Early Intervention For Children With Autism Spectr

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Early Intervention for Children With Autism Spectrum Disorder Under 3 Years
of Age: Recommendations for Practice and Research
Article in Pediatrics · October 2015

DOI: 10.1542/peds.2014-3667E
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Early Intervention for Children With Autism Spectrum
Disorder Under 3 Years of Age: Recommendations for
Practice and Research
AUTHORS: Lonnie Zwaigenbaum, MD,a Margaret L.
abstract Bauman, MD,b Roula Choueiri, MD,c Connie Kasari, PhD,d
Alice Carter, PhD,e Doreen Granpeesheh, PhD, BCBA-D,f Zoe
This article reviews current evidence for autism spectrum disorder Mailloux, OTD, OTR/L, FAOTA,g Susanne Smith Roley, OTD,
(ASD) interventions for children aged ,3 years, based on peer- OTR/L, FAOTA,h Sheldon Wagner, PhD,i Deborah Fein, PhD,j
reviewed articles published up to December 2013. Several groups Karen Pierce, PhD,k Timothy Buie, MD,l Patricia A. Davis,
have adapted treatments initially designed for older, preschool-aged MD,m Craig Newschaffer, PhD,n Diana Robins, PhD,n Amy
children with ASD, integrating best practice in behavioral teaching Wetherby, PhD,o Wendy L. Stone, PhD,p Nurit Yirmiya, PhD,q
Annette Estes, PhD,r Robin L. Hansen, MD,s James C.
methods into a developmental framework based on current scientific
McPartland, PhD,t and Marvin R. Natowicz, MD, PhDu
understanding of how infants and toddlers learn. The central role of aDepartment of Pediatrics, University of Alberta, Edmonton,
parents has been emphasized, and interventions are designed to in- Alberta, Canada; bDepartment of Anatomy and Neurobiology,
corporate learning opportunities into everyday activities, capitalize on Boston University School of Medicine, Boston, Massachusetts;
“teachable moments,” and facilitate the generalization of skills be- cDivision of Developmental and Behavioral Pediatrics, University
of Massachusetts Memorial Children’s Medical Center, Worcester,

yond the familiar home setting. Our review identified several compre- Massachusetts; dGraduate School of Education & Information
hensive and targeted treatment models with evidence of clear Studies, University of California Los Angeles, Los Angeles,
benefits. Although some trials were limited to 8- to 12-week outcome California; eDepartment of Psychology, University of
Massachusetts, Boston, Massachusetts; fCenter for Autism and
data, enhanced outcomes associated with some interventions were
Related Disorders, Tarzana, California; gDepartment of
evaluated over periods as long as 2 years. Based on this review, Occupational Therapy, Thomas Jefferson University, Philadelphia,
recommendations are proposed for clinical practice and future re- Pennsylvania; hUSC Mrs T.H. Chan Division of Occupational
search. Pediatrics 2015;136:S60–S81 Science and Occupational Therapy, Los Angeles, California;
iBehavioral Development & Educational Services, New Bedford,
Massachusetts; jDepartment of Psychology, University of

Connecticut, Storrs, Connecticut; kDepartment of Neurosciences,
University of California San Diego, La Jolla, California; lHarvard
Medical School and Massachusetts General Hospital for Children,
Boston, Massachusetts; mIntegrated Center for Child
Development, Newton, Massachusetts; nA.J. Drexel Autism
Institute, Drexel University, Philadelphia, Pennsylvania;
oDepartment of Clinical Sciences, Florida State University College
of Medicine, Tallahassee, Florida; pDepartments of Psychology,

and rSpeech and Hearing Sciences, University of Washington,
Seattle, Washington; qDepartment of Psychology, Hebrew
University of Jerusalem Mount Scopus, Jerusalem, Israel;
sDepartment of Pediatrics, University of California Davis MIND
Institute, Sacramento, California; tYale Child Study Center, New

Haven, Connecticut; and uGenomic Medicine Institute, Cleveland
Clinic, Cleveland, Ohio
ABBREVIATIONS
ABA—applied behavior analysis
ASD—autism spectrum disorder
ESDM—Early Start Denver Model
GRADE—Grading of Recommendations Assessment, Development,
and Evaluation
(Continued on last page)
S60 ZWAIGENBAUM et al
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SUPPLEMENT ARTICLE
The ultimate goal of early detection and cative processes. Infants depend on proach, with some discretion of the
screening is to ensure that children experiential learning within their nat- multidisciplinary expert working group,
with autism spectrum disorder (ASD) ural environments and on interactions was used instead to select articles of
can access evidence-based inter- rooted in social play that occur within highest relevance.
ventions to provide the best opportunity the context of everyday caregiving Each selected study was assessed, and
for optimal development and out- activities.1 Fortunately, over the past working group members were asked to
comes.1 With the advances reviewed by several years, a growing number of arrive at a consensus evaluation on each
Zwaigenbaum et al2,3 in this special studies have evaluated interventions article after a detailed discussion. The
issue of Pediatrics, and the growing specifically designed for children aged search was updated by using the same
evidence that ASD can be diagnosed ,2 to 3 years. An updated review of strategy to add articles published to
accurately before 2 years of age,4,5 the these interventions may provide needed December 31, 2013, which yielded an
need for ASD treatment programs direction and guidelines to clinicians additional 323 references; selection
specifically designed for this age group and policy makers. was again limited to clinical trials of
has never been greater. Some authors developmental/behavioral interventions
have also argued that the second year METHODS that included children aged ,36 months.
of life is a particularly critical de- The working group reviewed and ap-
Theworking group conducted a searchof
velopmental period for children with proved the final wording of the summary
the literature published online between
ASD, for various reasons. First, the and recommendations.
2000 and 2012 related to intervention
second year is a dynamic period of programs provided to children with ASD We recognize that in addition to com-
brain growth, during which increases aged ,3 years. The working group prehensive early intervention programs,
in brain volume and atypical connec- summarized published research on the management and treatment of young
tivity associated with ASD first emerge6,7 interventions developed for use in chil- children with ASD often involves speech
but also a time of substantial neural dren aged #36 months, even if the age and language and occupational and
plasticity providing greater potential range of samples of children being physical therapies, as well as manage-
to alter developmental course.8 Sec- evaluated extended beyond age 3 years ment of comorbid conditions such as
ond, a proportion of children with ASD (Table 1). A PubMed search was con- associated medical disorders (eg, sleep,
reportedly regress in the second year. ducted on June 30, 2010, for articles gastrointestinal),12 anxiety, and chal-
Recent research has indicated only published since January 1, 2000, by lenging and maladaptive behaviors.
modest agreement between retroac- using the search terms (“child de- However, a review of these targeted
tively reported regression and analysis velopmental disorders, pervasive” or interventions was beyond the scope of
of behavioral change as observed on “autistic disorder/” or “autism [tw]” or the current initiative.
serial home videos9 and that acute skill “autistic [tw]”) and (“Early Intervention/”
loss may exist along a continuum of or “intervention [tw]”), with an age LITERATURE REVIEW
gradually declining trajectories of so- filter (“infant, birth-23 months” or “Pre- Table 1 summarizes the key features
cial and communicative behavior.10,11 school child, 2-5 years”) and limited to and outcomes of 24 randomized con-
However, interventions during this pe- English-language articles. This search trolled, quasi-experimental, and open-
riod may counter the developmental yielded 419 references, which were label studies involving children with
cascade that contributes to pro- reviewed by Drs Zwaigenbaum and ASD aged ,3 years reviewed by the
gressive symptom development and Bauman, who selected articles focus- working group.13–38 Because few stud-
ultimately prevent ASD-related impair- ing on clinical trials of developmental/ ies focused exclusively on this age
ments before they fully manifest.8 behavioral interventions (ie, not medi- group, studies in which participants
Intervention approaches for children cations or trials of other biomedical included some children aged .3 years
aged ,2 to 3 years need to be de- therapies) that included children aged were assessed as long as there was
velopmentally appropriate. We cannot ,36 months. Search results were sufficient information to draw infer-
assume that findings from treatment complemented by additional pub- ences about younger children. The
research involving older children with lications identified by working group group reviewed additional reports,
ASD will generalize to infants and tod- members. Hence, although the search which have not been listed in Table 1,
dlers, who differ with respect to the strategy was comprehensive, selection including single-subject studies,39–44
nature of their social relationships as of articles was not systematic, which is other relevant studies,16,45–50 meta-
well as their cognitive and communi- an important limitation. A scoping ap- analyses,51,52 and reviews.53–56
PEDIATRICS Volume 136, Supplement 1, October 2015 S61

