Genomic Sequencing for Childhood Risk and Newborn Illness

Overview

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.

Full Title of Study: “Genomic Sequencing for Childhood Risk and Newborn Illness (The BabySeq Project)”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Other
    • Masking: None (Open Label)
  • Study Primary Completion Date: April 2020

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.

Interventions

  • Genetic: Genomic sequencing
    • Both sick and healthy infants randomized to receive genomic sequencing will receive a ‘Genomic Newborn Sequencing Report’ (GNSR) which will include pathogenic or likely pathogenic variants identified in genes associated with childhood-onset disease.
  • Other: Family history report
    • Participants from all arms of the study will have a family history taken by a study genetic counselor. Information collected through the family history will be summarized in a family history report that will be reviewed with all participants.

Arms, Groups and Cohorts

  • Other: Well Infant Cohort, No Sequencing
    • Healthy infants and their parents enrolled through the Brigham and Women’s Hospital (BWH) Well Newborn Nursery who are randomized not to receive sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, and any potentially medically relevant findings from the baby’s medical history/physical exam.
  • Other: Well Infant Cohort, Sequencing
    • Healthy infants and their parents enrolled through Brigham and Women’s Hospital (BWH) Well Newborn Nursery who are randomized to receive genomic sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, any potentially medically relevant findings from the baby’s medical history/physical exam, and the results of the genomic sequencing report.
  • Other: Sick Infant Cohort, No Sequencing
    • Infants and their parents enrolled through Boston Children’s Hospital (BCH) and the BWH Neonatal Intensive Care Unit who are randomized not to receive sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, and any potentially medically relevant findings from the baby’s medical history/physical exam.
  • Other: Sick Infant Cohort, Sequencing
    • Infants and their parents enrolled through Boston Children’s Hospital and the BWH Neonatal Intensive Care Unit who are randomized to receive genomic sequencing. Results disclosure sessions will include a discussion of: family history report, results from standard newborn screening, any potentially medically relevant findings from the baby’s medical history/physical exam, and the results of the genomic sequencing report.

Clinical Trial Outcome Measures

Primary Measures

  • Change in family/physician healthcare utilization immediately after results disclosure compared to 3 and 10 months post-disclosure
    • Time Frame: Immediately post-disclosure (parents-approximately 6 weeks after enrollment), Post-disclosure (physician surveys administered approximatley 4 weeks after results disclosure), 3 months post-disclosure (parents), 10 months post-dislcosure (parents)
    • Assessed in physician and parent surveys
  • Change in baseline family relationship and personal distress levels compared to immediately post-disclosure, 3 months post-disclosure and 10 months post-disclosure
    • Time Frame: Baseline, immediately post-disclosure (approximately 6 weeks after enrollment), 3 months post-disclosure, 10 months post-disclosure
    • Assessed in parent surveys via questions assessing: parent-child bonding, personal distress, perceptions of child, partner relationship, child-centered stress

Secondary Measures

  • Participant characteristics
    • Time Frame: Baseline
    • Assessed in parent and physician surveys via questions assessing: sociodemographics, personal and family history, genetic literacy and numeracy, dispositions
  • Change in baseline perceived utility of genomic results compared to post-disclosure
    • Time Frame: Baseline, 3 months post-disclosure (parents), post-disclosure (physicians – 4 weeks after results disclosure), end of study (physicians – up to 40 months after completion of the baseline survey)
    • Assessed in parent and physician surveys via questions assessing: expectations, satisfaction with and perceived utility of genomic results

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Brigham and Women’s Hospital
  • Collaborator
    • Boston Children’s Hospital
  • Provider of Information About this Clinical Study
    • Principal Investigator: Robert C. Green, MD, MPH, Associate Professor of Medicine, Division of Genetics, Department of Medicine – Brigham and Women’s Hospital
  • Overall Official(s)
    • Robert C. Green, MD, MPH, Principal Investigator, Brigham and Women’s Hospital
    • Alan Beggs, PhD, Principal Investigator, Boston Children’s Hospital

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