Pilot protocol for the Parent and Infant Inter(X)action Intervention (PIXI) feasibility study.

This paper provides the detailed protocol for a pilot study testing the feasibility, acceptability, and initial efficacy of a targeted two-phase, remotely delivered early intervention program for infants with neurogenetic conditions (NGC) and their caregivers. The Parent and Infant Inter(X)action Intervention (PIXI) is designed to support parents and infants with a NGC diagnosed in the first year of life. PIXI is implemented in two phases, with the first phase focusing on psychoeducation, parent support, and how to establish routines for supporting infant development. Phase II helps parents learn targeted skills to support their infant's development as symptoms may begin to emerge. The proposed non-randomized feasibility pilot study will establish the feasibility of a year-long virtually implemented intervention program to support new parents of an infant diagnosed with an NGC.

Toddlers at Elevated Likelihood for Autism: Exploring Sensory and Language Treatment Predictors.

Baseline child characteristics may predict treatment outcomes in children with or at elevated likelihood of developing autism (EL-ASD). Little is known about the role of child sensory and language features on treatment outcome. Participants were randomly assigned to a parent-mediated intervention or control condition. Analyses explored the relationship between baseline child sensory and language characteristics and changes in ASD symptoms over approximately 9 months. Higher baseline sensory hyporeactivity was significantly related to less improvement in social communication (SC) for the treatment group only. More baseline atypical vocalizations were significantly related to less improvement on SC across treatment and control groups. This work provides an initial framework to encourage the tailoring of interventions for EL-ASD children, suggesting sensory reactivity and atypical vocalizations may be useful behaviors to consider in treatment planning.

Measuring Transactional Engagement Among Young Children with Elevated Likelihood for Later Autism Spectrum Disorder Diagnosis.

This analytical study documented the presence of transactions in parent-child engagement within a sample of young children at an elevated likelihood for an eventual diagnosis of autism spectrum disorder (ASD). Specifically, the study examined the establishment of transactional engagement through reciprocal behaviors between parents and their young children at-risk for ASD. In the study sample, established transactional engagement occurred at a higher rate than other levels of engagement. Additionally, transactional engagement had a higher likelihood of being established when parents initiated. Post-hoc analyses revealed possible early markers of ASD within a certain behavior displayed in transactions. This study signifies the initial efforts in identifying transactions within parent-child engagement, and foremost, how transactional engagement is established.

Early measurement of autism risk constructs in the general population: A new factor structure of the First Years Inventory (FYIv3.1) for ages 6-16 months.

Early detection of autism risk in the community is critical to increasing families' access to early intervention, yet few measures have been developed and tested for the general population of infants <16 months to tap a broader range of autism risk constructs. This study aimed to (a) examine the factor structure of the First Years Inventory, version 3.1 (FYIv3.1), with a sample of 6454 infants 6-16 months, and (b) determine the ability of the resulting factors to discriminate clinical outcome groups at 3 years of age. The FYIv3.1 is a parent-report tool designed to detect early behavioral risk signs that may be associated with a later diagnosis of ASD and related neurodevelopmental conditions. Factor analytic models were used to determine the number of constructs and inter-factor correlations. Findings supported a seven-factor structure: communication, imitation and play (CIP); social attention and affective engagement (SAE); sensory hyperresponsiveness (HYPER); sensory hyporesponsiveness (HYPO); self-regulation in daily routines (SREG); sensory interests, repetitions, and seeking behaviors (SIRS); motor coordination and milestones (MCM). Mean comparisons on these factors demonstrated significant discrimination of the three outcome groups at age 3 years including those classified as having an ASD diagnosis and/or high autism symptoms, those classified as having other developmental disorders/conditions/concerns, and those classified with no known conditions/concerns. These findings support the validity and multidimensionality of early ASD risk constructs, as well as the potential use of the FYIv3.1 for phenotypic subtyping in the general population, and early detection in a broader age range of 6-16 months in future clinical studies. LAY SUMMARY: The FYIv3.1 is a 69-item parent-report questionnaire about infant behaviors that may indicate an elevated likelihood for later neurodevelopmental conditions such as autism. Analyses of responses from 6454 parents of infants 6-16 months indicated that items could be grouped reliably into seven categories. Compared to children with or without other developmental conditions, children in the outcome group with autism spectrum disorder and/or high autism symptoms at age three showed more behavioral risk signs in social-communication, sensory, and motor domains during infancy.

