Free
Research Article
Issue Date: July/August 2015
Published Online: June 23, 2015
Updated: April 30, 2020
Assessment of Autism Symptoms During the Neonatal Period: Is There Early Evidence of Autism Risk?
Author Affiliations
  • Roberta Pineda, PhD, OTR/L, is Assistant Professor, Program in Occupational Therapy, Department of Pediatrics, School of Medicine, Washington University, St. Louis, MO; pineda_r@kids.wustl.edu
  • Kelsey Melchior, MSOT, is Occupational Therapy Student, Program in Occupational Therapy, School of Medicine, Washington University, St. Louis, MO
  • Sarah Oberle, OTD, OTR/L, is Occupational Therapist, Program in Occupational Therapy, School of Medicine, Washington University, St. Louis, MO
  • Terrie Inder, MD, is Mary Ellen Avery Professor in Pediatrics in the Field of Newborn Medicine, Harvard Medical School, Boston, MA, and Professor in Pediatrics, Department of Pediatric Newborn Medicine, Brigham and Women’s Hospital, Boston, MA
  • Cynthia Rogers, MD, is Assistant Professor, Departments of Psychiatry and Pediatrics, School of Medicine, Washington University, St. Louis, MO
Article Information
Autism/Autism Spectrum Disorder / Neurologic Conditions / Pediatric Evaluation and Intervention / Vision / Children and Youth
Research Article   |   June 23, 2015
Assessment of Autism Symptoms During the Neonatal Period: Is There Early Evidence of Autism Risk?
American Journal of Occupational Therapy, June 2015, Vol. 69, 6904220010. https://doi.org/10.5014/ajot.2015.015925
American Journal of Occupational Therapy, June 2015, Vol. 69, 6904220010. https://doi.org/10.5014/ajot.2015.015925
Abstract

OBJECTIVE. To define neonatal social characteristics related to autism risk.

METHOD. Sixty-two preterm infants underwent neonatal neurobehavioral testing. At age 2 yr, participants were assessed with the Modified Checklist for Autism in Toddlers and Bayley Scales of Infant and Toddler Development, 3rd edition.

RESULTS. Positive autism screening was associated with absence of gaze aversion, χ = 5.90, p =.01, odds ratio = 5.05, and absence of endpoint nystagmus, χ = 4.78, p = .02, odds ratio = 8.47. Demonstrating gaze aversion was related to better language outcomes, t(55) = −3.07, p ≤ .003. Displaying endpoint nystagmus was related to better language outcomes, t(61) = −3.06, p = .003, cognitive outcomes, t(63) = −5.04, p < .001, and motor outcomes, t(62) = −2.82, p = .006.

CONCLUSION. Atypical social interactions were not observed among infants who later screened positive for autism. Instead, the presence of gaze aversion and endpoint nystagmus was related to better developmental outcomes. Understanding early behaviors associated with autism may enable early identification and lead to timely therapy activation to improve function.

Autism spectrum disorder (ASD) is characterized by impairments in social interaction and communication along with repetitive, restricted, and stereotyped behaviors, interests, and activities (American Psychiatric Association, 2013). The prevalence of ASD has been on the rise in recent years (Blumberg et al., 2013; Johnson et al., 2010), with the Centers for Disease Control and Prevention (2013)  estimating that 1 in 68 children are diagnosed with ASD. Although the etiology of ASD can be genetic, certain groups of children, including preterm infants, have a higher risk of ASD (Arpino et al., 2010).
Preterm infants demonstrate more ASD characteristics in infancy and early childhood than do infants born full term (Movsas & Paneth, 2012). Symptoms include difficulties with social awareness, cognition, communication, and motivation (Johnson et al., 2010; Movsas & Paneth, 2012). Mothers of preterm infants notice these symptoms 2–4 mo earlier than mothers of full-term infants, and ASD symptoms are more severe among preterm infants (Movsas & Paneth, 2012). Preterm infants also have been shown to fail the Modified Checklist for Autism in Toddlers (M–CHAT; Robins, Fein, Barton, & Green, 2001) at a rate 7%–27% higher than that of their full-term peers (Kuban et al., 2009; Moore, Johnson, Hennessy, & Marlow, 2012; Yamada et al., 2011), making these infants a good population to study in order to better understand ASD.
Early identification of ASD can lead to timely initiation of targeted therapies, which can optimize function (Bryson, Rogers, & Fombonne, 2003; Eikeseth, Klintwall, Jahr, & Karlsson, 2012; Peters-Scheffer, Didden, Korzilius, & Sturmey, 2011; Reichow, 2012). Although clinicians can now diagnose ASD earlier than in previous years, many children remain undiagnosed until age 6 yr or older (Shattuck et al., 2009). Differences in screening and diagnostic practices in various settings can affect timing of ASD identification (Shattuck et al., 2009), and later diagnosis results in missed opportunities for intervention. Although early identification is important, few studies have investigated behaviors during infancy that may signal ASD.
The emerging research on early identification of ASD has focused on behavioral and motor responses present during the 1st year of life and how they relate to later diagnosis of ASD. Children who receive a later diagnosis of ASD may demonstrate early deficits in social behavior, specifically in joint attention, eye contact, orienting to name, facial expressions, social smile, attention, and tolerance of social touch (Adrien et al., 1993; Baranek, 1999; Barbaro & Dissanayake, 2013; Bhat, Landa, & Galloway, 2011; Chawarska, Macari, & Shic, 2013; Clifford et al., 2007; Clifford & Dissanayake, 2008; Cornew, Dobkins, Akshoomoff, McCleery, & Carver, 2012; Elsabbagh et al., 2012, 2014; Hutman et al., 2010; Ibanez, Messinger, Newell, Lambert, & Sheskin, 2008; Iverson & Wozniak, 2007; Karmel et al., 2010; Mitchell et al., 2006; Nadig et al., 2007; Osterling, Dawson, & Munson, 2002; Ozonoff et al., 2010; Phagava et al., 2008; Rozga et al., 2011; Wan et al., 2013; Werner, Dawson, Osterling, & Dinno, 2000; Yirmiya et al., 2006; Zwaigenbaum et al., 2005). Motor deficits, including hypotonia, poor quality of movement, and head lag, also have been reported as early signs of ASD (Ferrari, Cioni, & Prechtl, 1990; Flanagan, Landa, Bhat, & Bauman, 2012; Karmel et al., 2010; Phagava et al., 2008).
Despite the emerging evidence of ASD markers in the 1st year of life, only one study has investigated ASD markers as early as the neonatal period (Karmel et al., 2010). In that study, no differences were observed in the neonatal period between children who were and were not later diagnosed with ASD. At age 1 mo, however, arm tone deficits and asymmetric visual tracking were observed in infants later diagnosed with ASD. Most studies of markers of ASD in infancy were conducted through retrospective analysis of home videos, which decreases the ability to differentiate infants who have a heightened risk of ASD. One recent study found that, contrary to the later presentation of the disorder, infants diagnosed with ASD demonstrated a clear orienting response to faces at 7 mo old (Elsabbagh et al., 2013). Research has also shown that the typical decline in social interaction occurs between age 2 mo and 6 mo (Jones & Klin, 2013).
This recent literature suggests that the recognized core features of ASD may not be present in early infancy. However, with only one study investigating neonatal markers of ASD, this body of knowledge is not complete. Nuanced social behavior that provides clues to later risk of autism may be present during the neonatal period. Therefore, this study aimed to explore early social interaction behavior of preterm infants at term-equivalent age and associations with ASD risk at age 2 yr. We hypothesized that infants who screened positive for ASD at 2 yr of age would demonstrate alterations in early social interaction behavior at term-equivalent age, such as gaze aversion, and would demonstrate better orientation to objects than to people at term-equivalent age. Because many children with ASD have comorbid developmental problems (Levy et al., 2010), we also explored a secondary hypothesis that early social interaction would also be related to developmental outcome.
Method
This study used a sample of 62 infants from an overarching, longitudinal study aimed at understanding brain development in very preterm infants. The Human Research Protection Office approved this study, and parents signed informed consent. Participants were admitted to the St. Louis Children’s Hospital neonatal intensive care unit (NICU) and enrolled by their 3rd day of life. Inclusion criteria, based on the criteria of the overarching study, were birth at ≤30 wk estimated gestational age and no known congenital anomaly. Social interaction behavior was assessed at term-equivalent age (37–40 wk postmenstrual age) in the NICU. Participants returned for developmental testing at 2 yr of age, which included assessing ASD risk.
Early Social Interaction
Early social interaction was captured from neurobehavioral testing using the NICU Network Neurobehavioral Scale (NNNS; Lester & Tronick, 2005). Neurobehavioral testing was conducted by a single, trained occupational therapist certified in the NNNS. The NNNS is a 115-item, comprehensive neurobehavioral assessment conducted over 20–25 min. Use of standardized assessment procedures and reliability of scoring each item were ensured through a certification process for the NNNS by a single, certified examiner. The NNNS has been shown to have good predictive validity (Lester & Tronick, 2005) and has been used extensively in other research investigating early infant outcomes. The NNNS requires the infant be in a specific state to enable appropriate assessment of specific domains of function. For example, visual and auditory items are not assessed in an infant who is not able to achieve an awake state.
Standardized scoring of the NNNS was used to document responses to handling, abnormal eye signs, and visual responses. Social interaction behaviors included cuddling; irritability; consolability; crying; and the presence of abnormal visual signs such as gaze aversion, visual locking, tight blinking, roving eye movements, endpoint nystagmus, sustained nystagmus, obligatory following, and hyperalertness (Table 1). Additionally, orientation items were captured and included visual tracking of a human face and auditory orienting to a human voice (including interactive prompting and calling the infant’s name), visual tracking of a red ball, and auditory orienting to the noise of a rattle (see Table 1).
Table 1.
Descriptions of Social Neurobehavioral Factors
Descriptions of Social Neurobehavioral Factors×
FactorDescription
Social interaction
 CuddlingInfant resists being held and/or failed to participate with whole body while cuddling in arms.
 IrritabilityInfant cries or fusses for most (>50%) of the interaction.
 ConsolabilityInfant is able to be soothed with human interaction, such as being talked to or held, moving from an active awake or crying state to a quiet alert, drowsy, or sleep state.
 CryingInfant cries for at least 15 s during the exam.
 Gaze aversionInfant actively moves eyes or head away from visual stimulus to avoid the stimulus.
 Visual lockingInfant demonstrates a stare at a stimulus that was difficult to break.
 Tight blinkingInfant closes eyes tightly to avoid the stimulus when stimulus is presented
 Roving eye movementsInfant demonstrates rapid eye movements that were not oriented to a stimulus when presented.
 Endpoint nystagmusInfant demonstrates rapid, repetitive horizontal eye movements when orienting to a stimulus at the end of the visual range.
 Sustained nystagmusInfant demonstrates rapid, repetitive horizontal eye movements during any attempts to visually orient.
 Obligatory followingInfant responds to a visual stimulus with an exaggerated response and rapid, predictable eye and head movements toward the stimulus.
 HyperalertnessInfant responds with overly intense alertness, often seen with bulging eyes and a panicked expression.
Visual and auditory orientation
  Auditory animate orientation (human voice)Poor = No auditory orientation
Fair = Brightening with shifting of eyes
  Auditory inanimate orientation (rattle)Good = Head turning to side of stimulus and localizing <2 out of 4 times
Excellent = Head turning and finding the stimulus ≥2 out of 4 times
  Visual animate orientation (human face)Poor = No visual tracking
Fair = Focusing on object with brief following <30°
  Visual inanimate orientation (red ball)Good = Tracking ≥30° to one side
Excellent = Full tracking to both sides with smooth eye movements
 Preference for animate objectsThe infant scores higher on animate visual and auditory orientation than on inanimate visual and auditory orientation.
Table 1.
