DOI: 10.1542/peds.2011-0366; originally published online January 4, 2012;Pediatrics

Jack P. Shonkoff, Linda Richter, Jacques van der Gaag and Zulfiqar A. BhuttaDevelopment

An Integrated Scientific Framework for Child Survival and Early Childhood  

  http://pediatrics.aappublications.org/content/early/2012/01/02/peds.2011-0366

located on the World Wide Web at: The online version of this article, along with updated information and services, is

 

of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2012 by the American Academy published, and trademarked by the American Academy of Pediatrics, 141 Northwest Pointpublication, it has been published continuously since 1948. PEDIATRICS is owned, PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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An Integrated Scientific Framework for Child Survivaland Early Childhood Development

abstractBuilding a strong foundation for healthy development in the early yearsof life is a prerequisite for individual well-being, economic productivity,and harmonious societies around the world. Growing scientific evi-dence also demonstrates that social and physical environments thatthreaten human development (because of scarcity, stress, or instabil-ity) can lead to short-term physiologic and psychological adjustmentsthat are necessary for immediate survival and adaptation, but whichmay come at a significant cost to long-term outcomes in learning, be-havior, health, and longevity. Generally speaking, ministries of healthprioritize child survival and physical well-being, ministries of educationfocus on schooling, ministries of finance promote economic develop-ment, and ministries of welfare address breakdowns across multipledomains of function. Advances in the biological and social sciencesoffer a unifying framework for generating significant societal benefitsby catalyzing greater synergy across these policy sectors. This synergycould inform more effective and efficient investments both to increasethe survival of children born under adverse circumstances and toimprove life outcomes for those who live beyond the early childhoodperiod yet face high risks for diminished life prospects. Pediatrics2012;129:1–13

AUTHORS: Jack P. Shonkoff, MD,a Linda Richter, PhD,b

Jacques van der Gaag, PhD,c and Zulfiqar A. Bhutta, MB,BS, PhDd

aCenter on the Developing Child at Harvard UniversityCambridge, Massachusetts; bHuman Sciences Research Counciland the University of the Witwatersrand, South Africa;cCenter for Universal Education, Brookings Institution, and theAmsterdam Institute for International Development, University ofAmsterdam, The Netherlands and dDivision of Women and ChildHealth, Aga Khan University, Karachi, Pakistan

KEY WORDSchild, child development, child survival, early childhooddevelopment, global health, health disparities, poverty, riskfactors, social policy

ABBREVIATIONSECD—early childhood developmentEFA—Education for AllHDI—Human Development IndexMDG—Millennium Development GoalsUNICEF—United Nations Children’s FundWHO—World Health Organization

As lead author, Dr Shonkoff assumed primary responsibility forconceptualizing the article, assigning the drafting of individualcontent sections by each of the co-authors, integrating all ofthe article’s sections, and producing a unified manuscript.Drs Shonkoff and Richter originated the idea for the article, andDr Richter wrote a preliminary draft that Dr Shonkoff built outconsiderably. Dr Richter contributed to all additions andrevisions of the paper. Dr Van der Gaag conceptualized andwrote the section on human capital formation, and Dr Bhuttacreated and produced the table, in addition to providing contentrefinement throughout the text.

www.pediatrics.org/cgi/doi/10.1542/peds.2011-0366

doi:10.1542/peds.2011-0366

Accepted for publication Sep 28, 2011

Address correspondence to Jack P. Shonkoff, MD, Center on theDeveloping Child at Harvard University, Harvard University, 50Church Street, Cambridge, MA 02138. E-mail:jack_shonkoff@harvard.edu

PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).

Copyright © 2012 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: The authors have indicated that theyhave no financial relationships relevant to this article todisclose.

PEDIATRICS Volume 129, Number 2, February 2012 1

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Buildinga strong foundation for healthydevelopment during the early yearsof life is an important prerequisite forlifelong well-being, successful commu-nities, economic productivity, and har-monious civil societies.1,2 Stated simply,a promising future belongs to thosenations that invest wisely in their youn-gest citizens. Increasing evidence indi-cates that the lifelong burden of earlydisadvantages can be difficult to re-verse, whereas a good start helpschildren develop capacities to cope suc-cessfully and contribute to the socio-economic development of the societyin which they live. Thus, as progress ismade in reducing child mortality, par-ticularly in the poorest countries thatcarry the greatest burden of unfulfilledhuman potential, improving the lifeprospects of those who survive pres-ents an equally compelling priority.3

To this end, new knowledge in thebiological and social sciences can in-form innovative strategies to addressthreats to child survival and well-being,and improve adult outcomes, as well,in ways that did not exist as recentlyas a decade ago.