Parent responsiveness mediates the association between hyporeactivity at age 1 year and communication at age 2 years in children at elevated likelihood of ASD.

Studies suggest that higher parent responsiveness is associated with higher child language abilities. Infants and toddlers later diagnosed with autism spectrum disorder (ASD) often display hyporeactivity to sensory stimuli, which has also been associated with lower child communication abilities and lower parent responsiveness. Yet, whether parent responsiveness mediates the relationship between child hyporeactivity and later communication outcomes remains unexplored. This study is a secondary data analysis which includes children (n = 83; 56 males) identified as at elevated likelihood of later ASD. Children completed an observational measure of sensory reactivity and a standard developmental assessment at 14 (Time 1) and 23 months old (Time 2). At each time point, parents reported on the child's adaptive communication behaviors and sensory behaviors, and Parent Verbal Responsiveness (AvgPVR) was coded from parent-child free-play videos. Results indicated that the association between child sensory hyporeactivity at Time 1 (observed and parent-reported) and communication at Time 2 (observed and parent reported) was significantly mediated by AvgPVR. Although child hyporeactivity predicts poorer communication outcomes, increased parent verbal responsiveness may attenuate this negative impact. Parent responsiveness, a focus of many parent-mediated interventions, may be an important mechanism of treatment response that should be directly tested in future research. LAY SUMMARY: Toddlers at elevated likelihood of autism spectrum disorder (ASD) are often under-reactive (hyporeactive) to sensory stimuli. This hyporeactivity slows learning of communication skills and provides parents with fewer opportunities to respond to their children. In this study, children with hyporeactivity at 14 months generally had poorer communication at 23 months; however, the more responsive their parents were, the weaker the relationship between early hyporeactivity and later communication. Thus, increasing parent responsiveness may lead to better communication outcomes for toddlers with the early ASD symptom of hyporeactivity.

Dynamic Eye Tracking as a Predictor and Outcome Measure of Social Skills Intervention in Adolescents and Adults with Autism Spectrum Disorder.

To evaluate an eye tracking task as a predictor and outcome measure of treatment response for autism spectrum disorder (ASD) social skills interventions, adolescents and young adults with ASD completed the eye tracking task before, immediately after, and two months after completing Social Cognition and Interaction Training for Autism (SCIT-A). The study compared SCIT-A participants (n = 20) to participants with ASD who received treatment as usual (TAU; n = 21). Overall, increased visual attention to faces and background objects and decreased attention to hands playing with toys at baseline were associated with improved social functioning immediately following intervention, suggesting this eye tracking task may reliably predict ASD social intervention outcomes.

Preferences for Accessing Electronic Health Records for Research Purposes: Views of Parents Who Have a Child With a Known or Suspected Genetic Condition.

OBJECTIVES: The purpose of this study was to examine parental preferences for researchers accessing their child's electronic health record across 3 groups: those with a child with (1) a known genetic condition (fragile X syndrome FXS), (2) a suspected genetic condition (autism spectrum disorder [ASD]), and (3) no known genetic condition (typically developing). METHODS: After extensive formative work, a discrete choice experiment was designed consisting of 5 attributes, each with 2 or 3 levels, including (1) type of researcher, (2) the use of personally identifiable information, (3) the use of sensitive information, (4) personal importance of research, and (5) return of results. Stratified mixed logit and latent class conditional logit models were examined. RESULTS: Parents of children with FXS or ASD had relatively higher preferences for research conducted by nonprofits than parents of typically developing children. Parents of children with ASD also preferred research using non-identifiable and nonsensitive information. Parents of children with FXS or ASD also had preferences for research that was personally important and returned either summary or individual results. Although a few child and family characteristics were related to preferences, they did not overall define the subgroups of parents. CONCLUSIONS: Although electronic health record preference research has been conducted with the general public, this is the first study to examine the opinions of parents who have a child with a known or suspected genetic condition. These parents were open to studies using their child's electronic health record because they may have more to gain from this type of research.

Joint Attention and Sensory-Regulatory Features at 13 and 22 Months as Predictors of Preschool Language and Social-Communication Outcomes.