Descriptions of Social Neurobehavioral Factors
Descriptions of Social Neurobehavioral Factors×
FactorDescription
Social interaction
 CuddlingInfant resists being held and/or failed to participate with whole body while cuddling in arms.
 IrritabilityInfant cries or fusses for most (>50%) of the interaction.
 ConsolabilityInfant is able to be soothed with human interaction, such as being talked to or held, moving from an active awake or crying state to a quiet alert, drowsy, or sleep state.
 CryingInfant cries for at least 15 s during the exam.
 Gaze aversionInfant actively moves eyes or head away from visual stimulus to avoid the stimulus.
 Visual lockingInfant demonstrates a stare at a stimulus that was difficult to break.
 Tight blinkingInfant closes eyes tightly to avoid the stimulus when stimulus is presented
 Roving eye movementsInfant demonstrates rapid eye movements that were not oriented to a stimulus when presented.
 Endpoint nystagmusInfant demonstrates rapid, repetitive horizontal eye movements when orienting to a stimulus at the end of the visual range.
 Sustained nystagmusInfant demonstrates rapid, repetitive horizontal eye movements during any attempts to visually orient.
 Obligatory followingInfant responds to a visual stimulus with an exaggerated response and rapid, predictable eye and head movements toward the stimulus.
 HyperalertnessInfant responds with overly intense alertness, often seen with bulging eyes and a panicked expression.
Visual and auditory orientation
  Auditory animate orientation (human voice)Poor = No auditory orientation
Fair = Brightening with shifting of eyes
  Auditory inanimate orientation (rattle)Good = Head turning to side of stimulus and localizing <2 out of 4 times
Excellent = Head turning and finding the stimulus ≥2 out of 4 times
  Visual animate orientation (human face)Poor = No visual tracking
Fair = Focusing on object with brief following <30°
  Visual inanimate orientation (red ball)Good = Tracking ≥30° to one side
Excellent = Full tracking to both sides with smooth eye movements
 Preference for animate objectsThe infant scores higher on animate visual and auditory orientation than on inanimate visual and auditory orientation.
×
For the purposes of this study, standard scoring was not used for orientation items, because they do not reflect quality of performance. Instead, orientation items were recoded on an ordinal scale to reflect scores that were poor, fair, good, or excellent to better define successful performance (see Table 1 for descriptions). Whether the infant responded better to human interaction, compared with interaction with objects and toys, was also captured, according to the best response to the orientation items.
These social factors from the neurobehavioral assessments were used to define social interaction behaviors in this study. Note that for the purposes of this study, the individual items of the NNNS were used to isolate specific social behaviors. However, the tool was designed to weight each individual item with final reporting of 13 summary scores rather than for the reporting of specific behaviors as was done for the purposes of this study.
Medical Complications and Interventions
Medical information was extracted from the electronic medical record. Descriptive factors (Table 2) included gender; race (White or non-White); estimated gestational age at birth; birth weight (in grams); days on the ventilator; initial medical severity; length of stay (in days); presence of moderate to severe brain injury; mother’s age; and whether the mother had a college education, was married, was on public insurance (Medicaid), or used illicit drugs during pregnancy (from toxicology reports). The Clinical Risk Index for Babies (CRIB; Tarnow-Mordi & Parry, 1993) score was used as a marker for initial medical severity. Moderate to severe brain injury was defined by routine cranial ultrasound and MRI at term-equivalent age. Moderate to severe brain injury was defined as Grade III or IV intraventricular hemorrhage, cystic periventricular leukomalacia, or cerebellar hemorrhage.
Table 2.
Sample Characteristics (N = 62)
Sample Characteristics (N = 62)×
Characteristicn (%), M (SD), or Median (IQ Range)
Child
 Female30 (48)
 White38 (61)
 Gestational age, wk26.7 (1.8)
 Birth weight, g961.9 (272.3)
 Days on ventilator3.0 (1.0–24.0)
 CRIB score3.5 (3.2)
 Length of stay, days91.7 (28.5)
 Moderate to severe brain injury12 (19)
Mother
 Age, yr29.5 (7.4)
 Has college education28 (45)
 Single34 (55)
 Public insurance34 (55)
 Illicit drug use during pregnancy2 (3)
Child developmental outcomes
 Bayley–III Cognitive86.2 (10.0)
 Bayley–III Motor83.7 (11.7)
 Bayley–III Language89.3 (11.7)
 Positive ASD screen on M–CHAT13 (21)
Table Footer NoteNote. ASD = autism spectrum disorder; Bayley–III = Bayley Scales of Infant and Toddler Assessment, 3rd ed.; CRIB = Clinical Risk Index for Babies; IQ = interquartile; M = mean; M–CHAT = Modified Checklist for Autism in Toddlers; SD = standard deviation.
Note. ASD = autism spectrum disorder; Bayley–III = Bayley Scales of Infant and Toddler Assessment, 3rd ed.; CRIB = Clinical Risk Index for Babies; IQ = interquartile; M = mean; M–CHAT = Modified Checklist for Autism in Toddlers; SD = standard deviation.×
Table 2.
Sample Characteristics (N = 62)
Sample Characteristics (N = 62)×
Characteristicn (%), M (SD), or Median (IQ Range)
Child
 Female30 (48)
 White38 (61)
 Gestational age, wk26.7 (1.8)
 Birth weight, g961.9 (272.3)
 Days on ventilator3.0 (1.0–24.0)
 CRIB score3.5 (3.2)
 Length of stay, days91.7 (28.5)
 Moderate to severe brain injury12 (19)
Mother
 Age, yr29.5 (7.4)
 Has college education28 (45)
 Single34 (55)
 Public insurance34 (55)
 Illicit drug use during pregnancy2 (3)
Child developmental outcomes
 Bayley–III Cognitive86.2 (10.0)
 Bayley–III Motor83.7 (11.7)
 Bayley–III Language89.3 (11.7)
 Positive ASD screen on M–CHAT13 (21)
Table Footer NoteNote. ASD = autism spectrum disorder; Bayley–III = Bayley Scales of Infant and Toddler Assessment, 3rd ed.; CRIB = Clinical Risk Index for Babies; IQ = interquartile; M = mean; M–CHAT = Modified Checklist for Autism in Toddlers; SD = standard deviation.
Note. ASD = autism spectrum disorder; Bayley–III = Bayley Scales of Infant and Toddler Assessment, 3rd ed.; CRIB = Clinical Risk Index for Babies; IQ = interquartile; M = mean; M–CHAT = Modified Checklist for Autism in Toddlers; SD = standard deviation.×
×
Autism Risk
ASD risk was determined at age 2 yr using the M–CHAT. The M–CHAT is a 23-item ASD screening tool for children ages 16–30 mo. The internal reliability of the M–CHAT is adequate (Cronbach’s α = .85), and a discriminant function analysis of the six critical items found that 99% of the time they correctly identified children as having ASD (Robins & Dumont-Mathieu, 2006). Sensitivity has been found to be between .70 (Snow & Lecavalier, 2008) and .97 (Robins et al., 2001), with specificity between .38 (Snow & Lecavalier, 2008) and .99 (Robins et al., 2001). A positive or negative screen for ASD on the M–CHAT was used as an outcome variable in the current study to define ASD risk. The M–CHAT is a screening tool, and a positive screen does not indicate a diagnosis of autism; it signals the need for formal diagnostic testing (Robins & Dumont-Mathieu, 2006). Although diagnostic testing is underway in the participants who screened positive in the current cohort, the results are not yet available for reporting.
Developmental Outcome
The 2-yr developmental outcome was assessed between ages 24 and 36 mo, using the Bayley Scales of Infant and Toddler Development, 3rd edition (Bayley–III; Bayley, 2006), and was conducted by a trained psychometrician who was supervised by a neuropsychologist. Composite scores for the Language, Motor, and Cognitive subscales at 2 yr corrected age were used as secondary outcome measures.
Statistical Analysis
Categorical variables related to early social interaction (cuddling, irritability, consolability, crying, gaze aversion, visual locking, tight blinking, roving eye movements, endpoint and sustained nystagmus, obligatory following, hyperalertness, and preference for human interaction rather than interaction with toys or objects) were investigated for associations with ASD risk on the M–CHAT using χ2 analyses. Continuous variables (visual and auditory orientation) were investigated for associations with ASD risk using logistic regression. Relationships between social interaction factors and developmental outcome (Language, Cognitive, and Motor outcome on the Bayley–III) were investigated using independent samples t tests and linear regression models. All analyses were conducted using α = .05. Analyses were rerun, controlling for CRIB and brain injury.
Results
All infants from the overarching study who had neurobehavioral testing at term-equivalent age and developmental follow-up testing at age 2 yr were included in this investigation (N = 62). Table 2 lists characteristics of the infants in the study sample, which were representative of the study site’s NICU population (Pineda et al., 2014).
Table 3 lists atypical social interaction traits for the entire sample, for those who screened positive and negative for ASD, and for those with and without developmental delay at age 2 yr. The number of infants tested for each trait was less than the total sample of 62, because not all infants met the requirements for testing each trait. For example, for visual and auditory orientation traits, not all infants achieved an awake state during testing, a requirement for appropriate assessment of these traits. Of the 62 participants, 13 (21%) had a positive autism screen, and 28 (45%) had developmental delay. As a result of reports that the Bayley–III underestimates developmental delay (Anderson, De Luca, Hutchinson, Roberts, & Doyle, 2010), we chose a conservative cutoff score; developmental delay was defined as having any of the three composite scores of the Bayley–III <85. Nine (69%) of the infants who screened positive for autism also had developmental delay.
Table 3.
Atypical Traits of Infants in the Sample
Atypical Traits of Infants in the Sample×
ASD Screen, M ± SD or n (%)Developmental Delay,a M ± SD or n (%)
Total for Each TraitPositive (n = 13, 21%)Negative (n = 49, 79%)Yes (n = 28, 45%)No (n = 34, 55%)
Traitpbpb
Social interactionc
 Poor cuddle (N = 56)28 (50)4 (14)24 (86).1913 (46)15 (54).79
 Irritability (N = 57)27 (47)5 (19)22 (81).669 (33)18 (67).13
 Poor consolability (N = 33)9 (27)2 (22)7 (78).933 (33)6 (67).39
 Cry56 (97)12 (21)44 (79).4624 (43)32 (57).84
 Gaze aversion41 (71)5 (12)36 (88).0114 (34)27 (66).03
 Visual locking25 (43)4 (16)21 (84).4410 (40)15 (60).68
 Tight blinking2 (3)0 (0)2 (100).460 (0)2 (100).21
 Roving eye movements46 (79)8 (17)38 (83).2318 (39)28 (61).23
 Endpoint nystagmus21 (36)1 (5)20 (95).025 (24)16 (76).03
 Sustained nystagmus7 (12)1 (14)6 (86).663 (43)4 (57).99
 Obligatory following16 (28)2 (13)14 (87).345(31)11 (69).26
 Hyperalertness12 (21)4 (33)8 (67).234 (33)8 (67).44
Visual and auditoryc
 Auditory animate orientationd (N = 49)2.1 ± 1.02.3 ± 1.02.0 ± 1.0.612.0 ± 1.02.1 ± 1.0.67
 Visual animate orientatione (N = 50)1.9 ± 0.91.4 ± 0.92.0 ± 0.9.141.6 ± 0.82.0 ± 1.0.18
 Auditory inanimate orientationd (N = 50)2.0 ± 1.02.2 ± 1.12.0 ± 1.0.552.1 ± 1.12.0 ± 1.0.66
 Visual inanimate orientatione (N = 51)1.6 ± 0.91.5 ± 1.01.7 ± 0.9.611.5 ± 0.91.7 ± 0.9.53
 Visual preference for object over human face (N = 50)40 (80)6 (15)34 (85).2716 (40)24 (60).56
 Auditory preference for sound over human voice (N = 48)24 (50)3 (13)21 (87).448 (33)16 (67).55
Table Footer NoteNote. M = mean; SD = standard deviation.
