Implementation of Whole Genome Sequencing as Screening in a Diverse Cohort of Healthy Infants

NCT05161169 | Completed

• 1 other identifier: The BabySeq2 Project
• Study Type: interventional
• Target: 500
• Locations: 1 country
• Sites: 4

Brief Summary

This research study is exploring the use of genomic sequencing in the newborn period to screen healthy babies for current and future health risks. The study will enroll a diverse cohort of 500 healthy infants and their parents from Boston, MA; New York City, NY; and Birmingham, AL. A small blood sample will be collected from each infant, and whole genome sequencing will be performed in 1/2 of the cohort following a randomized controlled trial design. 3 months later, the randomization status and sequencing results will be shared with parents and pediatricians. Investigators will study the medical, behavioral, and economic outcomes of genomic sequencing to better understand how this technology can be implemented in outpatient primary care settings.

Conditions

Genetic Predisposition to Disease; Hereditary Diseases

Keywords

genome sequencing; newborn screening; preventive medicine

Outcome Measures

Primary Outcomes (6)

• Monogenic disease risks (MDRs)

  Pathogenic (P) and likely pathogenic (LP) variants identified relevant to infant's health (dominant or biallelic recessive disease risks)

  3 months after enrollment

• Carrier status variants

  P and LP variants identified as recessive carrier status in infant

  3 months after enrollment

• MDR-associated phenotype

  Signs or symptoms of monogenic disease risk identified by genome sequencing

  3 months after enrollment and 1-year post-disclosure (15 months after enrollment)

• Parenting stress, relationship dysfunction

  Parenting Stress Index, 4th Edition Short Form (scored as a percentile 0 - 100%, higher scores indicate increased stress)

  Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)

• Relationship satisfaction

  Kansas Marital Satisfaction Scale (Scored 3 to 21, higher scores indicate better marital quality)

  Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)

• General anxiety

  General Anxiety Disorder-7

  Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)

Secondary Outcomes (8)

• MDR-associated family history

  3 months after enrollment and 1-year post-disclosure (15 months after enrollment)

• Intervention prompted by genetic or family history report

  6 months post-disclosure (9 months after enrollment)

• Suspected genetic condition

  6 months post-disclosure (9 months after enrollment)

• Child vulnerability

  Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)

• Feelings about genomic testing

  Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment)

Other Outcomes (3)

• Cost of attributable services

  6 months post-disclosure (9 months after enrollment)

• Cost of genomic services

  6 months post-disclosure (9 months after enrollment)

• All healthcare costs

  6 months post-disclosure (9 months after enrollment)

Study Arms (2)

Sequencing cohort

EXPERIMENTAL

Infants receive genome sequencing with analysis of approximately 1000 genes associated with childhood-onset and highly actionable adult-onset disease risks. Pathogenic and likely pathogenic variants are reported to the child's parents and pediatrician. Participants also receive a detailed family history report and standard well-child care.

Genetic: Genome Sequencing

Control cohort

NO INTERVENTION

Infants receive a detailed family history report plus standard well-child care.

Interventions

Genome Sequencing GENETIC

20 times read depth (20x) next-generation whole genome sequencing with comprehensive analysis.

Sequencing cohort

Eligibility Criteria

• Age: 0 Months - 12 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Infant participants
• Has not previously had exome or genome sequencing
• Age 0-12 months
• Seen for well-baby pediatric care at a recruiting site
• Primary healthcare provider completed the genomics education program
• At least one parent or guardian able to participate in the study
• Parent participants
• Biological parent or legal guardian of an infant participating in the study
• years of age or older
• Unimpaired decision-making capacity
• English or Spanish speaking
• Available to have genetic counseling and provide consent for testing the infant

You may not qualify if:

• Parents are unwilling to have genomic reports placed in the medical record or sent to their primary care pediatrician
• Any infant in which clinical considerations preclude collecting blood via heel stick

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Dartmouth-Hitchcock Medical Center: collaborator
• Harvard Pilgrim Health Care: collaborator
• HudsonAlpha Institute for Biotechnology: collaborator
• Massachusetts General Hospital: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• University of Alabama at Birmingham: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• Brigham and Women's Hospital: lead
• Baylor College of Medicine: collaborator
• Boston Children's Hospital: collaborator
• Broad Institute of MIT and Harvard: collaborator
• Howard University: collaborator

Study Sites (4)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Beaumont - Corewell Health East

Royal Oak, Michigan, 48073, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Genetic Predisposition to Disease; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Robert C. Green, MD, MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

• Ingrid A. Holm, MD, MPH

  Boston Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine (Genetics)

Model Details: Randomized controlled trial (control group vs. genome sequencing intervention)

Study Record Dates

• First Submitted: December 3, 2021
• First Posted: December 17, 2021
• Study Start: December 21, 2022
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: March 5, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Supporting information will be shared 6 months after study completion.

Locations

US (4)