulnerable
to the biological embedding of disease
CHILDHOOD ROOTS OF HEALTH DISPARITIES
2254 JAMA, June 3, 2009—Vol 301, No. 21 (Reprinted) ©2009 American Medical Association. All rights reserved.
at University of Calgary on June 16, 2009 www.jama.comDownloaded from
risk because of their disproportionate
exposure to highly stressful influences
such as neighborhood violence, dysfunc-
tional schools, personal maltreatment,
household chaos, and absent par-
ents.81,82 These risk factors are often com-
pounded by limited access to healthful
foods and high consumption of energy-
dense products83,84 that are contribut-
ing to the increasing prevalence of obe-
sity and diabetes, particularly among
low-income children. Children living in
disadvantaged environments are also
more likely to experience conflictive and
punitive parental behavior81,85,86 as well
as relatively fewer positive experiences
such as reading, interactive conversa-
tion, and after-school activities.87 In some
cases, the cumulative burden of mul-
tiple risk factors early in life may limit
the effectiveness of later interventions,
thereby making it impossible to com-
pletely reverse the neurobiological and
health consequences of growing up poor.7
Current research is charting new
territory in understanding the linkages
between differential childhood experi-
ences and several aspects of brain
development within regions tied to the
regulation of emotion and social be-
havior,reasoning capacity, language skills,
and stress reactivity.54 Children from
lower socioeconomic backgrounds show
heightened activation of stress-responsive
systems88,89 and emerging evidence sug-
gests that differences in parenting related
to income and education—as mediated
through parent-child interaction, expo-
sure to new vocabulary, and stability of
responsiveness—can alter the maturation
of selected brain areas, such as the pre-
frontal cortex.90,91 Animal models of early,
stress-related changes in brain circuitry
show that such changes can persist into
adult life and alter emotional states,
decision-making capacities, and bodily
processes that contribute to emotional in-
stability,substance abuse, aggression, obe-
sity, and stress-related disorders.92,93
Moreover, although early adversity can
lead to greater vulnerability later in life,
positive experiences can decrease such
risk. For example, capitalizing on natu-
rally occurring variation in maternal care-
taking behaviors in rats, studies have
demonstrated that pups experiencing
more intensive and responsive mater-
nal care have lower levels of the stress
hormone corticosterone. This predispo-
sition to a more modest stress response
continues into adult life and is transmit-
ted to the second and third generations
of offspring.94,95 Such effects are likely to
extend to humans and nonhuman pri-
mates as well and to involve modifica-
tions in the expression of glucocorti-
coid receptors in brain regions mediating
affect and cognition as well as neuro-
trophic factors operating throughout the
body.96,97 Such alterations of stress sys-
tems across generations—caused not by
genetic inheritance but by early experi-
ences—are facilitated by epigenetic
changes in DNA methylation and his-
tone modification of chromatin in re-
sponse to environmental cues that, in
turn, influence how the next genera-
tion’s genes are expressed.94,98-100
Although much of this research is
based on animal experiments, experi-
ence-related variation in gene expres-
sion may offer important clues about
how disparities in early exposure to ad-
versity can change adult health out-
comes in humans. A recent report on hu-
man brain autopsy material from
individuals who experienced child-
hood abuse revealed changes in DNA
methylation related to the glucocorti-
coid receptor that mirrors changes re-
ported in these same types of receptors
in brains of rodents that experienced
poor maternal care.96
Complexity of Early Childhood
Stress as a Policy Issue
Despite increasing evidence of the long-
term effects of early adversity on life-
long health, little attention has been
paid to the development of health pro-
motion and disease prevention strate-
gies based on the reduction of signifi-
cant stressors affecting everyday life for
vulnerable young children and their
parents. This potential shortsighted-
ness may in part be the result of a gen-
eralized misunderstanding about the
nature and effects of childhood stress.
For example, although mastery of rela-
tively minor adversity by children is
viewed as a necessary prerequisite for
developing resilience to later chal-
lenges, the public is less aware that lev-
els of stress associated with excessive,
persistent, and/or uncontrollable ad-
versity, without the buffering protec-
tion of stable adult support, are asso-
ciated with disruptive effects on
multiple organ systems that can lead to
lifelong disease. This is an area in which
further scientific advances linked to en-
hanced public understanding could in-
form innovative policy approaches.
The National Scientific Council on the
Developing Child proposed the follow-
ing simple taxonomy to describe 3 cat-
egories of stress experience—positive,
tolerable, and toxic—that can affect the
development of young children.101 In this
framework, stress refers to the physi-
ological expression of the stress re-
sponse system, not the nature of the
stressor nor the distinction between ob-
jectively measured and perceived stress.
