early identiﬁcation and interventions for autism...

Early Identification and Interventions for AutismSpectrum Disorder: Executive Summary

Autism spectrum disorders (ASDs) are neurodevelopmental disorderscharacterized by impaired social communication skills and isolatedareas of interest.1 The current prevalence of these disorders is esti-mated to be 1 in 68,2 and recent estimates of the risk of recurrence infamilies with at least 1 child diagnosed with ASD are 10% to 19%.3–5

Advances have been made in identifying genetic variants that canaccount for biological vulnerability to ASD,6,7 although recent studiesexamining patterns of heredity implicate environmental factors andpotential gene-by-environment interactions.8 Although the exact etiol-ogy remains unknown in most families, some researchers suggest thatthe pathogenesis of the disorder begins during prenatal life.9,10 It islikely that ASD is heterogeneous in its etiology as well as in its clinicalpresentation.11

The American Academy of Pediatrics has recommended screeningfor ASDs at 18 and 24 months of age,12 but recent research suggeststhat atypical behaviors may be detectable in some children at evenyounger ages.13,14 However, we are still learning how the timing anddevelopmental course of early ASD symptoms vary across childrenand how best to detect such symptoms across the continuum ofchildren seen in community practice. In addition, reports15 thatearly intervention can improve developmental and behavioraloutcomes in infants and toddlers have lent urgency to identifyingchildren across the autism spectrum at an earlier age. Advances ingenetic, neuroimaging, and other neurobiological research havealso raised the potential of biomarker screening. Given the prog-ress in these areas, a review of the current state of the scienceon early identification, screening, and intervention of ASD waswarranted.

These issues were the focus of an international, multidisciplinary panelof clinical practitioners and researchers with expertise in ASD anddevelopmental disabilities. A meeting of the panel was convened inMarina del Rey, California in October, 2010, to develop best practicestandards for early identification, screening, and early intervention forASD in very young children and to identify priorities for future research.To complement previously published reports, our literature review onearly identification and screening for ASD focused on children aged#24months, whereas our review of intervention studies focused on childrenaged #36 months. The panel reached consensus in 3 areas:

� What are the earliest signs and symptoms of ASD in children aged#24 months that can be used for early identification?

� How can we optimize developmental course and outcomes throughASD screening programs for children aged #24 months?

� What interventions have shown efficacy in children with ASD aged,36 months?

AUTHORS: Lonnie Zwaigenbaum, MD,a Margaret L.Bauman, MD,b Roula Choueiri, MD,c Deborah Fein, PhD,d

Connie Kasari, PhD,e Karen Pierce, PhD,f Wendy L. Stone,PhD,g Nurit Yirmiya, PhD,h Annette Estes, PhD,i Robin L.Hansen, MD,j James C. McPartland, PhD,k Marvin R.Natowicz, MD, PhD,l Timothy Buie, MD,m Alice Carter, PhD,n

Patricia A. Davis, MD,o Doreen Granpeesheh, PhD, BCBA-D,p

Zoe Mailloux, OTD, OTR/L, FAOTA,q Craig Newschaffer, PhD,r

Diana Robins, PhD,r Susanne Smith Roley, OTD, OTR/L,FAOTA,s Sheldon Wagner, PhD,t and Amy Wetherby, PhDu

aDepartment of Pediatrics, University of Alberta, Edmonton,Alberta, Canada; bDepartment of Anatomy and Neurobiology,Boston University School of Medicine, Boston, Massachusetts;cDivision of Developmental and Behavioral Pediatrics,University of Massachusetts Memorial Children’s MedicalCenter, Worcester, Massachusetts; dDepartment of Psychology,University of Connecticut, Storrs, Connecticut; eGraduate Schoolof Education & Information Studies, University of California LosAngeles, Los Angeles, California; fDepartment of Neurosciences,University of California San Diego, La Jolla, California; gDepartmentsof Psychology, and iSpeech and Hearing Sciences, University ofWashington, Seattle, Washington; hDepartment of Psychology,Hebrew University of Jerusalem Mount Scopus, Jerusalem, Israel;jDepartment of Pediatrics, University of California Davis MINDInstitute, Sacramento, California; kYale Child Study Center, NewHaven, Connecticut; lGenomic Medicine Institute, Cleveland Clinic,Cleveland, Ohio; mHarvard Medical School and MassachusettsGeneral Hospital for Children, Boston, Massachusetts; nDepartmentof Psychology, University of Massachusetts, Boston, Massachusetts;oIntegrated Center for Child Development, Newton,Massachusetts; pCenter for Autism and Related Disorders,Tarzana, California; qDepartment of Occupational Therapy,Thomas Jefferson University, Philadelphia, Pennsylvania; rA.J.Drexel Autism Institute, Drexel University, Philadelphia,Pennsylvania; sUSC Mrs T.H. Chan Division of Occupational Scienceand Occupational Therapy, Los Angeles, California; tBehavioralDevelopment & Educational Services, New Bedford,Massachusetts; and uDepartment of Clinical Sciences, FloridaState University College of Medicine, Tallahassee, Florida

