Neuroscience, Molecular Biology, and the Childhood Roots of Health Disparities Building a New Framework for Health Promotion and Disease Prevention Jack P. Shoko, MD W. Thomas Boyer, UD biologyarebuildingen increas” ingly persuasivecasefora new ay of thinking about health promotion and disease prevention that Focuses on the origins of persistent dis- parities in moxbidity ancl mortality the early years of life. Central wo this Irame- work is an increasing interest in the extent to which early experiences and exposuresare biologically embedded and have lifelong consequences ‘The following example illustrates hhow the translation of thisevolving sei- nce base into innovative policy can ‘generate new approaches to reducing, the burden: of preventable disease "n-2008, the Armrican Academy of Pe- diaries issued a report toaddressa“new urgency given hildhood ohesity with the subsequent mereasing risk of type 2 diabetes melli- ‘us, hypertension, and cardiovascular dis- ase in older childeen and adults" The report underscored the nesd fora more proactive approach in childhood to the prevention of cardiovascular disease through enhanced adherence o dietary guidelines, creasing physical activity, and consideration of pharmacologic treatment of dyslipiiemia beginning as early sage 8 years. What the report lic not consider the idea, based on grow- ing evidence of the cardiovascular se- queleeof earl ie axiversty, that new in- ceeventions to reduce significant stress ‘A scientific consensus is emerging that the origins of adult disease are of- ten found among developmental and biological disruptions occuring 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. sane, acc 252-2289 wie cn in early childhood may be a more ap- high-quality care to reduce socioeco- propriate strategy for preventing adult nomic and racial disparities in health out- Ihear disease than the offabel admin- comes is clear. Central to this under istration of statins to school-aged ehil- staudingis the persistence ofsocial class dren. In thisatile we explore the sei- _ gradients in dlsease prevalence and or entific validity of the proposition that tality rates in nations that provide wn reducing signiicant disadvantage ealy versal acess to health cate services. {life may bea powerful strategy for re- Somecrities have responded by suggest ducing the population-level bueden of ing grester focus on inequalities inser cheonie morbidtyand premature death, vice uilization and differentia! teat rent by the health cae syster. Others Emergence of a New Scientific nave called for grater attention to the ‘Approach for Health Policy role of broader social and economic i Dillrences tn health outcomes related ences om heath although the task of (ossocal class and otker markers ofis- translating this perspective into con- advantage have been well documented crete poliey initiatives bas gencrated across a broad range of cultures, aswell more rhetoric than action, While cli asinsocietsvathavavety ofhealthcare cans apply advances in the biomedkia systems?* Despite the unassailable re- Tatts obustassoction theela- ju sen ror Dt cation of precise causal mechanisms aardpeeny Canby Macao linking adversity o bealth status re-‘Faesene une of a Caen Urea mains elusive, and effectivepoicy rem Cra teen nchad a ewe ‘edies are not readily apparent See cee eee Notwithstanding the furdanentalime Eoreperig hr nk Sontel, MO, Ce potance ofhigh-quatty mesiccarefor Senne Beso, Che, aad Uns, those whoareill thelimitedcapaclty of ¢ onsite 2282. JAH je 3, 2000-voL 30, N20 Repretesh {©2009 American Medical Associaton, Al ight reserved. Downloaded from war jaena.com by guest on June 2, 2008sciences to transform their capacity to taeat patients who are sick, policy mak- fers who are interested in popniation health wouldbe well served bya deeper ‘mnderstanding of che underlying biol- gy of ealy adversity. For much of the 20th century, adult conditions such as coronary hear dis- cease, stroke, diabetes, and cancer were regarded solely as products of alt be- havior and lifestyles” By the century's end, however, att extensive body of evi- dence linked adult chronic disease to processes and experiences occurring de- ‘eadesbelere, in some casesas early as in- trnuterine life, aerossa wide range ofim- ppairments, Longitudinal studies have ‘demonstrated that pulmonary disease adulthood iscormmonly associated with, ‘history of respratory illnesses inchild- hhood.® Intrauterine exposure to dieth- ‘lstilbestrol was discovered to underlie vaginal and cervical cancers in young women Prenatal processes have beet associated with the later manifestations ‘ofschizophrenia** and autism,"*and carly social environments have been shown to play formative roles in eogni- tive and socioemotional develop- ment" Researchers have also found that cardiovascular disease in laterlifecan be Linked to nutritional deficits and growth impairments inthe prenatal period !