COURRENT PINION Measurement framework for the Environmental influences on Child … · 2020-06-30 · how physical disabilities interfere with a child’s everyday life and physical

REVIEW

CURRENTOPINION Measurement framework for the Environmental

influences on Child Health Outcomes researchprogram

Copyright

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Courtney K. Blackwell, Lauren S. Wakschlag, Richard C. Gershon,David Cella, with the ECHO PRO Core

Purpose of review

Diverse methodological approaches pose significant challenges to assess environmental exposure effects onchild health outcomes. Although transdisciplinary research efforts offer unique opportunities forunderstanding the complex and multidimensional facets of lifespan health and disease trajectories, ashared measurement strategy is necessary for ensuring cohesion and comprehensibility across disciplinesand domains.

Recent findings

Exposure science often focuses on one life stage, one primary outcome domain and/or one environmentalcontext without regard for understanding the complexity of exposome pathways and outcomes across adevelopmental continuum. As part of the National Institutes of Health Environmental influences on ChildHealth Outcomes Program, the Person Reported Outcomes Core developed a unifying measurementframework that takes a lifespan development approach to assess physical, mental and social healthoutcomes within the complex matrix of environmental exposure pathways.

Summary

The proposed framework offers a shared methodological approach to health outcome assessment, with aparticular emphasis on person-reported outcomes. This framework will be instrumental for future large-scaleconsortia and transdisciplinary team science efforts by providing a common structure, measurementguidance and consistent terminology.

Keywords

Environmental influences on Child Health Outcomes, lifespan development, measurement, person-reportedoutcomes

Department of Medical Social Sciences, Feinberg School of Medicine,Northwestern University, Chicago, Illinois, USA

Correspondence to David Cella, PhD, Department of Medical SocialSciences, Feinberg School of Medicine, Northwestern University, 633 N.Saint Clair Street, 19th Floor, Chicago, IL 60611, USA.Tel: +1 312 503 1086; e-mail: [email protected]

Curr Opin Pediatr 2018, 30:276–284

DOI:10.1097/MOP.0000000000000606

INTRODUCTION

Environmental exposures profoundly shape lifespanhealth and disease trajectories [1,2]. Robust evi-dence from preclinical and clinical studies showsthat pre- and perinatal exposure can permanentlyalter the developing brain and associated regulatorysystems to increase susceptibility to a host of dis-eases and developmental challenges, at levels ofexposure not generally toxic to adults [3–5]. Adverseenvironmental exposures have short- and long-termconsequences for children’s health [6]. Conversely,positive exposures, such as high-quality caregiving[6,7], can promote health and well-being [8

&

]. How-ever, because prior research emanates from diversedisciplines with varied methodological approaches(e.g., behavioural teratology, environmental epide-miology, sociology and paediatrics), a comprehen-sive measurement framework for assessing the

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impact of exposures on child health and diseaseoutcomes is lacking. Such an absence impedescross-study comparisons and replications, as wellas the ability to draw causal conclusions so vitalto prevention.

As part of the Environmental influences on ChildHealth Outcomes (ECHO) Program, the PersonReported Outcomes (PRO) Core addresses the defi-ciency by employing state-of-the-art measurement

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KEY POINTS

� The proposed measurement framework provides sharedmethodology to assess children’s physical, mental andsocial health outcomes in large-scale transdisciplinaryresearch consortia.

� Key measurement considerations include balancingexposure biomarkers, developmentally sensitivemeasures with lifespan coherence and efficiency ofperson-reported outcomes with nuanced performance-based and observational assessments.

� Person-reported outcomes offer opportunities tocomplement biomarker assessments and provide themost holistic understanding of child health outcomes inthe context of diverse environmental exposures.

