Congenital Heart Disease: Impact on Learning and Development in Down Syndrome (CHILD-DS)

Study Overview
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Brief Summary
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The study objective is to compare neurodevelopmental (ND) and behavioral outcomes between children with Down syndrome (DS) who had complete atrioventricular septal defect (CAVSD) repair and children from the same clinical sites with DS without major congenital heart disease (CHD) requiring previous or planned CHD surgery.

Detailed Description
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We are conducting a multicenter cohort study, ancillary to the Pediatric Heart Network (PHN) Residual Lesion Score (RLS) study, to investigate determinants of ND and behavioral outcomes in children with DS, focusing on the role of CHD surgery. We are including children with DS who had CAVSD repair, as this group comprises 91% of all children with DS in the RLS Study, with similar underlying congenital cardiac defect and surgical repair complexity, allowing our children with DS and CHD to be a homogeneous group. Moreover, one in five individuals with DS is born with an AVSD, a 2000 times higher incidence than in those with normal chromosomes. In addition to recruiting children with DS who had CAVSD repair, we will recruit similarly-aged children with DS who do not have documented major CHD (i.e., CHD requiring previous or planned CHD surgery) to come into the same PHN site for a single study visit consisting of detailed phenotyping by completion of a Health & Developmental History Intake form, ND and behavioral assessments, and optional collection and storage of saliva specimens in the PHN Biorepository. By building our sample from RLS Study participants and recruiting additional children who had infant CAVSD repair and meet study eligibility criteria, as well as a comparison group from the same PHN sites, we are leveraging rich prospective data in a group of DS children with CAVSD repair from a nationally representative sample, and the expertise of the PHN and Boston Children's Hospital (BCH).

Official Title
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Congenital Heart Disease: Impact on Learning and Development in Down Syndrome (CHILD-DS)

Conditions
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Down Syndrome, Congenital Heart Disease

Intervention / Treatment
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* Other: Stanford Binet Intelligence Scales, Fifth Edition
* Other: Vineland Adaptive Behavior Scales Third Edition
* Other: Peabody Picture Vocabulary Test, Fifth Edition
* Other: Expressive Vocabulary Test, Third Edition
* Other: Leiter International Performance Scale, Third Edition
* Other: Social Communication Questionnaire, Current Form
* Other: Aberrant Behavior Checklist
* Other: Repetitive Behavior Scale, Revised


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Down Syndrome CAVSD Repair Group: Trisomy 21 Male or Female, ages 5 years through 12 years Had CAVSD repair within the first year of life Parent or guardian and patient willing to comply with protocol and complete all study assessments; parent or guardian willing to provide written informed consent Child able to speak and understand English Down Syndrome Comparison Group Trisomy 21 Male or Female, age 5 years through 12 years No major CHD, defined as CHD requiring previous or planned CHD surgery Parent or guardian and patient willing to comply with protocol and complete all study assessments; parent or guardian willing to provide written informed consent Child able to speak and understand English Exclusion Criteria: Both Groups - Mosaic DS Down Syndrome CAVSD Repair Group only - Did not have CAVSD repair in the first year of life Down Syndrome Comparison Group only - Major CHD requiring previous or planned CHD surgery - i.e., CHD surgery occurring (a) in the period between birth and time of recruitment into the CHILD-DS Study, or (b) planned for a future date.

