Clinical trial NCT02422511: Genomic Sequencing for Childhood Risk and Newborn Illness
Official title: Genomic Sequencing for Childhood Risk and Newborn Illness (The BabySeq Project)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hereditary Disease
Genetic Predisposition to Disease
Keywords: Genome Sequencing
Exome Sequencing
Newborn Screening
Childhood Onset Genetic Conditions
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Boston Children's Hospital
name: Baylor College of Medicine
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Human Genome Research Institute (NHGRI)
name: Massachusetts General Hospital
First posted: 2015-04-21
Enrollment: 1205
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The Genomic Sequencing for Childhood Risk and Newborn Illness (the BabySeq Project) is a research study exploring the use of genomic sequencing in newborns. The National Institutes of Health is funding this study.

The investigators will enroll 240 healthy infants and their parents from the Brigham and Women's Hospital (BWH) Well Newborn Nursery and 240 sick infants and their parents at Boston Children's Hospital (BCH) or the BWH Neonatal Intensive Care Unit (NICU). A small blood sample will be collected from each infant and genome sequencing may be performed. Six weeks later, results are returned and explained. Over 12 months the investigators are studying the experiences of parents and pediatricians of infants who receive sequencing to help understand how best to use genomics in pediatric care.

Detailed description: The objective of this research protocol is to conduct a randomized clinical trial to assess the benefits and risks of adding the information from a genomic sequencing report to physician-mediated medical care of newborns during their pediatric years.

The investigators will enroll 240 healthy infants and their parents from the Brigham and Women's Hospital (BWH) Well Newborn Nursery and 240 sick infants and their parents at Boston Children's Hospital (BCH) or the BWH Neonatal Intensive Care Unit (NICU).

A small blood sample will be obtained from each enrolled infant. Samples will be collected from all infants enrolled, regardless of the arm to which they are assigned, in order to follow the same protocol for all subjects prior to randomization.

Infants within each cohort will be randomized (1:1) to either standard-of-care (family history and standard newborn screening report) or to standard-of-care plus genomic sequencing.

A study physician and genetic counselor will disclose the infant's randomization assignment and study results during an in-person consultation with each family. The study physician and genetic counselor will provide the consultation to families utilizing all available medical information. In the sequencing arm of the study, this will include the medical history, physical exam, family history, standard newborn screening (NBS) report and sequencing report(s). In the non-sequencing arm of the study, this will include the medical history, physical exam, family history and standard NBS report.

Parents will be surveyed at four points over the 12 months after enrollment: baseline, immediately post-disclosure (approximately 6 weeks after enrollment), 3 months post-disclosure, and at 10 months post-disclosure.

Eligibility criteria: Newborns and Parents at Brigham and Women's Hospital (BWH) Well Newborn Nursery:

Inclusion Criteria :

1. Infants born at BWH and admitted to the Well Newborn Nursery
2. At least one biological parent is physically available to have genetic counseling, donate DNA, and provide consent for testing the infant. If the second biological parent is known but not physically present, the second biological parent must be available to have genetic counseling by phone, return a signed consent form by mail, and donate DNA via a mailed saliva kit. If there is a "rearing parent" (an individual who is not biologically related to the infant, but who is dedicated to raising the child), that individual must also provide consent but will not be asked to submit a saliva sample.
3. Mother (either rearing or biological) carried the pregnancy

Exclusion Criteria:

1. Parents are non-English speaking
2. Parents are unwilling to have genomic reports placed in the medical record or sent to their primary care pediatrician
3. Mother or father younger than 18 years of age
4. Mother or father with impaired decisional capacity
5. Age of infant is older than 30 days
6. One of a multiple gestation
7. Any infant in which clinical considerations preclude drawing 1.0 ml of blood
8. Missing consent of either biological parent (if known) or rearing parent (if applicable)

Sick Newborns and Parents at Boston Children's Hospital (BCH) or the BWH NICU:

Inclusion Criteria:

1. Infants admitted to BCH or the BWH NICU
2. At least one biological parent is physically available to have genetic counseling, donate DNA, and provide consent for testing the infant. If the second biological parent is known but not physically present, the second biological parent must be available to have genetic counseling by phone, return a signed consent form by mail, and donate DNA via a mailed saliva kit. If there is a "rearing parent" (an individual who is not biologically related to the infant, but who is dedicated to raising the child), that individual must also provide consent but will not be asked to submit a saliva sample.
3. Mother (either biological or rearing) carried the pregnancy

Exclusion Criteria:

1. Parents are non-English speaking
2. Parents are unwilling to have genomic reports placed in the medical record or sent to their primary care pediatrician
3. Mother or father younger than 18 years of age
4. Mother or father with impaired decisional capacity
5. Age of infant is older than 30 days
6. One of a multiple gestation
7. Any infant in which clinical considerations preclude drawing 1.0 ml of blood
8. Hospital admission expected to be less than 72 hours
9. Missing consent of either biological parent (if known) or rearing parent (if applicable)
10. Previously performed exome/genome sequencing on patient

Primary outcomes:
measure: Downstream Health Care Costs Attributable to BabySeq Project Disclosure: Days of Inpatient Care
timeFrame: From disclosure through 10 Months post-disclosure (approx. 15 months after baseline).
measure: Parents' Distress
timeFrame: From baseline through 10 post-disclosure, with time points varying by measure. (Post-disclosure approx. 5 months after baseline; 3-months approx. 8 months after baseline; 10-months approx. 15 months after baseline)
measure: Parent-Child Relationship
timeFrame: From baseline through 10 post-disclosure, with time points varying by measure. (Post-disclosure approx. 5 months after baseline; 3-months approx. 8 months after baseline; 10-months approx. 15 months after baseline)
measure: Parents' Relationship
timeFrame: From baseline through 10 post-disclosure, with time points varying by measure. Post-disclosure approx. 5 months after baseline; 3-months approx. 8 months after baseline; 10-months approx. 15 months after baseline.
measure: Downstream Health Care Utilization Attributable to BabySeq Project Disclosure: Number of Health Care Provider Visits
timeFrame: From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)
measure: Downstream Health Care Utilization Attributable to BabySeq Project Disclosure: Number of Current Medications at 10 Months
timeFrame: From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)
measure: Downstream Health Care Utilization Attributable to BabySeq Project Disclosure: Number of ER Visits
timeFrame: From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)
measure: Downstream Health Care Utilization Attributable to BabySeq Project Disclosure: Number of Outpatient Lab Tests
timeFrame: From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)
measure: Downstream Health Care Utilization Attributable to BabySeq Project Disclosure
timeFrame: From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)
Secondary outcomes:
measure: Change in Perceived Utility Toward Genomic Sequencing
timeFrame: From Baseline to 3 Months post-disclosure (approx. 8 months after baseline)
Other outcomes:
measure: Understanding
timeFrame: Post-disclosure approx. 5 months after baseline
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
Study officials:
affiliation: Brigham and Women's Hospital
name: Robert C. Green, MD, MPH
role: PRINCIPAL_INVESTIGATOR
affiliation: Boston Children's Hospital
name: Alan Beggs, PhD
role: PRINCIPAL_INVESTIGATOR
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