Generating Intervals of Reference FFor Early Life Brain Biomarkers.

NCT07585149 | Recruiting

• 1 other identifier: DM_Giraffe01
• Study Type: observational
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

Highly sensitive immunoassays for the detection of neuro-specific biomarkers are becoming more accessible. Currently, the majority of these biomarkers are detected with the use of labour-intensive and highly skilled wet lab work. However, recent advancements have allowed for the introduction of these neuro-specific biomarkers into mainstream clinical chemistry analysers, bringing them closer to clinical care. There is a vast amount of published literature for neuro-specific biomarkers in an adult and ageing population, unfortunately, the same cannot be said for the neonatal population. From the limited available literature, clear differences are being documented in physiological levels of neuro-specific biomarkers in adults and infants. Neuro-specific biomarkers such as GFAP (Glial Fibrillary Acidic Protein) and Tau are demonstrating promise for the early detection and prediction of neuro-developmental disorders. There is a need for an understanding of physiological levels of these neuro-specific biomarkers in a neonatal population before they can be fully adopted into clinical routine. The development of a neonatal reference interval for neuro-specific biomarkers may provide a foundation for the accurate interpretation of neuro-specific biomarker elevations in neonatal brain injury, aiding in the development of biomarker-based screening tools for early diagnosis and intervention.

Conditions

Reference Intervals; Biomarker in Early Diagnosis; Neonatal

Keywords

Neurospecific; Biomarker; Neonatal; Reference Interval

Outcome Measures

Primary Outcomes (1)

• Neurospecific Reference Interval

  To examine the underlying normative neuro-specific protein profiles of term neonates.

  Birth to 1 week

Study Arms (1)

Term Neonate

Term neonate \>37 weeks gestational age, with planned venipuncture within their first week of life.

Eligibility Criteria

• Age: 0 Days - 7 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Healthy term neonates who are due to have routine clinical bloods within their first week of life will be recruited for this study.

You may qualify if:

• Term neonate (≥37 weeks)
• Planned routine venous blood drawn within one week of life
• Relevant demographic/clinical information available, including gestational age, day of life, birth weight, sex, race, mode of delivery, and 5-minute Apgar score
• Informed parental consent obtained prior to any study procedures

You may not qualify if:

• Pre-term neonates \<37 weeks
• Any clinical evidence of neurological/ CNS abnormalities.
• NICU admission
• Any neonates with Suspected or culture-positive sepsis or meningitis Any known inborn errors of metabolism (IEM). Any known chromosomal abnormalities or any apparent congenital abnormalities
• When the relevant demographic/clinical information is not available.

Sponsors & Collaborators

• University College Cork: lead
• INFANT centre, University College Cork, Republic of Ireland: collaborator

Study Sites (1)

Department of Paediatric and Child Health

Cork, T12 DC4C, Ireland

RECRUITING

Related Publications (13)

• O'Sullivan MP, Looney AM, Moloney GM, Finder M, Hallberg B, Clarke G, Boylan GB, Murray DM. Validation of Altered Umbilical Cord Blood MicroRNA Expression in Neonatal Hypoxic-Ischemic Encephalopathy. JAMA Neurol. 2019 Mar 1;76(3):333-341. doi: 10.1001/jamaneurol.2018.4182.

  PMID: 30592487 BACKGROUND

• Dakroub F, Kobeissy F, Mondello S, Yang Z, Xu H, Sura L, Rossignol C, Albayram M, Rajderkar D, Wang K, Weiss MD. MicroRNAs as biomarkers of brain injury in neonatal encephalopathy: an observational cohort study. Sci Rep. 2024 Mar 19;14(1):6645. doi: 10.1038/s41598-024-57166-z.

  PMID: 38503820 BACKGROUND

• Juul SE, Voldal E, Comstock BA, Massaro AN, Bammler TK, Mayock DE, Heagerty PJ, Wu YW, Numis AL; HEAL consortium. Association of High-Dose Erythropoietin With Circulating Biomarkers and Neurodevelopmental Outcomes Among Neonates With Hypoxic Ischemic Encephalopathy: A Secondary Analysis of the HEAL Randomized Clinical Trial. JAMA Netw Open. 2023 Jul 3;6(7):e2322131. doi: 10.1001/jamanetworkopen.2023.22131.

  PMID: 37418263 BACKGROUND

• Douglas-Escobar MV, Heaton SC, Bennett J, Young LJ, Glushakova O, Xu X, Barbeau DY, Rossignol C, Miller C, Old Crow AM, Hayes RL, Weiss MD. UCH-L1 and GFAP Serum Levels in Neonates with Hypoxic-Ischemic Encephalopathy: A Single Center Pilot Study. Front Neurol. 2014 Dec 19;5:273. doi: 10.3389/fneur.2014.00273. eCollection 2014.