Although much work remains to eluci-
date the underlying causal mecha-
nisms, the conceptual basis of this model
is grounded in well-established core bio-
logical principles.
Positive stress is characterized by mod-
erate, short-lived increases in heart rate,
blood pressure, and stress hormone lev-
els. Precipitants include the challenges
of dealing with frustration, receiving an
injected immunization, and other nor-
mative experiences. The essential na-
ture of positive stress is that it is an im-
portant aspect of healthy development
that is experienced in the context of
stable and supportive relationships that
facilitate adaptive responses, which, in
turn, restore the stress response system
to baseline status.
Tolerable stress refers to a physiologi-
cal state that could potentially disrupt
brain architecture (eg, through cortisol-
induced disruption of neural circuits or
neuronal death in the hippocampus) but
is buffered by supportive relationships
that facilitate adaptive coping. Precipi-
tants include the death or serious ill-
ness of a loved one, homelessness, or a
natural disaster. The defining character-
istic of tolerable stress is that it occurs
within a time-limited period, during
CHILDHOOD ROOTS OF HEALTH DISPARITIES
©2009 American Medical Association. All rights reserved. (Reprinted) JAMA, June 3, 2009—Vol 301, No. 21 2255
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which protective relationships help to
bring the body’s stress-response sys-
tems back to baseline, thereby giving the
brain time to recover from potentially
damaging effects.
Toxic stress refers to strong, frequent,
and/or prolonged activation of the body’s
stress-response systems in the absence
of the buffering protection of adult sup-
port. Major risk factors include ex-
treme poverty, recurrent physical and/or
emotional abuse, chronic neglect, se-
vere maternal depression, parental sub-
stance abuse, and family violence. The
defining characteristic of toxic stress is
that it disrupts brain architecture, af-
fects other organ systems, and leads to
stress-management systems that estab-
lish relatively lower thresholds for re-
sponsiveness that persist throughout life,
thereby increasing the risk of stress-
related disease and cognitive impair-
ment well into the adult years.
This simple taxonomy provides a
useful approach for helping policy mak-
ers differentiate normative life chal-
lenges that are growth-promoting from
significant adversities that threaten
long-term health and development. As
such, it provides a useful framework for
considering earlier opportunities for
preventive intervention.
Health Promotion
and Disease Prevention
Within a Science-Based,
Early Childhood Framework
Current efforts related to health promo-
tion and disease prevention in most eco-
nomically developed countries are gen-
erally guided by 3 strategies. The first
focuses on the provision of immuniza-
tions, anticipatory guidance, and early
identification and management of prob-
lems in the context of primary health care
for children who have access to medical
services, as well as public policies
designed to reduce injuries, such as man-
datory seat belt laws. The second
approach is directed toward programs
that encourage health-promoting behav-
iors in adults, such as better nutrition and
increased exercise. The third strategy is
focused on reducing health-threatening
behaviors in adults, such as smoking,
excessive alcohol consumption, illicit
substance abuse, and risk-taking behav-
iors associated with sexually transmit-
ted diseases. The first approach is embed-
ded largely in a model of individually
focused medical services for children. The
second and third strategies are grounded
in a theory of change based on the capac-
ity to modify the behavior of adults.
Although the potential benefits of
health education at any age should not
be underestimated, the ultimate im-
pact of policies designed to improve
population health through efforts that
begin in the adult years is limited by
3 important constraints. First, it is bur-
dened by the increasing difficulty of
changing behavior and lifestyles as in-
dividuals grow older. Second, it faces
the difficult challenge of overcoming
biological vulnerabilities that may have
been embedded physiologically as a re-
sult of early adversity and that might
have been prevented by changing the
environments in which young chil-
dren live. Third, by addressing adult be-
haviors, instead of the conditions faced
by children and their families, such poli-
cies shift the locus of responsibility to-
ward individuals whose health risks
have been influenced much earlier in
life and away from the potentially modi-
fiable circumstances that shaped them
in the first place.
These limitations of adult-focused
health promotion efforts lead to the
compelling hypothesis that a funda-
mental transformation in the circum-
stances of children who experience sig-
nificant adversity early in life could not
only affect their own individual well-
being but also improve societal health
and longevity. To this end, an inte-
grated developmental science of health,
learning, and behavior could support
several implications for health policy
and clinical practice. The following are
3 examples worthy of thoughtful con-
sideration.
Adult Disease Prevention Begins
With Reducing Early Toxic Stress.