ABBREVIATIONSASD—autism spectrum disorderDSM-5—Diagnostic and Statistical Manual of Mental Disorders,Fifth EditionM-CHAT—Modified Checklist for Autism in Toddlers

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METHODS

Before the conference, participantswere assigned to 1 of 3 working groups,each comprising 7 to 10 experts andfocusing on the early identification ofASD, early screening, and early inter-ventions and outcomes. The Early Iden-tification group comprised Drs Stone,Yirmiya (co-chairs), Chawarska, Estes,Hansen, McPartland, and Natowicz. TheEarly Screening group comprised DrsFein, Pierce (co-chairs), Baranek, Davis,Newschaffer, Robins, and Wetherby. TheEarly Intervention and Treatment Out-come group comprised Drs Choueiri,Kasari (co-chairs),Buie,Carter,Charman,Granpeesheh, Mailloux, Mesibov, SmithRoley, and Wagner.

To inform the work of each group, liter-ature searches were conducted on Med-line to identify relevant articles for eachtopic (the specific search terms areprovided in the other articles in thissupplement to Pediatrics16–18). Searchresultswere complemented by additionalpublications identified by working groupmembers. Although the search strategywas comprehensive, selection of articleswas not systematic, which is an impor-tant limitation. A scoping approach, withsome discretion by consensus of themultidisciplinary expert working group,was used instead to select articles ofhighest relevance and methodologicquality. Articleswere assigned toworkinggroup members for review.

During the conference, each group pre-sentedasynthesisofthecurrentliteratureand offered draft recommendations fordiscussion, modification, and ratificationby all attendees. Electronic voting wasused to express opinions and guide con-sensus building. A modified nominalgroup technique was used to reviewthe recommendations, with consensusreached by$1 round of voting. A totalof 18 to 21 participants voted on 28statements, and 16 statements receivedsolely agree or strongly agree votes. Thenumber of statements was condensed

to 25 during the writing process. Thefirst statement pertains to the literaturereview as a whole, with subsequentstatements specific to each of the 3sections. Some of the statements sum-marize the state of the literature,whereas others are in the form of rec-ommendations for research needed todeal with outstanding questions oraimed at addressing important clinicalpractice issues.

More recent peer-reviewed researchwas subsequently incorporated to en-sure that the final article reflected themost recent literature. The search foreach topic (ie, early identification,screening, intervention)was updated byusing the same strategy to add articlespublished to December 31, 2013. Evi-dence tables and text references wereupdated, and the working groupreviewedandapproved thefinalwordingof the summary and recommendations.

We recognize that transition to recentlypublished criteria for ASD as delineatedby theDiagnostic and StatisticalManualof Mental Disorders, Fifth Edition (DSM-5),1 may recast diagnostic boundaries,at least to somedegree.19,20 At this point,it is probably too soon to tell how therevised diagnostic criteria will affectthe identification and management ofthe ASDs, but it is likely that key princi-ples regarding best practice and the“state of the science” from previous re-search will apply to DSM-5–defined ASD.

RESULTS

Consensus statements are summarizedin Tables 1, 2, and 3 and are discussed indetail in the other articles of this sup-plement to Pediatrics.16–18 These otherarticles include tables summarizingthe original research articles thatsupport the recommendations.

