TABLE 2.
Selected Studies of Potential Markers Identifying ASD in Infants Aged 12 Months
| First Author and Year of Publication | Findings | Type of Study | Sample | Ascertainment | Outcome Diagnosis | Comments |
|---|---|---|---|---|---|---|
| Social/emotional behavioral markers (from studies with outcome assessment) | ||||||
| Bryson et al, 32 2007 | Between ages 6 and 12 mo, in subset of siblings with change in cognitive development between 12 and 24 mo, 5 of 6 infants were “more difficult to engage socially” (“less … eye contact, no or very little social smiling, and little interest or pleasure in interacting with others”); minimal exploration of toys; atypical sensory behavior (striking visual fixation); repetitive/atypical motor behaviors | Prospective case series | 9 SIBS-A later diagnosed with ASD | Recruited from multidisciplinary autism diagnostic and treatment centers | Gold standard diagnostic assessment for ASD at age 36 mo by using ADI-R, ADOS, and DSM-IV-TR criteria | Assessments every 6 mo from age 6–24 mo, including: |
| Clinical diagnosis of ASD for 4 children at 24 mo and for 3 at 30 mo | • AOSI and/or ADOS to assess for ASD symptoms | |||||
| • BSID-II to assess cognition | ||||||
| • CDI-WG to assess gestural and early language development | ||||||
| • Infant Temperament Scale or Toddler Behavior Assessment Questionnaire to assess temperament | ||||||
| Semi-structured interviews regarding parental concerns | ||||||
| Maestro et al, 71 2005 | • Between ages 0 and 6 mo, significant group differences in social attention (high scores in social versus nonsocial stimuli in “typical” infants) | Retrospective video study | • 15 children aged 3.5–5.2 y with AD diagnosis | Subjects with AD recruited from community sources referred to public academic hospital; controls were kindergarten attendees | Diagnosis made at study entry through symptom checklist based on DSM-IV plus ≥30 score on CARS | • From each group, home movies lasting at least 10 min coded by blinded observers for frequency of behaviors via an 8-item “grid” for assessment of social and nonsocial attention |
| • Between ages 7 and 12 mo, no group differences in social or nonsocial attention; but behaviors regarding attention to nonsocial stimuli increased in both AD and typical groups but “more evident” in the former | • 13 “typical” children with mean age of 4.7 y | • Social attention behaviors assessed: looking at people, orienting toward people, smiling at people, vocalizing to people | ||||
| • Nonsocial attention behaviors assessed: looking at objects, orienting toward objects, smiling at objects, vocalizing to objects | ||||||
| Maestro et al, 72 2002 | Between ages 0 and 6 mo, significant group differences in social attention and social behavior, including: | Retrospective video study | • 15 children aged 3.5–5.6 (mean: 4.1) y with diagnosis of AD (n = 7) or PPD-NOS (n = 8) | Controls were kindergarten attendees | Diagnosis made at study entry through symptom checklist based on DSM-IV plus score of ≥30 on CARS | • Home movies lasting at least 10 min for each subject during age 0–6 mo were rated by blinded observers for frequency of behaviors by using 13-item “grid” covering 3 developmental areas of social attention (eg, looking at people), social behavior (eg, anticipating the other’s aim), and nonsocial attention (eg, “explorative activity with object”) |
| • Less frequent looking at people (P < .001) | • 15 “typical” “normal” children with mean age of 4.7 y | |||||
| • Less frequent vocalizing to people (P < .001) | Matched for gender and age in home videos | |||||
| • Less frequent orienting toward people (P > .01) | ||||||
| No group differences in items referring to interest and attention versus nonsocial stimuli | ||||||
| Macari et al, 46 2012 | At 12 mo, 7 ADOS-T items optimized classification of children with and without ASD at 24 mo | Prospective longitudinal study | • 53 at-risk infants (SIBS-A); 13 diagnosed with ASD at 24 mo | Recruited from multiple sources (existing research programs, Web site, advertising, and word of mouth) | Clinical best diagnosis of ASD at 24 mo based on developmental and medical history, developmental and language assessments and ADOS, and DSM-IV criteria | • Subjects assessed at 12 mo and followed up to 24 mo |
