Neurodevelopment, Nutrition,

and Inflammation: The Evolving

Global Child Health Landscape
Zulfiqar A. Bhutta, MBBS, FRCPCH, FAAP, PhD,a,b Richard L. Guerrant, MD,c Charles A. Nelson III, PhDd,e,f

abstract The last decade has witnessed major reductions in child mortality and a focus on saving
lives with key interventions targeting major causes of child deaths, such as neonatal deaths
and those due to childhood diarrhea and pneumonia. With the transition to Sustainable
Development Goals, the global health community is expanding child health initiatives to
address not only the ongoing need for reduced mortality, but also to decrease morbidity and
adverse exposures toward improving health and developmental outcomes. The relationship
between adverse environmental exposures frequently associated with factors operating
in the prepregnancy period and during fetal development is well established. Also well
appreciated are the developmental impacts (both short- and long-term) associated with
postnatal factors, such as immunostimulation and environmental enteropathy, and the
additional risks posed by the confluence of factors related to malnutrition, poor living
conditions, and the high burden of infections. This article provides our current thinking
on the pathogenesis and risk factors for adverse developmental outcomes among young
children, setting the scene for potential interventions that can ameliorate these adversities
among families and children at risk.

aCentre for Global Child Health, The Hospital for Sick Children, Toronto, Ontario, Canada; bCentre of Excellence in Women and Child Health, Aga Khan University, Karachi, Pakistan; cCenter

for Global Health, Division of Infectious Diseases and International Health, University of Virginia School of Medicine, Charlottesville, Virginia; dLaboratories of Cognitive Neuroscience, Boston
Children's Hospital, Boston, Massachusetts; eDepartment of Pediatrics, Harvard Medical School, Boston, Massachusetts; and fHuman Development Program, Harvard Graduate School of
Education, Cambridge, Massachusetts

Dr Bhutta was a presenter at the original Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) scientific meeting, served as the
lead author for the paper, organized the writing team, drafted the initial manuscript, incorporated edits from the additional authors and editors, and finalized the
manuscript; Dr Guerrant was a presenter at the original NICHD scientific meeting, contributed to the writing of the initial manuscript, and reviewed and revised
subsequent versions of the manuscript; Dr Nelson was a panelist at the original NICHD scientific meeting, contributed to the writing of the initial manuscript, and reviewed
and revised subsequent versions of the manuscript; and all authors approved the final manuscript as submitted and are accountable for all aspects of the work.
DOI: 10.1542/peds.2016-2828D
Accepted for publication Dec 21, 2016
Address correspondence to Zulfiqar Bhutta, MBBS, FRCPCH, FAAP, PhD, Codirector, SickKids Centre for Global Child Health, The Hospital for Sick Children, 686 Bay St,
Toronto, ON M5G A04, Canada. E-mail: zulfi[email protected]
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright © 2017 by the American Academy of Pediatrics
FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.
FUNDING: This supplement was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at the United States
National Institutes of Health (NIH).
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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SUPPLEMENT ARTICLE PEDIATRICS Volume 139, Number s1, April 2017:e20162828
Important and heartening downward TABLE 1 Global Trends in Under-5 Mortality
trends in global mortality for The global under-5 mortality rate has dropped nearly 53% since 1990, from around 91 deaths per 1000
children <5 years of age have been live births to 43 per 1000 live births in 2015.4
achieved in recent years. For a In 2000, for example, there were 9.8 million annual deaths of children <5 years of age.5 Pooled estimates
for 42 countries that included >90% of all such deaths identified leading causes as:
summary, see Table 1. In light of
○ neonatal conditions (33%),
this encouraging progress, there ○ diarrhea (22%),
is an emerging recognition of the ○ pneumonia (21%),

importance of newborn survival in ○ malaria (9%), and

○ HIV (3%)5
reducing child mortality. Strategies
In 2013, mortality rates reduced to 5.9 million deaths per year6 with a major shift in the causes:
to address newborn survival1 will ○ preterm birth complications cause 15% of all under-5 deaths and, along with other neonatal causes,
also be a critical part of the maternal represent 44% of all deaths7;
and child health goals within ○ pneumonia (15%),

