PIXI intervention—Phase I.

Phase I will begin when the infant is between 3 and 7 months old, depending on the age of diagnosis and enrollment in the study. The intention is that all participants transition from Phase I to Phase II by the time the infant is 9 months of age. The first phase of PIXI aims to (1) establish rapport with the family and infant and develop a rhythm of scheduled sessions; (2) engage in parent-child interactive activities, setting the foundation for work covered during Phase II; and (3) provide support and psychoeducation to parents and families about their child’s diagnosed NGC and early child development. Sessions will be offered weekly or biweekly (frequency depending on the age of the infant and needs of the family), with a total of eight sessions administered. Phase I is designed to be flexible and be adapted based on the family or infant needs. However, each session will follow a structured format with guiding topics from the PAT curriculum. The format for Phase I sessions can be found in Table 2.

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Table 2. Sample Phase I session.

https://doi.org/10.1371/journal.pone.0270169.t002

PAT [7] is an evidence-based program based in human ecological and family systems theory that provides services within the family context focused on parent-child interaction and relationships. Initially developed to enhance knowledge around child development and positive parenting skills, PAT uses parent coaching and empowerment strategies in a variety of parent populations ranging from birth to school age with a focus on both parent- and child-level outcomes. PAT sessions include three primary components designed to provide support around enhancing family protective factors and parent empowerment: parent-child interaction, development-centered parenting, and family well-being. To accommodate unique challenges that may arise from new parents facing a potentially unexpected diagnosis, we will embed a psychoeducational component that includes opportunities for parents to gain additional knowledge about their child’s NGC and process their emotions about the diagnosis.

1. Parent-Child Interaction: The goal of parent-child interaction discussion and activities is to provide the opportunity for parents to learn how to interactively engage with their infant through a facilitated assisted-learning model. Parents are provided with activity sheets and handouts that provide context and guidance about the activity as the interventionist reviews and provides real-time affirmation of efforts. After the activity, parents are asked to reflect on things they noticed their baby doing and things they noticed in themselves. Phase I activities were selected from Foundational Curriculum materials that allowed for free play, sensory play, and motor activities.
2. Development-Centered Parenting: The PAT Foundational Curriculum includes a discussion of seven developmental topics: attachment, discipline, health, nutrition, safety, sleep, and transitions and routines. The goal is to have parents better understand developmental progress and adapt their parenting behaviors to meet their child’s needs at a specific stage in development. A review of all topics is included in Phase I, with flexibility around the discussion dependent on parent questions, family routines, and familiarity with concepts.
3. Family Well-Being: Within the PAT model, family well-being aims to bring to light the impact of parent and family circumstance and experience along with constant familial growth and change, on development, early learning, and overall health. Family well-being topics include basic essentials (e.g., food, nutrition, housing), education and employment (e.g., job training, college), physical health (e.g., medical and dental, injury prevention), mental health and wellness (e.g., stress, crisis intervention, community wellness services), early-care and education (e.g., childcare, preschool), relationships with family and friends (e.g., social support networks, community groups), and recreation and environment (e.g., community outings, leisure opportunities). All family well-being topics are presented to Phase I participants.
4. Psychoeducation about the NGC. Phase I includes provision of educational materials about their child’s NGC based on needs and questions raised by each participating family. Materials will be developed in conjunction with EI service providers with expertise in each target NGC, licensed genetic counselors, family advocates, and advocacy organizations (e.g., the National Fragile X Foundation). These resources include information about the basic genetics of the condition and generational family implications (if applicable); information for providers and physicians about the disorder; early child development topics such as feeding, eating, sleeping, and child development. Eligibility for community-based EI programming will be discussed with parents during this phase, and referrals made to local EI providers as warranted. With parent permission, PIXI interventionists will work closely with EI service providers to enhance communication and coordinated care across settings.

After completion of each session, the interventionist will complete a modified version of the PAT visit record to ensure consistent reporting of topics covered during each session, aligned with PAT fidelity, and the opportunity to integrate clinical notes used for iterative development and qualitative analysis of needs. See Table 2 for an outline of session flow and components.

Phase I to Phase II transition.

Upon completion of Phase I, a transition session will be completed between participants and interventionists. This transition session focuses primarily on the differences in procedures and protocols between the two phases, including session opening play sessions, topic review, parent coaching, and discussion of week-to-week practice topics. Interventionists will also take time during this session to orient to family priorities and current concerns, and answer questions. A 10-minute recorded parent-child free play interaction will also be conducted as a baseline assessment prior to Phase II. At the conclusion, a schedule for Phase II is discussed.