Advances in the life sciences havedeepened our understanding of theimportance of dynamic interactionsamong environmental influences (in-cluding exposure to toxic chemicals),social experiences (including the de-bilitating effects of poverty, populationdisplacement, unstable relationships,and exposure to violence), nutrition (in-cluding the consequences of both in-adequate and excessive food intake),and genetic predisposition (includingthe extent to which experiences caninfluence gene expression) in affectingboth individual and population well-being. New discoveries in molecularbiology and epigenetics are explain-ing how early adversity, as a result ofscarcity, stress, or instability, can leadto physiologic disruptions in the de-veloping brain, the cardiovascular

system, and other body organs, as wellas behavioral adaptations that havelifelong impacts on learning, behavior,and health.4 Under conditions of ex-treme disadvantage, short-term physi-ologic and psychological adjustmentsthat are necessary for immediate sur-vival may come at significant cost tolifelong health and development. In-deed, there is extensive evidence thatthe long-term consequences of depri-vation, neglect, or social disruption cancreate shocks and ripples that affectgenerations, not only individuals, andhave significant impacts that extendfar beyond national boundaries.5

CONFRONTING THE HUMAN ANDSOCIETAL TOLL OF POVERTY

Severe economic hardship and socialadversity impose a cumulative burdenof risk on hundreds of millions of chil-dren around the world, a burden thatundermines multiple dimensions oftheir lives, including resources, safety,care, and opportunities. Growing up inimpoverished or unsafe conditions isassociated with significant threats tolong-term physical and mental health,cognitive development, educationalachievement, emotionalwell-being, andsocial adjustment, and these impactsare particularly potent in early child-hood.6–10 Whereas poverty is measuredprimarily in terms of material assetsand purchasing power, associated so-cial and psychological dimensions suchas social exclusion, lack of empower-ment, and a sense of hopelessnessalso undermine family dynamics, child-rearing practices, and human devel-opment.11,12

The undernutrition linked to poverty isestimated to contribute to 35% of allchild deaths due to measles, malaria,pneumonia, and diarrhea, as well as tostunted growth for .200 million chil-dren worldwide.13 A recent analysis oflongitudinal data from low- andmiddle-income nations found that poverty and

undernutrition in the preschool yearsaccounted for a loss of more than twogrades in school and .30% in lateradult income.14 Poverty is also associ-ated with higher levels of exposure tostressful conditions linked to violence,poor infrastructure, and lack of serv-ices.15,16 The longer poor children areexposed to these destabilizing circum-stances, the greater the risk that theirstress response systems become dys-regulated, which leads to increased sus-ceptibility to illness, disability, impairedlearning, and social maladjustment inboth the short and long term.17–20

The failure to address conditions thatlimit the life prospects of young chil-dren seriously undermines the socialand economic development sought byall nations.21–23 Setting priorities formitigating the adverse impacts of pov-erty, discrimination, and/or violence onchildren, however, is not a simple task.The imperative of reducing prevent-able deaths is fundamental, and the im-plementation of effective interventionswithin existing health care systemsremains a challenge.24–34 Equally im-portant, however, is the realizationthat the campaign to save lives is in-complete if the future prospects ofthose who survive are constrained bycontinuing adversity, particularly inthe poorest countries. Thus, the timehas come to mobilize science to bothincrease child survival and promoteearly childhood development.

THE EARLY CHILDHOOD ROOTS OFHUMAN CAPITAL

In 1990, theUnitedNationsDevelopmentProgram adopted the Human Develop-ment Index (HDI), which incorporatesa rough assessment of health and ed-ucation along with income, as an alter-native to the Gross Domestic Productper capita as a measure of a country’soverall well-being.34 Ten years later, theinternational community adopted eightMillenniumDevelopment Goals (MDGs),

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several of which address child-relatedaspects of health and education. Thisperspective was reinforced further inthe recent report of the Commissionon the Measurement of Economic Per-formance and Social Progress, whichstated that “the time is ripe for ourmeasurement system to shift emphasisfrom measuring economic productionto measuring people’s well-being…ina context of sustainability.”35

The movement toward measures ofsocial and economic development thatinclude dimensions of human well-being (such as nutrition, health, cog-nitive skills, and social competence),rather than metrics that focus largelyon per capita income, underscores theargument for prioritized investment inthe early childhood period, when thetrajectories of these life outcomes arestrongly influenced by early experi-ences. Indeed, no country that hasfailed to invest in its young childrenhas experienced rapid development,as measured by the HDI or the so-calledcapability approach.36 Furthermore,although some countries (eg, Brazil,China, and India) have achieved rela-tively rapid economic growth in recentyears without substantial investmentin early childhood programs, their risingwealth has been accompanied by sig-nificant increases in income inequality,with large segments of the populationstill lacking access to adequate healthcare, education, and vital social services.

