Evaluation of a Novel Intervention for Infants At Risk for Neurodevelopmental Disorders
Condition: Autism Spectrum Disorder; Neurodevelopmental Disorders
MeSH terms: Autism Spectrum Disorder; Neurodevelopmental Disorders
Study type: Interventional

Summary: 
      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: 
      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.
    

Intervention name(s): Parents and Infants Engaged
Intervention type(s): Behavioral
Intervention description(s): 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.
Other intervention name(s): PIE
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Outcomes Assessor)
Primary purpose: Treatment
Keywords: communication; sensory; early intervention; parent coaching