Severity of Hypoxic Ischemic Encephalopathy and Neurological Pupil Index in Neonates

NCT07024771 | Not Yet Recruiting FDA Device

• 1 other identifier: REB25-0010
• Study Type: observational
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this observational study is to learn if the reactivity of a newborn's eye to light (measured as an index, using a new device -pupillometer) reflect the health of their brain recovering from disruption of blood/oxygen supply during birth (Hypoxic Ischemic Encephalopathy-HIE). The main questions it aims to answer are:

• With a decreasing reactivity index, does the chance of an abnormal electrical function of brain (noted by electroencephalography (EEG)) increase?
• With a decreasing reactivity index, do the odds of an indicator of severe impact on brain health (abnormal brain imaging, seizures, feeding difficulty) increase? Participants will undergo eye examination using the pupillometer instead of the regular penlight, as part of their routine neurological examination. This will not change the way in which the newborn is being treated and managed medically.

Conditions

Hypoxic Ischemic Encephalopathy (HIE)

Keywords

Neurological pupil index; Hypoxic ischemic encephalopathy; automated pupillometry; neonatal neurocritical care; severity of HIE; therapeutic hypothermia; cooling therapy; NPi; seizures; EEG

Outcome Measures

Primary Outcomes (1)

• Abnormal EEG pattern

  Abnormal EEG patterns will be monitored via continuous amplitude -integrated EEG (aEEG) . It will be scored by an expert neonatal neurologist into an objective score ranging from 0 to 5, where 0 = normal, 1=discontinuous, 2= Burst suppression, 3= isoelectric, 4= seizures and 5= not done. Any score from 1 to 4 will be considered as indicative of severe HIE, and will be considered collectively as "abnormal EEG pattern"

  From starting therapeutic hypothermia at admission (baseline) till completion of therapeutic hypothermia (72 hours from starting cooling therapy). EEG will be monitored CONTINUOUSLY during this period of 72 hours

Secondary Outcomes (3)

• Abnormal MRI findings

  MRI brain will be done and scored between day 4 and day 5 from admission

• Presence of seizure

  baseline (day of admission) till day 5 after admission

• persistent Feeding difficulty

  will be assessed at the time of discharge from NICU to home or transfer to ward (anytime between week 1 to week 4)

Study Arms (1)

HIE infants

Newborns diagnosed with HIE , more than 35 weeks of age, admitted to a neonatal neurocritical care unit in Alberta Children's hospital, undergoing therapeutic hypothermia

Device: Automated Pupillometer

Interventions

Automated Pupillometer DEVICE

An automated pupillometer will be used to measure pupil size and calculate NPi in newborns with HIE

Also known as: Neurological pupil index

HIE infants

Eligibility Criteria

• Age: Up to 6 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Neonates ≥35 weeks of GA, with Hypoxic ischemic encephalopathy admitted to neonatal neuro-intensive care unit at Alberta children's hospital, Calgary

You may qualify if:

• Neonates ≥35 weeks of GA, with Hypoxic ischemic encephalopathy admitted to neonatal neuro-intensive care unit at Alberta children's hospital, Calgary will be included in the study

You may not qualify if:

• Infants with chromosomal abnormalities/ syndromic associations
• Infants with ocular / orbital injuries or structural anomalies of the eye obscuring the pupillometry measurement
• Infants with inadequate pupillometry data / EEG data

Sponsors & Collaborators

• University of Calgary: lead

Study Sites (1)

University of Calgary

Calgary, Alberta, T2N1N4, Canada

Location

Related Publications (12)

• Oddo M, Sandroni C, Citerio G, Miroz JP, Horn J, Rundgren M, Cariou A, Payen JF, Storm C, Stammet P, Taccone FS. Quantitative versus standard pupillary light reflex for early prognostication in comatose cardiac arrest patients: an international prospective multicenter double-blinded study. Intensive Care Med. 2018 Dec;44(12):2102-2111. doi: 10.1007/s00134-018-5448-6. Epub 2018 Nov 26.

  PMID: 30478620 BACKGROUND

• Riker RR, Sawyer ME, Fischman VG, May T, Lord C, Eldridge A, Seder DB. Neurological Pupil Index and Pupillary Light Reflex by Pupillometry Predict Outcome Early After Cardiac Arrest. Neurocrit Care. 2020 Feb;32(1):152-161. doi: 10.1007/s12028-019-00717-4.