Note. M = mean; SD = standard deviation.×
Table Footer NoteaDevelopmental delay is defined as a score of <85 on any of the three composite scores (Language, Cognitive, or Motor) on the Bayley Scales of Infant and Toddler Development, 3rd ed. bUsed independent samples t tests for continuous variables and χ2 analyses for categorical variables. cN = 58 unless otherwise noted; although the total sample size was 62, not all infants met the requirements for testing all traits. dScaled score: 1 = no auditory orientation, 2 = brightening with shifting of eyes, 3 = head turning to side of stimulus and localizing <2 out of 4 times, or 4 = head turning and finding the stimulus ≥2 out of 4 times. eScaled score: 1 = no visual tracking, 2 = focusing on object with brief following <30°, 3 = tracking ≥30° to one side, or 4 = full tracking to both sides with smooth eye movements.
Developmental delay is defined as a score of <85 on any of the three composite scores (Language, Cognitive, or Motor) on the Bayley Scales of Infant and Toddler Development, 3rd ed. bUsed independent samples t tests for continuous variables and χ2 analyses for categorical variables. cN = 58 unless otherwise noted; although the total sample size was 62, not all infants met the requirements for testing all traits. dScaled score: 1 = no auditory orientation, 2 = brightening with shifting of eyes, 3 = head turning to side of stimulus and localizing <2 out of 4 times, or 4 = head turning and finding the stimulus ≥2 out of 4 times. eScaled score: 1 = no visual tracking, 2 = focusing on object with brief following <30°, 3 = tracking ≥30° to one side, or 4 = full tracking to both sides with smooth eye movements.×
Table 3.
Atypical Traits of Infants in the Sample
Atypical Traits of Infants in the Sample×
ASD Screen, M ± SD or n (%)Developmental Delay,a M ± SD or n (%)
Total for Each TraitPositive (n = 13, 21%)Negative (n = 49, 79%)Yes (n = 28, 45%)No (n = 34, 55%)
Traitpbpb
Social interactionc
 Poor cuddle (N = 56)28 (50)4 (14)24 (86).1913 (46)15 (54).79
 Irritability (N = 57)27 (47)5 (19)22 (81).669 (33)18 (67).13
 Poor consolability (N = 33)9 (27)2 (22)7 (78).933 (33)6 (67).39
 Cry56 (97)12 (21)44 (79).4624 (43)32 (57).84
 Gaze aversion41 (71)5 (12)36 (88).0114 (34)27 (66).03
 Visual locking25 (43)4 (16)21 (84).4410 (40)15 (60).68
 Tight blinking2 (3)0 (0)2 (100).460 (0)2 (100).21
 Roving eye movements46 (79)8 (17)38 (83).2318 (39)28 (61).23
 Endpoint nystagmus21 (36)1 (5)20 (95).025 (24)16 (76).03
 Sustained nystagmus7 (12)1 (14)6 (86).663 (43)4 (57).99
 Obligatory following16 (28)2 (13)14 (87).345(31)11 (69).26
 Hyperalertness12 (21)4 (33)8 (67).234 (33)8 (67).44
Visual and auditoryc
 Auditory animate orientationd (N = 49)2.1 ± 1.02.3 ± 1.02.0 ± 1.0.612.0 ± 1.02.1 ± 1.0.67
 Visual animate orientatione (N = 50)1.9 ± 0.91.4 ± 0.92.0 ± 0.9.141.6 ± 0.82.0 ± 1.0.18
 Auditory inanimate orientationd (N = 50)2.0 ± 1.02.2 ± 1.12.0 ± 1.0.552.1 ± 1.12.0 ± 1.0.66
 Visual inanimate orientatione (N = 51)1.6 ± 0.91.5 ± 1.01.7 ± 0.9.611.5 ± 0.91.7 ± 0.9.53
 Visual preference for object over human face (N = 50)40 (80)6 (15)34 (85).2716 (40)24 (60).56
 Auditory preference for sound over human voice (N = 48)24 (50)3 (13)21 (87).448 (33)16 (67).55
Table Footer NoteNote. M = mean; SD = standard deviation.
Note. M = mean; SD = standard deviation.×
Table Footer NoteaDevelopmental delay is defined as a score of <85 on any of the three composite scores (Language, Cognitive, or Motor) on the Bayley Scales of Infant and Toddler Development, 3rd ed. bUsed independent samples t tests for continuous variables and χ2 analyses for categorical variables. cN = 58 unless otherwise noted; although the total sample size was 62, not all infants met the requirements for testing all traits. dScaled score: 1 = no auditory orientation, 2 = brightening with shifting of eyes, 3 = head turning to side of stimulus and localizing <2 out of 4 times, or 4 = head turning and finding the stimulus ≥2 out of 4 times. eScaled score: 1 = no visual tracking, 2 = focusing on object with brief following <30°, 3 = tracking ≥30° to one side, or 4 = full tracking to both sides with smooth eye movements.
Developmental delay is defined as a score of <85 on any of the three composite scores (Language, Cognitive, or Motor) on the Bayley Scales of Infant and Toddler Development, 3rd ed. bUsed independent samples t tests for continuous variables and χ2 analyses for categorical variables. cN = 58 unless otherwise noted; although the total sample size was 62, not all infants met the requirements for testing all traits. dScaled score: 1 = no auditory orientation, 2 = brightening with shifting of eyes, 3 = head turning to side of stimulus and localizing <2 out of 4 times, or 4 = head turning and finding the stimulus ≥2 out of 4 times. eScaled score: 1 = no visual tracking, 2 = focusing on object with brief following <30°, 3 = tracking ≥30° to one side, or 4 = full tracking to both sides with smooth eye movements.×
×
Early Social Interaction Factors and Autism Spectrum Disorder Risk
A positive screen for ASD on the M–CHAT was associated with absence of gaze aversion (χ2 = 5.90, p = .01, odds ratio [OR] = 5.05) and absence of endpoint nystagmus (χ2 = 4.78, p = .02, OR = 8.47) in the neonatal period. No other significant associations were found between any of the social interaction factors and ASD risk.
Early Social Interaction Factors and Developmental Outcome
Demonstrating gaze aversion was associated with better Language scores on the Bayley–III, t(55) = −3.07, p = .003. Displaying endpoint nystagmus during the visual orientation task was associated with better Language, t(61) = −3.06, p = .003; Cognitive, t(63) = −5.04, p < .001; and Motor, t(62) = −2.82, p = .006, scores. Better responses to human interaction, compared with toys or objects, was associated with better Language scores (β = 3.79, p = .02). No other significant associations between early social interaction factors and developmental outcome were observed.
Among the 58 infants with visual signs reported, gaze aversion was observed in 41 (71%), and endpoint nystagmus was observed in 21 (36%). Gaze aversion and endpoint nystagmus were related to each other (p = .013): 19 infants with endpoint nystagmus (91%) also demonstrated gaze aversion. Because endpoint nystagmus could be observed during visual scanning at the extremes of range (as in gaze aversion), the relationship between visual tracking greater than 30° to the side and endpoint nystagmus was also investigated. There were no significant associations between visual tracking at end range and endpoint nystagmus (p = .36). All associations remained significant (p < .05) after controlling for CRIB score and brain injury.
Discussion
The key finding of this study was that, contrary to our hypothesis that preterm infants who demonstrated ASD risk at age 2 yr would demonstrate alterations in early social interaction behaviors, infants who went on to screen positive for ASD were less likely to demonstrate gaze aversion and endpoint nystagmus during social interaction in the neonatal period. The absence of gaze aversion and endpoint nystagmus was also related to impaired developmental outcome. The absence of gaze aversion was associated with poorer language outcome, and the absence of endpoint nystagmus was associated with poorer cognitive, motor, and language outcomes. Core features of ASD, including gaze aversion and avoidance of social interaction, were not present during the neonatal period in the infants who later screened positive for ASD in our study. Conversely, children with later ASD risk appeared to have a pattern of visual responses that was opposite to what has been reported in ASD later in life.
Gaze aversion is defined as actively moving the head or eyes away from a visual stimulus (see Table 1; Lester & Tronick, 2005). Children with gaze aversion have been reported to demonstrate greater social disability (Jones, Carr, & Klin, 2008). Subsequently, we hypothesized that infants with later risk for ASD would demonstrate more gaze aversion during the neonatal period. Our findings did not support our hypothesis, and we found less gaze aversion among infants with later ASD risk (12%) than among infants without later risk (88%). Infants demonstrating gaze aversion during the neonatal period were 5 times more likely to screen negative for ASD.
Although children with ASD may have differences in visual and social responses from infancy through childhood, it is also possible that gaze aversion is a protective social response that children with ASD do not demonstrate, contributing to their challenges with social engagement. Gaze aversion in preterm infants has been described as a response to stress, specifically stress related to imposed social interaction that the preterm infant is not neurologically mature enough to handle (De Schuymer, De Groote, Desoete, & Roeyers, 2012; Vergara & Bigsby, 2004). Therefore, gaze aversion in preterm infants may be a normal response, and reduced gaze aversion could reflect an inability to protect oneself from social stressors that are too intense when visual orientation may be reflexive (Vergara & Bigsby, 2004). Failing to demonstrate gaze aversion during the neonatal period could be evidence of alterations in social interaction, making the infant vulnerable to social stressors during overwhelming periods of engagement. Voluntary withdrawal of social interaction, rather than gaze aversion during the neonatal period, may be observed later in the developmental progression.
The association between absence of gaze aversion in the neonatal period and ASD risk is consistent with the literature on early ASD. One study found that infants at risk for ASD clearly orient to faces among distractions and tend to select and sustain attention to faces more than do their low-risk peers (Elsabbagh et al., 2013). Other recent studies identified that eye fixation in infants later diagnosed with ASD declines at approximately age 6 mo (Jones & Klin, 2013; Ozonoff et al., 2010; Rozga et al., 2011). These studies have suggested that alterations in social interaction may not be evident until later in infancy and that infants who are later diagnosed with ASD may have a heightened social engagement response early in the developmental trajectory. Better understanding of how ASD traits emerge along the developmental pathway is an important area for future research.
Endpoint nystagmus is defined as rapid, repetitive horizontal eye movements when orienting to a stimulus at the end of the visual range (see Table 1). It is considered an abnormal or immature visual response that may result from a stressed or atypically functioning nervous system (Lester & Tronick, 2005). We hypothesized that endpoint nystagmus would be related to poor outcome, including ASD risk. However, our findings did not support this hypothesis. Infants who demonstrated endpoint nystagmus in the neonatal period were 8 times more likely to screen negative for ASD. Demonstrating endpoint nystagmus was also associated with better Language, Cognitive, and Motor scores on the Bayley–III. Previous research has identified that endpoint nystagmus can be physiologically induced in healthy people during gaze or rotation (Abadi, 2002). The visual system develops rapidly in early infancy, and more research is needed to understand the significance of endpoint nystagmus in neonates.
Previous research has demonstrated diminished nystagmus responses in children with ASD, consistent with our findings. For example, Ritvo et al. (1969)  demonstrated that children diagnosed with early infantile autism had a significantly shorter length of postrotatory nystagmus than their non-ASD peers when the lights were on. The authors suggested that this response may be due to the effect of competing sensory systems on the nystagmus response. In addition, altered nystagmus responses later in childhood have been reported in children with ASD. Scharre and Creedon (1992)  reported that children with ASD had atypical nystagmus responses, such as delayed onset and shorter duration, when looking at a handheld rotary drum. Conversely, one study reported that children diagnosed with high-functioning ASD showed no significant differences in postrotatory nystagmus (Goldberg, Landa, Lasker, Cooper, & Zee, 2000). These studies are different from our study because we observed nystagmus responses in neonates, not children, during an orientation task when vestibular input was not intended. However, it is possible that a similar mechanism that causes decreased postrotatory nystagmus in children with ASD may also cause decreased endpoint nystagmus in infants later at risk for ASD.
