Behavioral, cognitive, and adaptive development in infants with autism spectrum disorder in the first 2 years of life

This study demonstrated robust differences at 6 months on standardized developmental measures in high-risk infants who go on to develop ASD at 24 months. These early decrements in cognitive and adaptive function were specific to the HR-ASD-High group compared to the LR-Neg group in the Gross Motor and Visual Reception domains on the MSEL and Motor domain on the VABS-II. There was no evidence of atypical social-communication or repetitive behavior at 6 months in the HR-ASD-High group, as indexed by the AOSI, but such features were evident at 12 months relative to other HR and LR infants. Notably, most cognitive and adaptive skill differences between the HR-ASD-Mod and non-ASD groups emerged at 24 months (with the exception of lower MSEL Expressive Language which emerged at 12 months).

Longitudinal trajectory findings revealed significant increasing group differentiation over time, from 6 to 24 months, across all domains (cognitive, adaptive, and behavioral features). A hierarchical pattern of symptom severity was observed with regard to mean group differences and developmental trajectories across all developmental domains: cognitive, adaptive, and behavioral features, with the HR-ASD-High group being the most severely affected at each age, followed by the HR-ASD-Mod, HR-Neg, and LR-Neg groups. Taken together, these data illustrate a pattern of unfolding symptoms in children with ASD, starting in the sensorimotor domain at 6 months and moving to the social-communication domain in the second year of life.

This unfolding is also reflected in the unique trajectories of the HR-ASD-Mod group. The HR-ASD-Mod group differed from the HR-ASD-High group demonstrating symptoms that emerged later in development, less severe behavioral features, and more advanced cognitive and adaptive functioning at 24 months. The more severely affected group presented initially with lower sensorimotor abilities relative to the non-ASD groups at 6 months, whereas the less severely affected subgroup demonstrated differences relative to the non-ASD groups at 12 months in the communication domain. Both the HR-ASD-High and the HR-ASD-Mod groups demonstrated increasing severity of cognitive and adaptive functioning deficits in the first 2 years of life. A follow-up with these children is underway to investigate diagnostic trajectories and patterns of symptom expression in the preschool and early school-age years.

There was a remarkable convergence across parent-report and direct clinical assessment identifying atypical motor development as early as 6 months in children with elevated ASD symptoms at age 2, suggesting motor development, which is not a diagnostic feature, may be disrupted very early in development in ASD. Indeed, motor and visual reception differences were detected earlier than reported in previous longitudinal studies of high-risk infants that used standardized developmental measures [21, 34]. Our findings are consistent with reports of subtle motor differences at 6–7 months with respect to head control [13], lower activity level [52], and saccadic reaction times [9] among infants who go on to develop ASD. Early motor deficits could play a role in later motor impairments, atypical control of eye movements, and/or delays in development of gestures such as pointing, associated with the emergence of joint attention, a commonly reported deficit in ASD. A dynamic system perspective suggests that motor and language development are intimately linked during infancy and toddlerhood, as emerging voluntary control over oculomotor, fine motor, and gross motor systems allows for increasingly complex interactions with one’s environment [18]. Notably, motor differences evident at 6 months did not increase over time (i.e., the longitudinal trajectory interaction term was not significant), and at 12 months, outcome groups did not differ. The pattern of group differences was similar when utilizing the VABS Motor scale or the VABS Gross Motor V scale (data available on request.) Future studies should clarify whether this pattern of motor development, in which groups diverge at 6 months and converge at 12 months, reflects qualities of the measurement tools or developmental processes related to the onset of ASD. It is also possible that differences identified at 6 months may be signs of risk for developmental disorders more generally, or comorbid intellectual disability, rather than precursors of ASD specifically. The defining behaviors of ASD (e.g., atypical or delayed verbal communication, lack of pretend play, poor reciprocal social interaction) begin to emerge around 12 months and are increasingly evident over the second year of life. Commonly used measures of social communication may not be designed detect the kinds of aberrant social-communicative behavior that emerge in the first year of life. Advances in measurement, particularly in the social-communication domain, may be needed to capture very early ASD-related behavioral manifestations.

Recent evidence, also from the IBIS network, demonstrates differences in DTI white matter fiber tract trajectories at 6 months of age [50]. These findings utilized the same research design and a subset of the sample reported here to characterize brain differences in infants who met the ADOS criteria for ASD (HR-ASD-High and HR-ASD-Mod combined) at 24 months compared with infants who did not (HR-Neg). The timing of behavioral differences observed in the expanded HR-ASD-High group reported here is consistent with the onset white matter tract differences, both observed at 6 months. Furthermore, the brain and behavioral differences in these reports both appear to unfold in a dynamic manner over the 6- to 24-month period. The precise nature and evolution of these differences requires further examination with more granular assessments delineating trajectories with greater precision and with varying comparison groups to determine whether these differences are specific to ASD or more general developmental risk factors. But, in combination, these data suggest a process of neurobehavioral alteration that begins early in infancy and unfolds over time.

