Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders

Study Overview
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Brief Summary
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This study entails a proof of concept evaluation of a novel intervention, Parents and Infants Engaged (PIE), for prodromal infants at-risk for neurodevelopmental disorders (NDs). The objectives of the current study are to examine whether the PIE intervention (a) transforms parent-infant transactions over time as intended, thereby facilitating increases in the time infants spend in joint engagement with their parents, and (b) is associated with improved social-communication functioning and positive changes in indices of autonomic self-regulation in infants at-risk for NDs.

Detailed Description
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Rationale: Providing intervention during infancy, before the full emergence of the symptoms that would lead to a diagnosis of ND based on a behavioral phenotype (e.g., autism spectrum disorder (ASD), language disorder, or attention-deficit/hyperactivity disorder) is supported by 4 premises: (1) The first two years of life are an especially active period of neural development. Due to rapid synaptic proliferation and experientially-influenced shaping of functional connectivity, interventions initiated in infancy may be powerful in promoting more typical neural connectivity (2) Biologically-based differences in infants at-risk for NDs lead to observable differences in sensory reactivity and communication behaviors in most infants by 9-15 months, prior to the full emergence of diagnostic symptoms. (3) Differences in infant behaviors influence the quantity and quality of parent responses. (4) Parent-child transactional processes begin early in infancy and impact long-term child outcomes. Based on these premises, the investigators propose a proof of concept evaluation of a novel intervention, Parents and Infants Engaged (PIE), for prodromal infants at-risk for NDs. PIE is designed to directly impact parent responses to behaviors commonly observed in infants at-risk for NDs. Without intervention, these behaviors may fail to elicit parent responses that efficiently scaffold child communication development. Extensive research shows positive associations between caregiver responsiveness and child communication outcomes. Responsiveness is defined by multiple dimensions (i.e., sensitivity, contingency, encouragement, matching interests/activity level, physical affection, quality of language input [e.g., verbal scaffolding], reciprocity, and shared control), which vary within and across caregivers. Children play an active role in eliciting responses from caregivers, emphasizing the co-regulatory or transactional nature of these interactions. This includes biobehavioral co-regulation of arousal levels. Whereas much research comes from studies of typical development, similar transactions occur with young children with NDs. Parent responses vary depending on the preceding behaviors of the child. For example, parents are more likely to respond, and to give a verbal response, to their one-year-olds' gestures than nongestural communicative bids (vocalizations, gaze, actions); also, adults are more likely to respond to infants' speech-like than nonspeech-like vocalizations. Parent responsiveness, in turn, predicts communication outcomes of children with varied NDs. Aims: Specific Aim 1: Evaluate the differential changes in attuned parent responsiveness following coaching on two PIE domains - responses to variable infant (a) sensory reactivity (SR) or (b) prelinguistic communication (PC) - as well as cumulative changes in attuned parent responses following coaching on both PIE domains. Specific Aim 2: Estimate the separate and combined effects of PIE intervention domains on parent-infant engagement and infant-initiated communication with parents. Specific Aim 3: Determine the extent to which autonomic indices of infant self-regulation change over the course of the PIE intervention. Recruitment: To identify infants at-risk for neurodevelopmental disorders, the investigators will use a population-screening method based on birth records in North Carolina, supplemented with distribution of postcards/flyers through physician's offices and public health clinics and email and listserv announcements. Completed First Year Inventories (FYIs) will be scored and screened for risk status. Infants who score at-risk will be flagged, and those families will receive a phone call informing them of the results of the screening (by a qualified/trained project coordinator), and they will be invited for a more comprehensive developmental assessment. Summary of Measures to be Completed at Each Assessment Time point: Baseline/Pretest Full Mullen Scales of Early Learning (MSEL) Sensory Processing Assessment (SPA) Brief Observation of Social Communication Change (BOSCC) (Respiratory Sinus Arrhythmia (RSA)/ Skin Conductance Level (SCL) Protocol Parent-Child Interaction Attention Following Protocol Sensory Experiences Questionnaire (SEQ) MacArthur Bates Communication Development Inventory (MB-CDI) Parent Stress Scale Posttest 1 (6-8 weeks after pretest): Parent- Child Interaction SEQ Posttest 2 (13-16 weeks after pretest): MSEL Receptive and Expressive Language SPA BOSCC RSA/SCL Protocol Parent-Child Interaction Attention Following Protocol SEQ Intervention Rating Profile (intervention group only) The