Our finding of a relationship between increased endpoint nystagmus and better developmental outcomes is a new contribution to the literature. The presence of endpoint nystagmus implies that infants were able to visually orient at the extremes of the visual field. Thus, infants who demonstrated endpoint nystagmus may have better orientation skills, making it plausible that they would have better developmental outcomes. However, secondary analyses investigating the relationship between visual orientation and endpoint nystagmus were not significant, indicating that infants without optimal visual orientation responses also demonstrated endpoint nystagmus. However, 91% of infants with gaze aversion demonstrated endpoint nystagmus, indicating that nystagmus responses can also be observed when infants avert their gaze at the extremes of the visual field. More research is needed to better understand endpoint nystagmus.
We hypothesized that infants with later ASD risk would have better interaction responses with toys and objects than with human interaction. However, no relationships between these early social interaction preferences and ASD risk were observed in the current cohort. Although other literature has reported no relationships between early social interaction factors or arousal-mediated attention and ASD diagnosis (Karmel et al., 2010), no other studies have investigated preferences for human versus nonhuman interaction this early in infancy.
Multiple studies have found that children with ASD orient less frequently than their peers without ASD to their names being called (Baranek, 1999; Nadig et al., 2007; Osterling et al., 2002; Werner et al., 2000; Zwaigenbaum et al., 2005). Although poorer orientation to name (which can be observed during animate auditory responses on the NNNS) among infants who later screened positive for ASD was not observed in this cohort, no other studies have investigated this connection as early as term-equivalent age. Although orienting to name with discrimination is not observed until later in development (Bayley, 2006), orientation to auditory stimuli, including name calling, occurs in the neonatal period (Lester & Tronick, 2005).
Although better auditory orientation to a human voice was not observed among infants who did not screen positive for ASD in this cohort, better orientation skills and a preference for human interaction over toys and objects were associated with better developmental outcome. Greater auditory attention to a human voice than to the sound of a rattle in infants who have better cognitive and language development is consistent with other research (Benasich & Tallal, 2002; Fellman et al., 2004). The foundations of learning are present in early human interaction, and infants who better attend to parents and others in the environment may be able to better reap the benefits of these early learning experiences.
Although this study was unable to demonstrate associations between ASD risk and neonatal social behaviors reflective of the core features of ASD, it is possible that a different pattern of social behaviors is present at term-equivalent age and that altered social interaction emerges later in infancy and childhood. It is also possible that premature infants, who are at a heightened risk of developmental impairment, may have a different developmental trajectory from that of full-term infants at risk of ASD. Identification of early behavioral differences that may signal ASD is a critical area of research, because doing so could lead to early, targeted interventions to optimize outcomes. In addition to early identification, understanding the expression of ASD across the lifespan will aid understanding of the disorder.
This study was limited by a small sample size. Only 13 infants (21%) in the cohort screened positive for ASD. In addition, the primary outcome was a screening measure, the M–CHAT, that has been criticized for overidentifying ASD risk in premature infants (Kuban et al., 2009; Luyster et al., 2011; Moore et al., 2012). Moreover, it is unclear whether the M–CHAT may have been sensitive in identifying developmental delay not specific to ASD. However, ASD is infrequently diagnosed as early as age 2 yr, and these findings contribute to better understanding the pathway to ASD diagnosis.
The social interaction factors assessed were collected during a neurobehavioral exam and were not naturally occurring. Although the components of social interaction were captured in a standardized fashion on the NNNS, the tool was not designed to investigate individual items. Preterm infants also may have medical factors that impede early neurobehavioral function, making it a challenge to distinguish ASD risk from other developmental impairment. However, controlling for brain injury and initial medical severity did not alter the findings.
The hypotheses and methodology conflate three important yet distinct skills that develop at different rates in infancy and have unique manifestations within the autism phenotype. Visual orientation, social cognition, and communication each may warrant a separate, focused investigation. In addition, the definitions of visual skills and social interaction in the current study may differ from those in other reports in the ASD literature. For example, gaze aversion has been defined elsewhere as the active avoidance of looking at faces and eyes (Senju & Johnson, 2009).
Finally, this study investigated relationships with many social interaction variables, increasing the chance of a Type I error, finding an association that does not actually exist. This study, however, is exploratory and sets the foundation for replication and extension with further longitudinal follow-up. As such, caution must be exercised in interpreting the results of this study.
Implications for Occupational Therapy Practice
The results of this study have the following implications for occupational therapy practice:
  • More research is needed to generate a better understanding of the relationship between early neurobehavioral function and the implications for long-term development.

  • Early neurobehavioral assessment can aid early identification of adverse outcomes, enabling earlier therapy.

  • Social interaction behaviors that manifest during the neonatal period appear to be related to developmental outcomes.

Conclusion
Several core features of altered social interaction during the neonatal period were not related to ASD risk in this cohort of premature infants. Instead, absence of both gaze aversion and endpoint nystagmus was observed during the neonatal period in infants who demonstrated ASD risk at age 2 yr. More research is needed to better define relationships between early social behavior and ASD risk, specifically from the neonatal period through early childhood. Understanding the expression of ASD across the lifespan can aid in discovery of the etiological mechanisms of the disorder. Additionally, early identification of ASD can enable early activation of targeted interventions to optimize outcome.
Acknowledgments
This project was supported by the National Institutes of Health (Grant ROI HD057098); the Washington University Intellectual and Developmental Disabilities Research Center (National Institute of Child Health and Human Development [NICHD] Grant P30 HD062171); the National Center for Advancing Translational Sciences (Grant UL1 TR000448), subaward (KL2 TR000450); and the Comprehensive Opportunities for Rehabilitation Research K12 award (National Center for Rehabilitation Research, NICHD, National Institute of Neurological Disorder and Stroke K12 HD055931). We thank Lauren Reynolds, Tricia Coffelt, Kelsey Dewey, Katie Ross, Laura Mazelis, Joy Bender, Hayley Chrzastowski, Odo Nwabara, Jessica Conners, and Rachel Paul.
References
Abadi, R. V. (2002). Mechanisms underlying nystagmus. Journal of the Royal Society of Medicine, 95, 231–234. http://dx.doi.org/10.1258/jrsm.95.5.231 [Article] [PubMed]
Abadi, R. V. (2002). Mechanisms underlying nystagmus. Journal of the Royal Society of Medicine, 95, 231–234. http://dx.doi.org/10.1258/jrsm.95.5.231 [Article] [PubMed]×
Adrien, J. L., Lenoir, P., Martineau, J., Perrot, A., Hameury, L., Larmande, C., & Sauvage, D. (1993). Blind ratings of early symptoms of autism based upon family home movies. Journal of the American Academy of Child and Adolescent Psychiatry, 32, 617–626. http://dx.doi.org/10.1097/00004583-199305000-00019 [Article] [PubMed]
Adrien, J. L., Lenoir, P., Martineau, J., Perrot, A., Hameury, L., Larmande, C., & Sauvage, D. (1993). Blind ratings of early symptoms of autism based upon family home movies. Journal of the American Academy of Child and Adolescent Psychiatry, 32, 617–626. http://dx.doi.org/10.1097/00004583-199305000-00019 [Article] [PubMed]×
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.×
Anderson, P. J., De Luca, C. R., Hutchinson, E., Roberts, G., & Doyle, L. W.; Victorian Infant Collaborative Group. (2010). Underestimation of developmental delay by the new Bayley–III Scale. Archives of Pediatrics and Adolescent Medicine, 164, 352–356. http://dx.doi.org/10.1001/archpediatrics.2010.20 [Article] [PubMed]
Anderson, P. J., De Luca, C. R., Hutchinson, E., Roberts, G., & Doyle, L. W.; Victorian Infant Collaborative Group. (2010). Underestimation of developmental delay by the new Bayley–III Scale. Archives of Pediatrics and Adolescent Medicine, 164, 352–356. http://dx.doi.org/10.1001/archpediatrics.2010.20 [Article] [PubMed]×
Arpino, C., Compagnone, E., Montanaro, M. L., Cacciatore, D., De Luca, A., Cerulli, A., . . . Curatolo, P. (2010). Preterm birth and neurodevelopmental outcome: A review. Child’s Nervous System, 26, 1139–1149. http://dx.doi.org/10.1007/s00381-010-1125-y [Article] [PubMed]
Arpino, C., Compagnone, E., Montanaro, M. L., Cacciatore, D., De Luca, A., Cerulli, A., . . . Curatolo, P. (2010). Preterm birth and neurodevelopmental outcome: A review. Child’s Nervous System, 26, 1139–1149. http://dx.doi.org/10.1007/s00381-010-1125-y [Article] [PubMed]×
Baranek, G. T. (1999). Autism during infancy: A retrospective video analysis of sensory–motor and social behaviors at 9–12 months of age. Journal of Autism and Developmental Disorders, 29, 213–224. http://dx.doi.org/10.1023/A:1023080005650 [Article] [PubMed]
Baranek, G. T. (1999). Autism during infancy: A retrospective video analysis of sensory–motor and social behaviors at 9–12 months of age. Journal of Autism and Developmental Disorders, 29, 213–224. http://dx.doi.org/10.1023/A:1023080005650 [Article] [PubMed]×
Barbaro, J., & Dissanayake, C. (2013). Early markers of autism spectrum disorders in infants and toddlers prospectively identified in the Social Attention and Communication Study. Autism, 17, 64–86. http://dx.doi.org/10.1177/1362361312442597 [Article] [PubMed]
Barbaro, J., & Dissanayake, C. (2013). Early markers of autism spectrum disorders in infants and toddlers prospectively identified in the Social Attention and Communication Study. Autism, 17, 64–86. http://dx.doi.org/10.1177/1362361312442597 [Article] [PubMed]×
Bayley, N. (2006). Bayley Scales of Infant and Toddler Development (3rd ed.). San Antonio, TX: Harcourt Assessment.
Bayley, N. (2006). Bayley Scales of Infant and Toddler Development (3rd ed.). San Antonio, TX: Harcourt Assessment.×
Benasich, A. A., & Tallal, P. (2002). Infant discrimination of rapid auditory cues predicts later language impairment. Behavioural Brain Research, 136, 31–49. http://dx.doi.org/10.1016/S0166-4328(02)00098-0 [Article] [PubMed]
Benasich, A. A., & Tallal, P. (2002). Infant discrimination of rapid auditory cues predicts later language impairment. Behavioural Brain Research, 136, 31–49. http://dx.doi.org/10.1016/S0166-4328(02)00098-0 [Article] [PubMed]×
Bhat, A. N., Landa, R. J., & Galloway, J. C. (2011). Current perspectives on motor functioning in infants, children, and adults with autism spectrum disorders. Physical Therapy, 91, 1116–1129. http://dx.doi.org/10.2522/ptj.20100294 [Article] [PubMed]
Bhat, A. N., Landa, R. J., & Galloway, J. C. (2011). Current perspectives on motor functioning in infants, children, and adults with autism spectrum disorders. Physical Therapy, 91, 1116–1129. http://dx.doi.org/10.2522/ptj.20100294 [Article] [PubMed]×
Blumberg, S. J., Bramlett, M. D., Kogan, M. D., Schieve, L. A., Jones, J. R., & Lu, M. C. (2013). Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011–2012. National Health Statistics Reports, 65, 1–11. [PubMed]
Blumberg, S. J., Bramlett, M. D., Kogan, M. D., Schieve, L. A., Jones, J. R., & Lu, M. C. (2013). Changes in prevalence of parent-reported autism spectrum disorder in school-aged U.S. children: 2007 to 2011–2012. National Health Statistics Reports, 65, 1–11. [PubMed]×
Bryson, S. E., Rogers, S. J., & Fombonne, E. (2003). Autism spectrum disorders: Early detection, intervention, education, and psychopharmacological management. Canadian Journal of Psychiatry, 48, 506–516.
