Genomic Sequencing for Childhood Risk and Newborn Illness

Genomic Sequencing for Childhood Risk and Newborn Illness (The BabySeq Project)

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02422511

Enrollment

1205

Registered

2015-04-21

Start date

2015-05-31

Completion date

2021-08-05

Last updated

2024-04-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Genetic Predisposition to Disease, Hereditary Disease

Keywords

Genome Sequencing, Exome Sequencing, Newborn Screening, Childhood Onset Genetic Conditions

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.

Interventions

GENETICGenomic 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.

OTHERFamily 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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

SINGLE (Subject)

Masking description

Families are masked to randomization until disclosure sessions

Eligibility

Sex/Gender

ALL

Healthy volunteers

Inclusion 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

Design outcomes

Primary

Measure	Time frame	Description
Downstream Health Care Utilization Attributable to BabySeq Project Disclosure	From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)	Per-patient means (SDs) for healthcare costs (in U.S. dollars) after disclosure of randomization status / genomic results from the BabySeq project. Services were identified through a combination of chart note review, medical record review and participant surveys.
Downstream Health Care Utilization Attributable to BabySeq Project Disclosure: Number of ER Visits	From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)	Per-patient counts number of ER visits. Services were identified through a combination of chart note review, medical record review and participant surveys.
Downstream Health Care Utilization Attributable to BabySeq Project Disclosure: Number of Outpatient Lab Tests	From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)	Per-patient counts for number of outpatient lab tests after results disclosure. Services were identified through a combination of chart note review, medical record review and participant surveys.
Downstream Health Care Costs Attributable to BabySeq Project Disclosure: Days of Inpatient Care	From disclosure through 10 Months post-disclosure (approx. 15 months after baseline).	Days spent in inpatient care from disclosure of randomization status / genomic sequencing results through 10 months post-disclosure. Services were identified through a combination of chart note review, medical record review and participant surveys.
Parents' Distress	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)	Parents' Distress was assessed using validated scales measuring Anxiety and Depression, and a novel item assessing Blame with responses ranging from 1 to 5. Higher scores indicate more distress. Anxiety per the Edinburgh Postnatal Depression Scale anxiety subscale (baseline, post-disclosure, and 3 months; scores ranging from 0 to 9); Anxiety per the Generalized Anxiety Disorder Scale-7 (3 months and 10 months; scores ranging from 0 to 21); Depression per the Edinburgh Postnatal Depression Scale (baseline, post-disclosure, and 3 months; scores ranging from 0 to 30); Depression per the Patient Health Questionnaire-9 (3 months and 10 months; scores ranging from 0 to 30); Self-blame per a novel item (3 months and 10 months)
Parent-Child Relationship	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)	Parent-Child Relationship was assessed using validated scales measuring parents' perceptions of parenting stress (General parenting stress per the Parenting Stress Index™, 4th Edition Short Form (10 months); scores range from 36 to 180), how vulnerable they perceive their child to be (Parents' perception of baby's vulnerability per the Vulnerable Baby Scale (baseline, postdisclosure, 3 months, 10 months); scores range from 4 to 20), and how they are bonding with their child (Parent-child bonding per the Mother-to-Infant Bonding Scale (baseline, postdisclosure, 3 months, 10 months); scores range from 0 to 24). Lower bonding scores indicate more problems with bonding. For other measures, higher scores indicate higher stress and perceptions of vulnerability.
Parents' Relationship	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.	Parents' Relationship was assessed using validated and novel measures of marital satisfaction using the Relationship satisfaction per the Kansas Marital Satisfaction Scale (3 months; scores ranging from 3 to 15), relationship conflict per a novel item (all time points; scores ranging from 1 to 5), and partner blame per a novel item (3 months and 10 months; scores ranging from 1 to 5). Higher scores on Satisfaction indicates more Satisfaction. Higher scores on Conflict and Blame indicate higher conflict and blame.
Downstream Health Care Utilization Attributable to BabySeq Project Disclosure: Number of Health Care Provider Visits	From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)	Per-patient counts for number of health care provider visits. Services were identified through a combination of chart note review, medical record review and participant surveys.
Downstream Health Care Utilization Attributable to BabySeq Project Disclosure: Number of Current Medications at 10 Months	From disclosure through 10 Months post-disclosure (approx. 15 months after baseline)	Per-patient counts for number of current medications at 10 months. Services were identified through a combination of chart note review, medical record review and participant surveys.

Secondary

Measure	Time frame	Description
Change in Perceived Utility Toward Genomic Sequencing	From Baseline to 3 Months post-disclosure (approx. 8 months after baseline)	A novel survey item asked participants to rate the usefulness of whole genome sequencing results for managing health on a 1-10 scale at baseline and 3 months post-disclosure. Responses were on a 10-point scale anchored by not at all useful (1) to extremely useful (10).

