Newborn Genomics Programme

NCT06081075 | Recruiting

• 1 other identifier: LIG-2301
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

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. 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. 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. 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.

Conditions

Genetic Disease; Newborn Morbidity

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (1)

Acutely ill neonates with suspected genetic condition, without a clear non-genetic aetiology

Other: Genetic testing

Interventions

Genetic testing OTHER

Rapid whole genome sequencing

Acutely ill neonates with suspected genetic condition, without a clear non-genetic aetiology

Eligibility Criteria

• Age: 0 Hours - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Liggins Institute: lead

Study Sites (1)

Auckland City Hospital

Auckland, New Zealand

RECRUITING

Related Publications (1)

• Nyaga DM, Tsai P, Gebbie C, Phua HH, Yap P, Le Quesne Stabej P, Farrow S, Rong J, Toldi G, Thorstensen E, Stark Z, Lunke S, Gamet K, Van Dyk J, Greenslade M, O'Sullivan JM. Benchmarking nanopore sequencing and rapid genomics feasibility: validation at a quaternary hospital in New Zealand. NPJ Genom Med. 2024 Nov 8;9(1):57. doi: 10.1038/s41525-024-00445-5.

  PMID: 39516456 DERIVED

MeSH Terms

Conditions

Genetic Diseases, Inborn

Interventions

Genetic Testing

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Genetic Techniques; Genetic Services; Health Services; Health Care Facilities Workforce and Services; Diagnostic Services; Preventive Health Services

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Deputy Director

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: October 12, 2023
• Study Start: January 15, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: May 7, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (1)