We also note several important limitations. A recent report on high-risk infants who do not go on to develop ASD, followed through 36 months, suggests that over a quarter of high-risk infants without a diagnosis of ASD will nonetheless demonstrate significant developmental difficulties such as ASD symptoms or lower developmental skills [37]. Thus, a follow-up of high-risk infants into preschool and school-age is clinically indicated and may reveal additional information about developmental trajectories, risk, and protective factors in ASD. There is a lack of consensus in the field about the interpretation of 24-month outcomes as compared with later outcomes in studies of infants at high risk for ASD. There is substantial precedent for early diagnoses of ASD in clinically ascertained samples with a high level of diagnostic stability at 24 months (e.g., [5, 16, 24, 25]). Classifying ASD in high-risk sibling cohorts at 24 months is also commonly reported (e.g., [10, 21, 30, 32, 49, 52]). However, there is concern that infants ascertained based on high familial risk may differ from similar-aged clinically ascertained children with ASD. In particular, careful prospective assessment may detect milder symptoms in high-risk infant siblings than studies using clinically referred samples. Nonetheless, high-risk infant sibling studies have reported high classification stability from 24 to 30/36 months (e.g., [19, 39, 41, 45]). There may be a proportion of high-risk children who fail to meet diagnostic thresholds for ASD earlier but go on to later meet the criteria for ASD [7, 39]. In one recent study, the high-risk children not diagnosed at 24 months but subsequently diagnosed at 36 months displayed subthreshold ASD symptoms at 24 months (e.g., ADOS Social Communication score mean 9.2) but met threshold at 36 months (e.g., ADOS Social Communication score mean 11.6) [39]. Since our outcome groups are based on cases who were diagnosed at 24 months of age, these findings may not generalize to cases in which a diagnosis is established later. This subset of children, if present in our sample, may reduce observed group differences because children with subthreshold ASD may be included in the non-ASD group. It has also been observed that a small subset of high-risk 2-year-olds who are classified as having ASD no longer meet the criteria later in development. A common interpretation is that this change reflects a misclassification at 24 months. However, it is perhaps more plausible that this could reflect the natural progression of ASD in these children or varied early experiences such as participation in high-quality early intervention or enriched social-communicative environments. Although it is well known that an ASD diagnosis had strong predictive validity, especially in comparison with other childhood psychiatric diagnoses, this should not be taken to suggest that an ASD classification, especially in very young children, is immutable [48]. Within the field of psychiatric nosology, there is little evidence for permanent diagnoses in childhood conditions. Longitudinal work has highlighted the transience of most psychopathology and the resilience of a large subgroup of children [40]. In sum, changes in symptom expression over the course of a psychiatric disorder should not be unexpected or invalidate a diagnosis at an earlier age.

A third caution is that group differences in motor skills at 6 months on the MSEL and VABS-II represent mild decrements in test scores, rather than frank developmental delays. As well, it is premature to generalize motor findings from a high-risk sample to ASD surveillance/screening efforts in the general population, as motor delays may indicate risk for a broad range of developmental disorders. Rather, we propose that subtle atypicalities in sensorimotor development at 6 months, followed by more pronounced developmental delays and behavioral signs, may inform risk profiles for ASD. Although we interpret the Visual Reception domain differences at 6 months as likely representing differences in the sensory domain and 12-month differences on the Communication domain (VABS-II) and Expressive Language subscale (MSEL) as relating to language abilities, future studies of sensory and language abilities will be needed to replicate and extend these findings. Future research is needed to evaluate the utility of such risk profiles for individual classification. Critically, investigation of combined bio-behavioral markers, utilizing measures of brain imaging, early attention, and other infant-specific approaches may enhance risk prediction over and above present capabilities. Models to improve early, accurate identification of ASD would allow earlier intervention at a time when neuroplasticity is highest [8, 22]. Efforts to develop interventions for children at this early stage of development, perhaps targeting very early differences in sensorimotor or visual tracking, are needed. For families with a history of ASD, earlier and more accurate understanding of ASD behavioral features could reduce parent stress and improve family adaptive functioning by reducing uncertainty [11] and allowing parents to act early to ensure the best possible outcome for their child.