Bryson, S. E., Rogers, S. J., & Fombonne, E. (2003). Autism spectrum disorders: Early detection, intervention, education, and psychopharmacological management. Canadian Journal of Psychiatry, 48, 506–516.×
Centers for Disease Control and Prevention. (2013). Autism spectrum disorder (ASD): Data and statistics. Retrieved from http://www.cdc.gov/ncbddd/autism/data.html
Centers for Disease Control and Prevention. (2013). Autism spectrum disorder (ASD): Data and statistics. Retrieved from http://www.cdc.gov/ncbddd/autism/data.html×
Chawarska, K., Macari, S., & Shic, F. (2013). Decreased spontaneous attention to social scenes in 6-month-old infants later diagnosed with autism spectrum disorders. Biological Psychiatry, 74, 195–203. http://dx.doi.org/10.1016/j.biopsych.2012.11.022 [Article] [PubMed]
Chawarska, K., Macari, S., & Shic, F. (2013). Decreased spontaneous attention to social scenes in 6-month-old infants later diagnosed with autism spectrum disorders. Biological Psychiatry, 74, 195–203. http://dx.doi.org/10.1016/j.biopsych.2012.11.022 [Article] [PubMed]×
Clifford, S. M., & Dissanayake, C. (2008). The early development of joint attention in infants with autistic disorder using home video observations and parental interview. Journal of Autism and Developmental Disorders, 38, 791–805. http://dx.doi.org/10.1007/s10803-007-0444-7 [Article] [PubMed]
Clifford, S. M., & Dissanayake, C. (2008). The early development of joint attention in infants with autistic disorder using home video observations and parental interview. Journal of Autism and Developmental Disorders, 38, 791–805. http://dx.doi.org/10.1007/s10803-007-0444-7 [Article] [PubMed]×
Clifford, S., Dissanayake, C., Bui, Q. M., Huggins, R., Taylor, A. K., & Loesch, D. Z. (2007). Autism spectrum phenotype in males and females with fragile X full mutation and premutation. Journal of Autism and Developmental Disorders, 37, 738–747. http://dx.doi.org/10.1007/s10803-006-0205-z [Article] [PubMed]
Clifford, S., Dissanayake, C., Bui, Q. M., Huggins, R., Taylor, A. K., & Loesch, D. Z. (2007). Autism spectrum phenotype in males and females with fragile X full mutation and premutation. Journal of Autism and Developmental Disorders, 37, 738–747. http://dx.doi.org/10.1007/s10803-006-0205-z [Article] [PubMed]×
Cornew, L., Dobkins, K. R., Akshoomoff, N., McCleery, J. P., & Carver, L. J. (2012). Atypical social referencing in infant siblings of children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 42, 2611–2621. http://dx.doi.org/10.1007/s10803-012-1518-8 [Article] [PubMed]
Cornew, L., Dobkins, K. R., Akshoomoff, N., McCleery, J. P., & Carver, L. J. (2012). Atypical social referencing in infant siblings of children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 42, 2611–2621. http://dx.doi.org/10.1007/s10803-012-1518-8 [Article] [PubMed]×
De Schuymer, L., De Groote, I., Desoete, A., & Roeyers, H. (2012). Gaze aversion during social interaction in preterm infants: A function of attention skills. Infant Behavior and Development, 35, 129–139. http://dx.doi.org/10.1016/j.infbeh.2011.08.002 [Article] [PubMed]
De Schuymer, L., De Groote, I., Desoete, A., & Roeyers, H. (2012). Gaze aversion during social interaction in preterm infants: A function of attention skills. Infant Behavior and Development, 35, 129–139. http://dx.doi.org/10.1016/j.infbeh.2011.08.002 [Article] [PubMed]×
Eikeseth, S., Klintwall, L., Jahr, E., & Karlsson, P. (2012). Outcome for children with autism receiving early and intensive behavioral intervention in mainstream preschool and kindergarten settings. Research in Autism Spectrum Disorders, 6, 829–835. http://dx.doi.org/10.1016/j.rasd.2011.09.002 [Article]
Eikeseth, S., Klintwall, L., Jahr, E., & Karlsson, P. (2012). Outcome for children with autism receiving early and intensive behavioral intervention in mainstream preschool and kindergarten settings. Research in Autism Spectrum Disorders, 6, 829–835. http://dx.doi.org/10.1016/j.rasd.2011.09.002 [Article] ×
Elsabbagh, M., Bedford, R., Senju, A., Charman, T., Pickles, A., & Johnson, M. H.; BASIS Team. (2014). What you see is what you get: Contextual modulation of face scanning in typical and atypical development. Social Cognitive and Affective Neuroscience, 9, 538–543. [Article] [PubMed]
Elsabbagh, M., Bedford, R., Senju, A., Charman, T., Pickles, A., & Johnson, M. H.; BASIS Team. (2014). What you see is what you get: Contextual modulation of face scanning in typical and atypical development. Social Cognitive and Affective Neuroscience, 9, 538–543. [Article] [PubMed]×
Elsabbagh, M., Gliga, T., Pickles, A., Hudry, K., Charman, T., & Johnson, M. H.; BASIS Team. (2013). The development of face orienting mechanisms in infants at-risk for autism. Behavioural Brain Research, 251, 147–154. http://dx.doi.org/10.1016/j.bbr.2012.07.030 [Article] [PubMed]
Elsabbagh, M., Gliga, T., Pickles, A., Hudry, K., Charman, T., & Johnson, M. H.; BASIS Team. (2013). The development of face orienting mechanisms in infants at-risk for autism. Behavioural Brain Research, 251, 147–154. http://dx.doi.org/10.1016/j.bbr.2012.07.030 [Article] [PubMed]×
Elsabbagh, M., Mercure, E., Hudry, K., Chandler, S., Pasco, G., Charman, T., . . . Johnson, M. H.; BASIS Team. (2012). Infant neural sensitivity to dynamic eye gaze is associated with later emerging autism. Current Biology, 22, 338–342. http://dx.doi.org/10.1016/j.cub.2011.12.056 [Article] [PubMed]
Elsabbagh, M., Mercure, E., Hudry, K., Chandler, S., Pasco, G., Charman, T., . . . Johnson, M. H.; BASIS Team. (2012). Infant neural sensitivity to dynamic eye gaze is associated with later emerging autism. Current Biology, 22, 338–342. http://dx.doi.org/10.1016/j.cub.2011.12.056 [Article] [PubMed]×
Fellman, V., Kushnerenko, E., Mikkola, K., Ceponiene, R., Leipala, J., & Naatanen, R. (2004). Atypical auditory event-related potentials in preterm infants during the first year of life: A possible sign of cognitive dysfunction. Pediatric Research, 56, 291–297. http://dx.doi.org/10.1203/01.PDR.0000132750.97066.B9 [Article] [PubMed]
Fellman, V., Kushnerenko, E., Mikkola, K., Ceponiene, R., Leipala, J., & Naatanen, R. (2004). Atypical auditory event-related potentials in preterm infants during the first year of life: A possible sign of cognitive dysfunction. Pediatric Research, 56, 291–297. http://dx.doi.org/10.1203/01.PDR.0000132750.97066.B9 [Article] [PubMed]×
Ferrari, F., Cioni, G., & Prechtl, H. F. (1990). Qualitative changes of general movements in preterm infants with brain lesions. Early Human Development, 23, 193–231. http://dx.doi.org/10.1016/0378-3782(90)90013-9 [Article] [PubMed]
Ferrari, F., Cioni, G., & Prechtl, H. F. (1990). Qualitative changes of general movements in preterm infants with brain lesions. Early Human Development, 23, 193–231. http://dx.doi.org/10.1016/0378-3782(90)90013-9 [Article] [PubMed]×
Flanagan, J. E., Landa, R., Bhat, A., & Bauman, M. (2012). Head lag in infants at risk for autism: A preliminary study. American Journal of Occupational Therapy, 66, 577–585. http://dx.doi.org/10.5014/ajot.2012.004192 [Article] [PubMed]
Flanagan, J. E., Landa, R., Bhat, A., & Bauman, M. (2012). Head lag in infants at risk for autism: A preliminary study. American Journal of Occupational Therapy, 66, 577–585. http://dx.doi.org/10.5014/ajot.2012.004192 [Article] [PubMed]×
Goldberg, M. C., Landa, R., Lasker, A., Cooper, L., & Zee, D. S. (2000). Evidence of normal cerebellar control of the vestibulo-ocular reflex (VOR) in children with high-functioning autism. Journal of Autism and Developmental Disorders, 30, 519–524. http://dx.doi.org/10.1023/A:1005631225367 [Article] [PubMed]
Goldberg, M. C., Landa, R., Lasker, A., Cooper, L., & Zee, D. S. (2000). Evidence of normal cerebellar control of the vestibulo-ocular reflex (VOR) in children with high-functioning autism. Journal of Autism and Developmental Disorders, 30, 519–524. http://dx.doi.org/10.1023/A:1005631225367 [Article] [PubMed]×
Hutman, T., Rozga, A., DeLaurentis, A. D., Barnwell, J. M., Sugar, C. A., & Sigman, M. (2010). Response to distress in infants at risk for autism: A prospective longitudinal study. Journal of Child Psychology and Psychiatry, 51, 1010–1020. http://dx.doi.org/10.1111/j.1469-7610.2010.02270.x [Article] [PubMed]
Hutman, T., Rozga, A., DeLaurentis, A. D., Barnwell, J. M., Sugar, C. A., & Sigman, M. (2010). Response to distress in infants at risk for autism: A prospective longitudinal study. Journal of Child Psychology and Psychiatry, 51, 1010–1020. http://dx.doi.org/10.1111/j.1469-7610.2010.02270.x [Article] [PubMed]×
Ibanez, L. V., Messinger, D. S., Newell, L., Lambert, B., & Sheskin, M. (2008). Visual disengagement in the infant siblings of children with an autism spectrum disorder (ASD). Autism, 12, 473–485. http://dx.doi.org/10.1177/1362361308094504 [Article] [PubMed]
Ibanez, L. V., Messinger, D. S., Newell, L., Lambert, B., & Sheskin, M. (2008). Visual disengagement in the infant siblings of children with an autism spectrum disorder (ASD). Autism, 12, 473–485. http://dx.doi.org/10.1177/1362361308094504 [Article] [PubMed]×
Iverson, J. M., & Wozniak, R. H. (2007). Variation in vocal–motor development in infant siblings of children with autism. Journal of Autism and Developmental Disorders, 37, 158–170. http://dx.doi.org/10.1007/s10803-006-0339-z [Article] [PubMed]
Iverson, J. M., & Wozniak, R. H. (2007). Variation in vocal–motor development in infant siblings of children with autism. Journal of Autism and Developmental Disorders, 37, 158–170. http://dx.doi.org/10.1007/s10803-006-0339-z [Article] [PubMed]×
Johnson, S., Hollis, C., Kochhar, P., Hennessy, E., Wolke, D., & Marlow, N. (2010). Autism spectrum disorders in extremely preterm children. Journal of Pediatrics, 156, 525–531. http://dx.doi.org/10.1016/j.jpeds.2009.10.041 [Article] [PubMed]
Johnson, S., Hollis, C., Kochhar, P., Hennessy, E., Wolke, D., & Marlow, N. (2010). Autism spectrum disorders in extremely preterm children. Journal of Pediatrics, 156, 525–531. http://dx.doi.org/10.1016/j.jpeds.2009.10.041 [Article] [PubMed]×
Jones, W., Carr, K., & Klin, A. (2008). Absence of preferential looking to the eyes of approaching adults predicts level of social disability in 2-year-old toddlers with autism spectrum disorder. Archives of General Psychiatry, 65, 946–954. http://dx.doi.org/10.1001/archpsyc.65.8.946 [Article] [PubMed]
Jones, W., Carr, K., & Klin, A. (2008). Absence of preferential looking to the eyes of approaching adults predicts level of social disability in 2-year-old toddlers with autism spectrum disorder. Archives of General Psychiatry, 65, 946–954. http://dx.doi.org/10.1001/archpsyc.65.8.946 [Article] [PubMed]×
Jones, W., & Klin, A. (2013). Attention to eyes is present but in decline in 2–6-month-old infants later diagnosed with autism. Nature, 504, 427–431. http://dx.doi.org/10.1038/nature12715 [Article] [PubMed]
Jones, W., & Klin, A. (2013). Attention to eyes is present but in decline in 2–6-month-old infants later diagnosed with autism. Nature, 504, 427–431. http://dx.doi.org/10.1038/nature12715 [Article] [PubMed]×
Karmel, B. Z., Gardner, J. M., Meade, L. S., Cohen, I. L., London, E., Flory, M. J., . . . Harin, A. (2010). Early medical and behavioral characteristics of NICU infants later classified with ASD. Pediatrics, 126, 457–467. http://dx.doi.org/10.1542/peds.2009-2680 [Article] [PubMed]
Karmel, B. Z., Gardner, J. M., Meade, L. S., Cohen, I. L., London, E., Flory, M. J., . . . Harin, A. (2010). Early medical and behavioral characteristics of NICU infants later classified with ASD. Pediatrics, 126, 457–467. http://dx.doi.org/10.1542/peds.2009-2680 [Article] [PubMed]×
Kuban, K. C., O’Shea, T. M., Allred, E. N., Tager-Flusberg, H., Goldstein, D. J., & Leviton, A. (2009). Positive screening on the Modified Checklist for Autism in Toddlers (M–CHAT) in extremely low gestational age newborns. Journal of Pediatrics, 154, 535–540. http://dx.doi.org/10.1016/j.jpeds.2008.10.011 [Article] [PubMed]
Kuban, K. C., O’Shea, T. M., Allred, E. N., Tager-Flusberg, H., Goldstein, D. J., & Leviton, A. (2009). Positive screening on the Modified Checklist for Autism in Toddlers (M–CHAT) in extremely low gestational age newborns. Journal of Pediatrics, 154, 535–540. http://dx.doi.org/10.1016/j.jpeds.2008.10.011 [Article] [PubMed]×
Lester, B. M., & Tronick, F. (2005). NICU Network Neurobehavioral Scale (NNNS) manual. Baltimore: Paul H. Brookes.