the United Nations’ Sustainable ○ diarrhea (9%),

○ malaria (7%), and
Development Goal 3 for health
○ AIDS (2%) deaths have declined in relative terms, and even more so in absolute terms.8
and well-being.2 Although global
burden of disease data have typically
focused on children <5 years of age, (eg, sanitation), poverty, and the implications of potential insults
more recent evidence points to a undernutrition.13 More recently, the are compounded by their timing
continued burden of morbidity and association of Zika virus infection (ie, during critical and sensitive
ill health among older children and during pregnancy and microcephaly periods of neurodevelopment).
adolescents.3 highlights the importance of A sensitive period is a time in
emerging infectious diseases and the development during which the brain
Increasingly, the global health risks of adverse neurodevelopmental is particularly responsive to stimuli
community is expanding child health outcomes.14 By using Early Child or insults followed by an extended
initiatives to address not only the Development Index data from period of ongoing responsiveness,
ongoing need for reduced mortality, Demographic and Health Surveys but to a lesser degree (eg, language
but also to decrease morbidity as well as Multiple Indicator Cluster development); by contrast, a
and adverse exposures toward Surveys in 35 low- and middle- critical period refers to a time in
improving health and developmental income countries, estimates of the development when the presence or
outcomes.9 In addition, reductions prevalence of neurodevelopmental absence of an experience results in
in child mortality have not been deficits have recently been published, irreversible change (eg, binocular
universally realized and significant indicating that 14.6% of children had vision).17,18 Figure 1 depicts neural
disparities exist for marginalized low Early Child Development Index
network development from the
populations.10 According to the scores in the cognitive domain, 26.2%
prenatal period into adulthood,
2016 Global Nutrition Report, had low socioemotional scores, and
including key time periods, sensitive
159 million children have stunted 36.8% performed poorly in either
and critical, for specific domains. An
growth worldwide, reflecting a or both domains.15 Risk factors for
example of the former might be the
rate of reduction that is far lower such deficits should be considered in
formation of a healthy attachment
than the targets set by the World the context of sensitive time periods
Health Assembly.11 The data suggest between infant and caregiver, which
in fetal and childhood physical
that, notwithstanding the leading requires an adult who is invested in
and neurodevelopment. For the
infectious disease–associated purposes of this journal supplement, the child’s needs during the first 2
deaths, iron deficiency anemia was neurodevelopment is defined as the years of life. An example of the latter
the leading cause of years lived dynamic interrelationship between is the need to treat children born
with disability among children and environment, genes, and the brain with cataracts in the first few months
adolescents, affecting 619 million whereby the brain develops across of life for children to ever develop
children in 2013.3 Not only are time to establish sensory, motor, normal vison. For most aspects of
developmental deficits important cognitive, socioemotional, cultural, human behavioral development, the
consequences of conditions and behavioral adaptive functions. concept of sensitive periods is the
associated with a higher risk of This definition has been modified most applicable, given the prolonged
mortality (such as intrauterine for this effort from an earlier version course of brain development and
growth restriction, prematurity, recently published in Nature.16 the enormous range of experiences
and birth asphyxia),12 but they may to which children from different
also be associated with a range of As will be explored more fully below cultures and societies are exposed.
factors related to living conditions and throughout this supplement, Although not all developmental

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PEDIATRICS Volume 139, Number s1, April 2017 S13
FIGURE 1
The neural network: development from the prenatal period into adulthood, including key time periods (ie, sensitive and critical) for specific domains.
(Reprinted with permission from Bhattacharjee Y. Baby Brains – The First Year. National Geographic. Available at: http://ngm.nationalgeographic.com/
2015/01/baby-brains/bhattacharjee-text.)

domains follow sensitive periods, typical trajectory, whereas negative and colleagues,19–21 may prove
of those that do, most sensitive experiences can undermine this particularly helpful in developing
periods occur during the first few trajectory. This association is new “late-onset” interventions.
years of life. Importantly, not all particularly true if such negative
sensitive periods are the same, even experiences continue beyond the Although healthy debates continue
within the same general domain. sensitive period. Accordingly, about the data quality, complexity of
For example, the acquisition of interventions are more likely to be causality, and mechanisms involved,
syntax likely follows a much more met with success when implemented multiple lines of evidence link
compressed time table than the early, when many brain regions and impaired early-life development
acquisition of vocabulary, which circuits are at their peak of plasticity. with later health impairment.
may extend throughout much of the
However, effective interventions Examples that provoke challenging
lifespan. Similarly, the formation of
are also needed throughout the life- genetic, epigenetic, microbiologic,
attachments likely follows a different
course from early childhood through and metabolomic models for
time table than the acquisition of
young adulthood to achieve the best understanding include potential
executive functions (ie, cognitive
control), which, like vocabulary, is possible outcomes for those who development and metabolic
apt to be broadly tuned. did not receive appropriate support consequences of diseases of poverty,
at earlier time points. For example, such as repeated enteric infections
During sensitive periods, when recent advances in understanding in early childhood in impoverished
there is maximal brain plasticity, the molecular signals that regulate areas.22 The associations of key
experiences can “cut both ways.” the opening and closing of sensitive prenatal factors and being small
That is, positive experiences are periods, such as those reported for gestational age (SGA) with
likely to direct development along a in animal models by Hensch an increased risk of mortality23