Traditional human capital theoryemploys a life cycle model that linksinvestment in human capacity, such aseducation, to increased productivity inthe labor market, which, in turn, leadsto higher wages and aggregate eco-nomic growth.37,38 Generally speaking,this extensive literature has focusedon the development of cognitive skills,based on the assumption that theymediate better school performance,higher levels of educational achieve-ment, increased income, and greater

prosperity.39,40 Recently, some econo-mists have looked beyond cognitionalone and emphasized the extent towhich emotional and social capacitiesfacilitate cognitive development41 andultimate labor market productivity.42,43

These analysts have also noted thatcompetencies achieved at one stageincrease the productivity of humancapital investments at a later stage,thus leading to dynamic multipliereffects over time and a strong case forearly intervention.44

Beyond the importance of attainingskills, health status (including nutri-tion) is also highly correlated witheconomic outcomes. An estimated 30%of the growth in per capita income thatoccurred in Britain between 1790 and1980 (a period that included the In-dustrial Revolution) has been explainedby the improved gross nutrition of thelabor force.45 The correlation betweenincome and health indicators otherthan nutrition is also strong, yet thecausal direction has been harder todetermine. That said, substantial prog-ress has been made in establishingthe impact of health on wages andproductivity, especially in low-incomesettings.46 Moreover, there is consid-erable evidence documenting the re-lation between early health status(including birth weight and growthduring the first few years) and laterhealth outcomes in adulthood, as wellas with educational achievement, familyincome, household wealth, individualearnings, and labor supply.47–51

Both the HDI and the MDGs recognizethe importance of health, nutrition, andeducation as necessary components ofwell-being that many view as a matterof basic human rights.52,53 It is also be-coming increasingly well understoodthat these dimensions of human devel-opment are important drivers of eco-nomic welfare generally and of povertyreduction specifically.54,55 Consequently,the usual trade-offs between investments

to reduce poverty and its correlates(eg, malnutrition, disease, illiteracy)versus investments to stimulate eco-nomic growth do not exist (in the longrun) for investments in young children,where the net result is synergy, notcompetition.

The economic literature on human cap-ital development and prosperity hasprogressed from the static life cyclemodels of the past, which focusedlargely on formal education and labormarket outcomes, to current dynamicmodels that recognize the importanceof the timing of investments, the rela-tions among cognition, executive func-tionskills (ie,workingmemory, cognitiveflexibility, and inhibitory control), andsocial competence, as well as interac-tions among multiple dimensions ofhuman capital such as nutrition, health,and school achievement.56,57 These con-temporary models also reflect greaterunderstanding of the intergenerationalnature of human capital formation, par-ticularly in terms of the links amongmaternal educational attainment, thesocial status of women, and the healthydevelopment of children.58,59 Buildingon these conceptual shifts in econom-ics, advances in neuroscience, genom-ics, and developmental psychology areshedding new light on the underlyingcausal mechanisms that link early lifeexperiences to adult human capital,thereby presenting an extraordinaryopportunity to reframe policy discoursein development economics.60,61

In 2002, the General Assembly of theUnited Nations endorsed a new agendaentitled A World Fit for Children, whichincluded an expanded commitment toearly childhood policies to enhancephysical, social, emotional, spiritual, andcognitive development.62 Despite thisbold declaration, an estimated 200 mil-lion children under age 5 currently failto meet their developmental potentialas a result of poverty and undernutri-tion.14 This figure is 20-fold higher than

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the number of children who die be-fore their fifth birthday and representsroughly one-third of all children underage 5 in the world.14 The economicimplications of these data are under-scored by recent longitudinal analysesthat reported significant loss of edu-cation and adult earnings attributableto early undernutrition in five low- andmiddle-income countries.63

BUILDING A COORDINATED,SCIENCE-BASED APPROACH TOCHILD SURVIVAL, CHILDDEVELOPMENT, AND LIFELONGHEALTH

Although full elucidation of the under-lying causal mechanisms that explainsocioeconomicdisparities inhealthandlearning awaits further investigation,a rich and growing science of earlychildhood development is available toinform the design of more effectiveinterventions to both increase survivalfor children born under conditions ofsignificant disadvantage and improvethe life prospects of those who do notdie yet face extraordinarily high risksfor poor outcomes.1 To this end, theNational Scientific Council on the De-veloping Child64 proposed a concep-tual framework that draws on thefollowing evidence-based principles:

� The architecture of the brain isconstructed through an ongoingprocess that begins before birth,continues into adulthood, and estab-lishes either a sturdy or a fragilefoundation for all the health, learn-ing, and behavior that follow.

� The interaction of genes and expe-riences literally shapes the cir-cuitry of the developing brain, andis critically influenced by the mu-tual responsiveness of adult-childrelationships, particularly in theearly childhood years.

� Skill begets skill as brains arebuilt in a hierarchical fashion fromthe bottom up, with increasingly

complex circuits building onsimpler circuits and increas-ingly complex and adaptive skillsemerging over time.

� Cognitive, emotional, and socialcapacities are inextricably inter-twined, and learning, behavior, andboth physical and mental healthare highly interrelated over the lifecourse.