Measurement Framework for ECHO Blackwell et al.

science strategies to develop a unifying measurementframework for assessing a range of environmentalexposures on diverse child health outcomes. Thisframework has guided the creation of the ECHO-wideCohort Data Collection Protocol, which unites 84individual cohort studies via a common set of dataelements and measures driven by high-impact scien-tific questions addressing ECHO’s five primary childhealth outcomes: obesity; upper and lower airways(e.g., asthma); neurodevelopment; pre-, peri- andpostnatal health; and positive health (assets thatstrengthen an individual’s capacity to adapt, satisfyneeds and fulfil goals) as well as the recent addition ofan ECHO focus on neonatal opioid withdrawal syn-drome (for an overview of ECHO, see Gillman andBlaisdell, p. 260, in this issue).

FRAMEWORK OVERVIEW

The overall aim of the proposed measurement frame-work is to provide structure and guidance regardingassessment of child health outcomes within theirbiological, psychological, social and environmentalcontexts and to use exposomics, the comprehensivemeasurement of exposures and associated biologicalresponse pathways over development, to assesscumulative risks and promote health. This multilevelapproach accounts for the complex matrix of expo-sures and the downstream effects on child healthfrom preconception through early adulthood by rec-ognizing health as continuous and transactional,resulting from multiple interactions between levelsand types of environmental contexts. This will opti-mize discovery of exposure-related heterogeneity indisease expression across development and acrosssocioeconomic or geographic boundaries.

The following framework for lifespan healthoutcomes (including parent and developing child)

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builds on the Patient-Reported Outcomes Measure-ment Information System (PROMIS) and NationalInstitutes of Health (NIH) Toolbox initiatives andincorporates the World Health Organization’sdomains of physical, mental and social health[9]. Particular emphasis is placed on PROs as acomplement to exposure and biological responsebiomarkers, with laboratory analysis occurringsimultaneously to provide the most holistic under-standing of child health outcomes [10,11]. Broadlydefined as any measures of an attribute of a personthat requires assessment, PROs are cross-cutting asthey focus on both health and disease, as opposedto the traditional binary framing of presence/absence of disease. PROs also encompass develop-mentally based measurement strategies and enableprecise tracing of the impact of children’s exposurehistory [12,13].

The measurement framework outlined hereemphasizes child health outcomes (Fig. 1) and par-ent health and functioning (Fig. 2), as parents rep-resent a proximal bio-ecological environment thataffects child health (for a review of the broad spec-trum of exposome measurement, see [14,15

&&

]).While this framework was developed as part ofECHO, the core components (i.e., domains andorganizing constructs) apply to broader researchendeavours assessing environmental exposures onchild health outcomes. Further, specific measure-ment examples from ECHO help contextualize theframework as well as provide foundational strategiesfor common measurement selection in future large-scale consortia research. Key considerations includebalancing exposure biomarkers with PROs; develop-mentally sensitive measures with lifespan coher-ence – both ‘tried’ and ‘true’ legacy measures aswell as innovative advancements in measurementapproaches and techniques (e.g., dimensionalassessments that capture the full range of normal/abnormal variation, computer adaptive testing);and efficiency of PROs with nuanced perfor-mance-based and observational assessments.

CHILD HEALTH OUTCOMES: PHYSICALHEALTH

This domain focuses on the structural, functionaland somatic aspects of physical health, beginning inutero and extending throughout childhood andadolescence. This approach allows for detection ofearly fetal abnormalities as well as identification ofmalformations that may not present until child-hood [16], while also acknowledging the experien-tial component (i.e., symptoms) associated withphysical health. The two organizing constructswithin this domain are growth and development

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FIGURE 2. Parent health and functioning measurement framework. Adapted with permission from the Patient-ReportedOutcomes Measurement Information System (PROMIS) measurement framework, developed as part of the National Institutes ofHealth (NIH)-funded PROMIS (U01AR052177).

FIGURE 1. Child health outcomes measurement framework. Adapted with permission from the Patient-Reported OutcomesMeasurement Information System (PROMIS) measurement framework, developed as part of the National Institutes of Health(NIH)-funded PROMIS (U01AR052177).

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and somatic experience and physiological functioning.Within this domain, ECHO places primary emphasison three outcome areas reflecting: perinatal out-comes proximal to exposure, a paediatric healthrisk pathway (i.e., obesity) that presages chronicdiseases of the lifespan, and a prevalent paediatrichealth condition (i.e., asthma) strongly tied toadverse exposures.

