Tracking the Development of ADHD in Toddlers Diagnosed with ASD
Background: Delayed walking is common in intellectual disability (ID) but may be less common when ID occurs with autism spectrum disorder (ASD). Previous studies examining this were limited by reliance on clinical samples and exclusion of children with severe motor deficits.
Objective: To examine in a population-based sample if age of walking is differentially related to intellectual ability in children with ASD versus other neurodevelopmental disorders (NDD).
Methods: Participants were from the nested Autism Birth Cohort Study of the Norwegian Mother, Father and Child Cohort Study (MoBa). Cox proportional hazards regression assessed if diagnosis (ASD n = 212 vs. NDD n = 354), continuous nonverbal IQ, and their interaction, were associated with continuous age of walking.
Results: The relationship between nonverbal IQ and age of walking was stronger for NDD than for ASD (Group × nonverbal IQ interaction, χ2 = 13.93, p = .0002). This interaction was characterized by a 21% decrease in the likelihood of walking onset at any given time during the observation period per 10-point decrease in nonverbal IQ (hazard ratio = 0.79, 95% CI: 0.78-0.85) in the NDD group compared to 8% (hazard ratio = 0.92, 95% CI: 0.86-0.98) in the ASD group.
Conclusions: The finding that age of walking is less strongly related to low intellectual ability in children with ASD than in children without other NDDs supports the hypothesis that ID in ASD may result from heterogeneous developmental pathways. Late walking may be a useful stratification variable in etiological research focused on ASD and other NDDs.
Keywords: Intellectual disability; MoBa; epidemiology; gross motor milestones; late walking.
This study investigated early posture development prospectively in infants at heightened (HR) vs. low risk (Low Risk; LR) for ASD. Fourteen HR infants diagnosed with ASD (HR-ASD), 17 HR infants with language delay (HR-LD), 29 HR infants with no diagnosis (HR-ND), and 25 LR infants were videotaped at home for 25 min during everyday activities and play at 6, 8, 10, 12, and 14 months. All postures were coded and the sustainment source was identified for supported postures. Relative to LR infants, HR-ASD infants and to a lesser extent HR-LD infants exhibited distinct postural trajectories that revealed slower development of more advanced postures. In addition, subtle differences in posture sustainment differentiated HR-ASD from HR-LD infants.
Keywords: Autism spectrum disorder; Infant siblings; Motor development; Posture.
Objective: We evaluated trajectories of attention-deficit/hyperactivity (ADHD)-relevant behaviors in a sample of infants at high and low familial risk for ADHD who were prospectively evaluated at 12, 18, and 24 months of age.Method: Participants included 43 infants at risk for ADHD based on family history (i.e., diagnosed first-degree relative) and 40 low-risk infants (i.e., no family history of ADHD). Instances of inattention, out-of-seat, and grabbing behavior were coded from video; analogous constructs were rated by examiners unaware of familial risk status after completing structured standardized assessments with the infants/toddlers. At the end of each study visit, examiners solicited parents’ concerns about their child’s behavior. Differences in ADHD-related behaviors and parent concerns were examined between 12 and 24 months of age.Results: Infants with an older sibling or parent diagnosed with ADHD were distinguishable from infants with no family history of ADHD as early as 12 months of age based on directly observed and examiner reports of behavior, particularly with respect to hyperactive-impulsive behavior. Parents of infants at familial risk for ADHD also reported significantly more behavior/temperament concerns as early as 12 months of age compared to parents of infants at low risk for ADHD.Conclusions: These findings highlight the ability to detect genetic liability for ADHD by the end of the first year of life, suggesting that well-designed family risk studies of ADHD are feasible and may be clinically valuable. They also suggest the potential for earlier detection of risk for ADHD than has previously been possible.
Background: Establishing reliable predictive and diganostic biomarkers of autism would enhance early identification and facilitate targeted intervention during periods of greatest plasticity in early brain development. High impact research on biomarkers is currently limited by relatively small sample sizes and the complexity of the autism phenotype.
Methods: EEG-IP is an International Infant EEG Data Integration Platform developed to advance biomarker discovery by enhancing the large scale integration of multi-site data. Currently, this is the largest multi-site standardized dataset of infant EEG data.
Results: First, multi-site data from longitudinal cohort studies of infants at risk for autism was pooled in a common repository with 1382 EEG longitudinal recordings, linked behavioral data, from 432 infants between 3- to 36-months of age. Second, to address challenges of limited comparability across independent recordings, EEG-IP applied the Brain Imaging Data Structure (BIDS)-EEG standard, resulting in a harmonized, extendable, and integrated data state. Finally, the pooled and harmonized raw data was preprocessed using a common signal processing pipeline that maximizes signal isolation and minimizes data reduction. With EEG-IP, we produced a fully standardized data set, of the pooled, harmonized, and pre-processed EEG data from multiple sites.
Conclusions: Implementing these integrated solutions for the first time with infant data has demonstrated success and challenges in generating a standardized multi-site data state. The challenges relate to annotation of signal sources, time, and ICA analysis during pre-processing. A number of future opportunities also emerge, including validation of analytic pipelines that can replicate existing findings and/or test novel hypotheses.