* Although full elucidation of the causal mechanisms that account for these associations avaits 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 dorailed analysis ofits policy implica tions are beyond the scope of a single report, The purpose ofthis article isto proposea framework forinereased cal- Taborative 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 ave postulated that carly experience canaflect adult health ‘mat least 2 ways—by accumulating damage aver tne or by the biological embedding of adversities during sen- sue developmental periods." im both cases, there can bealag of many years, (©2009 American Medical Assoctation All igh reserved. “GHILDHOOD ROOTS OF HEALTH DISPARITIES. even decades, before early adverse ex- periences ate expressed inthe form of illness If the damage occurs through cumulative process, chronic dis- ‘eases can be seen as he prodincs of = peated enconnters vith both psycho- Togically and physically stressful experiences. When exposures occur dating sensitive periods of develop- rent, their elects can become perma- rently incorporated into regulatory physiotogieal processes, and subse- quent adult disease may be viewed as the latent outcome of eritial events that ‘occurred during early perieds of spe- cial suseepuibility. ‘Cumulative Exposures to Stressful Expeniences, Strong associations have been sown Berween retrospective adult reports of increasing numbers of trau- matic childhood events with greater prevalence of wide array of health im- pairments, including coronary artery disease, chronic pulmonary dlsease, cancer, alcoholism, depression, and dlrug abuse" as wel as overlapping mental health problems,” teen prege nancies," and cardiovascular risk lac- tors such as obesity, physical inactiv- lay, and smoking," Otherlongitudinal studies have found similar link- ages 2" Recent prospective data have reinforced this association, cluding evidence that depressed adults with & documented history of maltreatmentin childhood are twice as likely to have linially relevant elevations of high- sensitivity C-reactive protein levels Compared with controls, whereas in- dlviduals with depression and no his- tory of maltreatment showed nonsig- rifieant increases inthis biomarker of greater isk of cardiovascular disease.” ‘Another body of research has sug- gested that “weathering” of the body lunder persistent adversity (ie, the increased wearaneltearinduced by sress- ful experiences that overuse and cys regulate pathways normally used for adaption to neat) reflects sm accel- tration of normal aging processes. Alrican Americans, for example, expe: rience eater deteriorations of heal in cumulative fshion, leading to progres: slvely larger health disparities with age and life expectancy that isto 6 years less than for whites.” One hypoth~ sized causal mechanism is the persis- rence of stress associated with discrimi- nation thataccelratesthe aging process" ‘Curmulative-exposure explanations of hronicadultclseaseareconsistent wth research that addresses the breakdown ‘of physiological steady state under conditions of chronic challenge=a ‘phenomenon referred to as “allostatic Toad." Undersuch elreumstances, act- vation of stress management systems in. the brain results ina highly integrated repertoite of responses involving secce- sion of stress hormones, increases im hheatt rate and blood pressure, protec- tive mobilizavion of nutrients, redirec- ton ofblood perfusion tothe bralu, and induction of vigilance and fear. These ‘neurobiological responses are essential ang generally protective, but when acti- vated persistently under circumstances of cheonic or overwhelming adversity, they ean become pathogenic!” *Within this context, extensive documentation ofthe disproportionate exposure oflow- incomechildrentocnvironmenta stess- ors, traumatic experiences, and fsmily chaos?! takes on a greater sense of ‘urgency. This threat isunderscored even further by recent evidence of higher ev- cls of physiological and emotional dys- regulation inthis high-risk group. Latent Effects of Adversity During Sensitive Periods. A considerable body of research also suggests that adult dis- easeand risk factors for poor health ean be embedded biologically during sensi- tiveperiodsin whieh the developing brain Ismore receptive to avariety of environ mental signals, whether positive or negative.” For example, poorlivingcon- ditions early in hfe eg, inadequate nstri- tion, other constraints on fetal and infant growth, and cecusrent infections) are associated with increased rates of ‘cardiovascular, respiratory, and psychi- tre diseases in adulthood" tnves- tigators have also documented an 3350 ciation bevween lower birth weight and several risk factors for heart disease, Includinghypertension, central bod fat discribution, insulin resistance, meta- bolic syndrome, and type 2 diabetes.” (Gent) AMA ja 3. 