Purpose The purpose of this study was to understand how joint attention and sensory-regulatory features are related in early childhood and predict language and social-communication outcomes in preschool in order to build mechanistic theories that can inform early intervention directed at improving these outcomes. Method Cross-lagged panel analysis models were used to examine the association between joint attention and sensory-regulatory features at 13 and 22 months of age in children (n = 87) who were identified via community screening at 12 months as having a higher likelihood than the general population for being diagnosed with autism spectrum disorder. Results Significant concurrent correlations and predictive correlations were found between these constructs at 13 and 22 months. Joint attention skills at 13 months predicted both joint attention and sensory-regulatory features at 22 months. Distal language and social-communication outcomes at preschool age (n = 48) were best predicted by sensory-regulatory features at 22 months. Conclusions Both joint attention and sensory regulation are important factors in the first and second years of life for impacting later preschool language and social-communication outcomes in this sample. These findings may have implications for future early childhood intervention research for children at a higher likelihood for autism spectrum disorder.

Ethical, Legal, and Social Issues Related to the Inclusion of Individuals With Intellectual Disabilities in Electronic Health Record Research: Scoping Review.

BACKGROUND: Data from electronic health records (EHRs) are increasingly used in the field of genetic research to further precision medicine initiatives. However, many of these efforts exclude individuals with intellectual disabilities, which often stem from genetic conditions. To include this important subpopulation in EHR research, important ethical, legal, and social issues should be considered. OBJECTIVE: The goal of this study was to review prior research to better understand what ethical, legal, and social issues may need further investigation when considering the research use of EHRs for individuals with genetic conditions that may result in intellectual disability. This information will be valuable in developing methods and best practices for involving this group in research given they are considered a vulnerable population that may need special research protections. METHODS: We conducted a scoping review to examine issues related to the use of EHRs for research purposes and those more broadly associated with genetic research. The initial search yielded a total of 460 unique citations. We used an evaluative coding process to determine relevancy for inclusion. RESULTS: This approach resulted in 59 articles in the following areas: informed consent, privacy and security, return of results, and vulnerable populations. The review included several models of garnering informed consent in EHR or genetic research, including tiered or categorical, blanket or general, open, and opt-out models. Second, studies reported on patients' concerns regarding the privacy and security of EHR or genetic data, such as who has access, type of data use in research, identifiability, and risks associated with privacy breach. The literature on return of research results using biospecimens examined the dissension in the field, particularly when sharing individualized genetic results. Finally, work involving vulnerable populations highlighted special considerations when conducting EHR or genetic research. CONCLUSIONS: The results frame important questions for researchers to consider when designing EHR studies, which include individuals with intellectual disabilities, including appropriate safeguards and protections.

Preferences for the research use of electronic health records among young adults with fragile X syndrome or autism spectrum disorder.

BACKGROUND: Health researchers are increasingly using electronic health records (EHRs) to study the health care needs of people with neurodevelopmental disorders (NDDs). However, little is known about the preferences of people with NDDs for sharing EHRs for research. OBJECTIVE: To explore preferences for sharing EHRs for research among young adults ages 18-40 who make their own legal decisions and who have autism spectrum disorder (ASD), fragile X syndrome (FXS), or no NDDs. METHODS: We conducted a qualitative study with seven focus groups: 2 ASD groups, 3 FXS groups, and 2 no-NDD groups. We asked participants about factors that could affect their willingness to share their EHRs for research: type of organization, type of information, study purpose, duration, contact frequency, return of results, benefits, and risks. We analyzed the qualitative data using directed content analysis. RESULTS: Participants with NDDs valued personally relevant and directly beneficial EHR research. Participants with NDDs expressed willingness to share sensitive data if the study was personally relevant. Most participants wanted to receive results, but only participants with FXS indicated it would affect their willingness to participate. Participants were concerned about privacy risks, discrimination, researcher misconduct, and financial conflicts of interest. CONCLUSION: This study provides initial evidence suggesting that young adults with NDDs prefer EHR research that is personally relevant, benefits themselves and their communities, and is conducted in the context of trusting, reciprocal participant-researcher relationships. The findings point to the need for researchers to improve the informed consent process and to better engage individuals with NDDs in research.

Sensory Reactivity at 1 and 2 Years Old is Associated with ASD Severity During the Preschool Years.

Children with Autism Spectrum Disorder (ASD) often display atypical sensory reactivity within the first years of life, prior to a diagnosis. This study examined sensory reactivity patterns at 14 months, changes from 14 to 23 months, and later ASD severity at 3 to 5 years of age in children (n = 87) at elevated likelihood of ASD. Results indicated that observed hyporeactivity at 14 months and increases from 14 to 23 months were related to higher ASD severity during the preschool years. Parent report of hyperreactivity at 14 months was associated with higher ASD severity in the RRB domain during the preschool years. Early hypo and hyperreactivity may predict later severity of ASD and aid in subtyping and developing individualized treatments.