TABLE 1 Selected Intervention Studies Involving Children Aged ,3 Years (2000–2013)
S62
Reference N, Chronological Design Dose Treatment Outcomes Degree of Comments GRADE Quality of GRADE
Age, Gender Parental Evidence13 Recom-
Content Approach Involvement mendation13
Rogers N = 98 with ASD RCT 1 h parent training Comprehensive ESDM (see Dawson No main treatment Implemented by Both groups showed Moderate/high Weak
14 17
et al, (screen-positive on per week 3 12 wk, et al, below), effects on parent parents improvement in
2012 the ITC and ESATand plus self- adapted as briefer acquisition of ESDM child outcomes,
diagnosis by using instruction parent training intervention skills related to hours of
ZWAIGENBAUM et al
ADOS-T and clinical manual for model nor improvement in intervention and
judgment) parent to review child development older child age at
or ASD symptoms baseline
Aged 12–24 mo (mean: Stronger working
21.0 mo); 76 boys alliance with primary
therapist in ESDM
group compared
with community
intervention controls
Carter N = 62 with ASD RCT 1 group session with Targeted Hanen No main treatment effects Implemented by Missing data Moderate/high Weak
15
et al, symptoms or at risk parents per week recommendations: on parent responsivity parents precluded ITT
2011 (STAT) 3 8 wk, plus 3 at- parent training in or child analysis
home small groups plus communication
a
individualized 1:1 outcomesimmediately
sessions for or 5 mo after
parent and child treatment (although
moderate to large
effect sizes for parent
responsivity gains)
Aged 15–25 mo (mean: All sessions In children with low Internal study validity
20.3 mo); 51 boys completed by baseline levels of questioned by
3.5 mo object interest, ↑ authors
gains in child
communication
5 mo posttreatment
b
“Business as usual” In those with high Size of parent groups
baseline object smaller than Hanen
interest, attenuated recommendations
growth in

communication
Landa N = 48 with ASD RCT 10 h/week 3 6 mo Targeted Social curriculum Significant (P = .02) Implemented by Control group without Moderate/high Weak
16 a
et al, (5:3, DTT, routines- between-group interventionists social curriculum
2011 based interactions) difference for nevertheless
added to socially engaged received some
comprehensive imitation imitation and JA
classroom-based (moderate effect intervention
intervention (AEPS) size at 6 mo, large
effect size at 12 mo)
But there was home-
based parent
training (1.5 h/mo
3 6 mo) and parent
education classes
(38 h)
TABLE 1 Continued
Aged 21–33 mo (mean: AEPS curriculum NS between-group
28.6, 28.8 mo); 40 (developmental differences in IJA
boys approach) without and shared positive
added intervention affect (moderate or
large effect sizes at
6 and 12 mo)
NS between-group
differences in
expressive
language or
nonverbal cognition
(moderate effect
PEDIATRICS Volume 136, Supplement 1, October 2015

sizes at 6 and 12 mo)
a
Dawson N = 48 with ASD RCT 20 h/week 3 2 y Comprehensive ESDM: 1:1, home- Significant between- Delivered by therapists Group differences Moderate/high Strong
17
et al, (therapists) plus based, ABA and group differences in and parents larger than those in
2010 $5 h/wk 3 2 y developmental IQ and adaptive studies of
(parents) approaches; plus behavior after 2 y comparable
other available developmental
c
therapies behavioral
approaches of
shorter duration
and fewer hours of
delivery per week
Aged 18–30 mo (mean: Actualmean:15.2h/wk
23.9, 23.1 mo); (therapists) plus
male-to-female 16.3 h/wk
ratio 3.5:1 (parents)
Mean: 9.1 h/wk Assess and monitor: ESDM group
individual referrals by maintained rate of
therapy plus community-based adaptive behavior
9.3 h/wk group providers growth compared

with normative
sample of TD
children, and the
comparison group
showed further lag
Green N = 152 with AD RCT 4 h/month 3 6 mo, Targeted PACT: intervention to NS between-group Parent mediated ADOS-G, used as Moderate/high Strong
18
et al, then 2 h/month increase parent difference in child primary outcome, (per parent
2010 3 6 mo sensitivity and autism symptom may not be sensitive report)
responsiveness; severity, language measure of change
a
1:1 with child measures, or
present; plus adaptive
d
treatment as usual functioning in
school at 13 mo
S63
SUPPLEMENT ARTICLE
TABLE 1 Continued
S64
Aged 24–60 mo (M: 45); Treatment as usual Large effect size for Weak (per child
d
138 boys (local services) parent measures)
synchronous
response to child;
ZWAIGENBAUM et al
small effect sizes
for other parent–
child interaction
measures (child
initiations with
parent, parent-child
shared attention)
19
Ingersoll, N = 21 with AD RCT 3 h/week 3 10 wk Targeted Behavioral Significantly more Implemented by Groups not matched Moderate/high Strong
2010 intervention (RIT): gains in elicited therapists pretreatment
laboratory setting, (P , .05) and (better imitation in
naturalistic spontaneous (P , RIT group)
techniques .02) imitation, in
both object (P ,
.05), and gesture
(P , .01) imitation
compared with
controls
Aged 27–47 mo (mean: “Treatment as usual”
41.4, 37.2 mo); 18 in community
boys
Kasari N = 38 with AD RCT 2 h/wk (three 40-min Targeted Immediate JA At 8 wk, significant Caregiver mediated Concurrent early Moderate/high Strong
20
et al, sessions) 3 8 wk intervention: (P , .05) between- intervention (9–40
2010 instructing group differences h/wk) received by
caregiver–child in level of joint both groups (no
dyad during play engagement, child differences in dose
e
routines; combined responsiveness to or type)
developmental and JA, and diversity of
ABA approach; functional play acts
laboratory setting (generally large

effect sizes)
At 1-y follow-up,
treatment gains
were maintained or
improved
Aged 21–36 mo (mean: Delayed JA Quality of caregiver
30.8); 29 boys intervention (wait- involvement, but not
listed group) treatment fidelity,
predicted child
outcome
TABLE 1 Continued
Oosterling N = 75 with ASD RCT Year 1: Group Targeted Parent training by After 12 mo: Parents as everyday Modeled on the Moderate to low/ Weak
21
et al, sessions 2 h/wk psychologists or therapists intervention of very low
37
2010 3 4 wk, then sociotherapists Drew et al, 2002
home visits 3 h/wk (nonintensive, (see below)
every 6 wk home-based, called
“focus parent
training”) plus care
f
as usual
Flawed randomization
of first 26
participants
f
Aged 12–24 mo (mean: Year 2: Home visits Care as usual No between-group Treatment integrity not