DISCUSSION

Earlydiagnosisand interventioncanhavea significant positive impact on the de-velopmental outcomes of children with

ASD21,22 and can also improve parentalwell-being by addressing concerns andreducing the stress associated with un-treated ASD and co-morbid behavioralchallenges.23 Moreover, the human brainundergoes a profound period of estab-lishing and refining connections be-tween neurons during the first years oflife. For example, synaptic density in thehuman prefrontal cortex (ie, the brainregion centrally involved in higher ordersocial behavior) peaks between 1 and 2years of age.24 Synaptic density in lan-guage areas, such as Wernicke’s andBroca’s areas, peaks shortly thereafterby age 3 years. A period of refinementoccurs after peaks in synapse number,during which effective connections arestrengthened and weak ones die away.This important developmental step,namely the construction of specificneural circuits and the pruning of ex-cess (unused) synapses, is believed todepend largely on input from the en-vironment.25 Thus, early identificationand intervention either before or whilebrain connections are being estab-lished may enable optimal prognosis.

The present review highlights the con-stellation of ASD-related symptomsemerging by the second year of life, thepotential utility of clinical screening tofacilitate early identification, and thegrowing number of empirically sup-ported interventions for very youngchildren. Considerable progress hasbeen made over the past decade indelineating the ASD phenotype duringthe first 2 years of life, providing a solidfoundation for early diagnosis. More-over, there have been parallel advancesin intervention research, ensuringthat early diagnosis can lead to sub-stantially improved outcomes. How-ever, much work remains to be doneto ensure that children across theASD spectrum can benefit from clinicaland therapeutic advances and thatpromising model programs can retaintheir effectiveness when implemented

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across a broad range of family andcommunity contexts.

There is now robust evidence acrossa diversity of study designs that be-havioral signs of ASD can be detected inthe second yearof life. Highly replicatedfindings point to impairments in socialattention (eg, reduced response toname) and social communication (eg,reduced joint attention behaviors), aswell as atypical object use (eg, re-petitive actions such as tapping andspinning) and abnormal visual atten-

tion, emergingby 12 to 18months of agein children subsequently diagnosedwith ASD. Other potential earlymarkerswhich have been less extensivelystudied but that may also contribute toidentifying at-risk toddlers include un-usual body movements, atypical emo-tional regulation, and reduced motorcontrol. Although research to date hasnot yet identified clear behavioralmarkers of ASD in infants aged ,12months, evidence is growing that de-velopmental trajectories (ie, change

over time) in early social orienting andlanguage and cognitive skills beginningas early as 6 months can be predictiveof ASD.26,27 Thus, longitudinal studies ofat-risk infants (eg, those with an oldersibling with ASD), as well as those de-tected early in the general population,may be particularly informative. Suchstudies have the added advantage ofincluding the potential to evaluate bothbiological and behavioral markers, thecombination of which may further aidin early identification. Future longitudinal

TABLE 1 Consensus Statements on Early Identification of ASD

No. Statement Key Messages

1. Evidence indicates substantial heterogeneity in the presentation andnatural history of clinical features associated with ASDs. Thisheterogeneity has ramifications for the interpretation of researchliterature as well as for clinical practice

• Given themarked clinical and etiologic diversity among individualswithASD, it is not surprising that early manifestations and developmentalcourse vary as well

• Methodologic differences (eg, prospective versus retrospectivedesigns, measurement strategies) may affect comparability acrosspublished studies

2. There is evidence that reduced levels of social attention and socialcommunication, as well as increased repetitive behavior with objects,are early markers of ASD between 12 and 24 mo of age. Additionalpotential markers include abnormal body movements andtemperament dysregulation

• Evidence supporting this statement is summarized in Table 1 of thearticle on early identification by Zwaigenbaum et al16

• “Strong evidence” refers to replicated findings in multiple prospectivesamples from independent research groups (with further supportfrom retrospective studies)

• “Potential evidence” refers to at least 1 finding from a prospectivesample, without replication, or inconsistent findings

3. Reliablebehavioralmarkers for ASD in childrenaged,12mohavenot yetbeen consistently identified

• Evidence supporting this statement is summarized in Table 2 of thearticle by Zwaigenbaum et al16

• Differences in social attention (as indexed by gaze orienting), motordevelopment, and general behavior (passivity versus irritability) havebeen reported as early as age 6 to 9 mo in some children laterdiagnosed with ASD

• However, overt, clinically apparent differences in social communicationhave not yet been identified before 12 mo of age