Keywords: Autism risk; Biomarkers; EEG; High performance computing; ICA; Pre-processing.
Importance: Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with different genetic etiologies. Prospective examination of familial-risk infants informs understanding of developmental trajectories preceding ASD diagnosis, potentially improving early detection.
Objective: To compare outcomes and trajectories associated with varying familial risk for ASD across the first 3 years of life.
Design, setting, and participants: This longitudinal, prospective cohort study used data from 11 sites in the Baby Siblings Research Consortium database. Data were collected between 2003 and 2015. Infants who were younger siblings of children with ASD were followed up for 3 years. Analyses were conducted in April 2018. Of the initial 1008 infants from the database, 573 were removed owing to missing necessary data, diagnostic discrepancies, or only having 1 older sibling.
Exposures: Number of siblings with ASD.
Main outcomes and measures: Outcomes included ASD symptoms, cognitive abilities, and adaptive skills. Diagnosis (ASD or no ASD) was given at 36-month outcome. The no-ASD group was classified as atypical (developmental delays and/or social-communication concerns) or typical for some analyses. Generalized linear mixed models examined developmental trajectories by ASD outcome and familial-risk group.
Results: In the 435 analyzed participants (age range at outcome, 32-43 months; 246 male [57%]), 355 (82%) were from single-incidence families (1 sibling with ASD and ≥1 sibling without ASD) and 80 (18%) were from multiplex families (≥2 siblings with ASD). There were no significant group differences in major demographics. Children from multiplex families were more likely than those from single-incidence families to be classified as having ASD (29 of 80 [36%] vs 57 of 355 [16%]; 95% CI, 9%-31%; P < .001) and less likely as typical (26 of 80 [33%] vs 201 of 355 [57%]; 95% CI, -36% to -13%; P < .001), with similar rates of atypical classifications (25 of 80 [31%] vs 97 of 355 [27%]; 95% CI, -7% to 15%; P = .49). There were no differences in ASD symptoms between multiplex and single-incidence groups after controlling for ASD outcome (95% CI, -0.02 to 0.20; P = .18). During infancy, differences in cognitive and adaptive abilities were observed based on ASD outcome in the single-incidence group only. At 36 months, the multiplex/no-ASD group had lower cognitive abilities than the single-incidence/no-ASD group (95% CI, -11.89 to -2.20; P = .02), and the multiplex group had lower adaptive abilities than individuals in the single-incidence group after controlling for ASD outcome (95% CI, -9.01 to -1.48; P = .02).
Conclusions and relevance: Infants with a multiplex family history of ASD should be monitored early and often and referred for early intervention at the first sign of concern. Direct examination of genetic contributions to neurodevelopmental phenotypes in infants with familial risk for ASD is needed.
Early intervention is important for preschoolers on the autism spectrum, but little is known about early intervention classrooms in the community. This study found that children with better language skills and lower autism severity have more verbal interactions with their classmates, especially in classrooms with typically developing peers (inclusion settings). Findings suggest that natural language sampling is a useful method for characterizing autistic children and their early intervention settings. In addition, natural language sampling may have important implications for understanding individual opportunities for development in community early intervention settings.
Keywords: autism spectrum disorders; communication and language; early intervention; education services; environmental factors; pre-school children.
Background: Concerns have been raised that scores on standard measures of autism spectrum disorder (ASD) symptoms may differ as a function of sex. However, these findings are hindered by small female samples studied thus far. The current study evaluated if, after accounting for age, IQ, and language level, sex affects ASD severity estimates from diagnostic measures among children with ASD.
Methods: Data were obtained from eight sources comprising 27 sites. Linear mixed-effects models, including a random effect for site, were fit for 10 outcomes (Autism Diagnostic Observation Schedule [ADOS] domain-level calibrated severity scores, Autism Diagnostic Interview-Revised [ADI-R] raw scores by age-based algorithm, and raw scores from the two indices on the Social Responsiveness Scale [SRS]). Sex was added to the models after controlling for age, NVIQ, and an indicator for language level.
Results: Sex significantly improved model fit for half of the outcomes, but least square mean differences were generally negligible (effect sizes [ES] < 0.20), increasing to small to moderate in adolescence (ES < 0.40). Boys received more severe RRB scores than girls on both the ADOS and ADI-R (age 4 + algorithm), and girls received more severe scores than boys on both SRS indices, which emerged in adolescence.
Conclusions: This study combined several available databases to create the largest sample of girls with ASD diagnoses. We found minimal differences due to sex beyond other known influences on ASD severity indicators. This may suggest that, among children who ultimately receive a clinical ASD diagnosis, severity estimates do not systematically differ to such an extent that sex-specific scoring procedures would be necessary. However, given the limitations inherent in clinically ascertained samples, future research must address questions about systematic sex differences among children or adults who do not receive clinical diagnoses of ASD. Moreover, while the current study helps resolve questions about widely used diagnostic instruments, we could not address sex differences in phenotypic aspects outside of these scores.
Keywords: Sex differences; autism spectrum disorder; restricted and repetitive behavior; social impairment.