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

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.

Study Overview

• Status: Completed
• Conditions: Down Syndrome; Congenital Heart Disease
• Intervention / Treatment: 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

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 273

Contacts and Locations

• Study Contact: Name: Maria VanRompay, PhD; Phone Number: 617-584-7142; Email: MVanRompay@HealthCore.com
• Study Contact Backup: Name: Marissa Esposito; Phone Number: 848-303-6942; Email: mesposito@healthcore.com

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • Hospital for Sick Children
• United States
  • Delaware
    • Wilmington, Delaware, United States, 19899
      • Alfred I. DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Children's National Hospital
  • Georgia
    • Atlanta, Georgia, United States, 30033
      • Children's Healthcare of Atlanta at Egleston
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Boston Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Health System/Mott Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia College of Physicians and Surgeons
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine - Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • Primary Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 9 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

PHN RLS Study participants with DS and CAVSD repair from the PHN sites are eligible to participate in this study. Children with a diagnosis of mosaic DS will be excluded, as these forms of DS show different ND trajectories and are usually excluded. While data on mosaic DS were not collected in the RLS Study, we anticipate few if any to have this diagnosis. The DS comparison group will be required to have no major CHD, defined as CHD that requires CHD surgery (a) in the period between birth and recruitment into the CHILD-DS Study or (b) planned for a future date.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DS with CAVSD Repair; 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; 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.; Other Names: SB-5; Other: Vineland Adaptive Behavior Scales Third Edition; 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.; Other Names: VABS-3; Other: Peabody Picture Vocabulary Test, Fifth Edition; 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.; Other Names: PPVT-5; Other: Expressive Vocabulary Test, Third Edition; 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.; Other Names: EVT-3; Other: Leiter International Performance Scale, Third Edition; 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).; Other Names: Leiter-3; Other: Social Communication Questionnaire, Current Form; The SCQ is a parent-report measure of social communication, social interactions, play, and behavior.; Other Names: SCQ; Other: Aberrant Behavior Checklist; 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.; Other Names: ABC-2; Other: Repetitive Behavior Scale, Revised; The RBS-R is a parent report measure that comprehensively surveys for the presence of repetitive behaviors.; Other Names: RBS-R
DS without major CHD; 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; 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.; Other Names: SB-5; Other: Vineland Adaptive Behavior Scales Third Edition; 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.; Other Names: VABS-3; Other: Peabody Picture Vocabulary Test, Fifth Edition; 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.; Other Names: PPVT-5; Other: Expressive Vocabulary Test, Third Edition; 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.; Other Names: EVT-3; Other: Leiter International Performance Scale, Third Edition; 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).; Other Names: Leiter-3; Other: Social Communication Questionnaire, Current Form; The SCQ is a parent-report measure of social communication, social interactions, play, and behavior.; Other Names: SCQ; Other: Aberrant Behavior Checklist; 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.; Other Names: ABC-2; Other: Repetitive Behavior Scale, Revised; The RBS-R is a parent report measure that comprehensively surveys for the presence of repetitive behaviors.; Other Names: RBS-R

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Carelon Research
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Maria VanRompay, PhD, Carelon Research

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: February 24, 2020
• First Submitted That Met QC Criteria: March 31, 2022
• First Posted (Actual): April 5, 2022

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Congenital Heart Disease; Down Syndrome; CHD; Pediatric Heart Network; INCLUDE
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Cardiovascular Abnormalities; Abnormalities, Multiple; Chromosome Disorders; Heart Diseases; Syndrome; Down Syndrome; Heart Defects, Congenital
• Other Study ID Numbers: CHILD-DS; 3U24HL135691-03S1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Public Use Datasets are created after study closeout and are made available on the PHN public website. Annotated study data collection forms, Statistical Analysis Program (SAS) datasets, and excel datasets are made available, as well as de-identified study cohort characteristics.
• IPD Sharing Time Frame: Data is available one year after study closeout and is available indefinitely.
• IPD Sharing Access Criteria: log-in and password
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No