Growth and development includes assessingattributes related to body size (e.g., length/height,weight and waist circumference) and composition(e.g., percentage lean body mass and fat distribu-tion), as well as growth trajectories and subse-quent childhood obesity outcomes. ECHO has aparticular focus on perinatal growth and develop-ment given the presaging developmental healthrisks associated with structural and functionalabnormalities including more vulnerable organsystems and childhood obesity [17]. Attributes ofneonatal growth include body composition mea-sured via the ponderal index and biometry; birthdefects or congenital anomalies using medicalrecords and, when valid, parental report; and birthweight, with specific indicators for low birthweight (<2500 g) and gestational age at delivery,particularly for preterm birth (<37 weeks post lastmenstrual period).

Somatic experience and physiological functioningrefers to somatic and physical disabilities whereeffects can be direct and indirect (through diseaseonset), with particular sensitivity to adverse earlyexposures [17–21]. Components include motordevelopment (e.g., reflexes, gross/fine motor devel-opment, strength and endurance), sleep health andecology (e.g., regulation of sleep/wake cycles andcircadian rhythm), neurosensory functioning (e.g.,vision, hearing, taste/olfaction and vestibular bal-ance), organ system function (e.g., cardiac, pulmo-nary, kidney, liver and gastrointestinal functioning)and symptoms (e.g., pain and fatigue).

Although all components of this domain arecovered in ECHO using PRO measures to assesshow physical disabilities interfere with a child’severyday life and physical functioning (e.g.,PROMIS Pediatric Asthma Impact [22]) or perfor-mance-based assessments to measure actual phys-ical functioning (e.g., NIH Toolbox Motor Battery[23]), one area of particular interest to ECHOinvestigators is sleep health. Measured from birththrough adolescence, sleep health captures tim-ing, chronotype, duration, quality and satisfac-tion. Sleep ecology assesses sleep routines andpractices. In addition to novel measurementapproaches with wearable technology, sleephealth and ecology are primarily assessed in ECHOby self-report [24], including age-appropriate



versions of the PROMIS Pediatric Parent Proxyand Child Self-Report Sleep-Related Impairmentand Disturbance scales [25

&

].

CHILD HEALTH OUTCOMES: MENTALHEALTH

This domain captures how the child organizes, reg-ulates and processes information from, as well asthrough interactions with, the environment,including atypical neurodevelopmental processesand their clinical expression [e.g., autism, opposi-tional defiant disorder, depression and attentiondeficit hyperactivity disorder (ADHD)] as affectedby exposures [26,27

&

,28,29]. Measurement involveschild self-report, parent proxy report, observationand performance-based measures. Special attentionis paid to innovative measurement approaches andinstruments that are sensitive to development, orthose that assess skills, processes and outcomesacross the full range of normative variation andatypical functioning defined in relation to age-graded capacities [13,30

&

]. This domain is organizedaround three concepts: behavioral and emotional self-regulation, social cognitive processes and cognition, allof which have been robustly linked to early lifeexposures [31–34]. Although prior behavioural ter-atological research has relied on traditional clinicalclassification systems, it is increasingly evident thatexposure-related problems in this domain requiresensitive, developmentally based measurement ofdimensional constructs [35–37].

Behavioural and emotional self-regulation reflectsa child’s capacities for behavioural, attentional andemotional control in response to demands of thereal-world environment [38] as well as volitionaldeployment of cognitive resources in the face ofcompeting stimuli [39,40]. Development of suchcapacities manifests as emotional and behavioralself-regulatory competency and positive health out-comes [41

&&

,42]. When these capacities do notdevelop well, mental health problems tend to occur[41

&&

,43&&

]. On the ‘externalizing’ side, normativedevelopmental processes are those underpinningbehavioural regulation, including compliance,attention orienting, self-control and persistence[41

&&

,43&&

]. Clinically, atypical patterns are encom-passed within an externalizing spectrum reflectingsyndromes of under-control, including ADHD,oppositional defiant disorder, conduct disorderand substance use/abuse [43

&&

,44&

,45,46]. On the‘internalizing’ side, normative developmental pro-cesses support emotion regulation including bothtemperamental differences in affectivity and regu-latory strategies [43

&&

,47,48&

]. Clinical manifesta-tions reflect the emotion dysregulation of the




internalizing spectrum such as depression, anxietyand posttraumatic syndromes [49,50].

