Genetic Predisposition to Disease, Hereditary Diseases
Conditions
Keywords
genome sequencing, newborn screening, preventive medicine
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.
Detailed description
The objective of this research protocol is to assess the impacts of genomic sequencing in healthy infants from ethnically and racially diverse communities as part of routine pediatric care. Investigators will enroll a cohort of 500 healthy, ethnically and racially diverse infants from Boston, Massachusetts; New York City, New York; and Birmingham, Alabama, with planned expansion to other U.S. cities and recruitment sites. As part of this study, a stakeholder board comprised of diverse community members will provide early and regular feedback throughout the study on anticipated and ongoing community reaction to the work with sensitivity to historical injustices and cultural diversity Primary care pediatricians from each recruitment site will be enrolled for a brief genomics education curriculum. Only infants whose healthcare providers have joined the study will be enrolled. A small blood sample will be obtained from each enrolled infant. Participants will randomized (1:1) to receive either a family history report or a family history report plus whole genome sequencing. Genome sequencing data will be analyzed for pathogenic and likely pathogenic variants in genes associated with childhood-onset disease risks, as well as highly actionable adult-onset disease risks. If infants have a dominant risk identified, parents may choose to be screened as part of the study. The study team will disclose the infant's randomization status and study results during a consultation with each family, and results will be sent to the infant's pediatrician. Parents will be surveyed at three time points over the 12 months after enrollment: baseline, immediately post-disclosure (approximately 3 months after enrollment), and 6 months post-disclosure. Surveys will assess psychosocial impacts of newborn sequencing. Chart reviews will be performed to assess the medical outcomes and healthcare utilization costs of newborn genome sequencing.
Interventions
GENETICGenome Sequencing
20 times read depth (20x) next-generation whole genome sequencing with comprehensive analysis.
Sponsors
Brigham and Women's Hospital
Baylor College of Medicine
Boston Children's Hospital
Broad Institute of MIT and Harvard
Dartmouth-Hitchcock Medical Center
Harvard Pilgrim Health Care
Howard University
HudsonAlpha Institute for Biotechnology
Massachusetts General Hospital
Icahn School of Medicine at Mount Sinai
University of Alabama at Birmingham
National Center for Advancing Translational Sciences (NCATS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
DOUBLE (Subject, Caregiver)
Intervention model description
Randomized controlled trial (control group vs. genome sequencing intervention)
Eligibility
Sex/Gender
ALL
Age
0 Months to 12 Months
Healthy volunteers
Yes
Inclusion criteria
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 * 18 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Carrier status variants | 3 months after enrollment | P and LP variants identified as recessive carrier status in infant |
| MDR-associated phenotype | 3 months after enrollment and 1-year post-disclosure (15 months after enrollment) | Signs or symptoms of monogenic disease risk identified by genome sequencing |
| Parenting stress, relationship dysfunction | Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) | Parenting Stress Index, 4th Edition Short Form (scored as a percentile 0 - 100%, higher scores indicate increased stress) |
| Relationship satisfaction | Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) | Kansas Marital Satisfaction Scale (Scored 3 to 21, higher scores indicate better marital quality) |
| General anxiety | Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) | General Anxiety Disorder-7 |
| Monogenic disease risks (MDRs) | 3 months after enrollment | Pathogenic (P) and likely pathogenic (LP) variants identified relevant to infant's health (dominant or biallelic recessive disease risks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| General depression | Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) | Patient Health Questionnaire (PHQ)-8 |
| MDR-associated family history | 3 months after enrollment and 1-year post-disclosure (15 months after enrollment) | Signs or symptoms of monogenic disease risk or recessive condition present in infant's biological family |
| Self blame | Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) | Novel item (higher scores indicate increased blame) |
| Intervention prompted by genetic or family history report | 6 months post-disclosure (9 months after enrollment) | Healthcare intervention prompted by MDR or recessive carrier variant |
| Suspected genetic condition | 6 months post-disclosure (9 months after enrollment) | Any phenotype that develops in an infant or a family history suspected to have a genetic cause |
| Child vulnerability | Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) | Vulnerable Baby Scale (scored 0-50, higher scores indicate increased perceptions of child vulnerability) |
| Feelings about genomic testing | Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) | Feelings About genomiC Testing Results (FACToR) Questionnaire |
| Partner blame | Baseline, post-disclosure (3 months after enrollment), 6 months post-disclosure (9 months after enrollment) | Novel item (higher scores indicate increased blame) |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRobert C. Green, MD, MPH
Brigham and Women's Hospital
PRINCIPAL_INVESTIGATORIngrid A. Holm, MD, MPH
Boston Children's Hospital
Outcome results
None listed