2009-301, No 22359, Downloaded from wonv ama.com by guest on June 2, 2008GHILDROOD ROOTS OF HEALTH DISPARITIES “These findings are supported by ev- dlence from bot animal and human studies, For example, lower irh weight dducto baranterine growth restriction in rats has been associated with higher bloed pressive,” and sties of human infants have linked poor tntrauterine growdkodefictsin neural comrol ofthe ean and kyperension™ Early expe- ences of child maltreatment and pox erty have been associated wit height ened Immune responses in adulthood that are know isk factors far the de- ‘velopment of cardiovascalar disease, ia- betes, asthma, and chronic lung dis- cease So-called naual experiments bhave provided additional, corroborat- ing support for this association. Indi ‘viduals exposed toseverenutritona det- Gitsin wero during tke Dutch fine of 1944, for example, showed a higher prevalence of coronary heart disease ‘when evaluated 50 years lac. Sim larly, hildren in @ Helsinki birth co hort evacuated to temporary foster ere ducing World Wer Il have shown higher rates of both eadiovescular morbidity and syenptoms af depression compared ‘with thetrnonevacuated peers"? The Central Rale ofthe Brain. As the primary organ of stress and adapta- tion, the bran i both vulnerable and adaptable, interpretsand regulates be- hhaviorl, neroendocrine,auconoric, and immunological responses to ad- verse events, servesasa target of acute and chronte psychosocial and physi- cal stes, and changes both structur- ally and functionally as a esa of sige alleant adversity." Animal models have provided considerable insights into diflerental responsivity to tress among diferent brain regions, inelud- ing the hippocampus, amygciala, and prefrontal cortex. Studies have shown both adaptive and maladaptive eflects of stress hormones throughout the if ovse, wich early ie events influenc- ing lifelong paters ofemotionalityand ‘ness responsiveness as well as alter- ing the rate of brain and body aging Stres-indaced remodeling of neato- nal stcture and connectivity in these regions alters behavioral and physi ological responses, inluding anxiery 2984 9168 june 3, 000 et 33, No 21 epre aggression, mental flexibility, memory, and ather cognitive processes. ‘New imaging tecianiques are driv- Ing rapid atvances in knowledge about how the hurnan bean changes with ex- perience. Recent findings inciude the association of reduced hippocampal Vohime with prolonged perceived stress as well as with diagnosed con- ditions such as diabetes, major depres- son, Cushing disease, and posttrax- atic stress disorder.” In coutrast, physical activity and fimess in elderty individuals is associated with in- ‘creased hippocampal volume and bet- termemory funerion aswell as greater activation of prefrontal cortical activ. ‘tyand enhanced execntive function “Te prcirontal cortex, which is in- volved in executive functions such as working memory and behavioral inhi- bition, as wel as top-down contro! of autonomicnervoussystem balance, has ‘been found to be smaller in individy- als with major depression® and in in- dividuals who sef-reporc lower socio- economic status In addition, the prefrontal cortex has been shown to be Srmpaired transiently By mereased lev- els of perceived steess in medical sti- denis studying for board examina tion.® Functional activation of the prefrontal cortex isalso associated with blood pressure responses,” whereas {greater functional activation of the amygdala isassociated with the cevel- ‘opment of atherosclerosis" ‘The Complexity of Heterogeneous Response. Although evidence conti tes to accumulate supporting both c rnulative and latent elfect models of how early adversities may amplify ong- term disease risks, studies also reveal compelling individual differences in the raghitude 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 a5, adults (compared with 18.5% of those reporting no emotional abuse), yet nearly of 5 emotionally abused indi- viduals had no such impairment.” ‘Sirialy,althorgh the risk of coto- nary beartalseae is neuly $ nesmore frequent among adults with birth weights less than 2500 g (15%) compared with Individuals with birth weights greater than 4000 g (4%), these risk rata tend t obscure the counterobservation that 185% of low-birth-weight infants did not develop later heart disease.® Such marked heterogeneity in the longitudl- nal consequences of early life experi ‘ences suggests underlying differences in vulnerability that may moderate these as- seeiations *" Evidence for suck effect ‘modification hasbeen derived from stud tes of gene-environment interaction in which allelic variations in neuroregula- tory and transcription factor-encoding genesareassocated with greater isksre- lated to early stressors” *as wellas from studies showing that individual difer- ‘ences in neurobiological seritvity to so- cia environments ean bias outcomes Doth positively and negatively, depend ing on the protective vs injurious ture of early exposures "7°" Biological Embedding. The epige- netic pathways by which adversity is teansmotedince lastingalterations indis- cease risk are an example of the broader adaptive processes through which eatly influences affect the regulation of bio- Togical systers.