A Study of a Blood Marker in Newborns With Brain Injury Caused by Lack of Oxygen at Birth

NCT07292220 | Not Yet Recruiting DMC

• 1 other identifier: kırıkkale medical university
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Perinatal asphyxia is a significant health problem with an incidence of 1 to 8 per 1,000 live births and can lead to serious morbidity and mortality during the neonatal period. One of its most severe consequences is hypoxic-ischemic encephalopathy (HIE), a condition that causes irreversible damage to the newborn brain due to hypoxia and ischemia. HIE is one of the leading causes of long-term neurological sequelae. Therapeutic hypothermia initiated within the first six hours after birth has been shown to significantly reduce both mortality and neurodevelopmental impairments associated with HIE. However, biomarkers that can reliably predict individual treatment response or objectively demonstrate the severity of brain injury at an early stage remain limited. Neurofilament light chain (NfL) is a protein found within the cytoskeletal structure of myelinated axons. When axonal injury occurs, NfL is released into the interstitial space and subsequently enters the cerebrospinal fluid and systemic circulation, where it can be measured. Increased NfL levels have been identified in a variety of neurological conditions, including neurodegenerative disorders and traumatic brain injury. Recent findings show that both cerebrospinal fluid and serum/plasma NfL levels are elevated in newborns diagnosed with HIE, supporting its potential role as a biochemical marker of axonal injury. The primary aim of this study is to investigate the time-dependent changes in serum NfL levels in newborns diagnosed with HIE and undergoing therapeutic hypothermia, and to evaluate the relationship between these changes, clinical findings, and neuroimaging results. For this purpose, serum NfL levels were measured at four specific time points: within the first six hours after birth (preferably cord blood), upon reaching the target cooling temperature (approximately 12-24 hours), during the rewarming phase (72-96 hours), and on the day of magnetic resonance imaging (preferably day seven). The results are expected to provide insights into the prognostic utility of NfL in HIE and contribute to determining the optimal timing for clinical sampling. The secondary objective of the study is to compare NfL levels of newborns diagnosed with HIE to those of a control group without HIE, thereby identifying potential cut-off values that may help distinguish between affected and unaffected infants.

Conditions

Hypoxic-Ischemic Encephalopathy

Keywords

Hypoxic-ischemic encephalopathy (HIE); Neurofilament light chain (NfL); Newborn; Therapeutic hypothermia

Outcome Measures

Primary Outcomes (4)

• 1. Serum NfL Level at 0-6 Hours After Birth

  Measurement of serum neurofilament light chain concentration in blood collected within 0-6 hours after birth. Unit of Measure: pg/mL

  Assessed at 0-6 hours after birth

• Serum NfL Level at 12-24 Hours After Birth

  Measurement of serum NfL concentration in blood collected after achieving target therapeutic hypothermia temperature.Unit of Measure: pg/mL

  Assessed at 12-24 hours after birth

• Serum NfL Level at 72-96 Hours After Birth

  Measurement of serum NfL concentration during the rewarming phase.Unit of Measure: pg/mL

  Assessed at 72-96 hours after birth

• Serum NfL Level at Approximately Day 7

  Measurement of serum NfL concentration on the day of clinically indicated brain MRI.Unit of Measure: pg/mL

  Assessed at approximately 7 days after birth

Secondary Outcomes (7)

• Sarnat Encephalopathy Stage at 0-6 Hours

  Assessed at 0-6 hours after birth

• Sarnat Encephalopathy Stage at 72-96 Hours

  Time Frame: Assessed at 72-96 hours after birth

• Sarnat Encephalopathy Stage at 12-24 Hours

  Assessed at 12-24 hours after birth

• Thompson Score at 0-6 Hours

  Assessed at 0-6 hours after birth

• Thompson Score at 12-24 Hours

  Time Frame: Assessed at 12-24 hours after birth

Study Arms (1)

case

control case

Eligibility Criteria

• Age: 0 Days - 28 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Cases admitted to the Neonatal Intensive Care Unit of Kırıkkale University Faculty of Medicine Hospital with a diagnosis of hypoxic-ischemic encephalopathy (HIE) and started on therapeutic hypothermia (TH) treatment were prospectively recorded.