Lester, B. M., & Tronick, F. (2005). NICU Network Neurobehavioral Scale (NNNS) manual. Baltimore: Paul H. Brookes.×
Levy, S. E., Giarelli, E., Lee, L.-C., Schieve, L. A., Kirby, R. S., Cunniff, C., . . . Rice, C. E. (2010). Autism spectrum disorder and co-occurring developmental, psychiatric, and medical conditions among children in multiple populations of the United States. Journal of Developmental and Behavioral Pediatrics, 31, 267–275. http://dx.doi.org/10.1097/DBP.1090b1013e3181d1095d1003b. [Article] [PubMed]
Levy, S. E., Giarelli, E., Lee, L.-C., Schieve, L. A., Kirby, R. S., Cunniff, C., . . . Rice, C. E. (2010). Autism spectrum disorder and co-occurring developmental, psychiatric, and medical conditions among children in multiple populations of the United States. Journal of Developmental and Behavioral Pediatrics, 31, 267–275. http://dx.doi.org/10.1097/DBP.1090b1013e3181d1095d1003b. [Article] [PubMed]×
Luyster, R. J., Kuban, K. C., O’Shea, T. M., Paneth, N., Allred, E. N., & Leviton, A.; ELGAN Study Investigators. (2011). The Modified Checklist for Autism in Toddlers in extremely low gestational age newborns: Individual items associated with motor, cognitive, vision and hearing limitations. Paediatric and Perinatal Epidemiology, 25, 366–376. http://dx.doi.org/10.1111/j.1365-3016.2010.01187.x [Article] [PubMed]
Luyster, R. J., Kuban, K. C., O’Shea, T. M., Paneth, N., Allred, E. N., & Leviton, A.; ELGAN Study Investigators. (2011). The Modified Checklist for Autism in Toddlers in extremely low gestational age newborns: Individual items associated with motor, cognitive, vision and hearing limitations. Paediatric and Perinatal Epidemiology, 25, 366–376. http://dx.doi.org/10.1111/j.1365-3016.2010.01187.x [Article] [PubMed]×
Mitchell, S., Brian, J., Zwaigenbaum, L., Roberts, W., Szatmari, P., Smith, I., & Bryson, S. (2006). Early language and communication development of infants later diagnosed with autism spectrum disorder. Journal of Developmental and Behavioral Pediatrics, 27(Suppl.), S69–S78. http://dx.doi.org/10.1097/00004703-200604002-00004 [Article] [PubMed]
Mitchell, S., Brian, J., Zwaigenbaum, L., Roberts, W., Szatmari, P., Smith, I., & Bryson, S. (2006). Early language and communication development of infants later diagnosed with autism spectrum disorder. Journal of Developmental and Behavioral Pediatrics, 27(Suppl.), S69–S78. http://dx.doi.org/10.1097/00004703-200604002-00004 [Article] [PubMed]×
Moore, T., Johnson, S., Hennessy, E., & Marlow, N. (2012). Screening for autism in extremely preterm infants: Problems in interpretation. Developmental Medicine and Child Neurology, 54, 514–520. http://dx.doi.org/10.1111/j.1469-8749.2012.04265.x [Article] [PubMed]
Moore, T., Johnson, S., Hennessy, E., & Marlow, N. (2012). Screening for autism in extremely preterm infants: Problems in interpretation. Developmental Medicine and Child Neurology, 54, 514–520. http://dx.doi.org/10.1111/j.1469-8749.2012.04265.x [Article] [PubMed]×
Movsas, T. Z., & Paneth, N. (2012). The effect of gestational age on symptom severity in children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 42, 2431–2439. http://dx.doi.org/10.1007/s10803-012-1501-4 [Article] [PubMed]
Movsas, T. Z., & Paneth, N. (2012). The effect of gestational age on symptom severity in children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 42, 2431–2439. http://dx.doi.org/10.1007/s10803-012-1501-4 [Article] [PubMed]×
Nadig, A. S., Ozonoff, S., Young, G. S., Rozga, A., Sigman, M., & Rogers, S. J. (2007). A prospective study of response to name in infants at risk for autism. Archives of Pediatrics and Adolescent Medicine, 161, 378–383. http://dx.doi.org/10.1001/archpedi.161.4.378 [Article] [PubMed]
Nadig, A. S., Ozonoff, S., Young, G. S., Rozga, A., Sigman, M., & Rogers, S. J. (2007). A prospective study of response to name in infants at risk for autism. Archives of Pediatrics and Adolescent Medicine, 161, 378–383. http://dx.doi.org/10.1001/archpedi.161.4.378 [Article] [PubMed]×
Osterling, J. A., Dawson, G., & Munson, J. A. (2002). Early recognition of 1-year-old infants with autism spectrum disorder versus mental retardation. Development and Psychopathology, 14, 239–251. http://dx.doi.org/10.1017/S0954579402002031 [Article] [PubMed]
Osterling, J. A., Dawson, G., & Munson, J. A. (2002). Early recognition of 1-year-old infants with autism spectrum disorder versus mental retardation. Development and Psychopathology, 14, 239–251. http://dx.doi.org/10.1017/S0954579402002031 [Article] [PubMed]×
Ozonoff, S., Iosif, A. M., Baguio, F., Cook, I. C., Hill, M. M., Hutman, T., . . . Young, G. S. (2010). A prospective study of the emergence of early behavioral signs of autism. Journal of the American Academy of Child and Adolescent Psychiatry, 49, 256–266. [PubMed]
Ozonoff, S., Iosif, A. M., Baguio, F., Cook, I. C., Hill, M. M., Hutman, T., . . . Young, G. S. (2010). A prospective study of the emergence of early behavioral signs of autism. Journal of the American Academy of Child and Adolescent Psychiatry, 49, 256–266. [PubMed]×
Peters-Scheffer, N., Didden, R., Korzilius, H., & Sturmey, P. (2011). A meta-analytic study on the effectiveness of comprehensive ABA-based early intervention programs for children with autism spectrum disorders. Research in Autism Spectrum Disorders, 5, 60–69. http://dx.doi.org/10.1016/j.rasd.2010.03.011 [Article]
Peters-Scheffer, N., Didden, R., Korzilius, H., & Sturmey, P. (2011). A meta-analytic study on the effectiveness of comprehensive ABA-based early intervention programs for children with autism spectrum disorders. Research in Autism Spectrum Disorders, 5, 60–69. http://dx.doi.org/10.1016/j.rasd.2010.03.011 [Article] ×
Phagava, H., Muratori, F., Einspieler, C., Maestro, S., Apicella, F., Guzzetta, A., . . . Cioni, G. (2008). General movements in infants with autism spectrum disorders. Georgian Medical News, 3(156), 100–105.