4. Developmental trajectories may also serve as risk indicators of ASD • Prospective studies assessing HR infants at multiple ages havesuggested that time course (rather than just cross-sectionaldifferences) in language and cognitive development, socialcommunication, and patterns of gaze orienting may predicta subsequent ASD diagnosis

5. Caution should be exercised in drawing conclusions about early riskmarkers of ASD from studies that do not include individual-leveloutcome data

• Some studies report group differences between HR and LR infants• If diagnostic outcomes are not reported at an individual level (ie, if it isnot known which HR infants were later diagnosed), group differencesare not necessarily related to ASD

6. Caution should be exercised in generalizing findings from studies ofHR infants

• Findings from HR samples might not generalize to the generalpopulation due to differences in research design (eg, ascertainment)and biology

7. Research about early markers of ASD should include diverse HR andLR samples

• Although most current prospective studies involve younger siblings ofchildren with ASD, studies of other HR infants (eg, premature infants)might also inform the field

• In addition, it is essential that findings from HR samples be validated inLR (ie, community) samples

8. Future research should aim to identify: (1) early markers that can bemeasured in routine clinical practice; (2) early biological processes;and (3) combined approaches

• There have been advances in technology-dependent risk markers (eg,eye tracking) that could have future utility in community settings,although early detection still depends on features that can beobserved by parents and clinicians

• There is much promise from emerging research on biomarkers,however, both alone and in combination with behavioral markers

HR, high-risk; LR, low-risk.

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research would benefit from the use ofboth high- and low-risk comparisongroups, to ensure that risk profilesadequately distinguish between ASDand other developmental disorders,rather than just ASD and typical de-velopment.

Our review of published research eval-uating ASD screening tools (Table 3)supports current American Academyof Pediatrics’ recommendations of ASDscreening in the second year.28 These

tools include both those targeted atASD-specific behaviors (eg, the Modi-fied Checklist for Autism in Toddlers[M-CHAT]) as well as measures target-ing a broader range of delays (eg, theCommunication and Symbolic BehaviorScales Infant/Toddler Checklist). Datafrom large community-based samplessuggest that ASD screening by usingthe M-CHAT (specifically, its currentversion [revised, with follow-up])29

or the Infant/Toddler Checklist30 can

identify children with ASD earlier andwith greater sensitivity compared withopen-ended questions regarding pa-rental concerns and thus offers advan-tages over general developmentalsurveillance. There is some support forthe potential utility of ASD screeningbefore 18 months of age. For example,a positive screen on the Infant/ToddlerChecklist at 12 months (as part of theFirst Year Check-Up model)31 was as-sociatedwith a positive predictive valueof 0.75 for ASD or other developmentaldelays but with considerable loss tofollow-up (based on the∼1 in 7 screen-positive children who were ultimatelyseen for diagnostic assessment).

Other ASD screens targeting thisyounger age group have shownsome promise. For example, the EarlyScreening of Autistic Traits question-naire can identify ASD as early as 14months but with a low case detectionrate and presumably low sensitivity,32

and the First Year Inventory may detectsome children with ASD at 12 monthsbut also with only modest sensitivity.33

Further research on ASD screening forthis age group is needed. It is alsorecognized that younger siblings ofchildren with ASD are at substantialrisk for the disorder (with estimatedrecurrence as high as 18.7%),4 as wellas other developmental challenges,34

and thus warrant additional monitor-ing. It is also important to take intoconsideration what populations havebeen investigated for currently avail-able screens (Table 3) and the degreeto which this analysis may influencegeneralizability to other contexts. Forexample, community pediatric practicescan be a highly informative setting toassess the screening properties ofparticular measures in children with-out specific risk factors but may notfully reflect the diversity (eg, socio-economic, ethnic) of a true populationsample. Screening must be linkedto timely referral foradditional evaluation

TABLE 2 Consensus Statements on Early Screening of ASD


1. Evidence supports the usefulness of ASD-specificscreening at age 18 and 24 mo

• Evidence supporting this statement issummarized in Table 1 of the article byZwaigenbaum et al17 on early screening.