Phase II.

Phase II will adapt Infant Start [8], a downward extension of the Early Start Denver Model (ESDM) curriculum [15], as an individualized, low-intensity parent-delivered intervention targeted at reducing and altering six developmental target symptoms and developmental patterns of ASD. Infant Start attempts to meet the unique needs of young infants suspected and later diagnosed on the autism spectrum by implementing practices identified in efficacious interventions for infants, including (1) parent coaching with a focus on both parental responsivity and sensitivity to child cues and teaching families to implement infant interventions; (2) individualization to each infant’s developmental profile; (3) a focus on a broad rather than a narrow range of learning targets, and (4) interventions beginning as early as possible and providing greater intensity and duration of the intervention [16]. Infant Start is a manualized, unpublished intervention in which parents are coached on techniques to address six target symptoms: (1) visual fixations on objects; (2) abnormal repetitive behaviors; (3) lack of intentional communicative acts; (4) lack of coordination of gaze, affect, and voice in reciprocal turn-taking interactions; (5) lack of age-appropriate phonemic development; and (6) decreasing gaze, social interest, and engagement. A pilot study of Infant Start found significantly fewer symptoms and lower rates of ASD and developmental quotient scores under 70 at age 36 months in participating infants than a similarly symptomatic group of infants not enrolled in the study [16]. The model was well received by parents, and parents were able to achieve high fidelity of implementation at a low intensity (12 weekly sessions).

In addition to the core themes and manualized chapters of the original Infant Start manual, an additional chapter focused on motor development has been developed to meet the unique needs of infants with NGCs. This chapter, developed in collaboration with one of the Infant Start co-developers and infant physical and occupational therapists, focuses on supporting parental observation and understanding of infant motor development along with strategies to foster strength building and increased functional movements of the baby’s hands and body.

PIXI child participants will begin Phase II by 9 months of age. Phase II consists of 12 weekly or bi-weekly, 1-hour telehealth sessions. Based on completed milestone checklists and discussion with parents about current concerns and goals for intervention, the interventionist develops three to six learning objectives to target during treatment. Learning objectives are based on each infant’s developmental profile of strengths and areas of weakness, with focus in domains that are related to social learning and social-cognitive development, including verbal and nonverbal language, social orienting, and joint attention. Learning objectives also include a focus on motor development, as this is often one of the first symptoms reported by parents of infants with the target NGCs [17], and delays in motor skills often lead to delays in communication. Learning objectives are targeted during each session and embedded into the practice and reflection activities.

Prior to each session, the interventionist will send the family a corresponding coaching chapter, capturing a summary of the topic and written explanation of strategies and scenarios to be the focus of that upcoming session. Each session consists of six sequenced 5- to 10-minute activities. Sessions begin with a greeting/check-in in which the interventionist gathers information about implementation of strategies and child progress throughout the time between sessions, followed by a warm-up activity between child and parent to demonstrate previously learned skills and provide a reflection opportunity with interventionist on goals and elicited child behaviors. The interventionist then introduces topic and theme for the session and provides verbal and written information to parent about manualized session content (see Table 3). The parent then practices using the strategies while the interventionist uses coaching strategies to support the parent’s implementation and self-reflection. The parent is then encouraged to practice the strategy within another play or caregiving activity (e.g., feeding, dressing, books, social play), while the interventionist again coaches the parent in implementation and self-reflection. The session closing involves a discussion between the parent and interventionist about how to generalize these strategies across settings, routines, materials, and family members (see Table 3).

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Table 3. Sample Phase II session.

https://doi.org/10.1371/journal.pone.0270169.t003

The interventionist uses parent-coaching strategies [18] to help parents use the interactive strategies with their infant. The first six sessions of Phase II focus on setting the stage for parent-child interactions, getting into the spotlight, following the infant’s lead, and supporting early language development. After session 6, the family participates in a mid-point check-in for the family to provide updates on family status, ask questions about the NGC or Phase I topics (e.g., development-centered parenting, family well-being), and follow up on any coordination of community-based EI services. The remaining six sessions focus on motor development, restricted and repetitive play and behaviors, joint attention, and bundling social communication skills. After completing all 12 sessions, families collaborate with the interventionist to identify a topic for a booster session in which previous sessions are repeated. Determination of topic may be based on parents’ goals and/or interventionist’s evaluation of parent’s implementation of strategies. A minimum of one booster session is completed, with a maximum of three booster sessions delivered bi-weekly until the child turns 15 months of age.