"Just tell me what's going on": The views of parents of children with genetic conditions regarding the research use of their child's electronic health record.

OBJECTIVE: The purpose of this study was to understand the ethical, legal, and social issues described by parents of children with known or suspected genetic conditions that cause intellectual and developmental disabilities regarding research use of their child's electronic health record (EHR). MATERIALS AND METHODS: We conducted 4 focus groups with parents of children with a known (n = 12) or suspected (n = 11) genetic condition, as well as 2 comparison groups with parents who had a child with no known genetic condition (n = 15). Focus group transcripts were coded and analyzed using directed content analysis. RESULTS: After weighing the risks and benefits, parents of children with known or suspected genetic conditions were willing to share their child's EHR for research studies under certain conditions. Preferences were for studies conducted by universities or nonprofits that might benefit their child or others with the same condition. Parents also valued return of research results. DISCUSSION: Trust, transparency, altruism, and concerns about privacy emerged as factors that affect parents' willingness to allow research use of their child's EHR. CONCLUSION: Researchers should consider how to build trust with parents by increasing transparency of the research process and explaining specifically how they will ensure the confidentiality of EHR data.

"If He Has it, We Know What to Do": Parent Perspectives on Familial Risk for Autism Spectrum Disorder.

OBJECTIVE: Predictive testing for familial disorders can guide healthcare and reproductive decisions. Familial disorders with onset in childhood (e.g., autism spectrum disorder [ASD]) are promising targets for presymptomatic prediction; however, little is known about parent perceptions of risk to their children in the presymptomatic period. The current study examined risk perceptions in parents of infants at high familial risk for ASD enrolled in a longitudinal study of brain and behavior development. METHODS: Semistructured interviews were conducted with 37 parents of high-risk infants during the presymptomatic window (3-15 months) that precedes an ASD diagnosis. Infants were identified as high familial risk due to having an older sibling with ASD. Parent interview responses were coded and interpreted to distill emerging themes. RESULTS: The majority of parents were aware of the increased risk of ASD for their infants, and risk perceptions were influenced by comparisons to their older child with ASD. Parents reported a variety of negative emotions in response to perceived risk, including worry, fear, and sadness, and described impacts of perceived risk on their behavior: increased vigilance to emerging symptoms, altered reproductive and healthcare decisions, and seeking ongoing assessment through research. CONCLUSIONS: Parents of children at high familial risk for childhood-onset disorders like ASD face a period of challenging uncertainty during early development. In anticipation of a future in which presymptomatic testing for ASD is made available, it is important to understand how parents react to and cope with the elevated-but still highly uncertain-risk conveyed by family history.

The Performance of the First Year Inventory (FYI) Screening on a Sample of High-Risk 12-Month-Olds Diagnosed with Autism Spectrum Disorder (ASD) at 36 Months.

This study examined the performance of the First Year Inventory (FYI; version 2.0), a community-normed parent-reported screening instrument, in a high-risk (HR) sample of 12-month-olds with older siblings diagnosed with autism spectrum disorder (ASD). The FYI 2.0 was completed by parents of 86 HR infants and 35 low-risk control infants at age 12 months, followed by clinical diagnosis at 36 months. HR infants later diagnosed with ASD had significantly higher FYI 2.0 risk scores in both the social-communication and sensory-regulatory domains than typically developing infants. New FYI 2.0 cutoff scores for HR sample were explored by evaluating various cutoff options after considering tradeoffs between sensitivity and specificity and sample characteristics.

Preliminary Efficacy of Family Implemented TEACCH for Toddlers: Effects on Parents and Their Toddlers with Autism Spectrum Disorder.

This study examined the effects of an intervention to support parents and promote skill development in newly diagnosed toddlers with ASD. Participants included 50 children with ASD under 3 and their parents who were randomly assigned to participate in a 6-month intervention, Family Implemented TEACCH for Toddlers (FITT) or 6 months of community services as usual. FITT included 90-min in-home sessions (n = 20) and parent group sessions (n = 4). Results revealed significant treatment effects on parent stress and well-being, with families in the FITT group showing decreased stress and improved well-being over time. While no treatment effects were found for global child measures, there were significant treatment effects on social communication skills.