� Although manageable levels ofstress are normative and growth-promoting, toxic stress in the earlyyears (ie, the physiologic disrup-tions precipitated by significantadversity in the absence of adultprotection) can damage the devel-oping brain and other organ sys-tems and lead to lifelong problemsin learning and social relationshipsas well as increased susceptibilityto illness.

� Brain plasticity and the ability tochange behavior decrease overtime, so getting things right thefirst time is less costly, to societyand individuals, than trying to fixthem later.

� We have the capacity to measureeffectiveness factors that make thedifference between interventionsthat work and those that do notwork to support healthy child de-velopment.

The link between significant adversityin childhood and increasing risk forlater disorders in physical and mentalhealth has been documented exten-sively.4,65–67 Low birth weight and poorinfant growth, for example, are asso-ciated with a range of metabolic dis-orders.68 Children who have beenneglected, abused, or malnourishedare more likely to have heart diseaseas adults.69–73 They are also at greaterrisk for a variety of health-threateningbehaviors such as smoking and sub-stance abuse, as well as depressionand anxiety disorders.74–77

The most widely postulated biologicalexplanation for these well-establishedassociations points to the long-termconsequences of short-term adapta-tions in neuroendocrine, autonomic,immunologic, and neuropsychologicalsystems78 that are designed to copewith immediate threat, yet becomeproblematic in the face of excessiveactivation.4,79 Alterations in electroen-cephalography tracings and elevatedlevels of cortisol and norepinephrine inchildren exposed to repeated traumaand maltreatment are examples ofsuch responses.65,80 Converging evi-dence from epidemiology and neuro-science also indicates that a varietyof stresses in early life, including ad-verse intrauterine influences such asnutritional deficiencies, can cause en-during abnormalities in brain organi-zation and structure, as well as inendocrine regulatory processes, thatlead to reduced immune competenceand higher or less regulated cortisollevels, among other consequences.63,81,82

Extreme stress and fear in infancy canalso result in later patterns of hyper-vigilance and dysregulated relation-ships that impair learning, socialization,and productivity.78

To fully understand the ways in whichsurvival, growth, learning, and healthare interrelated and undermined in com-parable ways by significant adversity, itis essential to understand the centralrole of the brain in interpreting andregulating the body’s neuroendocrine,autonomic, and immunologic respon-ses to stressful events. Stated simply,the brain is the body’s central controlcenter that influences both physiologicand behavioral responses to threat aswell as the development of copingskills in the face of adversity.83 More-over, the brain is not only an engineof physiologic change in other organsystems, but it is also itself a targetof acute and chronic stress, both phys-ical and psychological, and therefore it

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changes both structurally and function-ally in response to significant threat.84

The biology of adversity and resiliencedemonstrates that significant stres-sors, beginning in utero and continuingthroughout the early years, can lead toearly demise or produce long-lastingimpacts on brain architecture andfunction that are associated with latervariations in stress responsiveness,learning, and relationships, as well aswith alterations in health and the rateof aging. Stress-induced changes havebeenwell documented inmultiple brainregions, with the most extensive workfocused on the hippocampus (whichspecializes in circuits associated withsimple memory), the amygdala (whichmediates fear and aggression), and theprefrontal cortex (which mediates ex-ecutive functions such as planning andself-regulation). These changes involvestress-induced remodeling of neuro-nal structure and connectivity, whichcan alter a range of behavioral andphysiologic responses, including anxi-ety, aggression, mental flexibility, andmemory, among other processes.84

When stress response systems areoveractivated during the early years,they are programmed to adapt to anenvironment that is “expected” to re-main adverse. As a result, the thresh-old for activation is lower and the “hairtrigger” nature of the stress responseresults in greater risk for overly rigidand often aggressive behavior.

Beyond the impact of stress-inducedchanges in brain circuitry on behavior,the consequences for lifelong healthand well-being are also apparent. Forexample, functional activation of theprefrontal cortex has been shown tobe related to changes in blood pres-sure, and elevated amygdala activityhas been linked to the developmentof atherosclerosis.85 Reduced hippo-campal volume seen in association withyears of chronic stress86 has also beendocumented in individuals with diabetes,

Cushing’s disease, major depression,and posttraumatic stress disorder, aswell as in predisease states associatedwith elevations in circulating inflamma-tory cytokines.87,88 Moreover, researchbased on the “Barker (thrifty pheno-type) hypothesis” has produced con-siderable evidence documenting anassociation between adverse fetal con-ditions, as reflected in relatively lowerbirth weight and the subsequent pat-terning of growth in the first 2 yearsof life, and a variety of poor healthoutcomes in adulthood. These includeincreased risk of coronary artery dis-ease, hypertension, and stroke,72 aswell as diabetes89 and obesity,90 all ofwhich are modified by the speed andpatterning of subsequent growth dur-ing childhood, also in response toenvironmental conditions.91 Relativelylarger birth weight, in contrast, hasbeen found to be associated with in-creased risk of some hormone-relatedcancers.92