• ASD screening before age 24 mo may beassociated with higher false-positive ratesthan screening at age $24 mo

• Broadband screening in children aged,24mocan also assist in early detection of ASD

2. Siblings of children with ASD are at elevated riskfor ASD and other developmental disordersand thus should receive intensifiedsurveillance

•With risk of ASD as high as 18%,4 and of mildersymptoms and/or developmental delays at$15%,16 siblings of children with ASD arehigh-risk group

3. Children identified through ASD-specificscreening should be immediately referred fordiagnostic evaluation and appropriateintervention

• The potential benefits of a positive screen willbe realized only if followed by consistentreferral and timely access to specializedassessment and intervention services

4. The long-term stability of ASD diagnosis inchildren $24 mo of age is well established

• Evidence supporting this statement issummarized in Table 2 of the article byZwaigenbaum et al17

• Emerging data suggest that ASD diagnosesbefore 24 mo of age are stable, althoughfurther research is needed, particularlyinvolving children identified via earlyscreening

5. Barriers to ASD-specific screening in the healthcare systemneed to be identifiedand removedto facilitate rapid diagnosis and earlyintervention

• Reported barriers include insufficient timeand/or reimbursement and other logisticchallenges (eg, disruption of work flow, lackof office-based systems for making referrals)

• Health care provider beliefs regarding thepotential benefits and risks can also influenceparticipation in screening programs

6. Methodologically rigorous research in ASD-specific screening should be a high priority

• Recommendations for future research includeapplying current screens in large diversecommunity samples to maximizegeneralizability, assessing clinically relevantoutcomes (eg, age of diagnosis), follow-up ofboth screen-positive and screen-negativechildren, and more detailed samplecharacterization to better understand whatfactors may influence accuracy of screening

7. There are several additional priorities for futureASD screening research

• Considerations for future research alsoinclude incorporating combined broadbandand ASD-specific screening, randomizeddesigns, repeat screening, use of technology,biomarkers, and examining factors that mayinfluence screening uptake and outcomes.


for risk-positive children as well asprompt access to interventions tar-geted to specific, identified functionalconcerns while diagnostic status is

being clarified. Earlier research sug-gests only a modest increase in ASDscreening in pediatric practice35; theroutine implementation of diagnostic

measures could be enhanced, however,by providing administrative support toassist with processing completedscreens and facilitating subsequent

TABLE 3 Consensus Statements on Early Intervention and Outcomes of ASD


1. Current bestpractice interventions forchildrenaged,3 ywith suspectedor confirmed ASD should include a combination of developmental andbehavioral approaches and begin as early as possible

• Evidence supporting this statement is summarized in Table 1 of thearticle by Zwaigenbaum et al18 on early intervention

• Behavioral interventions (ie, based on applied behavioral analysis) useevidence-based principles to systematically change behavior

• Developmental models of intervention use developmental theory todesign approaches to target ASD-related deficits

• In practice, many empirically supported interventions for childrenaged ,3 y blend features of both approaches

2. Current bestpractice interventions forchildrenaged,3 ywith suspectedor confirmed ASD should have active involvement of families and/orcaregivers

• Active family involvement is consistent with best practices ofinterventions for children aged ,3 y

• Parents and caregivers can capitalize on teachable moments as theyoccur, provide learning opportunities during daily routines, andfacilitate the generalization of learned skills across environments

3. Interventions should enhance developmental progress and improvefunctioning related to both the core and associated features of ASD,including social communication, emotional/behavioral regulation, andadaptive behaviors

• Targeted early interventions have been associated with improvementsin early functional domains relevant to ASD, specifically in jointattention and other aspects of social communication, imitation, andfunctional and symbolic play

• Comprehensive interventions for young children with ASD have also ledto improvements in adaptive functioning

4. Intervention services should consider sociocultural beliefs of the familyand family dynamics and supports, as well as economic capability, interms of both the delivery and assessment of factors that moderateoutcomes

• Respect for the perceptions, priorities, and preferences of familymembers is an important “family-centered” tenet to keep in mindwhen working with children with ASD

• Service provider training should promote cultural competence, andfamilies should be provided with culturally appropriate programmaterials

• Cultural as well as socioeconomic factors may present barriers toaccessing services

5. Intervention research should include socially and culturally diversepopulations and evaluate familial factors thatmay affect participation,acceptability, and outcomes of therapeutic approaches as well aswillingness to participate

• Recruitment to intervention research should emphasize social andcultural diversity, to maximize generalizability and applicability of theinterventions being studied