34.4 mo); 52 boys every 3 mo plus differences in formally verified
plenary sessions language
every 6 mo development,
global clinical
development, or
mediating
outcomes (ie, child
engagement, early
precursors of social
communication,
parental skills)
Zachor and N = 78 with ASD Quasi-experimental 20 h/wk 3 1 y Comprehensive ABA-based NS between-group Stronger parent Groups not randomly Moderate Weak
22 a
Ben-Itzchak, intervention: 1:1, differences in involvement in assigned
2010 child-centered; part change in ASD eclectic group
of community diagnostic
center–based ASD- classification,
specific preschool cognitive abilities,
program (40 h/wk) or adaptive skills
Aged 15–35 mo (mean: 19 h/wk 3 1 y ED: mix of In subgroup with less

25.4); 71 boys developmental, DIR, severe baseline ASD
a
and TEACCH; 7:5 ; symptoms, eclectic
part of same .ABA in adaptive
preschool program skills
(40 h/wk)
Ben-Itzchak N = 68 with AD Open 35 h/wk 3 1 y Comprehensive ABA-based early NS effect of type of Implemented by Moderate Strong
and intervention as part intervention on therapists and
23
Zachor, of center-based change in autism special education
2009 autism-specific severity (∼20% in teachers
a
preschool; 1:1 each group
changed diagnostic
classification at 1 y)
S65
SUPPLEMENT ARTICLE
TABLE 1 Continued
S66
Aged 18–35 mo (mean: Eclectic as part of Compared with But parent training is
25.4 mo); 62 boys center-based children with part of eclectic
autism-specific unchanged status programs
preschool; mix of (n = 53), those with
ZWAIGENBAUM et al
treatment improved
approaches, small classification
groups (n = 15) gained
significantly more
in cognitive abilities
(P , .01), adaptive
skills (P , .05 for
communication
scores), and
stereotyped
behaviors (P , .05)
Eikeseth N = 20 with AD Open Range of supervision Comprehensive EIBI (UCLA/Lovaas Intensity of supervision Implemented by tutors 3 children excluded Very low/low Weak
24
et al, intensity: 2.9–7.8 model): home- significantly from data analysis
a
2009 h/month (M: 5.2) based, 1:1 ; mean: (P , .05) correlated (2 withdrew from
34.2 h/wk 3 50 wk, with changes in IQ study; 1 required
parent-managed and visual-spatial IQ increased
service after 14 mo supervision)
Aged 28–42 mo (mean: NS correlation with But parent training on Study designed to find
34.9 mo) adaptive ABA methods only association
functioning between
supervision
intensity and
outcome
Of 23 who entered
study, 17 boys
Ben-Itzchak N = 25 with AD Open $35 h/wk 3 1 y Comprehensive Intensive ABA- Significant (P , .001) Implemented by No control group Low/moderate Weak
and intervention: improvements after therapists
25 a
Zachor, center-based, 1:1, 1 y in imitation,
2007 addressing receptive/expressive

developmental and language, nonverbal
behavioral areas communication, play
skills, and
stereotyped
behaviors
Aged 20–32 mo (mean: Children with higher IQ Parent training on how
26.6 mo); 23 boys or fewer social to use behavioral
interaction deficits methods at home
before treatment
showed better
acquisition of
receptive/
expressive
language and play
skills
TABLE 1 Continued
Goin-Kochel N = 29 with ASD Open $30 h/wk 3 12–18 Comprehensive EIBI: ASD-specific Significant group Parents “required” to No control group Low Weak
26
et al, mo preschool program progress over time provide EIBI at
2007 in private school across multiple home, 10 h/wk, to
setting; ABA-based skills (P , .001 for supplement school-
g g
(ABLLS ) all ABLLS domains ) based intervention
a
curriculum; 1:1
plus small groups
g
Aged 29.6–61.4 mo Baseline ABLLS score Access to archival
(mean: 45.7 mo); 27 and rate of learning school data only
boys during first 6 mo (not known whether
best predicted other interventions
outcome were received)

9/16 discharged to
inclusive
kindergarten or
first grade with
assistance of aide;
all needed special
education services
Magiati N = 44 with ASD Quasi-experimental 18–40 h/wk 3 2 y Comprehensive EIBI in community NS group differences in In 23 of 28 families, 1 Groups not randomly Low/moderate Weak
27
et al, (M, 33.2 at end of setting: home cognitive ability, parent trained as assigned
a
2007 2 y) based; 1:1 ; DTTand, language, play a therapist
in 2 families, verbal skills, or ASD
behavior severity at 2 y
Aged 23–54 mo (mean: Moderate to large Treatment fidelity not
38.0, 42.5); 39 boys effect sizes for assessed directly
adaptive behaviors;
moderate effect size
for ASD severity
15–30 h/wk 3 2 y ED (including PECS, Baseline IQ and Nursery programs
(M, 27.4 at end of SPELL, and TEACCH) language level best emphasized “close

2 y) in autism-specific predicted overall liaison with
nurseries: 1:1 to progress parents”
a
3.3:1
Reed N = 27 with ASD Quasi-experimental 20–40 h/wk (M, 30.4) Comprehensive Home-based, high- Significant (P , .01) Some involvement by Groups not randomly Low/moderate Weak
28
et al, 3 9–10 mo intensity ABA between-group family members assigned
2007 programs, mostly differences in
a
1:1 and in natural educational
settings: functioning
Aged 31–48 mo (mean: UCLA/Lovaas model NS between-group Within the high-
42.9, 40.8 mo); all differences in intensity groups, ↑
boys intellectual temporal input (h/
functioning, wk) was not
adaptive behavior, associated with ↑
and ASD severity gains
S67
SUPPLEMENT ARTICLE
TABLE 1 Continued
S68
CABAS: emphasizing Largeeffectsizesforhigh-
teacher–student intensity group in
interaction as unit intellectual and
of analysis educational
ZWAIGENBAUM et al
functioning;moderate
effect sizes for low-
intensity group
Verbal behavior: focusing Small effect sizes for all
on developing verbal groups in adaptive
responses behavior
11–20 h/wk (mean: Home-based, low- Of 3 high-intensity
12.6) 3 9–10 mo intensity, generic programs, CABAS
ABA program had best effect sizes
Remington N = 44 with AD Quasi-experimental 18.4–34.0 h/wk Comprehensive EIBI: ABA-based; home Significant main effects EIBI delivered by Groups not randomly Moderate Strong
29
et al, (mean: 25.6) 3 2 y setting; delivered by of group for IQ, daily therapists and assigned
2007 multiple service living skills, and parents
providers; plus motor skills;
“usual” significant
h
treatments differences in
languageabilitiesat1
and 2 y favoring EIBI
Aged 30–42 mo (mean: Effect sizes at 2 y: large Potential examiner
35.7, 38.4 mo) for IQ, moderate for bias
adaptive behaviors
“Treatment as usual”: At 2 y, more children in Investigators could not
no intensive or EIBI group attended control practical
a
predominantly 1:1 mainstream aspects of
h
intervention ; schools (17/23 interventions
publicly funded compared with
education provision 10/21)
Response to EIBI
predicted by higher
baseline intellectual