The most widely accepted explanationof these findings has been describedas “programming,” whereby a spe-cific exposure during a sensitive periodis hypothesized to exert irreversible,long-term effects through epigeneticmechanisms (with or without parallelpsychological adaptations) that “read”the environment in ways that informsubsequent health or developmentalprocesses. In the case of undernutri-tion, for example, the fetus adapts toa condition of scarcity in the intra-uterine environment to improve its im-mediate chances of survival as a hedgeagainst future food shortages.93 Suchadaptations cause permanent changesin endocrine physiology and metabolicregulation that result in higher ratesof obesity in the face of later caloricsufficiency, as well as increased riskfor a variety of adult diseases such asdiabetes and hypertension. These samephysiologic systems can be over-whelmed and result in early death or

continue to respond to ongoing adver-sity during early childhood in ways thatultimately lead to greater risk of im-paired health and compromised func-tionality in the adult years.94,95

THE GLOBAL LANDSCAPE FORCHILD SURVIVAL AND EARLYCHILDHOOD DEVELOPMENT

The systematic tracking of child mor-tality on a global scale began in the1960s, and efforts to improve survivalrates were accelerated in the early1980s under the vigorous leadershipof the United Nations Children’s Fund(UNICEF). The combined impacts of arange of interventions during this pe-riod led to a global drop in under-5mortality from an estimated 121 perthousand in 1980 to 88 per thousand in1986, saving the lives of some 12 to 25million children.96,97 Over the ensuingdecades, the application of both tradi-tional public health principles and newbiomedical advances have fueled anumber of highly effective initiatives,and overall child mortality has contin-ued to decline to an estimated 68 perthousand in 2008.98

Despite important progress towardMDG #4, which is focused on the re-duction of child mortality, the prema-ture deaths of.8million children eachyear remain a formidable challenge.Worldwide, children under 5 are aboutfour times more likely to die thanadults between 15 and 59 years ofage,99–101 and 90% of those who diebefore their fifth birthday live in thepoorest 42 countries in sub-SaharanAfrica and South Asia.97,102,103 In 2005,the World Health Assembly passed aresolution putting maternal and childhealth and survival at the top of theirlist of priorities, which was followedby substantial budget commitmentsto extend interventions for child sur-vival.104–106 A recent report for the periodfrom 2000 to 2010 found that, althoughoverseas development assistance for

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maternal, newborn, and child healthhad increased, funding for this sectoraccounted for only 31% of all devel-opment assistance for health in 2007.26

In an effort to spur greater progresstoward meeting MDG goals in this area,the United Nations launched a GlobalStrategy for Women’s and Children’sHealth in 2010 with a stated objectiveof saving 16 million lives by 2015.107

The major causes of death under theage of 5 in the wealthiest nationscurrently include neonatal conditions,congenital anomalies, motor vehicleaccidents, and cancer. The most com-mon causes of childhood mortality inthe poorest countries are diarrhea,pneumonia, measles, and neonatal con-ditions, with undernutrition as a majorunderlying contributing factor. Malariaand HIV add significant additional ca-sualties in vulnerable areas. The cur-rent knowledge base driving the childsurvival agenda is grounded in tradi-tional public health principles and thedemonstrated effectiveness of interven-tions such as the provision of adequatenutrition, clean water, sanitation, andbasic medical care; promotion of earlyand exclusive breastfeeding; immuni-zation, oral rehydration therapy, andvitamin A supplementation; the use ofinsecticide-treated bed nets to preventmalaria; and prevention and treat-ment of HIV/AIDS. Table 1 provides a list-ing of recent reviews of interventionsdesigned to improve maternal, new-born, and child health and nutrition.

While it is clear that continuing bio-medical research will advance ourability to further reduce mortality ona global scale, important challenges tochild survival in the developing world stillremain within the realm of political willand effective delivery of basic nutrition,sanitation, and personal health services.These challenges are manifested in theneed forexistinghealth systems todeliveran effective combination of health promo-tion, disease prevention, and therapeutic

interventions. The successful imple-mentation of these services requirescompetent governance, functional facili-ties and supply chains, a well-trained andmotivated health care work force, andadditional resources.108 Increasing de-mand through community engagementand mobilization are other critically im-portant factors influencingmaternal andnewborn care in poor countries.109

Equally important, and deserving ofincreased attention, the biology ofadversity suggests that social inter-ventions that reduce or mitigate thephysiologic consequences of toxicstress associated with significant ma-terial deprivation (with or without theadditional burdens of recurrent abuse,chronic neglect, intrafamily and civicviolence, and maternal depression) rep-resent a promising enhancement ofexisting strategies for reducing earlychildhood mortality. To this end, inter-ventions focused on strengthening thecapacities of families to meet theirchildren’s needs in the face of desti-tution or threat suggest two causalpathways to prevent premature death.The first is predicated on more effec-tive utilization of preventive and ther-apeutic health services. The second isbased on the protective influence ofparents’ ability to promote greaterresilience in their children by facilitat-ing effective coping mechanisms in theface of adversity.