6. Future research should prioritize well-defined sampling strategies,rigorous investigative design, fidelity of implementation, andmeaningful outcome measurements

• Future directions include: identifying characteristics of children andfamilies who would benefit most from particular interventions andsystematically varying components of multifaceted interventionprograms to identify critical ingredients

• Randomized controlled trials are generally the optimal design,although other designs can be informative, especially at the feasibilitystage

• Intervention studies should include measures that are responsive tochange and index relevant areas of functioning

7. Research is needed to sort the specific active components of effectiveinterventions

• These might include (but are not limited to): the type of treatmentprovided; agent implementing the intervention(s) (parent, therapist,teacher, or combination); consistency of service provision acrossenvironments and between providers; and duration of treatment andhours per week

8. Adopting a common set of research-validated core measures of ASDsymptoms that can be used across multiple sites will facilitatecomparisons across studies of children with ASD aged ,3 y

• Outcome measures do not need to be identical across studies, butagreement on a subset of standardized instruments to use, whichmayassess changes in cognitive function, core autism symptoms, andadaptive and language behavior, would facilitate future comparisons

9. Future research should examine biological and behavioral heterogeneityas moderators of individual responses to interventions

• Subtypes of individualswith ASD need to be identified to understand thecause of their disorder, the associated neurobiologic mechanisms atwork, and to be able to offer more directed interventions dependingon the biological (and/or behavioral) subtype when known

10. Intervention providers should monitor for medical disorders that mayaffect a child’s response to an intervention and refer to appropriatehealth care providers as indicated

•Medical factors such as seizures, sleep disruption, and gastrointestinalsymptoms may affect daytime functioning and should thus beconsidered as possible moderators of treatment response

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referrals.31,36 Placing screening in thebroader context of ASD assessmentmay also help engage communityphysicians.37 Additional barriers, in-cluding third-party reimbursement,lack of monitoring systems to trackpositive screening results, and chal-lenges accessing early interventionservices, need to be addressed to en-hance incorporation of recommendedscreening practices into routine carefor community practitioners.

Although some studies have reportedthat screening can identify childrenwith ASD earlier and more consistentlythan routine inquiry about parentalconcerns,31 none has examinedwhetherinterventions offered to children withASD identified solely according toscreening yield improved outcomes.Indeed, screening effectiveness is gen-erally assessed with respect to classi-fication accuracy (ie, sensitivity andspecificity) rather than clinically mean-ingful outcomes (ie, changes in de-velopmental trajectories related toearlier initiation of intervention), animportant focus for future ASD screen-ing research.

Considerable progress has also beenmade in developing and evaluating ASDintervention models specific to theneeds of children ,3 years of age.Several groups have adapted treat-ments initially designed for olderpreschool-aged children with ASD byintegrating best practice in behavioralteaching methods into a developmentalframework based on current scientificunderstanding of how infants and tod-dlers learn. The central role of parentshas been emphasized, and interventionsare designed to incorporate learningopportunities into everyday activities,capitalize on “teachable moments,” andfacilitate the generalization of skills be-yond the familiar home setting. Al-though some trials were limited to 8- to12-week outcome data, enhanced out-comes associated with some inter-

ventions (eg, the Early Start DenverModel) were evaluated over periodslasting as long as 2 years.21

Although no studies to date have directlycomparedinterventionmodelsinchildrenwith ASD aged,3 years (even for olderchildren, such studies are rare), there isclear evidence that interventions initiatedat this early age can lead to markedimprovements in targeted skills (eg, so-cial communication, imitation)38,39 aswellas more global improvements in cogni-tive and adaptive functions.21,40 Althoughadditional research is needed to furtheroptimize existing models (eg, to differ-entiate the specific active ingredients),accumulating evidence indicates thattoddlers with ASD benefit from early,diagnosis-specific interventions, thusplacing greater urgency on the need toensure broader dissemination anduptake of evidence-based practicesbeyond initial research settings. Re-cent data41 that such interventions notonly improve adaptive and socialbehaviors but also lead to normalizedpatterns of brain activity in response toviewing faces further emphasize thepotential to improve long-term neuro-developmental trajectories. Efforts toimplement effective research programsin formats that can reach larger num-bers of children through innovativetraining approaches (eg, an Internet-based distance learning model forEarly Start Denver Model therapists)have also been encouraging.42

STUDY LIMITATIONS

The recommendations outlined in thepresent article (and discussed ingreater detail in the other articlescomprising this supplement16–18) wereinformed by a review of the publishedliterature as well as consensus of ourexpert group. However, it is importantto acknowledge that the selection ofarticles for review by the workinggroups was not systematic. A scopingapproach was instead used to select

articles of highest relevance andmethodologic quality; it is possible thatthis process excluded key referencesthat might have further informed therecommendations.