ECHO employs a developmental frameworkthat captures assessment of early developmentalprocesses that may serve as precursors to psychopa-thology (e.g., the Infant and Child Behavior Ques-tionnaires [51,52]); traditional symptom-basedbehavioural checklists (e.g., Behavior AssessmentSystem for Children [53] and Child BehaviourChecklist [54]); and developmentally based dimen-sional assessments emphasizing normal/abnormaldifferentiation within developmental contexts [e.g.,Multidimensional Assessment Profile of DisruptiveBehavior (MAP-DB) [55]]. For more nuanced assess-ment during early childhood when children cannotbe interviewed, performance-based assessments arerecommended, such as the Berkeley Puppet Inter-view Symptomology Scales (BPI-S) [56], as are stan-dardized diagnostic observations, such as theDisruptive Behavior Diagnostic Observation Sched-ule (DB-DOS) [57] and the Anxiety DiagnosticObservation Schedule (ANX-DOS) [58]. These in-depth observational assessments provide unique,developmentally appropriate complements toparental report of externalizing and internalizingpatterns.

Social cognitive processes focus on the develop-ment of intrapersonal social abilities, and includessociability, social responsiveness and social capac-ity. These measures are distinguished from thosemeasured in the social functioning domain becausethey are intrinsic to the child. A child’s level of socialresponsiveness, for example, reflects intrapersonalneurodevelopmental functioning, not interpersonalinteractions. Normative capacities include jointattention, theory of mind and shared positive affect,while atypical processes include the clinical featuresof Autism Spectrum Disorder (ASD) [59].

In ECHO, the majority of cohorts do not includeASD as a main outcome focus, thus requiring ameasurement approach that balances efficiencywith depth to assess the social cognitive processes.To achieve this, ECHO includes the full version ofthe Social Responsiveness Scale (SRS) [60] as well asan option to use the newly developed SRS short form[61], both of which are dimensional measures ofunderlying ASD-related phenotypes. These parentreport questionnaires enable feasible and meaning-ful data contributions from every child in ECHO,with ASD-specific risk screeners (e.g., M-CHAT) [62]and in-depth measures (e.g., Autism Symptom Inter-view [63] and videoreferenced Reciprocal SocialBehavior Scale [64]) recommended for more special-ized studies seeking the full range of variation inearly manifestations of ASD-related impairment inearly childhood.

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Cognition refers to neurocognitive developmentand information processing and is typically evalu-ated using performance-based discrete tasks thatmeasure a range of specific sub-concepts of generalintelligence. Within the proposed framework, theorganizing facets of cognition are 1) receptive andexpressive language, including symbolic communica-tion and pre-language; word learning; lexical, syn-tactic and pragmatic development; and thelanguage/cognition interface in which wordsacquire generalizable meaning [65,66]; 2) fluid rea-soning, or the ability to apply logical thinking tosolve novel problems, including visual–spatial proc-essing and pattern recognition [67]; and 3) executivefunction, or cognitive processes serving goal-ori-ented behaviour, including working memory, cog-nitive flexibility and inhibitory/effortful control ofpre-potent responses [41

&&

,68].At the earliest ages (0–36 months), measure-

ment focuses on key developmental milestonesvia performance-based instruments such as theMullen Scales of Early Learning [69], and BayleyScales of Infant and Toddler Development [70], aswell as parent-report measures such as the Ages andStages Questionnaire [71]. Cognition measures atolder ages include full scale and abbreviated scalesof intelligence (e.g., Wechsler [72] and Stanford-Binet Intelligence Scales [73]), as well as newertouchscreen-based cognition batteries such as theNIH Toolbox Cognition Battery [74–76]. For execu-tive function measurement in particular, perfor-mance-based measures are favoured due torelatively poor correspondence of parental ratingmeasures with performance-based tasks [77].