intervention phases of the study will use a randomized comparative trial design, with two phases. For Intervention Study Phase 1, dyads will participate in the Pretest assessment battery; then the project methodologist will randomize families of eligible infants, stratifying randomization by age (<13 months, 30 days or ≥ 14 months). Families will be randomized to one of two treatment arms: Arm 1 families will participate in initial coaching on the SR domain of PIE, and Arm 2 families will participate in initial coaching on the PC domain of PIE. Families will participate in 6 coaching sessions in their respective treatment arms, and then return for Posttest-1 (to test the separate impacts of the PIE content domains on parent responses and infant outcomes). For Intervention Study Phase 2, dyads in Arm 1, will receive 6 coaching sessions on the PC domain, and dyads in Arm 2 will receive 6 coaching sessions on the SR domain; coaching for each group will also review their respective content domain coached in Intervention Study Phase 1. Then families will return for Posttest-2 (to evaluate the effects of the full PIE intervention). Due to COVID-19 restrictions, intervention may be carried out via video-conference platform for no more than one session. Parent-report questionnaires only will be collected in lieu of in-person assessments for Posttest-2 for participants unable to attend in-person. Data Analyses: All data will be cleaned and inspected for outliers, missing data and distributional irregularities. Where error distributions potentially deviate from normality, or heteroscedasticity is suspected, the tests of the contrasts will be conducted using exact (resampling-based) nonparametric methods. Proportional outcomes will be arc sin transformed before entering them into the models. For the frequency count outcome, if counts are not sufficiently large (e.g., ≥ 8) that a normal approximation to a Poisson error distribution is appropriate, Poisson or negative binomial regression methods or nonparametric approaches may be employed. All primary analyses will be conducted to explore a priori contrasts of interest within a repeated measures framework. Of primary interest will be the contrast of Pretest to Posttest-1 scores and the contrast of Pretest to Posttest-2 scores (time effect). In addition, the models will include terms for treatment arm effects and treatment arm-by-time interactions. At Posttest-1, the investigators anticipate statistically significant time, treatment arm, and arm-by-time interactions, with parents showing differentially greater attuned responses to infant SR or PC, consistent with their respective treatment arm. By Posttest-2, however, the investigators predict group equivalence in responsiveness, with no differential time effects. A follow-up test of the contrast between Posttest-1 and Posttest-2 will verify that parents in Arm 1 maintained their attuned SR responsiveness gains, while parents in Arm 2 caught up on attuned SR responsiveness, and vice versa for PC attunement. For H2a, the investigators expect increases in joint engagement from Pretest to Posttest-1, with additional increases at Posttest-2 (time effects), and no differential treatment arm effects or interactions at either Posttest. For H2b, the investigators anticipate minimal increases in infant intentional communication at Posttest-1 in either treatment arm, with comparable improvements (time effects) in each group at Posttest-2. Similarly, on the physiological measures addressing H3a (measured only at Pretest and Posttest-2) the investigators anticipate comparable improvements in RSA and SCL (time effect) in both arms. Although the investigators are performing multiple statistical tests across outcomes and hypotheses in addressing the specific aims, in this project it is more important to avoid overlooking statistical signals of effectiveness of the innovative PIE intervention approach (Type II errors), than avoiding false assertions of effectiveness (Type I errors). The investigators believe it is premature, therefore, to employ conservative adjustments to the Type I error rates in statistical tests, which would compromise the power of statistical tests to detect such signals. Assuming recruitment of 44 infant-parent dyads and allowing for a 9% (n=4) dropout rate, which is consistent with high retention rates (> 95%) in our prior intervention studies, 40 dyads (20 per treatment arm) will have complete data for analyses. Assuming a conventional Type I error rate of .05, and intercorrelations among the repeated measures from .3 to .7, the magnitude of treatment group effects detectable with a .80 statistical power will range from f=.37 to .42, respectively, which are large standardized effects. The magnitude of time effects and time-by-treatment arm interaction effects detectable with a .80 power will range from .27 to .18, also respectively, which are medium-sized standardized effects. Thus, the study is underpowered to detect any but large differences between the treatment arms and medium-sized or larger effects on time and time-by treatment arm interactions. More importantly than the statistical comparisons, though, the analyses will yield key descriptive characterizations of the treatment-arm effects at the two posttest points (i.e.,means, medians, proportions, and variances) on key outcomes, as well as effect size estimates that can be used in planning a larger scaled efficacy trial of the PIE intervention.