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S14 BHUTTA et al
and subsequent stunting are well neurodevelopment.24,25 Figure 2 such children worldwide has been
recognized.13 illustrates an early adversity causal made,29 such as with recently
model of the interactions between developed nutritional guidelines
early childhood adversity, biological for preterm infants.30
RISK FACTORS FOR IMPAIRED changes, and long-term outcomes.
NEURODEVELOPMENT Specific examples of early-life insults • Nutrition: Malnutrition,
and adversities that are of particular including both undernutrition
The fact that a range of and overnutrition, clearly has
periconceptual, fetal, and relevance to LRS include:
implications for all aspects of
postnatal factors affect health and • Prematurity: Preterm birth, child development. An abundance
neurodevelopmental outcomes particularly in LRS where fewer of evidence exists implicating
in an interconnected manner is interventions and services undernutrition as an independent
well established. Increasingly, at are available, can lead to both causal factor in altering physical
both the population and individual short- and long-term deficits in and neurologic development,
level, there is a cooccurrence of neurodevelopment,26 including with both short- and long-term
malnutrition (ie, both overnutrition specific impairments in attention27 implications for health and quality
and undernutrition) and infectious and higher-order cognitive skills.28 of life.31
and noncommunicable diseases, Although multifactorial in origin,
each of which has strong nutritional prematurity risks include maternal • Infectious disease and
and inflammatory components undernutrition, micronutrient inflammation: It is well known
that impact and are impacted by deficiencies, as well as subclinical that chronic diarrheal illness, often
neurodevelopment, particularly infections and inflammation; due to poor sanitation, food safety,
in the context of pregnancy, these risks may vary in different and water quality, is associated
birth outcomes, infant feeding, populations and are affected with chronic inflammation. In
and maternal health, including by genetic influences. Given the a cohort of Bangladeshi infants
adolescents. A host of environmental prevalence of prematurity in the living in poverty, Jiang et al32 have
factors have been identified in low- United States and globally, it is reported decreased scores on the
resource settings (LRS) that increase fortunate that some progress on Bayley Scales of Infant and Toddler
the risk for altering the course of solutions to the health care of Development33 in association with

FIGURE 2
Early adversity causal model: Interactions between early childhood adversity, biological changes, and long-term outcomes. Reprinted and adapted with
permission from Annie E. Berens, medical student, Harvard Medical School. IUGR, intrauterine growth restriction; LBW, low birth weight; SGA, small for
gestational age.