CHILD HEALTH OUTCOMES: SOCIALHEALTH

This domain describes the developmental processesand perceived functioning of social relationshipsand the enactment of social interactions andbroader role performances in a range of social con-texts. Conceptually organized around the mostproximal social ecologies (e.g., family, peers, schooland community) [78], the social health domain ischaracterized by both the quality of social interac-tions as well as the competencies of social participa-tion, with two primary organizing constructs: socialrelationships and social role functioning and perfor-mance (Fig. 1).

Social relationships describe the structure andquality of interactions an individual has with othersin a range of social contexts. Positive relationshipsare fundamental to child attainment of short- andlong-term health and developmental outcomes [79],with the quality of such relationships representing




the basic human needs of care and affiliation. ECHOemphasizes three types of social relationships: 1)family relationships, which includes the stressorsand supports between and with all family members,with particular emphasis on the unique features ofthe child-parent relationship and caregiving qual-ity; 2) peer relationships, including feelings of beingaccepted and supported by peers as well as socialwithdrawal, peer rejection and bully victimization;and 3) teacher connectedness, which describes thechild’s perceptions that teachers are invested intheir personal and academic lives.

Measurement for all three social facets empha-sizes the child’s subjective experience of feelingaccepted, cared for and supported by others, as wellas feeling that others can be trusted and dependedon for help and understanding [80]. Particularly inearly development, observed parent–child interac-tion is a key assessment tool to enable measurementof dyadic processes that transcend individual behav-iours [81,82]; in ECHO, tools such as the NICHDParent–Child Interaction Observation [83] and theHOME Inventory [84] are used to capture caregivingquality in the early years. Such direct observationmeasures are complemented with parent question-naires describing various components of family rela-tionships, such as cohesion and conflict (e.g.,Family Environment Scale [85]). In subsequent lifestages, measurement focuses on parent proxy andchild self-report measures, including the PROMISPeer and Family Relationships scales [86,87

&

] andthe NIH Toolbox Positive Peer Interactions Scale[88], as well as the Panorama Student–Teacher Rela-tionships Scale to assess teacher connectedness [89].

Social role functioning and performance reflectsperformance in life areas that are socially and cul-turally recognized as important for people giventheir developmental level. Individuals adjust such‘performances’ based on the social roles of impor-tance to specific cultural contexts, audiences anddevelopmental level, and through such perfor-mances, develop their social identity [90].

For children and adolescents, one of the mostsalient contexts for social role performance andfunctioning is the school environment. Thisincludes both academic performance, or how wella child is doing in school and in specific subjectareas, and student engagement, which represents achild’s interest in school and motivation to succeed.Measurement focuses on PROs starting in the pre-school years (ages 2–5 years) with the NationalChildren’s Health Survey parent report of early aca-demic abilities [91] and continuing with parentproxy and child self-report measures using theHealthy Pathways Academic Performance scales[12,92]. Student engagement assessment draws on



the Panorama Student Engagement Scales for 3rd to12th graders to capture children’s own attitudestowards school [89].

PARENT HEALTH AND FUNCTIONING

As both a biological risk transmission and the mostproximal environmental influence on children’sphysical, social and mental health, parents repre-sent a particularly salient pathway through whichexposures are transmitted. Parents are also an envi-ronmental exposure in and of themselves and canmediate (both positively and negatively) the extentto which the full range of environmental exposuresultimately affect such child health outcomes. Mea-surement of parent health and functioning parallelsthat of child health, with physical, mental andsocial domains. Given ECHO’s focus on child healthoutcomes, the framework highlights representativemeasurements from each component to exemplifyexposure risk, biological and social risk transmis-sion, and the extent to which the parent exposurepathway ultimately affects children’s health.