Cascading effects of attention disengagement and sensory seeking on social symptoms in a community sample of infants at-risk for a future diagnosis of autism spectrum disorder.

Recent work suggests sensory seeking predicts later social symptomatology through reduced social orienting in infants who are at high-risk for autism spectrum disorder (ASD) based on their status as younger siblings of children diagnosed with ASD. We drew on extant longitudinal data from a community sample of at-risk infants who were identified at 12 months using the First Year Inventory, and followed to 3-5 years. We replicate findings of Damiano et al. (in this issue) that a) high-risk infants who go on to be diagnosed with ASD show heightened sensory seeking in the second year of life relative to those who do not receive a diagnosis, and b) increased sensory seeking indirectly relates to later social symptomatology via reduced social orienting. We extend previous findings to show that sensory seeking has more clinical utility later in the second year of life (20-24 months) than earlier (13-15 months). Further, this study suggests that diminished attention disengagement at 12-15 months may precede and predict increased sensory seeking at 20-24 months. Findings add support for the notion that sensory features produce cascading effects on social development in infants at risk for ASD, and suggest that reduced attention disengagement early in life may set off this cascade.

Parent-Mediated Intervention for One-Year-Olds Screened as At-Risk for Autism Spectrum Disorder: A Randomized Controlled Trial.

Theoretically, interventions initiated with at-risk infants prior to the point in time a definitive autism spectrum disorder (ASD) diagnosis can be made will improve outcomes. Pursuing this idea, we tested the efficacy of a parent-mediated early intervention called Adapted Responsive Teaching (ART) via a randomized controlled trial with 87 one-year-olds identified by community screening with the First Year Inventory as at-risk of later ASD diagnoses. We found minimal evidence for main effects of ART on child outcomes. However, ART group parents showed significantly greater increases in responsiveness to their infants than control group parents. Further, significant indirect (mediation) effects of assignment group on multiple child outcomes through changes in parent responsiveness supported our theory of change.

Predictors of Parent Responsiveness to 1-Year-Olds At-Risk for Autism Spectrum Disorder.

Parent responsiveness is critical for child development of cognition, social-communication, and self-regulation. Parents tend to respond more frequently when children at-risk for autism spectrum disorder (ASD) demonstrate stronger social-communication; however, it is unclear how responsiveness is associated with sensory characteristics of children at-risk for ASD. To address this issue, we examined the extent to which child social-communication and sensory reactivity patterns (i.e., hyper- and hypo-reactivity) predicted parent responsiveness to 1-year-olds at-risk for ASD in a community sample of 97 parent-infant pairs. A combination of child social-communication and sensory hypo-reactivity consistently predicted how parents played and talked with their 1-year-old at-risk for ASD. Parents tended to talk less and use more play actions when infants communicated less and demonstrated stronger hypo-reactivity.

Late Positive Potential ERP Responses to Social and Nonsocial Stimuli in Youth with Autism Spectrum Disorder.

We examined the late positive potential (LPP) event related potential in response to social and nonsocial stimuli from youths 9 to 19 years old with (n = 35) and without (n = 34) ASD. Social stimuli were faces with positive expressions and nonsocial stimuli were related to common restricted interests in ASD (e.g., electronics, vehicles, etc.). The ASD group demonstrated relatively smaller LPP amplitude to social stimuli and relatively larger LPP amplitude to nonsocial stimuli. There were no group differences in subjective ratings of images, and there were no significant correlations between LPP amplitude and ASD symptom severity within the ASD group. LPP results suggest blunted motivational responses to social stimuli and heightened motivational responses to nonsocial stimuli in youth with ASD.

Brief Report: Cognitive Control of Social and Nonsocial Visual Attention in Autism.

Prosaccade and antisaccade errors in the context of social and nonsocial stimuli were investigated in youth with autism spectrum disorder (ASD; n = 19) a matched control sample (n = 19), and a small sample of youth with obsessive compulsive disorder (n = 9). Groups did not differ in error rates in the prosaccade condition for any stimulus category. In the antisaccade condition, the ASD group demonstrated more errors than the control group for nonsocial stimuli related to circumscribed interests, but not for other nonsocial stimuli or for social stimuli. Additionally, antisaccade error rates were predictive of core ASD symptom severity. Results indicate that the cognitive control of visual attention in ASD is impaired specifically in the context of nonsocial stimuli related to circumscribed interests.