Building on these efforts, as child mor-tality rates continue to fall, the founda-tional importance of the early childhoodperiod for lifelong health and develop-ment suggests that survival alone canno longer be a sufficient goal, espe-cially for thepoorest countries. Indeed,the scientific concepts outlined in thisarticle suggest a common underlyingvulnerability that leads to a continuumof risk, from early mortality througha broad spectrum of compromisedlearning aswell as impairments in bothphysical and mental health. Thus, the

extent to which persistent scarcity,stress, and social instability pose con-tinuing threats to the life prospects ofchildren must be a focus for moreproactive intervention.

As the science of early childhood de-velopment (ECD) has received increas-ing recognition globally, the demandfor greater attention to the needs ofyoung children has been incorporatedinto several high-profile internationaldocuments, including the World Decla-ration on Education for All (EFA)110 andthe Dakar Framework for Action,111 theMillennium Development Goals, andthe Report of the World Health Orga-nization (WHO) Commission on SocialDeterminants of Health.112 In 2006,UNICEF reported that .30 low- andmiddle-income countries had estab-lished national ECD policies, and .70nations had some type of national com-mission to coordinate ECD programsacross ministries and sectors.113 Thesecalls for greater investment in youngchildren have been buttressed by in-creasing evidence of the effectivenessof early childhood interventions on arange of health and developmentaloutcomes in low- and middle-incomecountries.29,114,115 Within this increas-ingly receptive environment, advancesin the biology of adversity offer con-siderable promise as an additionalcatalyst to help stimulate the designand testing of coordinated strategiesto further reduce preventable deathand to build a foundation for a life-time of healthy development.24,32,63,116–135

When viewed through this broaderlens, current medically based inter-ventions that are designed primarily toimprove maternal and child survivalare also likely to have positive influen-ces on child development, yet theseoutcomes have not been measured inmost evaluations of such programs.For example, antenatal services forwomen that lead to lower rates of in-trauterine growth retardation24 result

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TABLE1

Review

sof

Interventions

Focusedon

Maternal,Newborn,and

Child

Health

andNutrition

Review

Focus

Scope

DataSources

Findings/Recom

mendations

Lancetreview

ofchild

survival(2003)

32Child

mortalityunderage5

Comprehensive

review

23interventions

Groups

ofpreventiveandtreatm

ent

interventions

butn

odelivery

strategies

WHO

review

ofpractices

thatprom

ote

child

survival,growth,and

developm

ent(2004)

31

Childrenunderage5

Review

ofevidence

for12

keypractices

identified

byUN

ICEF

andWHO

12keypractices

Underscoredimportance

oflinking

practices

atcommunity

levelw

ithserviceavailability

Lancetreview

ofneonataloutcom

es(2005)

28

Newborn

mortality

Community-based

interventions

review

(few

RCTs)

43interventions

16newborn

interventions

packaged

into

threedeliverystrategies

(com

munity,

outreach,and

facilitylevels)

Lancetreview

ofmaternalsurvival

(2006)

27

Maternalm

ortalityandmorbidity

Literature

andprogramreview

(few

RCTs)

120interventions

Recommendedfacility-basedskilled

care

atchildbirthas

thecore

intervention

Review

ofmaternaland

perinatal

prioritiesindeveloping

countries

(2006)

30

Maternalcare

Literature

review

andcomponent

analysisforcost-effectiveness

84interventions

5interventionpackages

considered

(with

orwithoutn

utritional

supplements)

Lancetreview

ofchild

developm

ent

programs(2007)

29

Child

andadultcognitiveandother

developm

entaloutcomes

Literature

andprogramreview

(few

RCTs)

20programs

Recommendationtointegrateearlychild

stimulationandnutrition

programs,

andevaluateatscale

Lancetreview

ofmaternal,newborn,

andchild

care

(2007)

33

Maternal,newborn,and

child

mortality

Literature

anddeliverystrategy

review

forinterventions

across

continuum

ofcare

190interventions

8packages

ofinterventions

targeted

atfour

levels(householdand

community,outreach,upperand

lower

levelfacilities)

Lancetreview

ofundernutrition(2008)

24Maternal,newborn,child,and

adult

mortalityandmorbiditydueto

undernutrition

Literature

andprogramreview

(RCTsandobservationalstudies)

45interventions

Maternalnutritionandsupportive

interventions

targeted

tochildren

during

thefirst24months

Lancetreview

ofprimaryhealth

care

(2008)

25

Interventions

relevant

tomaternal,

newborn,and

child

survivaland

selected

keyrisk

factors

Literature

andprogramreview

(RCTs&observationalstudies)

156interventions

37keyinterventions

recommendedfor

inclusioninprimarycare

settings

Lancetreview

ofcountdow

ntomaternal,

newborn,and

child

survivalgoals

(2010)

26

Focuson

maternal,newborn,and

child

survival-related

interventions

and

tracking

coverage

Review

ofrelevant

inform

ationfrom

DHSandMICsdatasources

22interventions

and

respectivecoverage

Better

coverage

seen

with

programmableinterventions

such

asEPIvaccinations,vitaminA

supplementation,etc.

