Newborn Genomic Sequencing Pilot Study

Rady Pediatric Genomics & Systems Medicine Institute

Status: Completed

Conditions: Genetic Disease

Treatments: Genetic: WES; Genetic: BeginNGS test; Genetic: Whole genome sequencing

Study type: Interventional

Funder types: Other

Identifiers

NCT06276348

20226892

Details and patient eligibility

About

The goal of this clinical trial is to test a new method for newborn screening using whole genome sequencing, called BeginNGS. Newborns who are not suspected of having genetic diseases and who are admitted to the NICU at Rady Children's Hospital, San Diego, will be enrolled. The main questions this study aims to answer are:

• What is the diagnostic yield of diagnostic whole genome sequencing (DWGS) in this population?
• What is the diagnostic sensitivity and specificity of BeginNGS and whole exome sequencing (WES) as compared to DWGS?
• What are the potential issues related to implementing DWGS in this population?

Enrolled newborns will have a blood sample taken and will receive three tests:

• DWGS
• BeginNGS
• WES

Full description

Newborn screening (NBS) by testing dried blood spots (DBS) identifies newborns with a few diseases for which effective treatments are available to enable treatment at or before symptom onset. Because NBS improves outcomes in these diseases, it is performed on almost all US babies. The current Federal recommended NBS list is limited to 35 conditions and identifies ~6,600 affected children per year. In genetic diseases not screened by NBS, however, outcomes remain poor because of delays in diagnosis and treatment. The investigators recently developed a system for NBS for 434 severe, childhood genetic diseases for which effective treatments are available using whole genome sequencing (WGS), called BeginNGS. Retrospective studies showed BeginNGS to have a true negative rate (specificity) of 99.7% and true positive rate (sensitivity) of 88.8%. The investigators now propose to undertake a first prospective study in newborns admitted to the Neonatal Intensive Care Unit (NICU) at Rady Children's Hospital, San Diego (RCHSD) to compare the sensitivity and specificity of BeginNGS with that of standard, diagnostic rapid whole genome sequencing (DWGS) and whole exome sequencing (WES). This study is in preparation for larger, future clinical trials.

Enrollment: 120 patients

Sex: All

Ages: 1 to 10 days old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Neonates less than or equal to 10 days old who are admitted to the RCHSD NICU.

Exclusion criteria

1. Neonates who have enrolled in another clinical study at Rady Children's Institute for Genomic Medicine or in whom DWGS has been ordered or is being considered.
2. Neonates whose mother is less than 18 years of age.
3. Neonates who are wards of the state.
4. Neonates whose parent/legal guardian is unable to provide consent.

Trial design

Primary purpose: Screening

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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120 participants in 1 patient group

Enrollees

Experimental group

Description:

Enrolled infants will receive 3 tests (DWGS, BeginNGS, and WES). DWGS will be performed in a standard manner. BeginNGS and WES will be performed in a batch after completion of enrollment. The diagnostic sensitivity and specificity of BeginNGS and WES will be compared to DWGS (a standard clinical test compliant with the Clinical Laboratory Improvement Amendments Act).

Treatment:

Genetic: Whole genome sequencing

Genetic: BeginNGS test

Genetic: WES