The interventionist fidelity of treatment implementation is assessed and measured using the ESDM Parent(s) Coaching Fidelity system [14], a 5-point rating scale of 13 coaching behaviors: (1) review of progress; (2) demonstration of parent implementation; (3) introduction of topic; (4) coaching on topic; (5) coaching on generalization of topic; (6) discussion of generalization; (7) collaboration and partnership with parent; (8) reflection coaching (9) non-judgmental feedback; (10) conversation and reciprocity; (11) ethical conduct; (12) organization and management of session; and (13) management of conflict or implementation difficulties.

Interactions with community EI programming.

PIXI is not meant to replace community-based EI programming. PIXI interventionists will encourage all families to connect with EI providers and will make appropriate referrals where warranted. With parental permission, the PIXI interventionist will communicate directly with the family’s EI coordinator and collaborate with services providers to support synergistic intervention delivery.

Project website.

A website and accompanying smartphone app will be available to help sharing information, scheduling sessions, and completing study measures.

Retention.

Interventionists will be in close contact with all families across their first year of participation. Communication will occur via email and over video-conferencing weekly. A separate team of assessors will communicate with the family to schedule assessments. Resources and access to interventionists will be provided via the project website and app in addition to traditional email/phone call options. Upon the completion of each assessment timepoint, parents will be provided $50 via e-gift card for their time and insight. Parents do not receive financial incentives for participating in intervention sessions.

Primary outcome measures.

Primary outcome measures address feasibility and acceptability of the intervention.

1. Recruitment will be deemed feasible if we can meet our target of 20–30 families enrolled within the study period. Qualitative notes on barriers to participation for those who express interest but cannot enroll will inform potential future challenges for scaling up the intervention model.
2. Retention goals will be assessed by determining the number and percentage of families who complete at least 75% of the proposed 20 sessions and at least two post-intervention assessments. A retention of 80% of the sample (at least 16–24 families completing the sessions) will be considered acceptable.
3. Acceptability of the intervention will be assessed through use of a social validity questionnaire and an interview with each family by an independent research associate not on the intervention team. The social validity measure was developed by one of the current investigators to examine acceptability of EI programs. The measure asks questions about the family’s experience with various components (e.g., materials, activities, interventionist, virtual format) and with the intervention as a whole. This will be conducted after each phase of the intervention. The interview targets domains of acceptance, satisfaction, and feasibility of the intervention as a whole and will be conducted at the conclusion of the intervention. Rapid qualitative analysis of the targeted domains will be conducted following the completion of all participant interviews and will be used to assess acceptability and identify areas for modification/improvement for future iterations of the program.
4. Parent and therapist fidelity of intervention administration will be assessed with the adapted Parent Implementation Rating Form [19] and the Infant Start Parent Fidelity Tool [19, 20].

The Parent Implementation Rating Form includes eight items rated on a 7-point Likert scale by the interventionist after each session. The measure captures parent’s participation and engagement behaviors, including (1) readiness for session; (2) use of knowledge and skills between sessions; (3) reflection of changes in child’s behaviors; (4) engagement and attentiveness; (5) interactions with infant; (6) relevant questions and comments; (7) demonstrated understanding of topic; and (8) collaboration in generating ideas for practice. Scores were tallied, and an overall rating of effectiveness (minimal, moderate, maximum) was identified for each session.

Secondary outcome measures.

The secondary outcome measures examine fidelity of parent implementation, early developmental skills, and autism symptomology using a combination of parent report and observational standardized assessment measures for remote administration.

A modified version of the Infant Start Parent Fidelity Tool will be used. This tool includes 14 items rated on a 3-point Likert scale (seldom present, sometimes present, always present). Items are associated with the parenting behaviors and strategies discussed during weekly sessions (see Table 1). Parent fidelity will be consensus-coded based on a review of video-taped interactions for all participants by two team members who are blinded to topic session and number.

A diagnostic clinical assessment will be conducted with each child participant, administered by licensed clinicians who are not part of the intervention team. Participants will receive a remotely delivered assessment that includes a diagnostic interview and the TELE-ASD-PEDS [21]. The TELE-ASD-PEDS is a telehealth-based assessment that involves the parent engaging in basic tasks with their young child while being observed by a trained clinician. Observations are combined with diagnostic interview data to determine the likelihood that the child has an ASD. Seven symptoms of ASD are coded on a three-point Likert scale (symptom not present; symptom present but at subclinical levels; symptom obviously consistent with autism). These symptoms are totaled to provide an overall score along with the clinician’s certainty of their diagnostic impression.