Lancetreview

ofstillbirths

(2011)

34Focuson

strategies

toinfluencefetal

healthandgrow

thaffectingstillbirths

Comprehensive

review

ofavailable

inform

ationandtrialdata

35interventions

10evidence-based

interventions

recommendedforinclusionin

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in the birth of babies who are at lowerrisk biologically for developmentalimpairments. Another example is pro-vided by interventions that promotebreastfeeding to enhance both nutri-tional status and immunologic compe-tence,32,119,125 which are also likely topromote early developmental progressby strengthening maternal-infantattachment. In a reciprocal fashion,strategies that focus explicitly onstrengthening caregiver-child inter-actions and expanding early learningopportunities in the face of significantmaterial deprivation are likely to re-duce or mitigate the biological impactsof adversity on very young children,thereby enhancing both their survivaland their development.

Although the underlying science thatsupports investment in early child-hood development has advanced con-siderably, and the literature on effectivedemonstration projects in low-incomecountries is growing, empirical evidenceof the successful scale-up of specificinterventions across national and cul-tural settings is less well developed.Moreover, EFA Goal 1 addresses earlychildhood objectives, yet it is the onlyeducation goal without a quantifiableindicator against which progress canbe measured.136 Similarly, more thanhalf of the world’s governments haveECD policies that are statements of in-tent rather than enforceable mandates.These concerns are compounded by thelimited number of major internationaldonors who have identified ECD asa specific focus, the majority of whomallocate ,2% of their education fund-ing to the early childhood years.136

Over the past several decades, earlychildhood policies and practices havebeen guided by several theoretical mod-els of human development that havebeen refined over time. These includethe transactional model formulated bySameroff and Chandler137 and lateradapted to the challenges of early

childhood intervention by Sameroffand Fiese138; the ecological model ar-ticulated by Bronfenbrenner139; and theconcepts of vulnerability and resiliencedeveloped by Werner and Smith,140

Garmezy and Rutter,141 and Rutter.142

Together, these frameworks underscorethe extent to which life outcomes areinfluenced by a dynamic interplay be-tween the cumulative burden of riskfactors and the buffering effects ofprotective factors that can be identifiedwithin the individual, family, commu-nity, and broader socioeconomic andcultural contexts. Each of these modelsalso emphasizes the influence of re-ciprocal child-adult interactions in thedevelopmental process, thereby under-scoring the importance of stable andnurturing relationships and recognizingthe active role that young children playin their own development. The chal-lenges of actually applying this multi-dimensional framework include bothavoiding the lure of simplistic solutionsand making strategic decisions aboutwhich factors to address and which toomit in designing a specific policy, pro-gram, or empirical study.143

In response to these challenges, earlychildhood intervention services typicallyinclude nutrition supplements, basichealth services, and a combination ofnurturing care and enriched learningopportunities for children, linked toamix of parenting education, emotionalsupport, and social protection and so-cial services for their families. Over fourdecades of program development andevaluation, this approach has beenimplemented in demonstration projectsaround the world that have confirmedtheability toproducesignificant impactsacross a range of outcomes.144 Althoughmuch of the empirical literature hascome from the United States, wherepositive returns on investment havebeen documented in cost savings fromdecreased grade retention and refer-rals for special education as well as

lower prevalence of later welfare de-pendence and incarceration,1 the evi-dence base for successful interventionacross a broad diversity of nations isgrowing.

In low- and middle-income countries,model programs that combine nutritionand psychosocial stimulation serviceshave demonstrated the greatest impacton disadvantaged populations.145 A re-view of 20 programs that met rigorousscientific criteria found that all butone (which was delivered at a very lowlevel of intensity) had positive effectson children’s cognitive development,whereas some also reported gains insocial competence, with effect size esti-mates ranging from 0.3 to1.8.29 A morerecent meta-analysis of evidence from30 interventions utilizing a variety ofapproaches in 23 countries in Europe,Asia, Africa, and Latin America alsofound moderately positive effects acrossmultiple developmental domains.146 Ofthemodels studied, eight provided earlyeducation, five provided child care,five focused on nutrition, four combinednutrition and early education, two linkednutrition and child care, one providedboth early education and child care,and six focused primarily on cashtransfers. On average, the magnitudeof the long-term effects was aboutone-quarter to one-third of a SD, withcognitive impacts at the higher end(particularly in programs with an ex-plicit education component) and posi-tive effects sustained through adulthoodwhen long-term data were obtained.114