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PEDIATRICS Volume 139, Number s1, April 2017 S15
 febrile illness as a clinical marker function, and gene expression. median prevalence of stunting in
of inflammation and a variety of Animal and human studies have the 65 countdown countries with
proinflammatory cytokines. This found associations between early- data from 2009 or later is 32%, and
is an impressive demonstration life adversity and toxic stress to ranges from 9% in China to 58% in
that children experiencing early changes in brain architecture Burundi. Progress in these domains
inflammatory processes are at and gene expression, potentially has been relatively slow, despite the
risk for diminished or delayed resulting in long-term and even calls for action at the World Health
development. Whether there is intergenerational physical and Assembly and through The Lancet
catch-up later in life is unknown. mental health consequences. Undernutrition Series in 2013.13,44
Importantly, toxic stress is most Few countries have launched
• Violence: Child maltreatment
deleterious to the developing comprehensive programs integrating
increases the risk of both adverse
brain when it occurs during a child survival and nutrition at
neural34,35 and cardiovascular
sensitive or critical period of scale.11,46
outcomes.36 A recent systematic
development and may have lifelong
review of population-based A significant advance in recent years
effects. Consequently, toxic stress
surveys, including data for 96 is the recognition of the relationship
is an important concept with
countries, estimates that 1 billion between maternal undernutrition,
implications for the research,
children ages 2 to 17 years, indeed even preconceptional factors,
clinical, and policy arenas.
representing over half of all such as maternal height, and fetal
children globally, experienced growth restriction, resulting in SGA
violence in the past year.37 This THE IMPACT OF NUTRITION ON births.47 Not only has SGA been
pervasive exposure to conflict and NEURODEVELOPMENT shown to compound the risk of
violence in early childhood can neonatal mortality, especially among
The evidence to support the intimate
have far-reaching consequences for preterm infants,47 but it has also been
and inextricable role of food and
the physical and mental health of shown to account for at least a fifth of
nutrition, including in mortality and
future generations.38 all stunting in children at 18 months
human development is compelling.13
of age.13 This association could be
• Toxic stress: For the purposes Suboptimal nutrition, associated with
stronger in South Asia, which has
of this article, toxic stress fetal growth restriction, stunting,
significantly higher rates of maternal
will be defined by using key wasting, and deficiencies of vitamin
malnutrition and SGA births. To
concepts introduced by the A and zinc, along with suboptimal
illustrate, both maternal height and
National Scientific Council on breastfeeding, is associated with
BMI were found to be independently
the Developing Child, which ∼45% of all deaths of children
associated with childhood stunting in
described toxic stress as being the <5 years of age.13 The Pelotas
Pakistan,48 and similar relationships
excessive or prolonged activation cohort of 3500 infants followed
have been shown from an analysis of
of the physiologic stress response up to 30 years of age, adjusted for
data from the National Family Health
systems in the absence of the potential confounders, showed that
Survey of India.49,50
buffering protection afforded by participants who were breastfed for
stable, responsive relationships at least 12 months, as compared with Stunting has been associated with
and the result of cumulative <1 month, scored on average 3.76 impaired cognitive development,
adverse childhood experiences.39 points higher on IQ tests, achieved effects that are only partially
There is now extensive evidence 0.91 extra years of education, and mitigated by schooling.51 In addition,
from neuroscience, molecular earned higher monthly incomes.43 although the magnitude and duration
biology, and epigenetics illustrating These effects are especially notable of effects in the postnatal period and
that increases in heart rate, blood given the known benefits of exclusive infancy remain controversial, relative
pressure, and serum glucose, breastfeeding for newborn and to the importance of maternal and
coupled with elevations in stress child survival44 and the impacts fetal effects, some studies have
hormones and inflammatory on the burden of morbidity due to provided intriguing insight into
cytokines fuel the fight or flight gastrointestinal and respiratory critical opportunities for benefit. In
response to deal with acute infections.45 Stunting is included a large study in rural Pakistan with
threat.39–42 Furthermore, excessive among the 2013 World Health community health workers providing
or prolonged activation of stress Assembly nutrition targets, but the integrated nutrition and child
response systems can lead to world is off track for achieving the development messaging, although
long-term disruptions in brain global target of reducing stunting there were developmental benefits
development, immune status, prevalence by 40% by 2025.11 at 24 months of age, there was no
metabolic systems, cardiovascular As per the latest estimates,46 the impact on nutritional outcomes.52