functioning, more
baseline problem
behaviors, more
severeASDsymptoms
Zachor N = 39 with ASD Quasi-experimental 35 h/wk 3 1 y Comprehensive ABA-based early ABA . ED in Implemented by ADOS used to measure Low Weak
30
et al, intensive improvements in therapists changes in ASD core
2007 intervention: language and symptoms
a
center-based, 1:1, communication
DTT, naturalistic (P , .01) and
techniques reciprocal social
interaction
(P = .07): only ABA
showed significant
improvement in
former domain; ABA
had larger effect
size in latter
TABLE 1 Continued
Aged 22–34 mo (mean: 35 h/wk 3 1 y ED approach: center- ABA . ED in changes in
27.7, 28.8 mo); 37 based, mix of diagnostic
i
boys methods ; focused classification
on teaching (P , .05)
imitation and
awareness of social
a
interactions; 1:1
plus small groups
Cohen N = 42 with ASD Quasi-experimental 35–40 h/wk 3 47 Comprehensive EIBI (UCLA/Lovaas Significant differences Implemented by tutors Groups not randomly Very low/low Weak
31 j
et al, wk/y 3 3 y model): community in IQ (P = .03) and assigned
a
2006 based, 1:1 home adaptive behavior
instruction, DTT; (P = .01) favoring

plus classroom- EIBI
based regular
education
preschool
Aged 20–41 mo (mean: IQ and adaptive EIBI: parent training; Significantly (P , .05)
30.2, 33.2 mo); 35 behavior gains in parents more children with
boys EIBI group tended to encouraged to AD in EIBI group
plateau after 1 y participate actively
in intervention (no
set number of hours
required)
NS between-group Treatment fidelity not
difference in assessable in
language comparison group
comprehension or
nonverbal skills
#15–25 h/wk 3 3 y Special education At year 3, 17 of 21 EIBI At year 3, EIBI children
(for 17 of 21 classes at local children in regular trained in advanced
children) public schools education (6 social skills

(mixed approaches; without support) vs
a
1:1 to 3:1 ) 1 of 21 in
comparison group
Kasari N = 58 with AD RCT 2.5 h/wk 3 5–6 wk Targeted JA intervention: child- After 6 wk: Children directly After 5–6 wk, children Moderate/high Strong
32
et al, centered ABA and taught by trained transitioned off EIP
2006 milieu teaching interventionists to community
strategies added to services without JA
EIP; laboratory or SP intervention
setting
Kasari Aged 3–4 y (mean: 43.2, 2.5 h/wk 3 5–6 wk SP intervention using ↑ JA skills in JA group Control group then
33
et al, 42.7, 41.9 mo); 46 same strategies, and ↑ diversity and received more
2008 boys added to same EIP; sophistication of hours of
laboratory setting play in SP group intervention
compared with services than
controls (large former JA (P , .05)
effect sizes) and SP (P , .01)
groups
S69
SUPPLEMENT ARTICLE
TABLE 1 Continued
S70
EIP: 30 h/wk 3 5–6 Control group: Same Acquired skills
wk EIP without JA or SP generalized to play
intervention: with mothers (large
hospital day- effect sizes for JA
ZWAIGENBAUM et al
treatment program and SP)
for children with
developmental
disabilities and/or
behavioral
disorders; 1:1 or 1:2
ABA-based
techniques; adult-
centered, response-
oriented approach
to teaching
Some general effects of
therapy (JA,
functional play
skills) in JA and SP
groups
At 12-mo follow-up:
Significantly (P , .01)
greater growth in
expressive
language for JA and
SP (moderate effect
sizes for JA and SP
versus control)
Children with lowest
language levels
pretreatment had
significantly (P ,
.001) better

language outcomes
with JA than with
SP or EIP (moderate
to large effect sizes
for JA)
JA and SP groups
continued to show
growth and
generalization in
skills and
outperform control
group
TABLE 1 Continued
Wetherby N = 17 with ASD Quasi-experimental 2 home visits/wk 3 Targeted ESI: family training to Significant Implemented by Not known whether Very low/low Weak
and 1y follow child’s focus improvements from parents groups were
34
Woods, of attention and baseline for ESI matched at baseline
2006 build child’s skills in group in 11 of 13 (age 2 y)
daily routines social
(developmental communication
approach, natural measures (large
environment) effect sizes for 12
CSBS DP behavioral
sample measures,
moderate effect size
for 13th measure)

Aged 12–24 mo (mean: Plus 1 supervised At age 3 y, ESI . Actual intervention
18.2 mo); 15 boys parent–child play contrast group in intensity not
group (including social documented
TD children) per communication
week 3 9 wk 3 1 y (large effect size for
8 of 13 CSBS DP
measures)
n = 18 with ASD No-treatment contrast
group at third year
Aged 25–36 mo (mean:
31.6 mo); 14 boys
Yoder and N = 36 with ASD RCT 1 h/wk (three 20-min Targeted University clinic– RPMT . PECS in Parent training (up to Examiners conducting Moderate/high Weak
35
Stone, sessions) 3 6 mo based PECS: 6 facilitating 15 h) to support pre/post
2006 instructional frequency of intervention use assessments not
phases conducted generalized IJA (in outside clinic blinded to
by speech-language children with some treatment status
pathologists pretreatment IJA)
and generalized
turn taking (large

and moderately
large effect sizes,
respectively)
Aged 18–60 mo; 31 University clinic– In children with little
a
boys based RPMT: 1:1 ; pretreatment IJA,
can advance to PECS . RPMT in
Milieu Language facilitating
Teaching; Hanen generalized
curriculum for requests (large
parent support effect size)
a
Howard N = 61 with ASD Quasi-experimental 25–40 h/wk 3 14 mo Comprehensive EIBI: 1:1 ; home, school, EIBI . AP: significantly Delivered by trained Groups not randomly Very low/ Weak
36
et al, or community higher group mean tutors assigned moderate
2005 setting scores for IQ,
nonverbal,
language, overall
communication,
and social skills
S71
SUPPLEMENT ARTICLE
TABLE 1 Continued
S72
Aged ,48 mo (mean: 25–30 h/wk 3 14 mo Intensive, eclectic, NS differences in group Parents to implement No direct group
30.9, 37.4, 34.6 mo); autism-specific mean scores programs outside comparison;
54 boys educational between AP and GP of scheduled statistical analysis
programming (AP): intervention hours of group mean
ZWAIGENBAUM et al
a
1:1 or 2:1 ; public scores
school classroom-
based; including
DTT, PECS, and
TEACCH
15 h/wk 3 14 mo Nonintensive generic ↑ Learning rates at Many techniques not
educational 14 mo (P # .05) for operationally
programming (GP): EIBI versus other defined
a
6:1 ; community 2 groups in all
based; mix of domains except
methods motor skills
(normal or above-
normal rates,
especially in
acquisition of
language skills)
Drew N = 24 with AD RCT 3 h/wk every 6 wk 3 Targeted Parent training (home- NS group differences in Parent mediated Groups not matched on Very low/low/ Weak/moderate
37 l
et al, 12 mo based) that focused child language baseline nonverbal moderate
2002 on joint attention development after IQ
skills; plus available 12 mo
community
services
Aged ,24 mo (mean: NS group differences in Parents to use learned No data on parent
22.5 mo); 19 boys nonverbal IQ and techniques during training
symptom severity daily routines and in implementation
after 12 mo set-aside joint play
sessions (30–60
min/d)
Language ability in Total intervention