Official Title
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Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders

Conditions
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Autism Spectrum Disorder, Neurodevelopmental Disorders

Intervention / Treatment
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* Behavioral: Parents and Infants Engaged


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For the intervention trial: infant must meet risk criteria on the First Years Inventory (Calculated based on data collected in another study where risk status on the FYI was confirmed with follow up at 3 years. We empirically determined combinations of the two FYI domain scores that would sort respondents into at-risk and not-at-risk. The resulting cut-points enabled us to sort children such that we capture about 1/3 of those who would go on to be confirmed as having a autism spectrum diagnosis while misclassifying less than 5% of the typically developing (TD) sample as at-risk). Infants also must score at least one s.d. below the mean on either the Receptive or Expressive subscale t scores AND meet the following SPA inclusion criteria on hyporeactivity (HYPO) or hyperreactivity (HYPER): HYPO: Cut-point (equal or greater than) of 1.69 for Mean of the raw orienting score across 7 items, each with the range of 1 to 4 possible points) HYPER: Cut-point (equal or greater than) of .333 for Mean of the raw approach/avoid novel toys score across 9 items, each with the range of 0 to 2 possible points) OR Any clear defensive response on orienting items or Yes to covering ears to sound (in stereotypies checklist) Exclusion Criteria: families who speak English < 50% of the time at home infants with previously identified genetic disorders (e.g., Down syndrome) infants with identified vision/hearing/physical impairments.

Ages Eligible for Study
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Minimum Age: 11 Months
Maximum Age: 16 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The intervention phases of the study will use a randomized comparative trial design, with two phases. For Study Phase 1, dyads will participate in pretesting; then families will be randomized, stratifying by child age, to one of two treatment arms. Arm 1 families will participate in initial coaching on the PIE sensory reactivity (SR) domain, and Arm 2 families will participate in initial coaching on the PIE prelinguistic communication (PC) domain. Families will participate in 6 weekly coaching sessions in their respective treatment arms, and return for Posttest-1. For Study Phase 2, dyads in Arm 1 will receive 6 weekly coaching sessions on the PC domain, and dyads in Arm 2 will receive 6 weekly coaching sessions on the SR domain. Then families will return for Posttest-2.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PC followed by SR<br>Parents will be coached for 6 weekly sessions in the Parents and Infants Engaged (PIE) intervention pre-linguistic (PC) domain to identify their child's pre-linguistic communication bids during daily routines and respond to those bids in ways that optimize parent-child engagement. After posttest 1, they will be coached for 6 weekly sessions on sensory reactivity bids. | Behavioral: Parents and Infants Engaged<br>* A novel in-home parent coaching intervention addressing transactions between pre-linguistic communication and sensory reactivity in infants at-risk for autism and other NDs on the one hand, and parent responses to infant cues on the other hand, using live coaching and video feedback methods.<br>* Other names: PIE;|
| Experimental: SR followed by PC<br>Parents will be coached for 6 weekly sessions in the Parents and Infants Engaged (PIE) intervention sensory reactions (SR) domain to identify their child's sensory reactions to daily activities and respond to those reactions or modify the environment in ways that optimize parent-child engagement. After posttest 1, they will be coached for 6 weekly sessions on pre-linguistic communication bids. | Behavioral: Parents and Infants Engaged<br>* A novel in-home parent coaching intervention addressing transactions between pre-linguistic communication and sensory reactivity in infants at-risk for autism and other NDs on the one hand, and parent responses to infant cues on the other hand, using live coaching and video feedback methods.<br>* Other names: PIE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Percent of Parent Child Dyadic Engagement Over Time From Baseline to Posttest 1 | This system entails continuous coding of infants' attention engagement into one of 6 mutually exclusive states: unengaged, onlooking, object engaged, person-engaged, supported joint engagement, and coordinated joint engagement. Due to the importance of the construct of engagement to our PIE theory of change, the total percent of time in dyadic engagement (higher level supported + coordinated) will serve as the most proximal intervention outcome (i.e., changes expected at Posttest-1). Recent studies with children with NDs have shown that the coding system is sensitive to change in joint engagement after relatively short interventions. | Baseline, Posttest 1 (6-8 weeks after baseline) | 