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S16 BHUTTA et al
However, nutritional intervention aspects of child development Evidence continues to mount that
in the first 2 years of life has been has been greatly informed by the enteric infections and enteric or
reported to be associated with as recognition of both the prevalence systemic inflammation in early
much as a 10% higher IQ score and and nature of “environmental childhood or prenatally can impair
46% higher wages in later life.53 enteropathy” (EE).58 EE with growth and development and
disrupted intestinal barrier function, perhaps even increase later life
Given the close nexus between
intestinal inflammation, and impaired associations with obesity, metabolic
poverty and undernutrition, it
absorptive function is postulated to syndrome or cardiovascular
is not surprising that significant
impair early childhood growth and disease.22,32,73 Murine models also
correlations between poverty and
neurodevelopment. The fact that confirm that infection can impair
brain development have been
inflammation during key life periods growth and undernutrition can
demonstrated.54,55 Other research
may play a critical role in affecting greatly worsen infection burdens
looking at factors associated with
nutrition, EE, and development has and their growth impairment,
neurodevelopment and poverty
been well recognized for well over documenting a potential
has focused on the toxic effects of
2 decades59 and was convincingly “vicious cycle” with such enteric
violence, abuse, and exposure to
demonstrated in a series of studies pathogens as cryptosporidium or
conflict. Data from the recent Lancet
in Malawi and Zimbabwe.60–62 These enteroaggregative Escherichia coli.74,75
series on early child development56
indicate that low-grade exposure Although stunting may be an
also suggest that by using conjoint
to environmental pathogens increasingly imperfect surrogate
estimates of poverty and stunting,
may create an environment of for the long-term effects of early life
some 200 million children
immunostimulation and may relate enteric infections, Victora et al43 have
worldwide are at risk for suboptimal
to changes in the microbiome63 or the noted that the height-for-age z score
development with huge economic
insulinlike growth factor axis.64 In around the second birthday can be
costs over their lifetimes and
separate studies, children in Kenya or the best predictor of “human capital”
potentially across generations. These
Jamaica who received treatment with in terms of educational attainment,
data do not, as yet, take into account
the antihelminthic drug albendazole economic productivity, and even the
the number of families and young
compared with placebo had weight of future offspring.
children affected by violence, abuse,
significantly better growth, fitness,
and exposure to conflict. It is now
and cognitive function.65,66 Diarrheal illnesses, a surrogate for
estimated that at least 40% of the
enteric infections, EE, and stunting or
global burden of maternal and child
Despite surprisingly comparable impaired “catch-up growth”68 have
mortality lies in countries affected
growth curves in the first few also been associated with impaired
by national or subnational conflict
months of life, the fall from the cognitive development. Specifically,
and population displacement.57
expected growth trajectory from the cognitive impairment most
The growing knowledge of the
4 to 24 months of age in children affected appears to be semantic
biology of typical and atypical child
living in impoverished areas of (versus phonemic) fluency and
and brain development, and the
Asia, Africa, and Latin America higher executive function, somewhat
potential impact of interventions
has been remarkably consistent in analogous to the cognitive deficits
during sensitive periods of brain
decade-plus reviews as well as in seen in Alzheimer’s disease.76
development may ameliorate the
current multisite studies.3,67 The Because of this, a specific allele of
global burden of adversity and risk.
extent to which stunted growth is a the Apo-lipoprotein E (ApoE4),
The key focus on the first 1000 days
reflection of intestinal parasitic or which has been associated with
of life points to the importance of the
other infections or is predictive of an increased risk of late-onset
period of fetal development, during
impaired cognitive development, Alzheimer’s disease, has been
which the adverse effects on brain
or that the latter may occur with an examined and, surprisingly, has been
development and linear growth
EE independent of stunted growth, found to be protective against the
are maximal and the potential for
has been and remains the topic of cognitive deficits seen in children
interventions is at a maximum.
many studies ranging from work with heavy diarrhea burdens.77 Table
in Guatemala,53 the Philippines,51 2 provides some highlights of this
Kenya,63 Jamaica,64,67 Peru,68,69 and seminal research. Taken together,
THE IMPACT OF INFLAMMATION ON
Brazil70,71 to the current work by these findings of a potential benefit
NEURODEVELOPMENT
the Interactions of Malnutrition and of the ApoE4 allele in protecting the
Our appreciation of the interaction Enteric Infections: Consequences cognitive development of children (or
between inflammation associated for Child Health and Development enteropathy in mice)78 with repeated
with chronic infection and various consortium.72 diarrhea or enteropathy in early

