Newborn Genomics Programme

Genomic methods can significantly contribute to all facets of precision medicine, from diagnosis to prevention, therapeutic intervention, and management of acute and chronic illnesses. DNA based methods are already having a considerable impact across healthcare in fields that include: public health, infectious disease monitoring, acute and chronic disease, pharmacogenomics, prenatal testing and diagnosis, and therapeutic development. In this proposal, investigators are focusing on the application of genomic methods in precision medicine - specifically on rapid whole-genome sequencing of parents and children (i.e. a trio) for the identification of diseases that have genetic components.

Goals Primary goal: is to provide safe rapid whole genome sequencing to Neonatal Intensive Care Unit/Pediatric Intensive Care Unit patients.

Secondary goals: 1) Although several groups globally are implementing rapid sequencing of rare disease, these are predominantly in the research space, with many unanswered questions regarding the best way to implement them into a national healthcare system. Each country and their healthcare systems are unique, and valuable knowledge will be gained by implementing this process within a New Zealand context. As part of this the study will measure the impact on the individuals and families.

2) to expand the research team's understanding of non-coding disease-causing variants and methylation changes that contribute to severe disease in early life.

Primary Aims

1. To incorporate long-read RNA sequencing data into the diagnostic rapid Whole Genome Sequencing pipeline to provide a direct measure of the functional outcome of the variants of clinical concern.
2. To measure the clinical utility of analysing non-coding variants in the diagnosis of critically ill children who do not have pathogenic, likely pathogenic, or variants of unknown significance for mendelian disorders.
3. To identify, in a real-world setting within the New Zealand health-care system, the clinical and economic effects of deploying rapid Whole Genome Sequencing-informed rapid precision medicine for critically ill children.

Study Overview

• Status: Recruiting
• Conditions: Genetic Disease; Newborn Morbidity
• Intervention / Treatment: Other: Genetic testing

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Recruiting
    • Auckland City Hospital
    • Contact: Jodi Van Dyk; Phone Number: 021852051; Email: jodi.van.dyk@auckland.ac.nz
    • Principal Investigator: Patrick Yap, MBChB

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Children with suspected genetic conditions, and their families, will be recruited into the study from within the neonatal and paediatric intensive care units (i.e. NICU and PICU, respectively) from around New Zealand

Description

Inclusion Criteria:

• Acutely ill inpatient
• Admitted to NICU or PICU between April 2023 - March 2026
• Within 1 week of hospitalization or within 1 week of development of abnormal response to standard therapy for an underlying condition
• Suspected genetic condition, without a clear non-genetic aetiology

Exclusion Criteria:

• Patients whose clinical course is entirely explained by
• Isolated prematurity
• Isolated unconjugated hyperbilirubinemia
• Infection or sepsis with expected response to therapy
• A previously confirmed genetic diagnosis that explains the clinical condition -
• Isolated transient neonatal tachypnoea
• Meconium aspiration syndrome
• Trauma
• Inability to source blood and buccal samples for DNA extraction from at least the mother and child

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acutely ill neonates with suspected genetic condition, without a clear non-genetic aetiology	Other: Genetic testing; Rapid whole genome sequencing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To incorporate long-read RNA sequencing data into the diagnostic rapid Whole Genome Sequencing pipeline to provide a direct measure of the functional outcome of the variants of clinical concern	June 2025
To measure the clinical utility of analysing non-coding variants in the diagnosis of critically ill children who do not have pathogenic, likely pathogenic, or variants of unknown significance for mendelian disorders.	June 2025
To identify, in a real-world setting within the New Zealand health-care system, the clinical and economic effects of deploying rapid Whole Genome Sequencing-informed rapid precision medicine for critically ill children.	June 2025

Collaborators and Investigators

• Sponsor: Liggins Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: June 29, 2023
• First Submitted That Met QC Criteria: October 10, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Actual): May 7, 2025
• Last Update Submitted That Met QC Criteria: May 4, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn
• Other Study ID Numbers: LIG-2301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No