  PMID: 25566179 BACKGROUND

• Ennen CS, Huisman TA, Savage WJ, Northington FJ, Jennings JM, Everett AD, Graham EM. Glial fibrillary acidic protein as a biomarker for neonatal hypoxic-ischemic encephalopathy treated with whole-body cooling. Am J Obstet Gynecol. 2011 Sep;205(3):251.e1-7. doi: 10.1016/j.ajog.2011.06.025. Epub 2011 Jun 15.

  PMID: 21784396 BACKGROUND

• Stukas S, Cooper J, Higgins V, Holmes D, Adeli K, Wellington CL. Pediatric reference intervals for serum neurofilament light and glial fibrillary acidic protein using the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort. Clin Chem Lab Med. 2023 Oct 27;62(4):698-705. doi: 10.1515/cclm-2023-0660. Print 2024 Mar 25.

  PMID: 37882772 BACKGROUND

• Puravet A, Oris C, Pereira B, Kahouadji S, Gonzalo P, Masson D, Durif J, Sarret C, Sapin V, Bouvier D. Serum GFAP and UCH-L1 for the identification of clinically important traumatic brain injury in children in France: a diagnostic accuracy substudy. Lancet Child Adolesc Health. 2025 Jan;9(1):47-56. doi: 10.1016/S2352-4642(24)00295-5. Epub 2024 Dec 2.

  PMID: 39637879 BACKGROUND

• Mannix R, Borglund E, Monashefsky A, Master C, Corwin D, Badawy M, Thomas DG, Reisner A. Age-Dependent Differences in Blood Levels of Glial Fibrillary Acidic Protein but Not Ubiquitin Carboxy-Terminal Hydrolase L1 in Children. Neurology. 2024 Aug 13;103(3):e209651. doi: 10.1212/WNL.0000000000209651. Epub 2024 Jul 10.

  PMID: 38986044 BACKGROUND

• Cooper JG, Stukas S, Ghodsi M, Ahmed N, Diaz-Arrastia R, Holmes DT, Wellington CL. Age specific reference intervals for plasma biomarkers of neurodegeneration and neurotrauma in a Canadian population. Clin Biochem. 2023 Nov;121-122:110680. doi: 10.1016/j.clinbiochem.2023.110680. Epub 2023 Oct 24.

  PMID: 37884086 BACKGROUND

• Bazarian JJ, Biberthaler P, Welch RD, Lewis LM, Barzo P, Bogner-Flatz V, Gunnar Brolinson P, Buki A, Chen JY, Christenson RH, Hack D, Huff JS, Johar S, Jordan JD, Leidel BA, Lindner T, Ludington E, Okonkwo DO, Ornato J, Peacock WF, Schmidt K, Tyndall JA, Vossough A, Jagoda AS. Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study. Lancet Neurol. 2018 Sep;17(9):782-789. doi: 10.1016/S1474-4422(18)30231-X. Epub 2018 Jul 24.

  PMID: 30054151 BACKGROUND

• Rauchman SH, Pinkhasov A, Gulkarov S, Placantonakis DG, De Leon J, Reiss AB. Maximizing the Clinical Value of Blood-Based Biomarkers for Mild Traumatic Brain Injury. Diagnostics (Basel). 2023 Oct 28;13(21):3330. doi: 10.3390/diagnostics13213330.

  PMID: 37958226 BACKGROUND

• Yang Z, Wang KK. Glial fibrillary acidic protein: from intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 2015 Jun;38(6):364-74. doi: 10.1016/j.tins.2015.04.003. Epub 2015 May 11.

  PMID: 25975510 BACKGROUND

• Abdelhak A, Foschi M, Abu-Rumeileh S, Yue JK, D'Anna L, Huss A, Oeckl P, Ludolph AC, Kuhle J, Petzold A, Manley GT, Green AJ, Otto M, Tumani H. Blood GFAP as an emerging biomarker in brain and spinal cord disorders. Nat Rev Neurol. 2022 Mar;18(3):158-172. doi: 10.1038/s41582-021-00616-3. Epub 2022 Feb 3.

  PMID: 35115728 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood Plasma

Study Officials

• Deirdre M Murray, PhD

  INFANT Research Centre, University College Cork

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Conor L Vaughan, BSc, MSc

CONTACT

+353876068018; conor.vaughan@ucc.ie

Deirdre M Murray, PhD

CONTACT

d.murray@ucc.ie

Study Design

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

Study Record Dates

• First Submitted: April 21, 2026
• First Posted: May 13, 2026
• Study Start: April 13, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)