  PMID: 31069659 BACKGROUND

• Al-Obaidi SZ, Atem FD, Stutzman SE, Olson DM. Impact of Increased Intracranial Pressure on Pupillometry: A Replication Study. Crit Care Explor. 2019 Oct 30;1(10):e0054. doi: 10.1097/CCE.0000000000000054. eCollection 2019 Oct.

  PMID: 32166235 BACKGROUND

• Kim TJ, Park SH, Jeong HB, Ha EJ, Cho WS, Kang HS, Kim JE, Ko SB. Neurological Pupil Index as an Indicator of Neurological Worsening in Large Hemispheric Strokes. Neurocrit Care. 2020 Oct;33(2):575-581. doi: 10.1007/s12028-020-00936-0.

  PMID: 32096118 BACKGROUND

• Shah SS, Ranaivo HR, Mets-Halgrimson RB, Rychlik K, Kurup SP. Establishing a normative database for quantitative pupillometry in the pediatric population. BMC Ophthalmol. 2020 Mar 26;20(1):121. doi: 10.1186/s12886-020-01389-x.

  PMID: 32216772 BACKGROUND

• Sandroni C, Citerio G, Taccone FS. Automated pupillometry in intensive care. Intensive Care Med. 2022 Oct;48(10):1467-1470. doi: 10.1007/s00134-022-06772-4. Epub 2022 Jun 30. No abstract available.

  PMID: 35773500 BACKGROUND

• Jiang J, Sari H, Goldman R, Huff E, Hanna A, Samraj R, Gourabathini H, Bhalala U. Neurological Pupillary Index (NPi) Measurement Using Pupillometry and Outcomes in Critically Ill Children. Cureus. 2023 Oct 4;15(10):e46480. doi: 10.7759/cureus.46480. eCollection 2023 Oct.

  PMID: 37927706 BACKGROUND

• Couret D, Boumaza D, Grisotto C, Triglia T, Pellegrini L, Ocquidant P, Bruder NJ, Velly LJ. Reliability of standard pupillometry practice in neurocritical care: an observational, double-blinded study. Crit Care. 2016 Mar 13;20:99. doi: 10.1186/s13054-016-1239-z.

  PMID: 27072310 BACKGROUND

• Hall CA, Chilcott RP. Eyeing up the Future of the Pupillary Light Reflex in Neurodiagnostics. Diagnostics (Basel). 2018 Mar 13;8(1):19. doi: 10.3390/diagnostics8010019.

  PMID: 29534018 BACKGROUND

• Brown KL, Agrawal S, Kirschen MP, Traube C, Topjian A, Pressler R, Hahn CD, Scholefield BR, Kanthimathinathan HK, Hoskote A, D'Arco F, Bembea M, Manning JC, Hunfeld M, Buysse C, Tasker RC. The brain in pediatric critical care: unique aspects of assessment, monitoring, investigations, and follow-up. Intensive Care Med. 2022 May;48(5):535-547. doi: 10.1007/s00134-022-06683-4. Epub 2022 Apr 21.

  PMID: 35445823 BACKGROUND

• van Kooij BJ, van Handel M, Nievelstein RA, Groenendaal F, Jongmans MJ, de Vries LS. Serial MRI and neurodevelopmental outcome in 9- to 10-year-old children with neonatal encephalopathy. J Pediatr. 2010 Aug;157(2):221-227.e2. doi: 10.1016/j.jpeds.2010.02.016. Epub 2010 Apr 9.

  PMID: 20381069 BACKGROUND

• Hagberg H, David Edwards A, Groenendaal F. Perinatal brain damage: The term infant. Neurobiol Dis. 2016 Aug;92(Pt A):102-12. doi: 10.1016/j.nbd.2015.09.011. Epub 2015 Sep 25.

  PMID: 26409031 BACKGROUND

Related Links

• NeurOptics: NPI-200 Pupillometer. Instructions for use . (2021).

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Seizures

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; Neurologic Manifestations

Study Officials

• Khorshid Mohammad, MD, MSc, FRCP, FRCPC

  Cummings school of medicine, University of Calgary

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Khorshid Mohammad, MD, Mac, FRCP, FRCPC

CONTACT

587-893-0700; Khorshid.Mohammad@albertahealthservices.ca

Hari Prasath Ramachandran, MD

CONTACT

403-620-0975; hariprasath.ramachandran@albertahealthservices.ca

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2025
• First Posted: June 17, 2025
• Study Start: August 1, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: June 17, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)