* These adaptations are evolved mechanisms that monitor the environment, beginning during the pre- natal period, o adjust set points within ‘important bain circuits. Forexample,a fetus in an intrauterine enviconment characterized by poor nutrition may undergo energy-sparing, metabolic ‘changes thac are designed to he sdap- tive in a postnatal enviconment of food scarcity. While these metabolic changes ‘may be beneficial in the short run, later problems can arise when the adaptive prediction urns outtobe wrong, andthe tarly childhood environment is charac- terized by energy abundance, a carbo- hhydrate-rich dit, and a sedentary life- siyle:”Insuch arcumstances, according to some theorists, the risk of later obe= sity and other metabolic disorders can begin very early in ie"? ‘Children from families and conymu- pities with low income and love educa tion levels may be especially valnerable tw the biological embedding of disease 122009 American Medical Association, Alright reserved Downloeded from wor jama.com by guest on June 2, 2008risk because of their disproportionate exposure to highly stressal influences such s neighborhood valence, dys ional schools, personal maltreatment, household chaos, and absent par” ents These rik ficoesareoftencom- pout by limited acces to healthful foods and high consumption of energy dense products™* that are contsbt- ing.o the increasing prevalence of obe- sity and diabetes, particularly among, low-income cides. Children Uvingin disadvantaged environments ate also morelikely to experience conflctiveand punitive parental bchavi®' as ell 4 relatively fewer postive experiences such as reading, interactive conversa tin, andalterschoa acuvies insome cases, the cumulative burden of rul- tiple is factors eal in fe may limit the effectiveness of later interentions, hereby malang it impossible to com- pletely reverse the neurobiological snd health conseqwencesof grwingup poor” Current veseareh is charting new territory in understanding the linkages between dilferential childhood expen- ences and several aspects of brain development within regions ded tothe regulation of emotion and social be- vir, reasoningeapacty,angsagestis and stress reactivty® Children from lowersociceconomichackgrourdsshow Ieightenedativation ofsuess-responsive systcme!™ and emergingevidercesug sessthatdiferencesinpareningrelated toincome ard education—as mediated hough perent-child interaction expo- sure to new vocabulary, and stability of responsiveness cavalier thematuation ‘of selected brain areas, such as the pre- fromaleanex.™” Animalmodelsolealy, sstesselated changesinbrain circuitry show tht suck changes can petsistinto adult life end alter emotional states, Secison-making capacities, and bodily processes thatconribueto emotional ‘sash, substance abuse agaresion,obe- sity and stress-related disorders. Moreover allbough early aves dead to greater vulneabibiy ltr life, positive experiences can decrease such risk For example, capitalizing on nat rally oceurring vison inteateraal ae taking behaviors in rats, studies have (©2009 aresicen Medical Association Alright reserved. GHILDHOOD ROOTS OF HEALTH DISPARITIES, ‘demonstrated that pups experiencing rote intensive and responsive mater- nal care have lower levels ofthe sess hormone corticosterone This predispo- ‘ition 10.4 more modest stress response continues into adv life and istrasmit- ted to the second ane third generations ofoflspring *** Such effets are likely 10 extend to humans and noniuman pri- rates as well and to involve moaifica- tions in the expression of glucocort- coidreceptosin bran regions mediating alflect and cognition as well as neuro uwophic factors operating throughout the body. Such alterations of stress 5)5- tems across generations —caused not by genetic inheritance but by eaty exper ‘ences—are facihitated by epigenctic ‘changes in DNA methylation and his- tone modification of chromatia in re- sponse to environmental enes that, ia turn, influence how the next genera- tion's genes ae expressed. "se ‘Although much of this research is based on animal experiments, expert- ence-related variation in gene expres- sion may offer important clues about hhow disparities in early exposure wo ade versity can change adult health out- comesin humans. A recent report on ha- rman brain autopsy material from individwals who experienced chide Ihood abuse revealed changes in DNA ‘methylation relate to the ghicocozi- oid receptor that mirrors changes re- ported in these same types of