Recent modifications of conventionalECD programs have included greaterattention to financial and social pro-tection for parents, increasing focuson confronting violence against womenand young children, and the promo-tion of positive engagement of men inaddressing family needs. These andother program models have beendelivered through a variety of mecha-nisms including home visiting, primary

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health facilities,146,147 and group ses-sions with caregivers.148 In this context,a broader range of social interventions,such as conditional and unconditionalcash transfers, microcredit schemes,and voucher programs, are increasinglybeing adopted to meet the needs ofdisadvantaged, young children aroundthe world. Conditional cash transfersappear to be a particularly promisingstrategy to expand ECD impacts, be-cause they improve the immediate,material circumstances of poor families(by providing money), while also en-hancing the life prospects of the chil-dren by having the “conditions” linked toservices that strengthen their health,nutrition, and early educational experi-ences. Evaluations of these programshave documented positive impacts onchildren’s nutritional status;149 encour-aging evidence of their ability to addresscritical child needs in resource-poorsettings or areas that have beenstruck by extreme adversity such asinternal wars or large-scale epi-demics150,151; and promising reports oftheir implementation in sub-SaharanAfrica.152,153 For societies that are bur-dened by the highest levels of materialdeprivation and political instability, theneed for more innovative approachesthat go beyond the provision of conven-tional health care and early childhoodprograms clearly remains a particularlycompelling challenge. In such circum-stances, an integrated science of earlychildhoodhealth anddevelopment offersa powerful framework within whichcreative new strategies can be formu-lated, tested, and refined over time.

CONCLUDING COMMENTS

Extensive documentation of the valueof investing in healthy developmentbeginning at birth (and indeed, pre-natally) stands in stark contrast tocurrent policies regarding human capi-tal formation in virtually every nationin the world. A recent study of child well-being in 28 countries in the Organization

for Economic Cooperation and De-velopment (OECD) estimated per capitaexpenditures on children in the first 18years of life at $126 000, with an averageof only 24% spent during the periodfrom birth to age 5, compared with 36%spent from age 6 to 11 and 41% fromage 12 to 17.154 Comparable data onhuman capital investment in developingcountries are not available, yet the gapsbetween human needs and availableresources are known to be considerableat all age levels. This situation is mostsevere in sub-Saharan Africa, where theabsolute poverty rate for children is thehighest in the world, the rate of growthstunting exceeds 30%, and only 12%of children are enrolled in preschoolcompared with an average rate globallyof 32% in developing countries and 74%for developed nations.155 In 21 of the 48countries in the region, infant mortalityis well above 100 per thousand. In therealm of education, gross primary en-rollment rates approach 100% in manycountries, but primary grade completionremains below 50% in one-third of themand preprimary enrollment is typically inthe single digit range or nonexistent.155

Science tells us that the foundations oflifelong health and learning are builtin the earliest years of life. Therefore,the time has come to match continuingprogress in theglobal reductionof childmortality with greater investment inthe universal promotion of early child-hood development, particularly in thepoorest nations. Sustainable gains inchild survival have been generated bysocial interventions and health careinitiatives that focus on improving thephysical and mental health of mothers,promoting the stability and security offamilies, supporting child nutrition, en-suring child protection against signifi-cant adversity, securing basic healthservices of good quality, and buildingculturally compatible bridges betweenservice programs and homes. A sys-tematic analysis of these core strate-

gies for reducing mortality reveals aremarkable overlap with many of thekey characteristics of interventionsthat are effective in promoting healthydevelopment, which typically add theessential element of enriched learningopportunities in the early years of life.Central to both objectives is the im-portance of preventing, reducing, ormitigating the adverse physiologic con-sequences of toxic stress, which canrange from the life-threatening con-sequences of compromised immunefunction to the impaired learning thatresults from disrupted brain circuitry.Stated simply, the future of more ef-fective early childhood policy calls fora balanced approach to both stimu-lating minds and protecting brains.156

Recent reports from the AmericanAcademy of Pediatrics call for newapproaches to health promotionbased on this concept.157,158

Within this context, as ministries ofhealth continue to prioritize child sur-vival, ministries of education focus onschooling, and ministries of financepromote economic development, an in-tegrated biology of adversity offers acompelling knowledge base that couldinform a unifying strategy across policysectors. The fruits of that synergy, ahealthy and well-educated population,secure and well-functioning commu-nities, and a prosperous and self-sustaining society, will be harvestedby those nations that make science-based investments in the healthy de-velopment of their youngest members.

ACKNOWLEDGMENTSDr Shonkoff gratefully acknowledgesthe Norlien Foundation, the Pierre andPamela Omidyar Fund, and the MotherChild Education Foundation (AÇEV) ofTurkey, each of which has provided fi-nancial support for the global portfolioof the Center on the Developing Childat Harvard University, whose infra-structure and staffing supported theauthors.

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