Parent physical health focuses on 1) physicalfunctioning, which focuses on structural compo-nents including height, weight, body compositionand obesity status; and 2) somatic experience andphysiological functioning, which captures an indi-vidual’s experience of symptoms such as pain,fatigue and sleep health, as well as organ systemfunctioning (e.g., motor, neurosensory, sexual func-tion and need for assisted reproduction). In additionto physical examinations and medical record data,parent physical health is assessed via PROs, includ-ing the PROMIS Sleep Disturbance and Sleep-Related Impairment Scales as well as the PROMISGlobal Health Scale, which includes specific itemsrelated to an individual’s self-reported overall phys-ical health [93,94].

Parent mental health includes measures of nega-tive and positive affects, experiences of stress andwell-being, health risk behaviours such as smokingand substance abuse, and cognitive function. Of thethree parent heath domains, mental health isemphasized the most in ECHO, given associationsbetween parents’ neuropsychological health and awide range of child health and developmental out-comes [2,3,34]. In particular, maternal mentalhealth in the preconception, prenatal and postnataltime period is highlighted, including measures ofchildhood trauma, depression, anxiety and stress,which represent adverse risks to fetal and infantdevelopment. Additional measures of health riskbehaviours, such as smoking, alcohol use and othersubstance use/abuse, are also included in thisdomain. PROs are the primary measurement




strategy, and ECHO leverages the unique features ofPROMIS mental health domain scales (e.g., depres-sion and anxiety) and NIH Toolbox emotiondomain scales (e.g., Perceived Stress Scale), as scien-tifically rigorous, low burden assessments – includ-ing options for short forms and CATs – that areharmonized with or identical to legacy measures[88,95–97,98

&

].Parent social health refers to social functioning

within and outside the family, and the quantity andquality of social relationships, ranging from conflictand isolation to companionship and intimacy.Given the negative impact of prenatal stress onsubsequent child health outcomes [27

&

,32,33,44&

],ECHO emphasizes measurement of social supportand partner engagement during pregnancy, whichprovide buffers for and promote healthy child devel-opment. PRO measures include maternal reports viaPROMIS Emotional, Informational and Instrumen-tal Support scales [93,94] and the Early ChildhoodLongitudinal Study – Birth Cohort Paternal Involve-ment Scale [99].

CONCLUSION

Exposure science often focuses on one life stage,one primary outcome domain and/or one environ-mental context (e.g., built environment and asso-ciated chemical exposures), without regard for thecomplexity of exposome pathways and outcomesacross a developmental continuum. The proposedframework addresses this need by not only captur-ing the three primary domains of physical, mentaland social health within life stages, but also acrosslife stages, with particular emphasis on consistent,developmentally sensitive measurement to pro-vide coherence from birth through early adult-hood. Using a developmentally based model ofcontinuous outcome measurement across lifestages provides opportunities to assess facets ofchild health in a manner sensitive to developmen-tal capacities and constraints, while enablingmeaningful linkages across all life stages. Overall,this framework provides a shared understanding ofmeasurement strategies for conducting large scaleconsortia research and can be an impetus forfuture transdisciplinary team science effortswithin ECHO and across the broader scientificresearch community.

Acknowledgements

ECHO PRO Core Leadership Contributors (in alphabeti-cal order) are Katherine Bevans, PhD; Ann Borders, MD,MSc, MPH; Matthew Davis, MD, MPP; ChristopherForrest, MD, PhD; William Funk, PhD; Aaron Kaat,PhD; Bradley Marino, MD, MAPP, MSCE; Cindy



Nowinski, MD, PhD; Megan Roberts, PhD; and RosalindWright, MD, MPH.

Financial support and sponsorship

This review is supported in part by the NIH ECHOProgram (1U24OD023319-0).

Conflicts of interest

D.C. and R.C.G. received funding from NIH for thedevelopment of the NIH Toolbox (HHS-N-260-2006-00007-C) and PROMIS (U01AR052177). L.S.W.received funding from the National Institute ofMental Health for the development of the MAP-DB(1R01MH082830) and the DB-DOS (R01 MH068455).

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