| • 11 of 13 children with ASD and 68 of 71 children without ASD correctly classified | Ongoing | • 31 infants at no known risk (SIBS-TD) | • MSEL to assess development | |||
| These items included: level of engagement, amount of requesting, imitation, fussiness, showing, gestures, and intonation | • ADOS-T to measure social and communicative behaviors | |||||
| • Item-level analysis of ADOS-T, “decision tree” procedures to optimize prediction of ASD | ||||||
| Nadig et al, 38 2007 | At 6 mo, nonsignificant trend for controls to require fewer number of calls to respond to name | Prospective longitudinal study | • 55 at-risk infants (SIBS-A) | Enrolled in university-based study | Clinical best diagnosis of AD or PDD-NOS at 24 mo based on clinical observation, ADOS, DSM-IV criteria | • Subjects followed up to age 36 mo |
| • 82% of controls responded on first or second call of name vs. 66% of SIBS-A | Ongoing | • 43 infants at no known risk (SIBS-TD) | • MSEL to assess development | |||
| Aged 6 mo | • ADOS to measure social and communicative behaviors | |||||
| • Response-to-name experimental task videotaped at 6 and 12 mo and coded for number of calls it took for response to child’s name | ||||||
| • Same sample as in Merin et al, 73 2007 | ||||||
| Ozonoff et al, 22 2010 | At 6 mo: | Prospective longitudinal study | • 25 high-risk infants with later diagnosis of AD or PDD-NOS (22 were SIBS-A) | Sample drawn from larger longitudinal study | Classification as ASD or TD at 36 mo using Baby Siblings Research Consortium definitions (ADOS and DSM-IV-TR criteria for AD or PDD-NOS) | Assessments at ages 6, 12, 18, 24, and 36 mo of: |
| • No group differences in social communication behaviors (including frequency of gaze to faces, shared smiles, and vocalizations to others) | • 25 gender-matched SIBS-TD determined later to have TD | • Frequencies of 6 social communication behaviors (gaze to faces, gaze to objects, smiles, nonverbal vocalizations, single-word verbalizations, phrase vocalizations), recorded onto DVDs and coded during MSEL Visual Reception subtest | ||||
| • Better (NS) social communication behaviors for ASD versus TD outcome group “on all variables” | • Frequency of infant social engagement rated by blind examiners | |||||
| • MSEL to assess cognitive functioning | ||||||
| • Symptom onset by parent reports | ||||||
| Werner et al, 74 2000 | At 8–10 mo, significant (P < .05) main effect of diagnostic group for social behaviors, after children with late-onset ASD (n = 3) were removed from analysis | Retrospective video study | • 15 infants later diagnosed with AD (n = 8) or PPD-NOS (n = 7) | Participants of earlier study plus additional recruits from university infant research pool | Confirmation of AD or PPD-NOS based on DSM-III-R plus ≥30 score on CARS | • Home videos between ages 8–10 mo coded for presence or absence of behaviors categorized as social (e.g., looking at others, orienting to name being called), communication (vocalizations), and repetitive |
| • Infants with ASD “much less likely” (P < .005) than infants with TD to orient when their name was called | • 15 children with TD | |||||
| Young et al, 75 2009 | • No infant in Merin et al, 73 2007, who showed abnormal gaze behavior (decreased eye contact) at 6 mo had any signs of autism at outcome | Prospective | • 33 high-risk infants (SIBS-A) | Refer to Merin et al, 73 2007 (below) | Clinical diagnosis of autism at 18 and/or 24 mo based on ADOS-G supplemented by M-CHAT and MSEL | • Longitudinal follow-up for sample in Merin et al, 73 2007 |
| • The 3 infants in sample who were diagnosed with autism by 24 mo did not exhibit abnormal gaze patterns at 6 mo and had typical affective responses at 6 mo | • 25 infant SIBS-TD | Clinical outcome data available on 49 infants | • Assessment at 6 mo of eye-tracking data and behavioral data during live mother–infant interaction | |||
| • MSEL to assess development at 6, 12, 18, and 24 mo | ||||||
| • VABS to assess social, communication, and motor skills at 12, 18, and 24 mo | ||||||
| • CDI to assess language development at 18 and 24 mo | ||||||