Ages Eligible for Study
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Minimum Age: 60 Months
Maximum Age: 155 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DS with CAVSD Repair<br>Children ages 5 through 12 years with Down syndrome who had Complete atrioventricular septal defect (CAVSD) repair in the first year of life and their parent(s) will be administered the Stanford-Binet Intelligence Scales, Fifth Edition (SB-5), Peabody Picture Vocabulary Test, Fifth Edition (PPVT-5), Expressive Vocabulary Test, Third Edition (EVT-3), Leiter International Performance Scale, Third Edition (Leiter-3), Vineland-3 Q-global Comprehensive Report (Vineland-3) ,Social Communication Questionnaire, Current version (SCQ), Aberrant Behavior Checklist, Second Edition, (ABC-2) and Repetitive Behavior Scale, Revised (RBS-R) | Other: Stanford Binet Intelligence Scales, Fifth Edition<br>* The SB-5 is a comprehensive measure of cognitive and intellectual functioning for individuals from age two through 85 years of age. The SB-5 individually assess a child's functioning in five areas of cognitive functioning: Fluid Reasoning, Knowledge, Quantitative Reasoning, Visual Spatial, and Working Memory. The SB-5 is well established in the existing research literature as an assessment tool to evaluate developmental and intellectual abilities in children with ND disorders.<br>* Other names: SB-5;Other: Vineland Adaptive Behavior Scales Third Edition<br>* The VABS-3 are a parent report, interview style measure of adaptive behavior for individuals ages birth through 90 months. The VABS-3 assesses adaptive behavior in four broad domains of Communication, Daily Living Skills, Socialization, and Motor Skills, and includes a Maladaptive Behavior Domain that assesses problem behaviors.<br>* Other names: VABS-3;Other: Peabody Picture Vocabulary Test, Fifth Edition<br>* The PPVT-5 is a norm-referenced language measure that evaluates single-word receptive vocabulary. The PPVT-5 provides standard scores for individuals ages 2.6 through 90 years.<br>* Other names: PPVT-5;Other: Expressive Vocabulary Test, Third Edition<br>* The EVT-3 is a norm-referenced language measure that evaluates single-word expressive vocabulary. The EVT-3 provides standard scores for individuals ages 2.6 through 90 years.<br>* Other names: EVT-3;Other: Leiter International Performance Scale, Third Edition<br>* The Leiter-3 is a nonverbal measure of cognitive functioning and fluid reasoning skills in individuals ages 3 through 75 years. The Leiter-3 measures nonverbal IQ across four subscales, including Sequential Order (SO), Form Completion (FC), Classification and Analogies (CA), and Figure Ground (FG).<br>* Other names: Leiter-3;Other: Social Communication Questionnaire, Current Form<br>* The SCQ is a parent-report measure of social communication, social interactions, play, and behavior.<br>* Other names: SCQ;Other: Aberrant Behavior Checklist<br>* The ABC-2 is a parent report measure of problematic behavior at home and in the community. It measures behavior on five subscales (1) Irritability, (2) Social Withdrawal, (3) Stereotypic Behavior, (4) Hyperactivity/Noncompliance, and (5) Inappropriate Speech.<br>* Other names: ABC-2;Other: Repetitive Behavior Scale, Revised<br>* The RBS-R is a parent report measure that comprehensively surveys for the presence of repetitive behaviors.<br>* Other names: RBS-R;|
| DS without major CHD<br>Children ages 5 through 12 years with Down syndrome without major Congenital Heart Disease(CHD) and their parent(s) will be administered the Stanford-Binet Intelligence Scales, Fifth Edition (SB-5), Peabody Picture Vocabulary Test, Fifth Edition (PPVT-5), Expressive Vocabulary Test, Third Edition (EVT-3), Leiter International Performance Scale, Third Edition (Leiter-3), Vineland-3 Q-global Comprehensive Report (Vineland-3) ,Social Communication Questionnaire, Current version (SCQ), Aberrant Behavior Checklist, Second Edition, (ABC-2) and Repetitive Behavior Scale, Revised (RBS-R) | Other: Stanford Binet Intelligence Scales, Fifth Edition<br>* The SB-5 is a comprehensive measure of cognitive and intellectual functioning for individuals from age two through 85 years of age. The SB-5 individually assess a child's functioning in five areas of cognitive functioning: Fluid Reasoning, Knowledge, Quantitative Reasoning, Visual Spatial, and Working Memory. The SB-5 is well established in the existing research literature as an assessment tool to evaluate developmental and intellectual abilities in children with ND disorders.