FUTURE DIRECTIONS

Whereas better and earlier character-ization of behavioral symptoms shouldcontinue to be a significant focus of re-search (especially those early charac-teristics that can be more easily appliedin clinical practice), the active search forunderlying biological markers shouldremain a high priority. Promising find-ings from neuroimaging43–45 and neu-roelectrophysiology46 studies may alsoguide future biomarker-based strate-gies. For example, the observation ofenlarged brain volume early in life couldbe useful in some cases. In addition, thepursuit of biologic examination of cordblood, placenta, maternal blood, andamniotic fluid, when available, mayprovide useful and more feasibleresources for defining very earlyindicators of atypical neurologic de-velopment and might ultimately lead tomore specific treatment modalities.

Although disturbances in sensory pro-cessing have not always been consid-ered a core feature of ASD, atypicalsensory processing is frequently reportedby parents, therapists, teachers, andpatients themselves. With the publica-tion of the DSM-5 in May 2013, unusualsensory responses were included inthe restricted and repetitive interests/behaviors domain, thus acknowledgingthat these symptoms play a role inASD.47 More recently, imaging and neu-rophysiologic studies have reportedabnormalities in the white matter mi-crostructure of the brain in childrenwith sensory-processing disorders.48,49

How disorders of sensory processing50

(including modulation and integrationof sensory information) influencemany of the behaviors, and potentiallysome of the core features of ASD,51


remains poorly understood and will bean important area for future research;understanding thesemechanisms couldhave important implications for earlydiagnosis and treatment.

There is a growing appreciation thatASD is heterogeneous in its causes,underlying neurobiology, and clinicalpresentation and that the “autisms”comprise a continuum of signs andsymptoms, many of which may changeover time, either as the result of ageor therapeutic interventions or both.Currently, we have little understandingof the natural life history of ASD andhow the clinical changes in any indi-vidual patient may be reflective ofunderlying neurobiological mecha-nism(s) not yet defined. Large-scalelongitudinal studies designed to fol-low up cohorts of well-characterizedindividuals over time and examinethe interplay between biologicalprocesses and subsequent experi-ences could generate new insightsto help better individualize treatmentstrategies.

When considering research related tointervention outcomes, a more con-certed focus should be placed on theinvestigation of those childrenwith ASDwho make dramatic progress, some ofwhom eventually “lose” their diagno-sis (ie, the optimal outcome),52 andthose who, despite well-designed, high-quality programs and strong familysupport, fail to make any significantimprovement. Defining the differencesbetween these 2 groups could poten-tially provide important informationrelative to the underlying causes ofthese subsets of children and, fur-thermore, what specific interventionsshould be tailored to which type ofchild. Other indices of heterogeneity(eg, symptom severity, variation incognitive and language levels, comor-bid behavioral and medical conditions)should be more explicitly considered infuture studies to help better understand

variation in intervention outcomes. Itwill also be essential thatwe learnmoreabout how such diversity can affect theeffectiveness of early detection andscreening, and how this informationcan help us to develop multiprongedstrategies that lead to earlier diagnosisacross the autism spectrum.

The potential effects of co-morbidmedical conditions on the behavior,developmental progress, and generalwell-being of children with ASD arebecoming increasingly apparent andwarrant careful consideration, evenin the context of early intervention.The autism community has begun toappreciate that a variety of medicalconditions (including gastrointestinaldisorders, sleep, airway obstructionrelated to enlarged tonsils and ade-noids, and obesity) can—and do—occur among children with ASD and,when present, can negatively affectdevelopmental progress and qualityof life. Furthermore, some of the be-haviors frequently associated withASD (eg, stereotypies, aggression, self-injury) are often related to the painand discomfort associated with theseunderlying medical conditions. It willbe important to determine the preva-lence of these co-morbid conditions;to identify their presenting symptoms,which may differ from those seen intypically developing children; and toeffectively treat these conditions inconcert with other interventions.