both groups still hours higher
severely (P = .07) in control
compromised at group
12 mo
Available community Sometimes entirely Reliance on parent
k
services only delivered by report for language
therapists, outcomes
sometimes parent
involvement
TABLE 1 Continued
Smith N = 28 with ASD RCT 30 h/wk 3 2–3 y Comprehensive EIBI (UCLA/ Lovaas Significant (P , .05) Intensive treatment Lacked standardized Moderate/high Strong
38
et al, (decreasing in model): home- between-group implemented by diagnostic
a
2000 later years with based 1:1, then differences at age therapists instrument
progress by shifting to 7–8 y in IQ, visual
child) classroom setting; spatial skills, and
ABA-based language
development
favoring EIBI
Aged 18–42 mo (mean: 5 h/wk parent Parent training in same No differences in In both groups, parents Skewed distribution of
35.8, 36.1 mo); 23 training 3 3–9 treatment adaptive asked to provide scores precluded
boys mo plus 10–15 approaches; plus functioning or 5 h/wk of some statistical
h/wk of special special education behavior problems intervention analyses

education for classes for children
children
Improved school
placement in
intensive treatment
group
ABLLS, Assessment of Basic Language and Learning Skills; AD, autistic disorder; ADOS, Autism Diagnostic Observation Schedule; ADOS-G, Autism Diagnostic Observation Schedule–Generic; ADOS-T, Autism Diagnostic Observation Schedule–Toddler Module;
AEPS, Assessment, Evaluation, and Programming System for Infants and Children; AP, intensive eclectic autism-specific educational programming; CABAS, Complete Application of Behavior Analysis to Schools approach; CSBS DP, Communication and
Symbolic Behavior Scales Developmental Profile; DIR, Developmental, Individual Difference, Relationship; DTT, discrete trial training; ED, eclectic-developmental; EIBI, early intensive behavioral intervention; EIP, Early Intervention Program; ESAT, Early
Screening of Autistic Traits questionnaire; ESI, Early Social Interaction Project; GP, non-intensive generic educational programming; GRADE, Grading of Recommendations Assessment, Development, and Evaluation; IJA, initiating joint attention; ITC, Infant/
Toddler Checklist; ITT, intention-to-treat; JA, joint attention; PACT, Preschool Autism Communication Trial; PECS, Picture Exchange Communication System; RCT, randomized controlled trial; RIT, reciprocal imitation training; RJA, responding to joint attention;
RPMT, Responsive Education and Prelinguistic Milieu Teaching; SP, symbolic play; SPELL, Structure, Positive (approaches and expectations), Empathy, Low (arousal), and Links framework; STAT, Screening Tool for Autism in Two-Year-Olds; TD, typically
developing; TEACCH, Treatment and Education of Autistic and Related Communication Handicapped Children; UCLA, University of California, Los Angeles.
a Child-to-teacher ratio.
b Carter et al,15 2011: “Business as usual” interventions not specified in publication.
c Dawson et al,17 2010: Including speech, developmental preschool.
d Green et al,18 2010: Treatment as usual included group-based autism psychoeducation, communication-focused intervention, Portage therapy, speech and language therapy, and (for 1 child each in PACT group) home-based EIBI and Son-Rise therapy.
e Kasari et al,20 2010: Concurrent early interventions involved mostly ABA/educational services and speech and occupational therapy; study investigators did not coordinate with providers of these services.
f Oosterling et al,21 2010: Care as usual, including speech and language therapy, motor therapy, music therapy, play therapy, and parental counseling.

g Goin-Kochel et al,26 2007: ABLLS is a curriculum guide for children with language delays and a comprehensive behavioral assessment; ABLLS domains, language, social/play, academics, self-help, motor.
h Remington et al,29 2007: Treatment-as-usual interventions in both groups included PECS, TEACCH, speech therapy, dietary intervention, and prescription medications.
i Zachor et al,30 2007: ED approach included speech and language, occupational, and music therapies, plus structured cognitive teaching (DIR, TEACCH, and ABA techniques).
j Cohen et al,31 2006: 35 to 40 hours per week for children aged .3 years; 20 to 30 hours per week for children aged ,3 years.
k Drew et al,37 2002: Children in control group received mix of speech and language therapy, occupational therapy, and preschool services. Within 3 mo of initial assessment, 3 children in control group started on intensive, home-based ABA interventions
(UCLA/Lovaas model, 1:1, mean of 32.9 h/week for 12 months).