<br>* Other names: SB-5;Other: Vineland Adaptive Behavior Scales Third Edition<br>* The VABS-3 are a parent report, interview style measure of adaptive behavior for individuals ages birth through 90 months. The VABS-3 assesses adaptive behavior in four broad domains of Communication, Daily Living Skills, Socialization, and Motor Skills, and includes a Maladaptive Behavior Domain that assesses problem behaviors.<br>* Other names: VABS-3;Other: Peabody Picture Vocabulary Test, Fifth Edition<br>* The PPVT-5 is a norm-referenced language measure that evaluates single-word receptive vocabulary. The PPVT-5 provides standard scores for individuals ages 2.6 through 90 years.<br>* Other names: PPVT-5;Other: Expressive Vocabulary Test, Third Edition<br>* The EVT-3 is a norm-referenced language measure that evaluates single-word expressive vocabulary. The EVT-3 provides standard scores for individuals ages 2.6 through 90 years.<br>* Other names: EVT-3;Other: Leiter International Performance Scale, Third Edition<br>* The Leiter-3 is a nonverbal measure of cognitive functioning and fluid reasoning skills in individuals ages 3 through 75 years. The Leiter-3 measures nonverbal IQ across four subscales, including Sequential Order (SO), Form Completion (FC), Classification and Analogies (CA), and Figure Ground (FG).<br>* Other names: Leiter-3;Other: Social Communication Questionnaire, Current Form<br>* The SCQ is a parent-report measure of social communication, social interactions, play, and behavior.<br>* Other names: SCQ;Other: Aberrant Behavior Checklist<br>* The ABC-2 is a parent report measure of problematic behavior at home and in the community. It measures behavior on five subscales (1) Irritability, (2) Social Withdrawal, (3) Stereotypic Behavior, (4) Hyperactivity/Noncompliance, and (5) Inappropriate Speech.<br>* Other names: ABC-2;Other: Repetitive Behavior Scale, Revised<br>* The RBS-R is a parent report measure that comprehensively surveys for the presence of repetitive behaviors.<br>* Other names: RBS-R;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurodevelopmental outcomes between children with DS who had CAVSD repair and children from the same clinical sites with DS without major CHD. | Verbal and non-verbal ratio intelligent quotients (IQs) derived from the Stanford Binet Intelligence Scales will be compared between the children with DS and CAVSD repair and the children with DS without major CHD. | 1 day | 
| Behavioral outcomes between children with DS who had CAVSD repair and children from the same clinical sites with DS without major CHD. | Adaptive composite scores from the Vineland Adaptive Behavior Scales will be compared between the children with DS and CAVSD repair and the children with DS without major CHD. | 1 day | 
| Language abilities compared between the children with DS and CAVSD repair and the children with DS without major CHD. | Using the Peabody Picture Vocabulary Test, Expressive Vocabulary Test, and Leiter International Performance Scale total language, auditory comprehension, and expressive communication will be compared between the children with DS and CAVSD repair and the children with DS without major CHD. | 1 day | 
| Emotional outcomes compared between the children with DS and CAVSD repair and the children with DS without major CHD. | Using the Repetitive Behavior Scale and Aberrant Behavior Checklist , behavioral and emotional problems will be compared will be compared between the children with DS and CAVSD repair and the children with DS without major CHD. | 1 day | 
| Social Communication compared between the children with DS and CAVSD repair and the children with DS without major CHD. | Using the Social Communication Questionnaire, social communication, social interactions, play and behavior will be compared between the children with DS and CAVSD repair and the children with DS without major CHD. | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comorbidities as predictors of neurodevelopment and behavior | Comorbidities will be compared between the children with DS and CAVSD repair and the children with DS without major CHD. | 1 day | 
| Sociodemographic factors as predictors of neurodevelopment and behavior | Sociodemographic factors, such as will be compared between the children with DS and CAVSD repair and the children with DS without major CHD. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Down Syndrome, CHD, Congenital Heart Disease, Pediatric Heart Network, INCLUDE