Parent report of symptoms will be collected through the Communication and Symbolic Behavior Scales (CSBS; [22]); Modified Checklist for Autism in Toddlers (MCHAT; [23]); the Repetitive Behavior Scale for Early Childhood (RBS-EC; [24]); Sensory Profile-2, [25] and Vineland Adaptive Behavior Scales, Third Edition [26] The CSBS provides an overview of early predictors of language and social communicative behaviors, whereas the MCHAT is a validated tool for screening risk for ASD in children between 16 and 36 months of age. The RBS-EC and Sensory Profile-2 measure repetitive behaviors and sensory issues often observed in children with NGC, ASD, or both. The Vineland Adaptive Behavior Scales, Third Edition (Vineland-3; [26]) is a standardized parent/caregiver report measure of language, motor, social/leisure, and overall adaptive functioning in individuals across the lifespan, measuring what an individual does independently in day-to-day life.

Additional assessments will be collected at each timepoint to provide a comprehensive understanding of infant development within the first 3 years of life for children identified with NGC pre-symptomatically. These assessments include an examination of sleep [27], feeding [28, 29], and behavior [30, 31].

Understanding that an early diagnosis of an NGC can be difficult for parents and a supportive intervention may have positive impacts on caregivers, we will also assess parental mental health at each timepoint. Depressive symptomology/risk will be captured by the Edinburgh Postnatal Depression Scale [32] within the first year of life and Patient Health Questionnaire-9 [33], and symptoms of anxiety will be captured by the State-Trait Anxiety Inventory [34]. Parenting stress and social support will be examined using the Parenting Stress Inventory, Fourth Edition: Short Form [35] and Medical Outcomes Survey, Social Support Scale [36]. Additionally, the Behavior Rating Inventory of Executive Functioning, Second Edition, Adult Version [37] will be completed by participating mothers to capture general insight into cognitive functioning.

Data management and quality control.

This non-randomized feasibility pilot includes a variety of participant- and family-level data collected through parent report and direct assessment. Questionnaires will be completed primarily through online assessment portals and through the Research Electronic Data Capture system [38]. Data will be collected and managed by PIXI research staff, led by team members not engaged in direct intervention provision. Social validity and parent acceptability (i.e., completion interview) will be completed via phone in an interview format with participants by a qualitative research expert blind to study procedures and participant engagement.

Statistical methods.

Our primary outcomes are related to feasibility and acceptability metrics, which will involve descriptive data on the number of participants who complete most of the sessions and qualitative review of parent reports of satisfaction with the program as a whole and with specific components. Secondary analysis will involve data pertaining to child development and parent well-being. Individual scores on the secondary data measures will be plotted graphically, and visual analysis will be used to assess change across timepoints. We will also compare the overall mean scores on secondary outcome measures from our sample to that of prior published scores from natural history studies in the target NGCs. Because we will not be powered to accurately interpret results from statistical modeling, we will rely on visual analysis and simple descriptive statistics to inform decisions regarding signals of efficacy to support a larger-scale trial.

Research ethics approval, protocol amendments, consent.

Institutional Review Board (IRB) approval has been obtained through participating institutions; PIXI is also a registered clinical trial with clinicaltrials.gov (NCT03836300). Prior to participation, a research assistant will review the consent form with potential participants, providing details of what study involvement pertains, including potential benefits and risks. Any changes to the study protocol will undergo review by the IRB of record. Participants will be informed that participation is optional, that they can receive EI services through their community providers, and that they can discontinue with PIXI at any time.

Confidentiality.

All data will be kept in password-protected share drives or within electronically secure networks. Hard-copy data contain unique ID numbers and will be stored in a locked cabinet separate from identifiers.

Ancillary and post-trial care.

Participants will be provided contact information for their interventionist, as well as the study coordinator, study PI, and IRB representative. Parent mental health will be monitored formally through regular assessments and informally during study visits. Materials to support parental coping, including postpartum depression, will be provided to all families, with referrals to specialists made when warranted. The PIXI team includes three licensed mental health professionals who will be available to support interventionists in managing parents in need.

Dissemination policy.

The results of this non-randomized feasibility pilot will be published in a peer-review journal, regardless of the outcome of the study. We will also disseminate findings, including barriers and successes at national and international conferences targeting professionals who work with this population.