l Drew et al,37 2002: Reflects different assessments of 3 reviewers.
S73
SUPPLEMENT ARTICLE
Compared with early intervention models Denver Model [ESDM] and the UCLA/ volved 20 hours per week of therapist
evaluated for preschool-aged children Lovaas model) and the 4 targeted involvement plus additional parent-
(aged 3–5 years), programs for children interventions (focusing on social com- mediated intervention for 2 years.14
aged ,3 years were more likely to use munication or imitation skills) exhibited The study failed to detect improvements
developmental approaches, more in- significantly improved outcomes rela- in parental intervention skill acquisition
tensively involve parents, and target so- tive to comparison groups after thera- and child-related outcomes relative to
cial communication. These studies varied peutic durations of 8 weeks to 2 to 3 community intervention controls.
in sample size and severity of diagnosis, years. Several of the 6 studies reported Based on expert opinion that arose
dose (level of intensity/frequency of ser- effect sizes: large effect sizes after 6 and from the review and discussion of the
vice delivery), duration, agent (parent, 8 weeks of therapy for increases in joint existing evidence, members of the
therapist, or a combination), and for- attention skills,20,32 a moderate effect working group agreed on several sum-
mat of delivery (parent-managed/home- size after 12 months for expressive lan- mary statements intended to guide
based and/or center-based in a clinic or guage growth,33 and small effect sizes clinical practice and future research.
school) of the intervention. Some inter- after 13 months for parent–child in- Practice recommendations are high-
ventions were comprehensive, defined as teraction measures.18 It is notable that lighted in statements 1 through 4;
addressing multiple core ASD deficits, targeted interventions generally fo- consensus regarding future research
while others targeted specific areas of cused on outcomes related to ASD- directions is highlighted in statements
functioning. A word of caution is war- specific characteristics, whereas the 5 through 9. Statement 10 focuses on
ranted when interpreting any 1 inter- comprehensive models included teach- the importance of considering the po-
ventional study or model. In some cases, ing to the core deficits but often did not tential impact of medical comorbidities
elements of a particular programmatic measure changes in these core deficits on treatment and developmental out-
approach varied from study to study (eg, (or obtained nonsignificant findings); comes.
the addition of training in advanced so- they instead focused on gains in general
cial skills in 1 early intensive behavioral functioning (eg, cognitive and/or adap- SUMMARY STATEMENTS
intervention program).31 Furthermore, tive skills). Two nonrandomized con-
Statement 1: Current best
reported group differences may not re- trolled studies were rated as producing
practices for interventions for
flect the range of individual responses in strong recommendations: comprehen- children aged ,3 years with
any 1 study, and participants who dem- sive applied behavior analysis (ABA)- suspected or confirmed ASD
onstrated gains in some end points may type interventions were associated should include a combination of
have continued to show impairment in with significantly improved outcomes developmental and behavioral
others. relative to the comparison group after approaches and begin as early as
Six randomized controlled trials were 2 years (compared with publicly funded possible.
considered to produce strong recom- educational services)29 and with signifi- Based on current outcome data, the
mendations and an assessment that the cantly improved outcomes in a subset working group supported the provision
desirable effects of an intervention of participants after 1 year (compared of interventions targeted to the specific
clearly outweighed the undesirable with an eclectic mix of treatments).23 deficits of ASD (eg, language skills, joint
effects. Only 2 studies focused solely on Although other studies included in the attention, emotional reciprocity) (Ta-
children aged ,3 years; 1 was related to present review exhibited less than ble 1) for children aged ,3 years that
a comprehensive treatment approach,17 moderate quality of evidence and/or integrate both behavioral and de-
and 1 was a targeted intervention pro- produced weak recommendations, it velopmental approaches. Behavioral
gram.20 The remaining 4 studies in- was agreed that the findings in these interventions are techniques based on
cluded preschool-aged children as well studies might nevertheless inform behavioral analysis of antecedents and
as some children aged ,3 years or fo- treatment options as well as future re- consequences of specific behaviors,
cused on developmental tasks of infancy. search. Specifically, there were studies and they use principles derived from
Two of these studies evaluated the same rated as having a strong quality of evi- experimental psychology research to
sample of children aged 3 or 4 years at dence but equivocal findings.16 For ex- systematically change behavior. De-
the beginning of treatment.32,33 ample, a recent trial evaluated the ESDM velopmental models of intervention
To briefly summarize these 6 stud- in a brief format: 1 hour per week of use developmental theory to design
ies17–20,32,33,38: both of the comprehen- parent training for 12 weeks, as op- approaches to target ASD deficits.57
sive intervention programs (Early Start posed to the original ESDM, which in- Developmental approaches often
SUPPLEMENT ARTICLE
underlie community services, such as parents should help set goals and pri- Statement 3: Interventions should
public school programs implemented orities for their child’s treatment, enhance developmental progress
by special education specialists and identify and locate needed support for and improve functioning related to
speech and language pathologists.56 themselves, and teach or reinforce both the core and associated
However, the distinction between be- their child’s new skills at home and in features of ASD, including social
havioral and developmental strategies the community.60 communication, emotional/
may not be very helpful, as many in- behavioral regulation, and
Active family involvement can have adaptive behaviors.
tervention programs blend features of a positive impact on developmental
both approaches. The curricula of outcomes. Parental or caregiver in- Many behavioral interventions for ASD
a behavioral intervention may be de- focus on cognitive, behavioral, and
volvement increases the amount of in-
velopmentally informed and based on language outcomes, but interventions
tervention time delivered to the child
developmental sequences, whereas also need to address social com-
inasmuch as children in this age range
a developmental program could use munication challenges central to the
are likely to spend more time with
behavioral techniques to teach a cur- diagnosis. Sensory dysregulation,
their parents in their home and
riculum. challenging behaviors, and motor skills
neighborhoods than in other settings.
Our analysis supports the effectiveness are also common in children with ASD
Furthermore, parents and caregivers
of integrated developmental and be- and should be targeted by interventions
can capitalize on teachable moments
havioral interventions, outside of the when needed.
as they occur, provide learning oppor-
laboratory setting, in improving de- Despite an apparent lack of change on
tunities during daily routines, and fa-
velopmental quotients, adaptive func- standardized measures of social com-
cilitate the generalization of learned
tioning, and language skills.17,29 munication symptoms in 2 randomized
skills across environments. 15 Family
In line with the American Academy of controlled trials,17,37 a growing body
involvement is also likely to be cost-
Pediatrics, the working group recom- of research describes the beneficial
effective and increases the sense of
mended initiating interventions as soon effects early intervention has on the
empowerment on the part of parents
as a diagnosis of ASD is seriously development of communication and
and caregivers. In the 2 comprehensive social functioning. (This lack of change
considered or determined. 57 Data developmental/behavioral programs
available since 2001 support the fact may reflect the utilization of symptom
for which we have moderate or high measures such as the Autism Di-
that early intensive education and
evidence of effectiveness,17,29 parents agnostic Observation Schedule, which,
therapies can yield significantly im-
were supported in complementing as a diagnostic tool, was designed to be
proved developmental outcomes. In
educators and therapists in the de- relatively stable; measures specifically
addition, it has been suggested that
livery of the interventions because of designed and validated as being sen-
interventions initiated before 3 years of
the importance of, and challenges in- sitive to change are needed.) Specifi-
age may have a greater positive impact
herent in, carrying over services and cally, targeted interventions have been
than those begun after the age of
generalizing skills across multiple set- associated with gains in imitation,16,19
5 years.58–60
tings. Importantly, the concept of pa- joint attention,16,20,32,34 social engage-
Statement 2: Current best rental involvement is consistent with ment,20,32,33 other social communica-
practices for children aged ,3 the recommended broader best prac- tion measures,34 and functional and
years with suspected or confirmed tices that support working with young symbolic play.20,32
ASD should have active involvement children in natural environments. Sev- Impaired effortful control (ie, a reduced
of families and/or caregivers as eral parent-mediated interventions ability to regulate attention, emotions,
part of the intervention. have shown positive parent and/or and behavior to achieve goals) has been
There is a consensus that effective early child outcomes. However, the extent reported in children with ASD as early
intervention includes a family and/or to which these interventions are as as at 24 months of age.61 Interventions
caregiver component.57 For many in- effective as therapist-mediated inter- dealing with attention regulation in
tervention programs, this approach ventions or are more effective when young children with ASD have not yet
would mean parental involvement as added into comprehensive child ser- been reported, but in typically de-
a co-therapist, with appropriate su- vices, or with the combination of veloping children, short-term train-
pervision, training, and monitoring as therapist plus parent mediated inter- ing has improved attention control
part of the intervention. Specifically, ventions, requires further study.18,20 measures associated with effortful