| Change in Mean Percent of Parent Child Dyadic Engagement Over Time From Baseline to Posttest 2 | This system entails continuous coding of infants' attention engagement into one of 6 mutually exclusive states: unengaged, onlooking, object engaged, person-engaged, supported joint engagement, and coordinated joint engagement. Due to the importance of the construct of engagement to our PIE theory of change, the total percent of time in dyadic engagement (higher level supported + coordinated) will serve as the most proximal intervention outcome (i.e., changes expected at Posttest-1). Recent studies with children with NDs have shown that the coding system is sensitive to change in joint engagement after relatively short interventions. | Baseline, Posttest 2 (13-16 weeks after baseline) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Rating of Parent Responsiveness to Child Sensory Reactivity Cues From Baseline to Posttest 1 | Parent-child interaction videos will be coded for parent responsiveness to child sensory reactivity cues. These are each rated on a 0-7 scale. Higher scores indicate greater responsivity from parents. | Baseline, Posttest 1 (6-8 weeks after baseline) | 
| Change in Rating of Parent Responsiveness to Child Sensory Reactivity Cues From Baseline to Posttest 2 | Parent-child interaction videos will be coded for parent responsiveness to child sensory reactivity cues. These are each rated on a 0-7 scale. Higher scores indicate greater responsivity from parents. | Baseline, posttest 2 (13-16 weeks after baseline) | 
| Change in Rating of Parent Responsiveness to Child Prelinguistic Communication Cues From Baseline to Posttest 1 | Parent-child interaction videos will be coded for parent responsiveness to child prelinguistic communication cues. These are each rated on a 0-7 scale. Higher scores indicate greater responsivity from parents. | Baseline, Posttest 1 (6-8 weeks after pretest) | 
| Change in Rating of Parent Responsiveness to Child Prelinguistic Communication Cues From Baseline to Posttest 2 | Parent-child interaction videos will be coded for parent responsiveness to child prelinguistic communication cues. These are each rated on a 0-7 scale. Higher scores indicate greater responsivity from parents. | Baseline, Posttest 2 (13-16 weeks after baseline) | 
| Change in Rate of Infant Intentional Communication Over Time, Baseline to Posttest 1 | Rate of child intentional communication during parent-child interaction, coded from videos. Video recordings of parent-child interactions were coded for infants' intentional communication acts (i.e., acts directed to the parent): vocalizations, gestures, or both (acts combining vocalizations and gestures). A total acts variable was calculated for the sum of all communication acts in a recording. The total communication acts variable was transformed into a rate variable (instances per minute) for the purpose of this outcome. | Baseline, Posttest 1 (6-8 weeks after pretest) | 
| Change in Rate of Infant Intentional Communication Over Time, Baseline to Posttest 2 | Rate of infant intentional communication during parent-child interaction, coded from videos. Video recordings of parent-child interactions were coded for infants' intentional communication acts (i.e., acts directed to the parent): vocalizations, gestures, or both (acts combining vocalizations and gestures). A total acts variable was calculated for the sum of all communication acts in a recording. The total communication acts variable was transformed into a rate variable (instances per minute) for the purpose of this outcome. | Baseline, Posttest 2 (13-16 weeks after pretest) | 
| Change in Respiratory Sinus Arrhythmia From Baseline to Posttest 2 During Social Stimuli | Respiratory Sinus Arrhythmia (RSA) levels will be collected using a standard protocol while the child is seated in a high chair exposed to social and non-social stimuli. RSA indexes the variability in heartrate that is associated with respiratory inspiration and expiration. RSA levels are expected to increase with development during exposure to both social and nonsocial stimuli in the context of this protocol. Higher RSA levels during exposure to social stimuli involving child-directed speech have been predictive of better language outcomes in previous studies of preschoolers diagnosed with autism. | Baseline, Posttest 2 (13-16 weeks after baseline) | 
| Change in Respiratory Sinus Arrhythmia From Baseline to Posttest 2 During Non-Social Stimuli | Respiratory Sinus Arrhythmia (RSA) levels will be collected using a standard protocol while the child is seated in a high chair exposed to social and non-social stimuli. RSA indexes the variability in heartrate that is associated with respiratory inspiration and expiration. RSA levels are expected to increase with development during exposure to both social and nonsocial stimuli in the context of this protocol. Higher RSA levels during exposure to social stimuli involving child-directed speech have been predictive of better language outcomes in previous studies of preschoolers diagnosed with autism. | Baseline, Posttest 2 (13-16 weeks after baseline) | 
| Change in Skin Conductance Levels From Baseline to Posttest 2 | Skin conductance levels will be collected using a standard protocol while the child is seated in a high chair exposed to social and non-social stimuli. | Baseline, Posttest 2 (13-16 weeks after baseline) | 
| Change in The Behavioral Observation of Social Communication Change (BOSCC) From Baseline to Posttest 2 | A treatment response measure of social communication behaviors and other behaviors associated with autism spectrum disorder (ASD). Administration of the BOSCC involves a 12-minute video recorded interaction between an examiner and a young child using two standard sets of toys and play with bubbles. Behaviors are coded from video. Total score range is 16-80. Higher scores indicate more atypical social communication skills, lower scores indicate better skills. | Baseline, Posttest 2 (13-16 weeks after baseline) | 