Future research related to early iden-tification, screening, and interventionshould address the impact of socialand cultural beliefs and values, fam-ily expectations, stresses and in-volvement, and outcome goals. Beliefsystems among service providersmay influence utilization of early de-tection and screening and referral tospecialized assessment and inter-ventions.53 Belief systems amongfamilies regarding social behaviorand development, in addition to ear-

lier experiences with health careproviders, can influence communi-cation regarding early risk markersand participation in screening pro-grams. Cultural beliefs, as well asfamily dynamics and socioeconomiccircumstances, can also influencea family’s effective engagement inintervention programs and thus mayultimately affect outcomes.54 Futureresearch should take into accountthe diversity of beliefs and worldviews among families and considerhow to adapt early detection, screen-ing, and intervention strategies tominimize health disparities or sys-temic practices that marginalize his-torically underserved groups toensure that barriers and health caredisparities are overcome. The goal oftreatment is early detection, diagnosis,and access to effective interventions forall children across the autism spec-trum.

ACKNOWLEDGMENTSThe conference chairs and workinggroups acknowledge the preconfer-ence contributions of individuals whowere unable to attend the conference,including Grace Baranek, PhD, OTR/L,FAOTA, Tony Charman, PhD, KatarzynaChawarska, PhD, and Gary Mesibov,PhD. We also acknowledge the effortsof Katherine F. Murray, BSN, RN, Massa-chusetts General Hospital for Children,in coordinating the forum and sub-sequent conference report process,and Sifor Ng in the conference reportprocess.

Themeeting andconsensus reportweresponsored by the Autism Forum. An im-portant goal of the forum is to identifyearly indicators of ASDs that may leadto effective health care services. AutismForum programs are developed underthe guidance of its parent organization,the Northwest Autism Foundation. Forthis project, the Autism Research Insti-tute provided financial support.

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(Continued from first page)

Drs Zwaigenbaum and Bauman initiated a literature review, co-chaired the meeting that generated the consensus recommendations outlined in this article, and draftedthe initial manuscript; Drs Choueiri, Fein, Kasari, Pierce, Stone, and Yirmiya co-chaired the working groups that conducted the literature review, generated initialrecommendations that were discussed at the consensus meeting, and provided critical input to subsequent drafts of the manuscript; Drs Estes, Hansen, McPartland,Natowicz, Buie, Carter, Davis, Granpeesheh, Mailloux, Newschaffer, Robins, Smith Roley, Wagner, and Wetherby were members of the working groups that reviewedselected publications, contributed to recommendations, and critically reviewed the manuscript; and all authors approved the final manuscript as submitted.

www.pediatrics.org/cgi/doi/10.1542/peds.2014-3667B

doi:10.1542/peds.2014-3667B

Accepted for publication Aug 3, 2015

Address correspondence to Lonnie Zwaigenbaum, MD, Autism Research Center, Glenrose Rehabilitation Hospital, Room E209, 10230 111 Ave, Edmonton, AB, CanadaT5G 0B7. E-mail: [email protected]

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

Copyright © 2015 by the American Academy of Pediatrics

FINANCIAL DISCLOSURE: Dr Zwaigenbaum was the site Principal Investigator of a study sponsored by SynapDx (he received operating funds but no honoraria).Drs Fein and Robins are co-owners of M-CHAT, LLC, which licenses use of the Modified Checklist for Autism in Toddlers in electronic products. Dr Stone is the authorof the Screening Tool for Autism in Two-Year-Olds and receives a share of royalties from sales of this instrument. The authors received an honorarium as well astravel expenses from Autism Forum for contributing to the expert panels.

FUNDING: Sponsored by the Autism Forum under the guidance of the Northwest Autism Foundation and with the support of the Autism Research Institute.

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

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DOI: 10.1542/peds.2014-3667B2015;136;S1Pediatrics

Robins, Susanne Smith Roley, Sheldon Wagner and Amy WetherbyPatricia A. Davis, Doreen Granpeesheh, Zoe Mailloux, Craig Newschaffer, Diana Hansen, James C. McPartland, Marvin R. Natowicz, Timothy Buie, Alice Carter,Kasari, Karen Pierce, Wendy L. Stone, Nurit Yirmiya, Annette Estes, Robin L.

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