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PEDIATRICS Volume 139, Number s1, April 2017 S17
childhood (or specific infections in TABLE 2 Potential Role of ApoE4 in Cognition
mice) could help explain a potential A specific allele of ApoE4, which has been associated with an increased risk of late-onset Alzheimer’s
selective advantage for this ApoE4 disease, has been found to be protective against the cognitive deficits seen in children with heavy
allele despite its clear association with diarrhea burdens.77
The potential link between ApoE4 and cognition has been extended to targeted transgenic mice
an increased risk for Alzheimer’s
expressing the human ApoE4 allele. Findings include:
disease in later life (an effect that has protected intestinal villus morphometry,
been termed “antagonistic pleiotropy,” improved growth trajectories, and
or when a single gene controls more reduced shedding of Cryptosporidium parasites in experimental infections with malnutrition.78
than a single trait, ≥1 of which The bridge with basic studies may lie in Colton and Czapiga’s work79,80 showing that:
these mice exhibit increased expression of cationic amino acid transporter-1 that is responsible for
has beneficial and ≥1 of which has
arginine uptake
detrimental effects on the fitness
of the host). Thus, the evolutionary
benefit of ApoE4 (perhaps like innovative interventions to optimize targeting interventions. More
other genes, such as the sickle cell these critical determinants in recently, a systematic review of
trait gene) may only persist in the early childhood. The critical roles key interventions that can impact
presence of such health threats as of the microbiota in influencing maternal, newborn, and child health
diarrhea or enteropathy (or malaria). susceptibility to (and being and nutrition outcomes has shown
As conditions improve, one could influenced by) malnutrition and the potential of integrating strategies
imagine the changing “evolutionary enteric and other infections are for health, nutrition, and nurturing
value” of different traits over time. rapidly growing areas of research care across the life course89 with
and are beyond the scope of this much potential for intergenerational
The long-term and even
overview.85,86 Similarly, relevant benefits.56
transgenerational effects of early
metabolic and other biomarkers of
childhood infectious, inflammatory,
intestinal barrier function, microbial
or nutritional challenges increase Second, much more needs to be
translocation, inflammatory and
the human and health system costs. known about how experience is
immunologic signaling, and local and
These costs may be compounded biologically embedded. Acquiring
systemic inflammation are important
by potential epigenetic mechanisms this knowledge will require in-depth
areas of research and clinical
that may be involved, leading to research into potential mechanisms
application.87,88
long-term intergenerational effects. that link various stress and protective
Military recruits whose mothers pathways to tailor interventions
were pregnant with them in the IMPLICATIONS FOR RESEARCH, to different neural and behavioral
Dutch hunger winter of 1944 to PROGRAM, AND POLICY DEVELOPMENT systems. To address the burden of
1945 were more likely to be obese impaired neurodevelopment and
Based on what we know about
and, in later life, had problems with develop strategies that include an
the effects of early-life adversity
certain cognitive functions.81,82 appreciation of individual biological
and sensitive or critical periods
Potential mechanisms could involve differences, it is critically important
in development, what should our
leptin promoter methylation, which to link basic molecular research
research priorities be? First, we need
has been shown to occur during with complementary translational
to improve our understanding of the
postzygotic development in mice and clinical research and evidence-
dose, timing, and duration of early
and in humans.83 Indeed, leptin based service delivery. Such efforts
adversity. For example, which forms
promoter methylation has been must include an appreciation of host
of adversity, at which levels, and at
shown in recruits who were exposed genetic, microbiologic, metabolic,
which time periods exert the greatest
periconceptionally to the Dutch and environmental (including
impact on development? Why and
hunger winter.83,84 cultural, family, and community)
how does susceptibility to stress
Thus, translating basic laboratory vary with age, especially during factors. A systems biology approach
research and models into relevance sensitive periods of heightened and characterization of gene
to child nutrition, inflammation, and or diminished sensitivity to networks in the assessment of
neurodevelopment holds promise environmental influences? Are these neurodevelopmental disorders
for elucidating not only host and sensitive periods limited to early is emerging as a potential future
microbiome determinants of the childhood or could there be windows approach to assessing individual
metabolic pathways involved, but of opportunity even later, especially variations in neural network
also potential practical biomarkers in adolescence or adult life? If this configuration and differential
of risk. These biomarkers could be can be established, this information vulnerabilities to neurocognitive
used to assess the effectiveness of will be critical for developing and deficits.

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S18 BHUTTA et al
Third, it is imperative that we investments in monitoring and for Child Mortality Estimation. Lancet.
improve our armamentarium of tools evaluation. 2015;386(10010):2275–2286
that can be used to assess the impact 7. Lawn JE, Blencowe H, Oza S, et al;
of early adversity. Currently, the Lancet Every Newborn Study Group.
most widely used tools are relatively Every Newborn: progress, priorities,
ABBREVIATIONS
coarse behavioral measures (eg, and potential beyond survival. Lancet.
developmental exams) that lack ApoE4: apolipoprotein E4 2014;384(9938):189–205
EE: environmental enteropathy 8. Liu L, Oza S, Hogan D, et al. Global,
sensitivity to underlying neural
LRS: low-resource setting regional, and national causes of child
mechanisms, cannot be used early
SGA: small for gestational age mortality in 2000-13, with projections
in life given the infant’s limited
behavioral repertoire, and are largely to inform post-2015 priorities: an
updated systematic analysis. Lancet.
developed in Western, high-resource
2015;385(9966):430–440
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Neurodevelopment, Nutrition, and Inflammation: The Evolving Global Child
Health Landscape
Zulfiqar A. Bhutta, Richard L. Guerrant and Charles A. Nelson III
Pediatrics 2017;139;S12
DOI: 10.1542/peds.2016-2828D
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
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Neurodevelopment, Nutrition, and Inflammation: The Evolving Global Child
Health Landscape
Zulfiqar A. Bhutta, Richard L. Guerrant and Charles A. Nelson III
Pediatrics 2017;139;S12
DOI: 10.1542/peds.2016-2828D

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2017 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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