control. 62 Comprehensive inter- the lifestyle that has evolved around In addition to any cultural issues, when
ventions that blend developmental and the child with ASD, and the unmet parents are expected to be the thera-
behavioral approaches have success- needs among family members or peutic provider, assessment should
fully improved adaptive functioning problem areas that might otherwise go focus on more than just fidelity of
in many studies.17,23,29,31 Thus, future unaddressed.56 Service providers can implementation and adherence to
intervention studies should address be of assistance by monitoring the intervention goals. The quality of
and assess various developmental physical and mental health of the a parent’s involvement, consideration
domains as intervention and outcome family as well as that of the child with of a parent’s other responsibilities and
targets. ASD. Finally, respect for the percep- roles,20 and potential family stres-
tions, priorities, and preferences of sors15 arising from fulfilling their role
Statement 4: Intervention services family members is an important in an intervention or from coping with
should consider the sociocultural “family-centered” tenet to bear in mind care for a child with ASD warrant ex-
beliefs of the family and family when working with children on the amination to determine whether mod-
dynamics and supports, as well as autism spectrum and their complex erators of treatment are present or are
economic capability, in terms of needed. Apart from any possible re-
needs.63
both the delivery and assessment luctance by families to participate in
of factors that moderate research, there is also a need for
Statement 5: Intervention research
outcomes.
should include socially and investigators to make a particular ef-
Socioeconomic status, family charac- culturally diverse populations of fort to recruit as culturally diverse
teristics, and cultural factors may participants and evaluate familial a research sample as possible.
present barriers to service provision. factors that may affect
Families with lower socioeconomic participation, acceptability, and Statement 6: Future research
status are likely to have less access to outcomes of therapeutic should prioritize well-defined
services. Because cultural values and approaches as well as willingness sampling strategies, rigorous
differences can affect the goals and to participate in investigative investigative design, fidelity of
priorities of the family and may in some studies. implementation, and meaningful
cases lead to misunderstandings, Parents are expected to play a prom- outcome measurements.
clinicians and other service providers inent role in supporting optimal de- The methodologic rigor of intervention
should aim to understand the values, velopment and thus intervention trials in ASD is improving, but continued
beliefs, and accompanying practices of program delivery for their children, attention to key aspects of research
families of differing cultures and as- particularly at a very young age. An design is needed to further develop the
similate that knowledge into their important focus of intervention re- evidence base for toddlers.
practice parameters as it relates to search should therefore include fac- Future directions include identifying
autism occurring in ethnically diverse tors such as cultural background and characteristics of children and families
populations. Culturally competent care other family characteristics that may who would benefit most from particular
extends beyond fluency in a non-English influence participation in treatment interventions to support a more in-
language. As a minimum, culturally programs and interventional results. dividualized approach, as well as sys-
appropriate program materials should Due to attitudes concerning child- tematically varying components of
be developed for families. In addition, hood rearing and independence, shame multifaceted intervention programs to
training programs should be created regarding developmental delays and identify critical ingredients. Thorough
that can help service providers learn ASD, or other societal and cultural characterization of research partic-
how to promote culturally responsive beliefs, parents may be reluctant to ipants would help to define the subset
assessment and intervention ser- enroll a child in a research study. Cu- of children and families who most
vices.56 mulatively, such decisions can diminish strongly benefit from particular in-
Management of a child with ASD should the generalizability and clinical appli- tervention approaches. In addition, to
focus on the family as well as on the cability of reported interventions. In avoid systematic bias from confounding
child.57 Important considerations for addition, when there is participation, factors, research participants should
the clinician include the well-being of cultural differences and language bar- be randomly allocated to the treatment
each person in the family, the comfort riers might influence and moderate approaches that are being com-
and support of each family member, treatment effects. pared, and each treatment (including
SUPPLEMENT ARTICLE
community-based “as-usual” treatment) such information, future intervention emerged in this study except for
should be thoroughly described. Al- programs can be refined. the apparent benefit of imitation in 1
though the optimal study design to group. Nonetheless, this research
minimize bias in treatment research is Intensity of intervention paradigm provides a possible model
a randomized controlled trial, it is ac- The National Research Council has through which intervention research
knowledged that contexts occur in recommended a minimum intensity of may be implemented. Similarly, other
which other methods may be appropri- 5 hours a day, 5 days a week, for inter- investigators have evaluated the addi-
ate. For example, to determine whether ventions.60 However, some recent studies tive effects of joint attention or play
an intervention holds promise, it is im- have suggested the possibility of positive skills into an ABA program that did not
portant that intervention procedures outcomes with fewer hours of direct include a focus on these developmental
are carefully tested for feasibility and therapist involvement for young toddlers skills. Teaching these skills increased
acceptability. Moreover, single case with ASD, particularly when parents are their spontaneous occurrence in gen-
designs, carefully implemented and with actively engaged in the treatment pro- eralized contexts and further predicted
attention to appropriate measurement, cess. For example, gains in some social greater language outcomes compared
may also be informative.64 Attention to communication skills (eg, play, joint at- with the children in the ABA program
and systematic evaluation of fidelity of tention, imitation) were demonstrated in without a focus on play and joint at-
implementation and selection of well- some studies when directly targeted in tention.33,59
validated measures of key constructs interventions of relatively low intensity Incorporating teaching targets of joint
(eg, joint attention, imitation, other (based on hours per week or length of attention, play, and imitation are clearly
indicators of age-appropriate social and treatment).16,18,20 Notably, the “real-life” indicated for early intervention pro-
communication skills and function) that intensity of the intervention may be grams for ASD. However, given the
are responsive to change are also es- influenced by the degree to which heterogeneity of the disorder, it will be
sential. parents are implementing the strategies critical to determine how treatment
in natural routines throughout the day. strategies can be most effectively tai-
Statement 7: Research is needed to The effectiveness of interventions is also lored to the needs of subgroups of
determine the specific active likely to be influenced by whether train- children with ASD who have particular
components of effective ing and ongoing supports allow parents clinical profiles.
interventions, including but not to correctly implement the treatment
limited to the type of treatment strategies (ie, with fidelity to the treat- Statement 8: Adopting a common
provided, the agent implementing ment procedures as originally designed), set of research-validated core
the intervention(s) (parent, as has been reported in the treatment of measures of ASD symptoms
therapist, teacher, or preschool-aged children with ASDs.65 In (including but not limited to
combination), consistency of addition, other factors can affect the ex- cognitive function, communication,
service provision across tent to which such interventions are ef- and adaptive behavior) that can be
environments and between fective, including age, degree of used across multiple sites will
providers, and duration of impairment, and the extent to which facilitate comparisons across
treatment and hours per week. studies of children with ASD aged
the child receives other services.
Information is lacking regarding the ,3 years.
features of an intervention that drive its Treatment content The interpretation of study findings is
effectiveness, but progress is being A recent study in toddlers with ASD has often hampered when investigators use
made on identifying these active attempted to determine the additive different variables, or measures, to
ingredients or mechanisms of change. value of joint attention, imitation, and report outcomes. A consistent set of
Without appropriate study designs to affect on an intervention when applied core measures relevant to the specific
carefully examine the effect of specific within 2 developmental/behavioral intervention goal(s) of interest should
intervention strategies such as treat- toddler classroom environments.16 be adopted for studies of toddlers with
ment type, dose, and agent, we may be The investigators evaluated impact in 1 ASD as well as for older children. Out-
unable to determine which of the po- study group, and another group re- come measures do not need to be
tentially significant elements in an in- ceived the same overall comprehen- identical across studies, but agreement
tervention model are responsible for sive intervention but without the on a subset of standardized instru-
change and for which subgroups. With ingredient of interest. Few differences ments to use (which may assess