You may qualify if:

• Newborns with a gestational age ≥36 weeks (term)
• Diagnosis of hypoxic ischemic encephalopathy (HIE) based on clinical and/or laboratory findings
• Diagnosis of stage I, stage II, or stage III HIE according to the Sarnat staging system
• Therapeutic hypothermia (TH) treatment initiated within the first 6 hours after birth
• Written consent obtained from the legal parent(s) for participation in the study

You may not qualify if:

• Major congenital malformation or genetic syndrome (e.g., Trisomy 21, congenital heart disease)
• Newborns with suspected sepsis, metabolic disease, or other systemic disease
• Premature infants with a gestational age \<36 weeks
• Therapeutic hypothermia treatment not started on time or inadequately administered
• Medical conditions preventing blood sampling (e.g., severe coagulopathy, circulatory instability)

Sponsors & Collaborators

• Mustafa Gürkan: lead

Study Sites (1)

, Kirikkale University, Department of Pediatrics, Kirikkale

Kırıkkale, Yahşihan, 71450, Turkey (Türkiye)

Location

Related Publications (6)

• Ahearne CE, Boylan GB, Murray DM. Short and long term prognosis in perinatal asphyxia: An update. World J Clin Pediatr. 2016 Feb 8;5(1):67-74. doi: 10.5409/wjcp.v5.i1.67. eCollection 2016 Feb 8.

  PMID: 26862504 BACKGROUND

• Shah DK, Ponnusamy V, Evanson J, Kapellou O, Ekitzidou G, Gupta N, Clarke P, Michael-Titus AT, Yip PK. Raised Plasma Neurofilament Light Protein Levels Are Associated with Abnormal MRI Outcomes in Newborns Undergoing Therapeutic Hypothermia. Front Neurol. 2018 Mar 5;9:86. doi: 10.3389/fneur.2018.00086. eCollection 2018.

  PMID: 29556208 BACKGROUND

• Depoorter A, Neumann RP, Barro C, Fisch U, Weber P, Kuhle J, Wellmann S. Neurofilament Light Chain: Blood Biomarker of Neonatal Neuronal Injury. Front Neurol. 2018 Nov 20;9:984. doi: 10.3389/fneur.2018.00984. eCollection 2018.

  PMID: 30524361 BACKGROUND

• Kyng KJ, Wellmann S, Lehnerer V, Hansen LH, Kuhle J, Henriksen TB. Neurofilament Light Chain serum levels after Hypoxia-Ischemia in a newborn piglet model. Front Pediatr. 2023 Jan 9;10:1068380. doi: 10.3389/fped.2022.1068380. eCollection 2022.

  PMID: 36699314 BACKGROUND

• Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. Lancet Neurol. 2010 Jan;9(1):39-45. doi: 10.1016/S1474-4422(09)70295-9. Epub 2009 Nov 5.

  PMID: 19896902 BACKGROUND

• Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev. 2010 Jun;86(6):329-38. doi: 10.1016/j.earlhumdev.2010.05.010. Epub 2010 Jun 16.

  PMID: 20554402 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

In this study, only venous blood samples collected intravenously from participants will be used. The serum fraction obtained from the blood samples will be analyzed to measure neurofilament light chain (NfL) levels. No genetic analysis will be performed as part of this study, and no DNA, RNA, or cellular material isolation is planned.

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Charcot-Marie-Tooth disease, Type 1F

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Mustafa Gürkan

CONTACT

+905319215528; mustafagurkan288@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Weeks
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: assistant doctor

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: December 18, 2025
• Study Start: December 15, 2025
• Primary Completion (Estimated): June 14, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: no end date

Locations

TU (1)