receptors in brains of rodents that experienced ‘poor maternal care Complexity of Early Childhood Stress as a Policy Issue Despite increasing evidence ofthe long- term effects of early adversity on life- long health, litle attention has been pail wo dhe development of health pro- motion and disease prevention strate sits based on the reduetion of signifi- cantstessorsalfecting everyday life for vulnerable young children and their parents, This potential shortsighted- ‘ness may in part be the result of x gen: eralized misunderstanding about the nature and effects of childhood stress. Foresampl, although mastery of rla- tively minor adversity by children is Viewed as a necessary prerequisite for developing resillence to later chal- lenges, the publics less aware hat lev- tls of stress associated with excessive, persistent, and/or unconteoltable ac versity, without the buffering protec ‘ion of stable adult support. are ass0- ciated with disruptive effects on ‘muldle organ systems that can lead to Iifelongdiscase. Ths isan areain which farther scientific advances inked to en- hanced public understanding could in- form imuovative policy approaches. ‘The National Scientific Coureilon the Developing Child proposed the falow- ing simple tsxonomy to describe 3 cat ‘gories of stress experience —postive, tolerable, and toxic—that can affect the development of young tildren.® tn this Iramework, stress refers to the physi ‘logical expression of the stress re- sponse system, not the nature of the steessor nor the distinction between ob- jectively measured andl perceived stress. “Although much work remains to eluei date the underlying causal mecha nisms, the conceptual basis ofthis model Isgrounded in well-established care bio logical principles Paste stress is characterized by tod= erate, short-lived increases in hear rate, blood pressure, and stess hormone lev: els, Precipitants include the challenges of clealing with frasteation recelving an Injected immunization, and other nor- mative experiences, The essential nar ‘ane of positive stress is that itis 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 toa physiologi- cal state that eoule potentially disrupt Drain architecture (eg, through cortisol induced disruption of neural circuits or ‘neuronal death in the hippocampus) but 's buffered by supportive relationships that facilitate adapive coping, Precipt- tants include the death or serious il. ness ofa loved one, homelessness, ora natural disaster, The defining character- Ist of tolerable stress is that it occurs Within time-timited period, during (Reprtes) ANA je 3.2000) 301, No 21 2255 Downloaded from www Jamea.com by guest on June 2, 2009CHILDHOOD ROOTS OF HEALTH DISPARITIES which protective relationships help to bring the body's stress-response sys- temsback to baseline, thereby giving the ‘rata tue to recover from potentially damaging effects. Toxic stress refers to strong, frequent, andlor prolonged activation of the body's stress-response systems in the absence ofthe buffering protection of adult sup- port. Major risk factors include ex- {eeme poverty, recurrent physical andor emotional abuse, chronic neglect, se- vere maternal depression, parental Sub stance abuse, and family violence. The defining characteristic of toxie stress is that it disrupes brain architecture, af- fects other organ systems, an leads to siress-management systems that estab- lish relatively lower thresholds for re sponsiveness that persist throughout ie, thereby Increasing the risk of stress- related disease and cognitive impair- ‘ment well into dhe adult years, This simple taxonomy provides a useful approach orhelping policy mak- xs differentiate normative life chal- lenges that are growth-promoting ftom significant adversities that threaten long-term health and development. As such, tprovidesa useful framestork for considering earlier opportunities for preventive intervention, Health Promotion and Disease Prevention ‘Within a Science-Based, Early Childhood Framework CCurrenceffors related to health promo- on and disease prevention in mosteco- nomnically developed countries are gen- erally guided by 3 strategies. The first focuses on the provision of iamuniza- tions, anticipatory guidance, and early identificationand management of prob- lemsin the context primary healthcare forchildren who haveaccess to medical services, as well as public policies designed to redice injuries, such asman- datary seat belt laws, The second approach is directed toward programas that encourage health-promoting behav ‘orsinadilts suchasbetternptigonand increased exercise. The third strategy is focused on reducing health- threatening behaviors in adults, such as smoking, 256 JAMA, Jone 3, 2002! 