| Zwaigenbaum et al, 45 2005 | At 6 mo, siblings with later diagnosis of ASD showed: | Prospective longitudinal study | • 44 SIBS-A | Recruited mainly at age ≤6 mo from autism diagnostic and treatment programs; low-risk infants recruited from nurseries in same regions | Formal independent diagnostic assessment at 36 mo based on DSM-IV criteria, ADI-R, and ADOS | • AOSI at 6 and 12 mo to assess autism-specific behaviors |
| • No difference in number of risk markers measured by using AOSI | Ongoing (N = 88 followed up to age 24 mo; 6-mo data available on 44 SIBS-A) | • 15 low-risk infants (no first- or second- degree relatives with ASD) | Clinical diagnosis of ASD made at 24 mo in up to 7 SIBS-A who met DSM-IV criteria (confirmed by using ADI-R and ADOS) | • Computerized visual orienting task at 6 and 12 mo to assess ability to disengage from 1 of 2 competing visual stimuli (attentional disengagement) | ||
| • No difference (P = .12) in disengagement of visual attention | “Roughly” matched according to gender, birth order, and age; N values varied by assessment | • IBQ at 6 and 12 mo to measure infant temperament | ||||
| • Temperament characterized by marked passivity and decreased activity level (P = .019) | Available 6-mo outcome data for 44 SIBS-A: | • MSEL and CDI-WG at 12 mo to assess language and cognitive development | ||||
| Compared with non-ASD siblings and controls | • 4 with AD | |||||
| Behavioral observations at 6 mo do not predict later diagnosis | • 8 with ASD classification on ADOS | |||||
| • 32 without ASD | ||||||
| Social/emotional behavioral markers (from studies without outcome assessments) | ||||||
| Merin et al, 73 2007 | At 6 mo, diminished gaze to mother’s eyes relative to mouth (10 of 11 infants with this finding were in at-risk group) | Prospective | • 31 at-risk infants (SIBS-A) | Recruited by using research institute database and word of mouth | Not done | • Visual fixation assessment during reciprocal social interaction, conducted at age 6 mo via eye tracking during modified still-face paradigm |
| • 24 with an older sibling without autism | • Same sample as in Nadig et al, 38 2007 | |||||
| Noland et al, 76 2010 | At 6.5–9 mo, higher working memory scores for SIBS-A versus SIBS-TD for nonsocial stimuli; no group difference for social stimuli | Prospective | • 25 SIBS-A | SIBS-A recruited primarily through university-based service and ASD outreach program; SIBS-TD recruited from telephone contacts by using state birth record database | Not done | • Trials at age 6.5 mo and/or 9 mo involving tasks relating to orienting toward social and nonsocial targets (stimuli); correct response was infant gaze toward location where target most recently appeared |
| • 30 SIBS-TD | • Trials videotaped, coded for correct first looks | |||||
| Yirmiya et al, 48 2006 | At 4 mo: | Prospective | • 21 dyads of mothers and infants who were SIBS-A | Comparison group recruited from hospital maternity wards | At age 14 mo, 1 subject was suspected of having autism, a diagnosis confirmed at ages 24 and 36 mo by using ADI-R and ADOS-G | Measures at age 4 and 14 mo: |
| • No significant group difference in mother–infant synchrony, although SIBS-A exhibited weaker synchrony during infant-led interactions | Ongoing (N = 42 with 4-mo assessments) | • 21 dyads and infants who were SIBS-TD | • BSID-II to assess general development and language | |||
| • No significant group difference in infant gaze behavior during still-face procedure but more neutral affect and less upset with SIBS-A | Matched on 1-to-1 basis according to chronologic age, gender, birth order, number of children in family, and Bayley mental and motor scales | • ICQ to assess maternal perception of infant temperament | ||||
| • Significantly more SIBS-A responded to name being called by mother than SIBS-TD | Social engagement measures at 4 mo: | |||||
| • Synchrony during mother–child free play interaction | ||||||
| • Infant gaze and affect during still-face paradigm | ||||||
| • Procedure to assess responsiveness to name being called | ||||||
| Language/communication behavioral markers (from studies with outcome assessment) | ||||||