changes in cognitive function, core autism well as the associated neurobiological Statement 10: Intervention
symptoms, and adaptive and language mechanisms at work in each case, and providers should consider medical
behavior) would facilitate future com- to be able to offer more directed disorders that may affect a child’s
parisons.Someearlydevelopmentalskills interventions depending on the bi- clinical presentation (especially
could yield “early-read” measures that ological subtype when available and behavior) and response to an
are important to later developmental present. intervention and should refer to
outcomes. These early-read measures appropriate health care providers
A number of genetic and neurobiolog-
may include joint attention, shared affect, as indicated.
ical subgroups are already known to be
and imitation skills, with the expectation associated with ASD. The most well- It has become increasingly evident in the
that these early developmental tasks may known groups are children with frag- ASD population that changes in behavior
predict better functioning in later cogni- ile X syndrome, tuberous sclerosis, and may be associated with an underlying
tion, language, and adaptive behavior. duplication 15q. Other genetic dis- medical condition.13 For example, clinical
Early-read measures may provide im- orders have been identified as being experience would suggest that a child
portant information on the effectiveness associated with ASD features, and with ASD exhibiting behavioral changes
of short-term interventions and may also a growing number of candidate genes might be experiencing pain or discomfort
offer information on active ingredients are being explored. For example, owing to a medical problem such as otitis
essential to include in comprehensive Campbell et al66 reported that children media, a dental abscess, or constipation.
intervention programs. Additional meas- with ASD and MET gene mutations were Frequently encountered medical factors
ures related to the impact that having more likely to have gastrointestinal in ASD include: seizures, particularly in
a child with ASD has on family life and disorders, raising the possibility that children who also have severe intellect-
parental stress would also be important. medical comorbidities in children with ual disability, motor deficits, or a positive
ASD could index underlying genetic family history of epilepsy68,69; other gas-
Statement 9: Future research heterogeneity. It is thus important for trointestinal symptoms57,70; and sleep
should examine biological and future research to determine both bi- disturbances affecting daytime function-
behavioral heterogeneity as ological and clinical subtypes within ing. The full effect of medical factors on
moderators of individual the autism spectrum that may ulti- the clinical presentation of children aged
responses to interventions. mately affect the effectiveness of ,3 years with ASD is not known, nor has
In any sample population, positive re- treatment and intervention. the association between medical factors
sponsestoaninterventioncanrangefrom To date, few studies have been designed and maladaptive behaviors such as ag-
dramatic to extremely limited. Factors or powered for analysis of heteroge- gression and self-injury been well studied
that underlie such heterogeneity—pos- neous effects.67 Treatment modifiers in general in ASD. Nevertheless, best
sible moderators of individual responses— were recently identified in 2 studies practices would indicate that a patient
can include age at onset of intervention, based on appropriate study design with a potential medical comorbidity be
patient characteristics (eg, baseline and statistical analysis. In both stud- referred to a medical specialist for ap-
stage of development of cognitive func- ies, a measure developed to index the propriate evaluation, diagnosis, and
tion, language and preverbal skills, level of initial object exploration de- management. It is important that future
adaptive behavior, sociocultural char- termined the extent to which a child research address these and other po-
acteristics), and symptom severity. As would benefit more from 1 language- tential medical factors, how they may be
important, however, is the increasing based intervention versus another35 more reliably identified (especially in
appreciation that ASD is a heterogeneous or the extent to which children had nonverbal or hypo-verbal ASD individu-
disorder—etiologically, biologically, and better communication outcomes from als), and what effect treatment of these
clinically. Given this heterogeneity, it is a parent-mediated intervention.15 Ob- conditions may have on behavior, de-
highly likely that specific subsets of indi- ject exploration can reflect a child’s velopmental trajectory, and learning.
viduals with ASD may respond to specific flexibility in play and play level, both of
interventions more effectively than to which may influence later cognitive ACKNOWLEDGMENTS
others, perhaps based on etiology and and language outcomes. 59 Further Theconferencechairsandworking groups
underlying biological factors alone. Thus, studies like these are needed before acknowledge the preconference contribu-
there is a critical need to begin to identify we can make informed choices and tions of Tony Charman, PhD, and Gary
subtypes of individuals with ASD, to un- personalize the treatment of each in- Mesibov, PhD, who were unable to attend
derstand the cause of their disorder as dividual child. the conference. We also acknowledge the
SUPPLEMENT ARTICLE
efforts of Katherine F. Murray, BSN, RN, The meeting and consensus report were Forum programs are developed under
Massachusetts General Hospital for Chil- sponsored by the Autism Forum. An im- the guidance of its parent organization,
dren, in coordinating the forum and subse- portant goal of the forum is to identify the Northwest Autism Foundation. For
quentconferencereportprocess,andSifor early indicators of ASDs that may lead this project, the Autism Research Insti-
Ng in the conference report process. to effective health care services. Autism 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
drafted the initial manuscript; Drs Choueiri and Kasari co-chaired the working group that conducted the detailed literature review, generated initial recommen-
dations that were discussed at the consensus meeting, and provided critical input to subsequent drafts of the manuscript; Drs Carter, Granpeesheh, Mailloux, Smith
Roley, and Wagner were members of the working group that reviewed selected publications, contributed to initial recommendations that were reviewed at the
consensus meeting, and critically reviewed the manuscript; Drs Fein, Pierce, Buie, Davis, Newschaffer, Robins, Wetherby, Stone, Yirmiya, Estes, Hansen, McPartland,
and Natowicz contributed to the consensus meeting that formed the basis for the manuscript and critically reviewed the manuscript; and all authors approved the
final manuscript as submitted.
www.pediatrics.org/cgi/doi/10.1542/peds.2014-3667E
doi:10.1542/peds.2014-3667E
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, Canada
T5G 0B7. E-mail: lonniez@ualberta.ca
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
author of 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 as travel 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.

Lonnie Zwaigenbaum, Margaret L. Bauman, Roula Choueiri, Connie Kasari, Alice
Carter, Doreen Granpeesheh, Zoe Mailloux, Susanne Smith Roley, Sheldon Wagner,
Deborah Fein, Karen Pierce, Timothy Buie, Patricia A. Davis, Craig Newschaffer,
Diana Robins, Amy Wetherby, Wendy L. Stone, Nurit Yirmiya, Annette Estes, Robin
L. Hansen, James C. McPartland and Marvin R. Natowicz
Pediatrics 2015;136;S60
DOI: 10.1542/peds.2014-3667E
Updated Information & including high resolution figures, can be found at:
Services /content/136/Supplement_1/S60.full.html
References This article cites 66 articles, 12 of which can be accessed free
at:
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned, published,
and trademarked by the American Academy of Pediatrics, 141 Northwest Point Boulevard, Elk
Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Lonnie Zwaigenbaum, Margaret L. Bauman, Roula Choueiri, Connie Kasari, Alice
Carter, Doreen Granpeesheh, Zoe Mailloux, Susanne Smith Roley, Sheldon Wagner,
Deborah Fein, Karen Pierce, Timothy Buie, Patricia A. Davis, Craig Newschaffer,
Diana Robins, Amy Wetherby, Wendy L. Stone, Nurit Yirmiya, Annette Estes, Robin
L. Hansen, James C. McPartland and Marvin R. Natowicz
Pediatrics 2015;136;S60
DOI: 10.1542/peds.2014-3667E
The online version of this article, along with updated information and services, is
located on the World Wide Web at:
/content/136/Supplement_1/S60.full.html
PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright © 2015 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.
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Lonnie Zwaigenbaum Margaret L Bauman

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of Massachusetts Memorial Children’s Medical Center, Worcester,

Massachusetts; jDepartment of Psychology, University of

of Medicine, Tallahassee, Florida; pDepartments of Psychology,

Institute, Sacramento, California; tYale Child Study Center, New

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(UCLA/Lovaas model, 1:1, mean of 32.9 h/week for 12 months).

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