Policies and practices intended to focus
on health promotion and disease pre-
vention might be strengthened consid-
erably by greater attention to the poten-
tial effects of reducing toxic stress in early
childhood. An increasing amount of re-
search in neuroscience, social epidemi-
ology, and the behavioral sciences, re-
viewed selectively in this article, suggests
that a reduction in the number and se-
verity of early adverse experiences will
lead to a decrease in the prevalence of a
wide range of health problems.
Building on this increasing body of
evidence, the Centers for Disease Con-
trol and Prevention has proposed that
child abuse and neglect be defined as
a public health issue with lifelong con-
sequences.102 The implications of this
emerging science for clinical practice
are compelling. On the positive side, the
primary care setting is arguably the
most appropriate venue for a more pro-
active approach to the early identifica-
tion and mitigation of potential causes
of toxic stress in young children, such
as child maltreatment (7.5% of chil-
dren aged 2-5 years103), postpartum de-
pression (13% of new mothers104), and
parental substance abuse (9.8% of
households with children aged ⬍5
years105). Yet the challenges facing cli-
nicians are formidable, including in-
sufficient training and reimbursement
to address complex social problems and
limited access to specialized interven-
tion services.106 Nevertheless, the rela-
tively high prevalence of early child-
hood trauma across all income groups
underscores the need for greater atten-
tion, in both medical education and pri-
mary care practice, to its potential ef-
fects on lifelong health.
Early Childhood Programs Benefit
Lifelong Health, Not Just Education.
High-quality early childhood programs
designed to produce positive effects on
educational achievement and later work-
force participation offer an important,
unrecognized infrastructure for address-
ing the stress-related roots of social class
disparities in health. Cost-benefit assess-
ments of effective early childhood inter-
vention for low-income children have
documented significant financial re-
turns to society through greater eco-
nomic productivity, decreased welfare
dependence, and lower rates of incar-
ceration.107-109 The degree to which en-
CHILDHOOD ROOTS OF HEALTH DISPARITIES
2256 JAMA, June 3, 2009—Vol 301, No. 21 (Reprinted) ©2009 American Medical Association. All rights reserved.
at University of Calgary on June 16, 2009 www.jama.comDownloaded from
hanced efforts to reduce toxic stress
might also reduce the prevalence of life-
long disease and reduce later health care
costs also deserves careful consider-
ation. To this end, the increasing gap be-
tween advances in evidence-based treat-
ments for mental health impairments and
the limited availability of services for
those in need is highly problematic, par-
ticularly in the early childhood years.
When early childhood program staff are
not trained to address disruptive behav-
iors nor assisted in securing appropri-
ate treatment for children or parents with
serious mental health problems, oppor-
tunities for preventive intervention are
missed and many troubled children are
expelled from programs before they are
given a chance to succeed.110 Strength-
ening the capacity to address stress-
related problems within the context of
existing early care and education pro-
grams is likely to augment their effects.
Child Welfare Services: Missed Op-
portunity for Health Promotion. Pub-
licly mandated services to protect chil-
dren who have been abused or neglected
present a particularly compelling and un-
derused approach for addressing the im-
mediate and long-term consequences of
severe stress in early childhood. Since
their establishment more than a cen-
tury ago, child welfare services have fo-
cused exclusively on issues related to
physical safety, reduction of repeated in-
jury, and child custody. Advances in neu-
roscience now indicate that evaluations
of maltreated children that rely exclu-
sively on physical examination and ra-
diographic screening are insufficient and
must be augmented by comprehensive
developmental assessments and the pro-
vision of appropriate intervention by
skilled professionals as indicated.
A public infrastructure already ex-
ists to provide these additional services
for children younger than 3 years
through regularized referrals from child
protective services agencies (which are
mandated in each state) to early inter-
vention programs for children with de-
velopmental delays or disabilities (which
are available in all states under a fed-
eral entitlement). The most recent re-
authorizations of the relevant federal leg-
islation for both systems—the Keeping
Children and Families Safe Act and the
Individuals With Disabilities Educa-
tion Act—include requirements for es-
tablishing such linkages, but their imple-
mentation has been limited. Greater
public understanding of the effects of
early abuse and neglect on lifelong health
could help build support for more in-
formed policy and practice.
Summary and Future Directions
An increasingly persuasive amount of
research is emerging that supports the
thoughtful construction of a new frame-
work for health promotion and dis-
ease prevention. This model is based on
mounting evidence that the origins of
many adult diseases can be found
among adversities in the early years of
life that establish biological “memo-
ries” that weaken physiological sys-
tems and produce latent vulnerabili-
ties to problems that emerge well into
the later adult years.