| Colgan et al, 77 2006 | At 9–12 mo, decreased variety in types of social interaction gestures used was significantly associated with autism status | Retrospective video study | • 21 children later diagnosed with AD | Recruited through mailings to child care centers and developmental evaluation centers; parent advocacy group meetings; hospital clinics; university-based autism subject registry | Clinical diagnosis of AD made according to time of study recruitment (preschool age), by using DSM-III-R or DSM-IV criteria and, for 11 subjects, score >30 on CARS | Home videotapes from ages 9–12 mo collected; edited footage totaling 5 min and including social scenes, comparable across groups, were coded for use of gestures |
| • Other measures were not associated with an AD diagnosis: total number of social interaction gestures, number of child-initiated social interaction gestures | • 14 children with TD | • Only gestures defined as social interaction were used in this study (“gestural act used to attract or maintain attention of another for social purposes”; eg, waving hello or good-bye, shaking head yes or no) | ||||
| Landa and Garrett-Mayer, 49 2006 | At 6 mo, no significant group differences in domains of motor, visual reception, and language development | Prospective longitudinal | • 24 children with later diagnosis of ASD | SIBS-A recruited through Autism Society of America local chapters and university-based center for autism; children at low autism risk recruited through local physician offices and caregiver-child play groups | ASD classified at 24 mo based on PLS, ADOS, and CDI | MSEL to assess general and language development across 5 domains of nonsocial development (gross motor, fine motor, visual reception, receptive and expressive language); administered as close as possible to ages 6, 14, and 24 mo |
| • 11 with later diagnosis of language delay | ||||||
| • 52 classified as unaffected (at 24 mo) | ||||||
| 58 SIBS-A and infants with no family history of autism evaluated at 6 mo | ||||||
| Paul et al, 78 2011 | At age 6–12 mo, group differences for certain prelinguistic vocal behaviors | Prospective cross-sectional design | • 28–38 high-risk infants (SIB-A) | Recruited from university research pool; also referrals from local pediatric practices, local autism advocacy groups, word of mouth, advertising in parenting media | Provisional diagnoses at 24 mo based on clinical observations, ADOS-T, and MSEL | • Vocalization samples collected at age 6, 9, and 12 mo during play with mother and standard set of toys |
| • Significantly fewer speech-like vocalizations and more nonspeech vocalization | Ongoing (N = 43 who have participated in 24-mo follow-up) | • 20–31 low-risk infants (no sibling with ASD diagnosis) | Of the 24 high-risk subjects who made a 24-mo visit: | • Detailed analysis of vocal production (eg, for consonant inventory, presence of canonical syllables) and development of prespeech vocalization | ||
| • Significantly fewer consonant types | • 7 with ASD | • Discriminant function analyses included only children at high risk | ||||
| • Significantly fewer canonical syllable shapes | • 6 with symptoms without meeting full BAP criteria | |||||
| Differences in vocal production in first year of life associated with “outcomes in terms of autistic symptoms” in second year for children at high risk | • 1 with nonautistic developmental delay | |||||
| • 10 without a clinical diagnosis | ||||||
Studies may evaluate markers in >1 category (see “Comments”). AD, autistic disorder; ADI-R, Autism Diagnostic Interview–Revised; ADOS, Autism Diagnostic Observation Schedule; ADOS-G, Autism Diagnostic Observation Schedule–Generic; ADOS-T, Autism Diagnostic Observation Schedule–Toddler Module; AOSI, Autism Observation Scale for Infants; BAP, broader autism phenotype; BSID-II, Bayley Scales of Infant Development–2nd edition; CARS, Childhood Autism Rating Scale; CDI-WG, MacArthur Communicative Development Inventories–Words and Gestures; DSM-III-R, Diagnostic and Statistical Manual of Mental Disorders, Third Edition, Revised; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; DSM-IV-TR, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision; DVD, digital video disc (high-capacity optical disk); IBQ, Infant Behavior Questionnaire; ICQ, Infant Characteristics Questionnaire; M-CHAT, Modified Checklist for Autism in Toddlers; PLS, Preschool Language Scale; PDD-NOS, pervasive developmental disorder not otherwise specified; SIBS-A, younger siblings of children with ASD; SIBS-TD, younger siblings of children with typical development; TD, typical development; VABS, Vineland Adaptive Behavior Scales.