301, Ne 21 epee) ‘excessive aleohol consumption ict substance abuse, and risk-taking behav- ‘ors assoviated with sexually vansmit- ted diseases, The first approachisembed- ded largely in a model of individually focused medical servicesforctildren. The second and third suategiesare grounded. ina theory ofchange hased on the eapae- ty o molly the behavior of adults. ‘Although the potential benefits of heath education 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, itis bur- dened by the increasing diffiulty of ‘hanging behavior and lifestyess ix- dlviduals grow older. Second, it faces the difficult challenge of overcoming biological vutnerabilses that may have been emberided physiologically asare- sult of envy adversity and that might have been prevented by changing the environments in which young chile dren ive. Thitd, by addressingadulebe- ‘havior instead ofthe conditions faced by children and their families, such pol cles shiftthe locus of responsibilty t0- ‘ward individuals whose health risks have been influenced much earier in life and away from the potently modi- fable clrcumstances that shaped them in the fist place These limitations of adalt-ocused health: promotion efforts lead to the compelling hypothesis that funca- mental transformation in the circum stances of children who experience sig- rifcantadversity early in ifecould not only affect their own individual well- being but also improve societal health and longevity. To this end, an inte- grated developmental science af health, learning, and behavior could support several implications for health policy ‘and clinical practice, The followingare 3 examples worthy of thoughtfl eon- sideration. ‘Adult Disease Prevention Begins With Reducing Early Toxic Stress. Policies and preeices intended to focus ‘on health promotion an disease pre- sention might be strengthened consid erably by greater atention tothe poten- Ualelfensofreducingtoxicstressin early childhood. Aninereasingamount of re- search in neuroscience, social epidemi- ‘logy, and the behavioral sciences, e- viewed selectively in chisaricle, suggests that «reduction inthe nucnber ancl se- verity of early adverse experiences wil lead toa 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 ‘public health issue with lifelong con- sequences." The implications of this emerging science for clinical practice are compelling. On the positive side, the primary cere setting is arguably the most appropriate venue fora more pro- active approach to the early identifca- tion and mitigation of potential causes ‘of toxic stress in young children, such as child maltreatment (7.5% of chil dren aged 2-5 yeats™), postpartum de- pression (13% of new mothers™), ard parental substance abuse (9.8% of. households with children aged <5 years"). Yer the challenges facing cli- dlcians axe formidable, including in sufficient taining and tetebursement toaddress complex social problems and limited access to specialized interven: tion services." Nevertheless, te rela- lively high prevalence of early child- hood cata acrossall income gros “underscores the need for greater alten- tion noth medical education and pri- mary care practice. to its potential ef- feets on lifelong health Eatly Childhood Programs Benefit Lifelong Health, Not Just Education, High-quality early childhood programs designed to produce postive effects on educational achieverentand ate work- force participation offer an important, unrecognized infrasructoe foraddress- Ingthe stress-related roots of socal lass dlispities in health, Cost-benefit asses- rmentsof effective ey childhood inter- vention for low-income chiléren have documented significant financial re- tras to society through greater e=0- rnowie productivity, decreased welfare dependence, and lower rates of ncet- ceration “The degree wo which en- ©2009 American Medical Association, All eghs reserved, Downloaded from vn jama.com by guest on June 2, 2008hanced efforts to reduce tonie stress sight also reduce the prevalence of ie Jong disease and reduce ater health esre costs also deserves carelul consider- ation, Tothisend, the increasing gap be- ‘wveen advances in evidence-based treat ‘ments for mental health mpairmentsand the Limited availability of services for ‘those in ned ishighly problematic, par- ticularly inthe early childhood years. ‘When early childhood program staff sre nottrained wo address disnaptive behav- iors nor assisted in securing appropri- ate reatment or children or parenis with serious mental health problems, oppor- tunities for preventive intervention are missed and many troubled children are ‘expelled from programs before they are sven a chance t sueceed,' Strength tning the capacity to address stress- related problems within the context of cxisting csrly care and education pro rams is likely co augment ther effect, Child Welfare Services: Missed Op- portunity for Health Promotion. Pub- liely mendated services to protect chil- dren who have been abused or neglected presenta particularly compellingand un- dleruse approach for addressing the imn- ‘mediate