| Change in The Attention Following Protocol (AF Protocol) From Baseline to Posttest 2 | Designed to measure the extent to which children will follow attentional cues of the examiner. Six prompts for attention following are embedded into the larger study protocol. Items are scored dichotomously as yes 1 or no 0.Total score range is 0-6. Higher scores indicate more typical responses to bids for joint attention. | Baseline, Posttest 2 (13-16 weeks after baseline) | 
| Change in Mullen Scales of Early Learning Receptive Language T-Scores From Baseline to Posttest 2 | The Mullen Scales of Early Learning (MSEL) is a standardized developmental assessment for children birth to 58 months, frequently used in studies of children with NDs, This outcome comprises changes in standardized T-scores (Mean = 50, SD = 10) on the MSEL Receptive Language scale. Higher scores indicate greater developmental skills. | Baseline, Posttest 2 (13-16 weeks after baseline) | 
| Change in Mullen Scales of Early Learning Expressive Language T-scores From Baseline to Posttest 2 | The MSEL is a standardized developmental assessment for children birth to 58 months, frequently used in studies of children with NDs, This outcome comprises changes in standardized T-scores (Mean = 50, SD = 10) on the MSEL Expressive Language scale. Higher scores indicate greater developmental skills. | Baseline, posttest 2 (13-16 weeks after baseline) | 
| Change in Sensory Processing Assessment for Young Children From Baseline to Posttest 2 in Hypo-Reactivity | A play-based assessment used to measure children's approach-avoidance to novel sensory toys (i.e., hyper-reactivity) and orienting responses (i.e., hypo-reactivity) across three sensory modalities (auditory, visual, tactile). The investigators will report a mean score for Hypo (range = 1-5) and Hyper (range = 1-5) sensory subscales. Higher scores indicate greater sensory differences in that domain (e.g. a high hypo domain score would indicate more hyposensitive reactions to sensory stimuli seen in the child). | Baseline, posttest 2 (13-16 weeks after baseline) | 
| Change in Sensory Processing Assessment for Young Children From Baseline to Posttest 2 in Hyper-Reactivity | A play-based assessment used to measure children's approach-avoidance to novel sensory toys (i.e., hyper-reactivity) and orienting responses (i.e., hypo-reactivity) across three sensory modalities (auditory, visual, tactile). The investigators will report a mean score for Hypo (range = 1-5) and Hyper (range = 1-5) sensory subscales. Higher scores indicate greater sensory differences in that domain (e.g. a high hypo domain score would indicate more hyposensitive reactions to sensory stimuli seen in the child). | Baseline, posttest 2 (13-16 weeks after baseline) | 
| Change in The Sensory Experiences Questionnaire Version 2.1 From Baseline to Posttest 1 in Hypo-reactivity | A 43 item parent questionnaire that asks about the child's responses to various sensory stimuli in the context of functional activities and daily routines in the child's environment. It also documents strategies parents use to respond to their child's behaviors. Hyper and Hypo mean domain scores will be reported (range = 1-5). Greater domain scores indicate a greater presence of that type of sensory response. | Baseline, posttest 1 (6-8 weeks after baseline) | 
| Change in The Sensory Experiences Questionnaire Version 2.1 From Baseline to Posttest 1 in Hyper-reactivity | A 43 item parent questionnaire that asks about the child's responses to various sensory stimuli in the context of functional activities and daily routines in the child's environment. It also documents strategies parents use to respond to their child's behaviors. Hyper and Hypo mean domain scores will be reported (range = 1-5). Greater domain scores indicate a greater presence of that type of sensory response. | Baseline, posttest 1 (6-8 weeks after baseline) | 
| Change in The Sensory Experiences Questionnaire Version 2.1 From Baseline to Posttest 2 in Hypo-reactivity | A 43 item parent questionnaire that asks about the child's responses to various sensory stimuli in the context of functional activities and daily routines in the child's environment. It also documents strategies parents use to respond to their child's behaviors. Hyper and Hypo mean domain scores will be reported (range = 1-5). Greater domain scores indicate a greater presence of that type of sensory response. | Baseline, posttest 2 (13-16 weeks after baseline) | 
| Change in The Sensory Experiences Questionnaire Version 2.1 From Baseline to Posttest 2 in Hyper-reactivity | A 43 item parent questionnaire that asks about the child's responses to various sensory stimuli in the context of functional activities and daily routines in the child's environment. It also documents strategies parents use to respond to their child's behaviors. Hyper and Hypo mean domain scores will be reported (range = 1-5). Greater domain scores indicate a greater presence of that type of sensory response. | Baseline, Posttest 2 (13-16 weeks after baseline) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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communication, sensory, early intervention, parent coaching