Other

Measure	Time frame	Description
Understanding	Post-disclosure approx. 5 months after baseline	A novel item assessed participants' subjective understanding of their study results on a 1-5 scale, where higher scores indicate greater subjective understanding.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Well Baby Parents: Family History Only Parents of newborns in well-baby units receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Family History report only 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.	255
Well Babies: Family History Only Newborns in well-baby units receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Family History report only 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.	128
Well Baby Parents: Family History + Exome Sequencing Parents of newborns in well-baby units receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Genome Report and Family History report 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. 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.	257
Well Babies: Family History + Exome Sequencing Newborns in well-baby units receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Genome Report and Family History report 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. 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.	129
ICU Baby Parents: Family History Only Parents of newborns in intensive care units receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Family History report only 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.	66
ICU Babies: Family History Only Newborns in intensive care units receive an Annotated Family History Report only. Active Comparator: Standard of Care Only: Family History report only 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.	33
ICU Baby Parents: Family History + Exome Sequencing Parents of newborns in intensive care units receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Genome Report and Family History report 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. 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.	68
ICU Babies: Family History + Exome Sequencing Newborns in intensive care units receive a Genome Report and an Annotated Family History Report. Main Study Experimental: Genome Report and Family History report 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. 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.	34
Total	970

Baseline characteristics

Characteristic	Well Babies: Family History Only	Well Baby Parents: Family History + Exome Sequencing	Well Babies: Family History + Exome Sequencing	ICU Baby Parents: Family History Only	ICU Babies: Family History Only	ICU Baby Parents: Family History + Exome Sequencing	Well Baby Parents: Family History Only	ICU Babies: Family History + Exome Sequencing	Total
Age, Categorical <=18 years	128 Participants	0 Participants	129 Participants	0 Participants	33 Participants	0 Participants	0 Participants	34 Participants	324 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	257 Participants	0 Participants	66 Participants	0 Participants	68 Participants	255 Participants	0 Participants	646 Participants
Age, Continuous	.025 years STANDARD_DEVIATION 0.016	35 years STANDARD_DEVIATION 4.6	.027 years STANDARD_DEVIATION 0.017	32 years STANDARD_DEVIATION 5.29	.055 years STANDARD_DEVIATION 0.039	35 years STANDARD_DEVIATION 5.38	34 years STANDARD_DEVIATION 4.45	.060 years STANDARD_DEVIATION 0.031	34 years STANDARD_DEVIATION 4.75
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants	9 Participants	9 Participants	7 Participants	5 Participants	1 Participants	20 Participants	1 Participants	67 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	88 Participants	212 Participants	107 Participants	55 Participants	25 Participants	64 Participants	196 Participants	30 Participants	777 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	25 Participants	36 Participants	13 Participants	4 Participants	3 Participants	3 Participants	39 Participants	3 Participants	126 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants
Race (NIH/OMB) Asian	10 Participants	31 Participants	8 Participants	2 Participants	0 Participants	4 Participants	28 Participants	1 Participants	84 Participants
Race (NIH/OMB) Black or African American	9 Participants	8 Participants	2 Participants	3 Participants	2 Participants	1 Participants	12 Participants	0 Participants	37 Participants
Race (NIH/OMB) More than one race	12 Participants	9 Participants	24 Participants	0 Participants	2 Participants	0 Participants	5 Participants	3 Participants	55 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	3 Participants
Race (NIH/OMB) Unknown or Not Reported	7 Participants	24 Participants	16 Participants	4 Participants	2 Participants	4 Participants	15 Participants	2 Participants	74 Participants
Race (NIH/OMB) White	89 Participants	185 Participants	79 Participants	57 Participants	27 Participants	57 Participants	194 Participants	27 Participants	715 Participants
Region of Enrollment United States	128 participants	257 participants	129 participants	66 participants	33 participants	69 participants	255 participants	34 participants	647 participants
Sex: Female, Male Female	66 Participants	129 Participants	63 Participants	33 Participants	15 Participants	34 Participants	130 Participants	17 Participants	487 Participants
Sex: Female, Male Male	62 Participants	128 Participants	66 Participants	33 Participants	18 Participants	34 Participants	125 Participants	17 Participants	483 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk
deaths Total, all-cause mortality	0 / 255	0 / 128	0 / 257	0 / 129	0 / 66	0 / 33	0 / 68	0 / 34
other Total, other adverse events	0 / 255	0 / 128	0 / 257	0 / 129	0 / 66	0 / 33	0 / 68	0 / 34
serious Total, serious adverse events	0 / 255	0 / 128	0 / 257	0 / 129	0 / 66	0 / 33	0 / 68	0 / 34

Outcome results

Primary

Downstream Health Care Costs Attributable to BabySeq Project Disclosure: Days of Inpatient Care

Days spent in inpatient care from disclosure of randomization status / genomic sequencing results through 10 months post-disclosure. Services were identified through a combination of chart note review, medical record review and participant surveys.

Time frame: From disclosure through 10 Months post-disclosure (approx. 15 months after baseline).

Population: The analysis population included infants enrolled in the BabySeq project. Data was not available for all participants due to withdrawal or non-responsiveness to follow up surveys.

Arm	Measure	Value (MEAN)	Dispersion
Well Baby Family History Only	Downstream Health Care Costs Attributable to BabySeq Project Disclosure: Days of Inpatient Care	0.1 Days	Standard Deviation 0.4
Well Baby Family History + Exome Sequencing	Downstream Health Care Costs Attributable to BabySeq Project Disclosure: Days of Inpatient Care	0.0 Days	Standard Deviation 0.3
ICU Baby Family History Only	Downstream Health Care Costs Attributable to BabySeq Project Disclosure: Days of Inpatient Care	3.1 Days	Standard Deviation 12.9
ICU Baby Family History + Exome Sequencing	Downstream Health Care Costs Attributable to BabySeq Project Disclosure: Days of Inpatient Care	3.8 Days	Standard Deviation 12.9

Primary

Downstream Health Care Utilization Attributable to BabySeq Project Disclosure

Per-patient means (SDs) for healthcare costs (in U.S. dollars) after disclosure of randomization status / genomic results from the BabySeq project. Services were identified through a combination of chart note review, medical record review and participant surveys.