and long.term consequences of severe stress in early childhood. Since their establishment more than & cen- tary ago, child welfsre services have fo- ceused exclusively on issues related 10 ‘physical safey, reduction of repested in- Jury.and cid custody. Advances innen- roscience now indiate that ewsluations of maltreated children that rely exclue sively on physical examination and ra- diographic screeningace insulicent and ‘must be augmented by comprehensive developmental assessmentsand the pro- vision of appropriate intervention by sled professionals as indicated, A public infrastructure already ex- {ststo provide these additional services for children younger than 3 years «rough regularized rlerals rom child protective services agencies (which are mandated in each state) 10 early iter- Yention programs for children with de ‘elopmentaldelaysor disables (which are available in all states tmnder a fed teal entitlement). The most recent re- authorizations the ekevant feral eg- (©2009 Amesian Medial Astocntion. All ights reserved “GHIEDHOOD ROOTS OF HEALTH DISPARITIES Islation for both systems —the Keeping Children and Families Safe Actand the Individuals With Disabilities Ecuea- tion Act-—include requirements for es- Uublishing such linkages, but thelr inple- mentation has been limited. Greater public understanding of the effects of ently abuse and neglect on lifelong health could help build support for more tn formed policy and practice. Summary and Future Directions An increasingly persuasive amount of research is emerging that supports the ‘thoughtful onstruction ofa new frame~ work for health promotion and dis- case prevention. This model isbased on ‘mounting evidence that the origins of many adult discases can be found among adversities in the ealy years of life chat establish biological “memo- res” that weaken physialogicel sys- tems and produce latent vainerabilt- ties to problems that emerge well into the ater adult years. Thescientific concepts embedded in this frameworkare deeply grounded in the principles of evolutionary biology. “Beginnings early asthe fist weeks = terconception and continuing into early lnfancy, the immature "organism’ reads” key characteristics of its envi- ronmentand prepares to adapt oan ex: ternal world that can vary dramatt cally in ts levels of safety, sufficiency, and peril. When early experiences pre- pate a developing child for conditions Involving a high level of stress or in stability, the body’s systems retain that {nial programming and put the stress response system on a shartfuse and Ihigh-alert status. Under such eircusm- stances, the benefits ofshort-term su vival may come ata significant cost to Tonger-term health Beyond its promising policy implica- tions, the association between early ad- versity and subsequent health, learn ing, and behavior presents compelling ‘esearch agenda, Mtch work remains to be done to clucidate the precise causal riechanisms that explain these link ‘ages. The identification of lomarlers of toxic stress and its physiological conse ‘quences offers particular promise as @ source ofshort-and medium-term mea- ‘ures 1 assess the mediators of ont comes that require decades to conten 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 inthe early childhood years, must hoe another key priority. For example, testing new community-based interven tions or clinical treatments forpreschool- cers who have been abused ot seriously neglected ought to be at least as high a research priority as conducting clinical tsials of statins for school-aged children with elevated cholesterol levels. Focus: ing om access problems and differential treatment the health care system cer- tainly important, but confronting the carly childhood origins of disparities in ‘physical and mental health may offer far ‘greater return on investment. In 2000, the Institute of Medicine ane National Research Council retessed a report that synthesized existing knowl- edge about the effects of early expert- cence on child development, including itsunderlying necrobiology."* Over the ensving decade, public support for early childhood investment has increased substantially, with state expendituces for home visiting programs in the United States increasing from $13 mil- Hon" w $280 million and state pre-K from $1.6 billion!” 10 $4.5 bitlion.””" ‘Much of the impetus behind this ex- ‘panded investment comes from an i= creasing evidence base that demon- strates the extent to which effective, interventions early in life can produce measurable benclits in later educa sional achievement, economic prodic- tivity, and responsible citizenship.""* ‘Advances in neuroscience and the bi- ology ofstress provide a compelling ra- tionale for considering the inclusion of health promotion and disease preven- tion as a fully integrated part of that agenda. 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