Phagava, H., Muratori, F., Einspieler, C., Maestro, S., Apicella, F., Guzzetta, A., . . . Cioni, G. (2008). General movements in infants with autism spectrum disorders. Georgian Medical News, 3(156), 100–105.×
Pineda, R. G., Neil, J., Dierker, D., Smyser, C. D., Wallendorf, M., Kidokoro, H., . . . Inder, T. (2014). Alterations in brain structure and neurodevelopmental outcome in preterm infants hospitalized in different neonatal intensive care unit environments. Journal of Pediatrics, 164, 52–60. http://dx.doi.org/10.1016/j.jpeds.2013.08.047
Pineda, R. G., Neil, J., Dierker, D., Smyser, C. D., Wallendorf, M., Kidokoro, H., . . . Inder, T. (2014). Alterations in brain structure and neurodevelopmental outcome in preterm infants hospitalized in different neonatal intensive care unit environments. Journal of Pediatrics, 164, 52–60. http://dx.doi.org/10.1016/j.jpeds.2013.08.047×
Reichow, B. (2012). Overview of meta-analyses on early intensive behavioral intervention for young children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 42, 512–520. http://dx.doi.org/10.1007/s10803-011-1218-9 [Article] [PubMed]
Reichow, B. (2012). Overview of meta-analyses on early intensive behavioral intervention for young children with autism spectrum disorders. Journal of Autism and Developmental Disorders, 42, 512–520. http://dx.doi.org/10.1007/s10803-011-1218-9 [Article] [PubMed]×
Ritvo, E. R., Ornitz, E. M., Eviatar, A., Markham, C. H., Brown, M. B., & Mason, A. (1969). Decreased postrotatory nystagmus in early infantile autism. Neurology, 19, 653–658. http://dx.doi.org/10.1212/WNL.19.7.653 [Article] [PubMed]
Ritvo, E. R., Ornitz, E. M., Eviatar, A., Markham, C. H., Brown, M. B., & Mason, A. (1969). Decreased postrotatory nystagmus in early infantile autism. Neurology, 19, 653–658. http://dx.doi.org/10.1212/WNL.19.7.653 [Article] [PubMed]×
Robins, D. L., & Dumont-Mathieu, T. M. (2006). Early screening for autism spectrum disorders: Update on the Modified Checklist for Autism in Toddlers and other measures. Journal of Developmental and Behavioral Pediatrics, 27(Suppl.), S111–S119. http://dx.doi.org/10.1097/00004703-200604002-00009 [Article] [PubMed]
Robins, D. L., & Dumont-Mathieu, T. M. (2006). Early screening for autism spectrum disorders: Update on the Modified Checklist for Autism in Toddlers and other measures. Journal of Developmental and Behavioral Pediatrics, 27(Suppl.), S111–S119. http://dx.doi.org/10.1097/00004703-200604002-00009 [Article] [PubMed]×
Robins, D. L., Fein, D., Barton, M. L., & Green, J. A. (2001). The Modified Checklist for Autism in Toddlers: An initial study investigating the early detection of autism and pervasive developmental disorders. Journal of Autism and Developmental Disorders, 31, 131–144. http://dx.doi.org/10.1023/A:1010738829569 [Article] [PubMed]
Robins, D. L., Fein, D., Barton, M. L., & Green, J. A. (2001). The Modified Checklist for Autism in Toddlers: An initial study investigating the early detection of autism and pervasive developmental disorders. Journal of Autism and Developmental Disorders, 31, 131–144. http://dx.doi.org/10.1023/A:1010738829569 [Article] [PubMed]×
Rozga, A., Hutman, T., Young, G. S., Rogers, S. J., Ozonoff, S., Dapretto, M., & Sigman, M. (2011). Behavioral profiles of affected and unaffected siblings of children with autism: Contribution of measures of mother–infant interaction and nonverbal communication. Journal of Autism and Developmental Disorders, 41, 287–301. http://dx.doi.org/10.1007/s10803-010-1051-6 [Article] [PubMed]
Rozga, A., Hutman, T., Young, G. S., Rogers, S. J., Ozonoff, S., Dapretto, M., & Sigman, M. (2011). Behavioral profiles of affected and unaffected siblings of children with autism: Contribution of measures of mother–infant interaction and nonverbal communication. Journal of Autism and Developmental Disorders, 41, 287–301. http://dx.doi.org/10.1007/s10803-010-1051-6 [Article] [PubMed]×
Scharre, J. E., & Creedon, M. P. (1992). Assessment of visual function in autistic children. Optometry and Vision Science, 69, 433–439. http://dx.doi.org/10.1097/00006324-199206000-00004 [Article] [PubMed]
Scharre, J. E., & Creedon, M. P. (1992). Assessment of visual function in autistic children. Optometry and Vision Science, 69, 433–439. http://dx.doi.org/10.1097/00006324-199206000-00004 [Article] [PubMed]×
Senju, A., & Johnson, M. H. (2009). Atypical eye contact in autism: Models, mechanisms and development. Neuroscience and Biobehavioral Reviews, 33, 1204–1214. http://dx.doi.org/10.1016/j.neubiorev.2009.06.001 [Article] [PubMed]
Senju, A., & Johnson, M. H. (2009). Atypical eye contact in autism: Models, mechanisms and development. Neuroscience and Biobehavioral Reviews, 33, 1204–1214. http://dx.doi.org/10.1016/j.neubiorev.2009.06.001 [Article] [PubMed]×
Shattuck, P. T., Durkin, M., Maenner, M., Newschaffer, C., Mandell, D. S., Wiggins, L., . . . Cuniff, C. (2009). Timing of identification among children with an autism spectrum disorder: Findings from a population-based surveillance study. Journal of the American Academy of Child and Adolescent Psychiatry, 48, 474–483. http://dx.doi.org/10.1097/CHI.0b013e31819b3848 [Article] [PubMed]
Shattuck, P. T., Durkin, M., Maenner, M., Newschaffer, C., Mandell, D. S., Wiggins, L., . . . Cuniff, C. (2009). Timing of identification among children with an autism spectrum disorder: Findings from a population-based surveillance study. Journal of the American Academy of Child and Adolescent Psychiatry, 48, 474–483. http://dx.doi.org/10.1097/CHI.0b013e31819b3848 [Article] [PubMed]×
Snow, A. V., & Lecavalier, L. (2008). Sensitivity and specificity of the Modified Checklist for Autism in Toddlers and the Social Communication Questionnaire in preschoolers suspected of having pervasive developmental disorders. Autism, 12, 627–644. http://dx.doi.org/10.1177/1362361308097116 [Article] [PubMed]
Snow, A. V., & Lecavalier, L. (2008). Sensitivity and specificity of the Modified Checklist for Autism in Toddlers and the Social Communication Questionnaire in preschoolers suspected of having pervasive developmental disorders. Autism, 12, 627–644. http://dx.doi.org/10.1177/1362361308097116 [Article] [PubMed]×
Tarnow-Mordi, W., & Parry, G. (1993). The CRIB score. Lancet, 342, 1365. http://dx.doi.org/10.1016/0140-6736(93)92276-Y [Article] [PubMed]
Tarnow-Mordi, W., & Parry, G. (1993). The CRIB score. Lancet, 342, 1365. http://dx.doi.org/10.1016/0140-6736(93)92276-Y [Article] [PubMed]×
Vergara, E. R., & Bigsby, R. (2004). Developmental and therapeutic interventions in the NICU. Baltimore: Paul H. Brookes.
Vergara, E. R., & Bigsby, R. (2004). Developmental and therapeutic interventions in the NICU. Baltimore: Paul H. Brookes.×
Wan, M. W., Green, J., Elsabbagh, M., Johnson, M., Charman, T., & Plummer, F.; BASIS Team. (2013). Quality of interaction between at-risk infants and caregiver at 12–15 months is associated with 3-year autism outcome. Journal of Child Psychology and Psychiatry, 54, 763–771. http://dx.doi.org/10.1111/jcpp.12032 [Article] [PubMed]
Wan, M. W., Green, J., Elsabbagh, M., Johnson, M., Charman, T., & Plummer, F.; BASIS Team. (2013). Quality of interaction between at-risk infants and caregiver at 12–15 months is associated with 3-year autism outcome. Journal of Child Psychology and Psychiatry, 54, 763–771. http://dx.doi.org/10.1111/jcpp.12032 [Article] [PubMed]×
Werner, E., Dawson, G., Osterling, J., & Dinno, N. (2000). Brief report: Recognition of autism spectrum disorder before one year of age: A retrospective study based on home videotapes. Journal of Autism and Developmental Disorders, 30, 157–162. http://dx.doi.org/10.1023/A:1005463707029 [Article] [PubMed]
Werner, E., Dawson, G., Osterling, J., & Dinno, N. (2000). Brief report: Recognition of autism spectrum disorder before one year of age: A retrospective study based on home videotapes. Journal of Autism and Developmental Disorders, 30, 157–162. http://dx.doi.org/10.1023/A:1005463707029 [Article] [PubMed]×
Yamada, Y., Yoshida, F., Hemmi, H., Ito, M., Kakita, H., Yoshikawa, T., . . . Nakanishi, K. (2011). Atypical social development in neonatal intensive care unit survivors at 12 months. Pediatrics International, 53, 858–866. http://dx.doi.org/10.1111/j.1442-200X.2011.03367.x [Article] [PubMed]
Yamada, Y., Yoshida, F., Hemmi, H., Ito, M., Kakita, H., Yoshikawa, T., . . . Nakanishi, K. (2011). Atypical social development in neonatal intensive care unit survivors at 12 months. Pediatrics International, 53, 858–866. http://dx.doi.org/10.1111/j.1442-200X.2011.03367.x [Article] [PubMed]×
Yirmiya, N., Gamliel, I., Pilowsky, T., Feldman, R., Baron-Cohen, S., & Sigman, M. (2006). The development of siblings of children with autism at 4 and 14 months: Social engagement, communication, and cognition. Journal of Child Psychology and Psychiatry, 47, 511–523. http://dx.doi.org/10.1111/j.1469-7610.2005.01528.x [Article] [PubMed]
Yirmiya, N., Gamliel, I., Pilowsky, T., Feldman, R., Baron-Cohen, S., & Sigman, M. (2006). The development of siblings of children with autism at 4 and 14 months: Social engagement, communication, and cognition. Journal of Child Psychology and Psychiatry, 47, 511–523. http://dx.doi.org/10.1111/j.1469-7610.2005.01528.x [Article] [PubMed]×
Zwaigenbaum, L., Bryson, S., Rogers, T., Roberts, W., Brian, J., & Szatmari, P. (2005). Behavioral manifestations of autism in the first year of life. International Journal of Developmental Neuroscience, 23, 143–152. http://dx.doi.org/10.1016/j.ijdevneu.2004.05.001 [Article] [PubMed]
Zwaigenbaum, L., Bryson, S., Rogers, T., Roberts, W., Brian, J., & Szatmari, P. (2005). Behavioral manifestations of autism in the first year of life. International Journal of Developmental Neuroscience, 23, 143–152. http://dx.doi.org/10.1016/j.ijdevneu.2004.05.001 [Article] [PubMed]×
Table 1.
Descriptions of Social Neurobehavioral Factors
Descriptions of Social Neurobehavioral Factors×
FactorDescription
Social interaction
 CuddlingInfant resists being held and/or failed to participate with whole body while cuddling in arms.
 IrritabilityInfant cries or fusses for most (>50%) of the interaction.
 ConsolabilityInfant is able to be soothed with human interaction, such as being talked to or held, moving from an active awake or crying state to a quiet alert, drowsy, or sleep state.
 CryingInfant cries for at least 15 s during the exam.
 Gaze aversionInfant actively moves eyes or head away from visual stimulus to avoid the stimulus.
 Visual lockingInfant demonstrates a stare at a stimulus that was difficult to break.
 Tight blinkingInfant closes eyes tightly to avoid the stimulus when stimulus is presented
 Roving eye movementsInfant demonstrates rapid eye movements that were not oriented to a stimulus when presented.
 Endpoint nystagmusInfant demonstrates rapid, repetitive horizontal eye movements when orienting to a stimulus at the end of the visual range.
 Sustained nystagmusInfant demonstrates rapid, repetitive horizontal eye movements during any attempts to visually orient.
 Obligatory followingInfant responds to a visual stimulus with an exaggerated response and rapid, predictable eye and head movements toward the stimulus.
 HyperalertnessInfant responds with overly intense alertness, often seen with bulging eyes and a panicked expression.
Visual and auditory orientation
  Auditory animate orientation (human voice)Poor = No auditory orientation
Fair = Brightening with shifting of eyes
  Auditory inanimate orientation (rattle)Good = Head turning to side of stimulus and localizing <2 out of 4 times
Excellent = Head turning and finding the stimulus ≥2 out of 4 times
  Visual animate orientation (human face)Poor = No visual tracking
Fair = Focusing on object with brief following <30°
  Visual inanimate orientation (red ball)Good = Tracking ≥30° to one side
Excellent = Full tracking to both sides with smooth eye movements
 Preference for animate objectsThe infant scores higher on animate visual and auditory orientation than on inanimate visual and auditory orientation.
Table 1.
Descriptions of Social Neurobehavioral Factors
Descriptions of Social Neurobehavioral Factors×
FactorDescription
Social interaction
 CuddlingInfant resists being held and/or failed to participate with whole body while cuddling in arms.
 IrritabilityInfant cries or fusses for most (>50%) of the interaction.
 ConsolabilityInfant is able to be soothed with human interaction, such as being talked to or held, moving from an active awake or crying state to a quiet alert, drowsy, or sleep state.
 CryingInfant cries for at least 15 s during the exam.
 Gaze aversionInfant actively moves eyes or head away from visual stimulus to avoid the stimulus.
 Visual lockingInfant demonstrates a stare at a stimulus that was difficult to break.
 Tight blinkingInfant closes eyes tightly to avoid the stimulus when stimulus is presented
 Roving eye movementsInfant demonstrates rapid eye movements that were not oriented to a stimulus when presented.
 Endpoint nystagmusInfant demonstrates rapid, repetitive horizontal eye movements when orienting to a stimulus at the end of the visual range.
 Sustained nystagmusInfant demonstrates rapid, repetitive horizontal eye movements during any attempts to visually orient.
 Obligatory followingInfant responds to a visual stimulus with an exaggerated response and rapid, predictable eye and head movements toward the stimulus.