The scientific concepts embedded in
this framework are deeply grounded in
the principles of evolutionary biology.
Beginning as early as the first weeks af-
ter conception and continuing into early
infancy, the immature “organism”
“reads” key characteristics of its envi-
ronment and prepares to adapt to an ex-
ternal world that can vary dramati-
cally in its levels of safety, sufficiency,
and peril. When early experiences pre-
pare a developing child for conditions
involving a high level of stress or in-
stability, the body’s systems retain that
initial programming and put the stress
response system on a short-fuse and
high-alert status. Under such circum-
stances, the benefits of short-term sur-
vival may come at a significant cost to
longer-term health.
Beyond its promising policy implica-
tions, the association between early ad-
versity and subsequent health, learn-
ing, and behavior presents a compelling
research agenda. Much work remains to
be done to elucidate the precise causal
mechanisms that explain these link-
ages. The identification of biomarkers of
toxic stress and its physiological conse-
quences offers particular promise as a
source of short- and medium-term mea-
sures to assess the mediators of out-
comes that require decades to confirm.
In a parallel fashion, the design and
implementation of new approaches to
both the prevention and treatment of
toxic stress and its consequences, begin-
ning in the early childhood years, must
be another key priority. For example,
testing new community-based interven-
tions or clinical treatments for preschool-
ers who have been abused or seriously
neglected ought to be at least as high a
research priority as conducting clinical
trials of statins for school-aged children
with elevated cholesterol levels. Focus-
ing on access problems and differential
treatment in the health care system is cer-
tainly important, but confronting the
early childhood origins of disparities in
physical and mental health may offer far
greater return on investment.
In 2000, the Institute of Medicine and
National Research Council released a
report that synthesized existing knowl-
edge about the effects of early experi-
ence on child development, including
its underlying neurobiology.14 Over the
ensuing decade, public support for early
childhood investment has increased
substantially, with state expenditures
for home visiting programs in the
United States increasing from $13 mil-
lion111 to $280 million112 and state pre-K
from $1.6 billion113 to $4.5 billion.112
Much of the impetus behind this ex-
panded investment comes from an in-
creasing evidence base that demon-
strates the extent to which effective
interventions early in life can produce
measurable benefits in later educa-
tional achievement, economic produc-
tivity, and responsible citizenship.114
Advances in neuroscience and the bi-
ology of stress provide a compelling ra-
tionale for considering the inclusion of
health promotion and disease preven-
tion as a fully integrated part of that
agenda.
Author Contributions: Drs Shonkoff and Boyce shared
equally in the conceptualization, writing, and editing
of this article, and Dr McEwen made important ad-
ditional contributions.
Study concept and design: Shonkoff, Boyce, McEwen.
Analysis and interpretation of data: Shonkoff, Boyce,
McEwen.
Drafting of the manuscript: Shonkoff, Boyce, McEwen.
CHILDHOOD ROOTS OF HEALTH DISPARITIES
©2009 American Medical Association. All rights reserved. (Reprinted) JAMA, June 3, 2009—Vol 301, No. 21 2257
at University of Calgary on June 16, 2009 www.jama.comDownloaded from
Critical revision of the manuscript for important in-
tellectual content: Shonkoff, Boyce, McEwen.
Obtained funding: Shonkoff.
Administrative, technical, or material support:
Shonkoff.
Study supervision: Shonkoff, Boyce, McEwen.
Financial Disclosures: None reported.
Funding/Support: Primary funding for this article was
received from the Division of Violence Prevention, Na-
tional Center for Injury Control and Prevention, US
Centers for Disease Control and Prevention (CDC),
which reviewed previous versions of the manuscript.
No substantive changes were made to the manu-
script as a result of these comments, nor was ap-
proval of the manuscript offered to or given by the
funders. Additional funding, without manuscript re-
view, for the work of the authors as members of the
National Scientific Council on the Developing Child
has been provided by the Birth to Five Policy Alli-
ance, the Buffett Early Childhood Fund, the Pierre and
Pamela Omidyar Fund, and the John D. and Cather-
ine T. MacArthur Foundation.
Role of the Sponsors: Other than the CDC review
noted above, no funder participated in the design and
conduct of the study, collection, management, analy-
sis, and interpretation of the data, or preparation, re-
view, or approval of the manuscript.
Additional Contributions: We thank our colleagues on
the National Scientific Council on the Developing Child
for their comments on earlier drafts of the manuscript.
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