 HyperalertnessInfant responds with overly intense alertness, often seen with bulging eyes and a panicked expression.
Visual and auditory orientation
  Auditory animate orientation (human voice)Poor = No auditory orientation
Fair = Brightening with shifting of eyes
  Auditory inanimate orientation (rattle)Good = Head turning to side of stimulus and localizing <2 out of 4 times
Excellent = Head turning and finding the stimulus ≥2 out of 4 times
  Visual animate orientation (human face)Poor = No visual tracking
Fair = Focusing on object with brief following <30°
  Visual inanimate orientation (red ball)Good = Tracking ≥30° to one side
Excellent = Full tracking to both sides with smooth eye movements
 Preference for animate objectsThe infant scores higher on animate visual and auditory orientation than on inanimate visual and auditory orientation.
×
Table 2.
Sample Characteristics (N = 62)
Sample Characteristics (N = 62)×
Characteristicn (%), M (SD), or Median (IQ Range)
Child
 Female30 (48)
 White38 (61)
 Gestational age, wk26.7 (1.8)
 Birth weight, g961.9 (272.3)
 Days on ventilator3.0 (1.0–24.0)
 CRIB score3.5 (3.2)
 Length of stay, days91.7 (28.5)
 Moderate to severe brain injury12 (19)
Mother
 Age, yr29.5 (7.4)
 Has college education28 (45)
 Single34 (55)
 Public insurance34 (55)
 Illicit drug use during pregnancy2 (3)
Child developmental outcomes
 Bayley–III Cognitive86.2 (10.0)
 Bayley–III Motor83.7 (11.7)
 Bayley–III Language89.3 (11.7)
 Positive ASD screen on M–CHAT13 (21)
Table Footer NoteNote. ASD = autism spectrum disorder; Bayley–III = Bayley Scales of Infant and Toddler Assessment, 3rd ed.; CRIB = Clinical Risk Index for Babies; IQ = interquartile; M = mean; M–CHAT = Modified Checklist for Autism in Toddlers; SD = standard deviation.
Note. ASD = autism spectrum disorder; Bayley–III = Bayley Scales of Infant and Toddler Assessment, 3rd ed.; CRIB = Clinical Risk Index for Babies; IQ = interquartile; M = mean; M–CHAT = Modified Checklist for Autism in Toddlers; SD = standard deviation.×
Table 2.
Sample Characteristics (N = 62)
Sample Characteristics (N = 62)×
Characteristicn (%), M (SD), or Median (IQ Range)
Child
 Female30 (48)
 White38 (61)
 Gestational age, wk26.7 (1.8)
 Birth weight, g961.9 (272.3)
 Days on ventilator3.0 (1.0–24.0)
 CRIB score3.5 (3.2)
 Length of stay, days91.7 (28.5)
 Moderate to severe brain injury12 (19)
Mother
 Age, yr29.5 (7.4)
 Has college education28 (45)
 Single34 (55)
 Public insurance34 (55)
 Illicit drug use during pregnancy2 (3)
Child developmental outcomes
 Bayley–III Cognitive86.2 (10.0)
 Bayley–III Motor83.7 (11.7)
 Bayley–III Language89.3 (11.7)
 Positive ASD screen on M–CHAT13 (21)
Table Footer NoteNote. ASD = autism spectrum disorder; Bayley–III = Bayley Scales of Infant and Toddler Assessment, 3rd ed.; CRIB = Clinical Risk Index for Babies; IQ = interquartile; M = mean; M–CHAT = Modified Checklist for Autism in Toddlers; SD = standard deviation.
Note. ASD = autism spectrum disorder; Bayley–III = Bayley Scales of Infant and Toddler Assessment, 3rd ed.; CRIB = Clinical Risk Index for Babies; IQ = interquartile; M = mean; M–CHAT = Modified Checklist for Autism in Toddlers; SD = standard deviation.×
×
Table 3.
Atypical Traits of Infants in the Sample
Atypical Traits of Infants in the Sample×
ASD Screen, M ± SD or n (%)Developmental Delay,a M ± SD or n (%)
Total for Each TraitPositive (n = 13, 21%)Negative (n = 49, 79%)Yes (n = 28, 45%)No (n = 34, 55%)
Traitpbpb
Social interactionc
 Poor cuddle (N = 56)28 (50)4 (14)24 (86).1913 (46)15 (54).79
 Irritability (N = 57)27 (47)5 (19)22 (81).669 (33)18 (67).13
 Poor consolability (N = 33)9 (27)2 (22)7 (78).933 (33)6 (67).39
 Cry56 (97)12 (21)44 (79).4624 (43)32 (57).84
 Gaze aversion41 (71)5 (12)36 (88).0114 (34)27 (66).03
 Visual locking25 (43)4 (16)21 (84).4410 (40)15 (60).68
 Tight blinking2 (3)0 (0)2 (100).460 (0)2 (100).21
 Roving eye movements46 (79)8 (17)38 (83).2318 (39)28 (61).23
 Endpoint nystagmus21 (36)1 (5)20 (95).025 (24)16 (76).03
 Sustained nystagmus7 (12)1 (14)6 (86).663 (43)4 (57).99
 Obligatory following16 (28)2 (13)14 (87).345(31)11 (69).26
 Hyperalertness12 (21)4 (33)8 (67).234 (33)8 (67).44
Visual and auditoryc
 Auditory animate orientationd (N = 49)2.1 ± 1.02.3 ± 1.02.0 ± 1.0.612.0 ± 1.02.1 ± 1.0.67
 Visual animate orientatione (N = 50)1.9 ± 0.91.4 ± 0.92.0 ± 0.9.141.6 ± 0.82.0 ± 1.0.18
 Auditory inanimate orientationd (N = 50)2.0 ± 1.02.2 ± 1.12.0 ± 1.0.552.1 ± 1.12.0 ± 1.0.66
 Visual inanimate orientatione (N = 51)1.6 ± 0.91.5 ± 1.01.7 ± 0.9.611.5 ± 0.91.7 ± 0.9.53
 Visual preference for object over human face (N = 50)40 (80)6 (15)34 (85).2716 (40)24 (60).56
 Auditory preference for sound over human voice (N = 48)24 (50)3 (13)21 (87).448 (33)16 (67).55
Table Footer NoteNote. M = mean; SD = standard deviation.
Note. M = mean; SD = standard deviation.×
Table Footer NoteaDevelopmental delay is defined as a score of <85 on any of the three composite scores (Language, Cognitive, or Motor) on the Bayley Scales of Infant and Toddler Development, 3rd ed. bUsed independent samples t tests for continuous variables and χ2 analyses for categorical variables. cN = 58 unless otherwise noted; although the total sample size was 62, not all infants met the requirements for testing all traits. dScaled score: 1 = no auditory orientation, 2 = brightening with shifting of eyes, 3 = head turning to side of stimulus and localizing <2 out of 4 times, or 4 = head turning and finding the stimulus ≥2 out of 4 times. eScaled score: 1 = no visual tracking, 2 = focusing on object with brief following <30°, 3 = tracking ≥30° to one side, or 4 = full tracking to both sides with smooth eye movements.
Developmental delay is defined as a score of <85 on any of the three composite scores (Language, Cognitive, or Motor) on the Bayley Scales of Infant and Toddler Development, 3rd ed. bUsed independent samples t tests for continuous variables and χ2 analyses for categorical variables. cN = 58 unless otherwise noted; although the total sample size was 62, not all infants met the requirements for testing all traits. dScaled score: 1 = no auditory orientation, 2 = brightening with shifting of eyes, 3 = head turning to side of stimulus and localizing <2 out of 4 times, or 4 = head turning and finding the stimulus ≥2 out of 4 times. eScaled score: 1 = no visual tracking, 2 = focusing on object with brief following <30°, 3 = tracking ≥30° to one side, or 4 = full tracking to both sides with smooth eye movements.×
Table 3.
Atypical Traits of Infants in the Sample
Atypical Traits of Infants in the Sample×
ASD Screen, M ± SD or n (%)Developmental Delay,a M ± SD or n (%)
Total for Each TraitPositive (n = 13, 21%)Negative (n = 49, 79%)Yes (n = 28, 45%)No (n = 34, 55%)
Traitpbpb
Social interactionc
 Poor cuddle (N = 56)28 (50)4 (14)24 (86).1913 (46)15 (54).79
 Irritability (N = 57)27 (47)5 (19)22 (81).669 (33)18 (67).13
 Poor consolability (N = 33)9 (27)2 (22)7 (78).933 (33)6 (67).39
 Cry56 (97)12 (21)44 (79).4624 (43)32 (57).84
 Gaze aversion41 (71)5 (12)36 (88).0114 (34)27 (66).03
 Visual locking25 (43)4 (16)21 (84).4410 (40)15 (60).68
 Tight blinking2 (3)0 (0)2 (100).460 (0)2 (100).21
 Roving eye movements46 (79)8 (17)38 (83).2318 (39)28 (61).23
 Endpoint nystagmus21 (36)1 (5)20 (95).025 (24)16 (76).03
 Sustained nystagmus7 (12)1 (14)6 (86).663 (43)4 (57).99
 Obligatory following16 (28)2 (13)14 (87).345(31)11 (69).26
 Hyperalertness12 (21)4 (33)8 (67).234 (33)8 (67).44
Visual and auditoryc
 Auditory animate orientationd (N = 49)2.1 ± 1.02.3 ± 1.02.0 ± 1.0.612.0 ± 1.02.1 ± 1.0.67
 Visual animate orientatione (N = 50)1.9 ± 0.91.4 ± 0.92.0 ± 0.9.141.6 ± 0.82.0 ± 1.0.18
 Auditory inanimate orientationd (N = 50)2.0 ± 1.02.2 ± 1.12.0 ± 1.0.552.1 ± 1.12.0 ± 1.0.66
 Visual inanimate orientatione (N = 51)1.6 ± 0.91.5 ± 1.01.7 ± 0.9.611.5 ± 0.91.7 ± 0.9.53
 Visual preference for object over human face (N = 50)40 (80)6 (15)34 (85).2716 (40)24 (60).56
 Auditory preference for sound over human voice (N = 48)24 (50)3 (13)21 (87).448 (33)16 (67).55
Table Footer NoteNote. M = mean; SD = standard deviation.
Note. M = mean; SD = standard deviation.×
Table Footer NoteaDevelopmental delay is defined as a score of <85 on any of the three composite scores (Language, Cognitive, or Motor) on the Bayley Scales of Infant and Toddler Development, 3rd ed. bUsed independent samples t tests for continuous variables and χ2 analyses for categorical variables. cN = 58 unless otherwise noted; although the total sample size was 62, not all infants met the requirements for testing all traits. dScaled score: 1 = no auditory orientation, 2 = brightening with shifting of eyes, 3 = head turning to side of stimulus and localizing <2 out of 4 times, or 4 = head turning and finding the stimulus ≥2 out of 4 times. eScaled score: 1 = no visual tracking, 2 = focusing on object with brief following <30°, 3 = tracking ≥30° to one side, or 4 = full tracking to both sides with smooth eye movements.
Developmental delay is defined as a score of <85 on any of the three composite scores (Language, Cognitive, or Motor) on the Bayley Scales of Infant and Toddler Development, 3rd ed. bUsed independent samples t tests for continuous variables and χ2 analyses for categorical variables. cN = 58 unless otherwise noted; although the total sample size was 62, not all infants met the requirements for testing all traits. dScaled score: 1 = no auditory orientation, 2 = brightening with shifting of eyes, 3 = head turning to side of stimulus and localizing <2 out of 4 times, or 4 = head turning and finding the stimulus ≥2 out of 4 times. eScaled score: 1 = no visual tracking, 2 = focusing on object with brief following <30°, 3 = tracking ≥30° to one side, or 4 = full tracking to both sides with smooth eye movements.×
×