Neurodevelopmental Outcome in Newborn With Hypoxic-ischemic Encephalopathy Treated With Therapeutic Hypothermia

The goal of this observational study is to identify early signs of poor neurodevelopmental outcome by performing specific neurological, neurophysiological and neuroimaging assessments in newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.

The main questions it aims to answer are:

• Identify patients at risk of neuromotor, cognitive and epileptic sequelae
• Plan early rehabilitation programs and future trials on early neuroprotection in infant at risk of neurodevelopmental disability

Participants will be involved in serial assessment:

• Before and after therapeutic hypothermia and before discharge: neurological assessment, according to the modified Sarna (t) score, Thompson's score and Hammersmith Neonatal Neurological Examination (HNNE); General Movement Assessment
• Amplitude integrated electroencephalogram (aEEG) within 6 hours of life, for 6 hours.
• Neonatal Cranial Ultrasonography within 6 hours of life, in the third and seventh day of life.
• Brain magnetic resonance imaging between 7 and 14 days.
• Electroencephalogram (EEG) within 7 days.

After discharge study population will perform:

• EEG between 3 and 6 months.
• Neurological assessment using Hammersmith Infant Neurological Examination (HINE) at 3-6-9-12 months.
• General Movement Assessment at 3 months.
• Neurodevelopmental assessment using the Griffiths Mental Development Scales at 24 months.
• Cognitive assessment using the Wechsler Preschool and Primary Scale of Intelligence between 36 and 41 months.
• Motor performance assessment using Movement ABC between 42 and 48 months.

Study Overview

• Status: Recruiting
• Conditions: Encephalopathy, Hypoxic Ischemic
• Intervention / Treatment: Diagnostic test: Clinical and instrumental neurological assessment

• Study Type: Observational
• Enrollment (Anticipated): 70

Contacts and Locations

• Study Contact: Name: Domenico M Romeo, MD,PHD; Phone Number: 00390630156391; Email: domenicomarco.romeo@policlinicogemelli.it

Study Locations

• Italy
  • Rome, Italy, 00168
    • Recruiting
    • Domenico Marco Romeo
    • Contact: Domenico Marco Maurizio DR Romeo, MD,PHD; Email: domenicomarco.romeo@policlinicogemelli.it
  • Rome, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli -IRRCS
    • Contact: Domenico M Romeo, MD,PHD; Email: domenicomarco.romeo@policlinicogemelli.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 minutes to 6 hours (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypotermia

Description

Inclusion Criteria:All infants with gestational age ≥ 35 weeks and with a body weight ≥ 1800 g were considered eligible, if they satisfied the following criteria:

• Intrapartum hypoxia defined as follows: potential of hydrogen (pH)≤ 7.0 or B.E. ≥ 16 millimole liters (mmo/L) in the 1st hour of life, obtained from cord or arterial blood, or (ii) pathological intra-partum course (e.g., abnormal foetal heart rate, cord prolapse, uterine rupture, maternal haemorrhage/trauma/epileptic seizures/cardiorespiratory arrest, shoulder dystocia, fluid meconium-stained amniotic), or Apgar score ≤5 or continuous respiratory support at 10 minutes.
• Signs of moderate or severe encephalopathy according to the Sarna (t) score and Sarna (t) staging, performed at 30-60 minutes of life: stage 2 (lethargic, poor spontaneous activity, distal flexion posture, hypotonia, weak primitive reflexes, myotic pupils, bradycardia or periodic breathing) or stage 3 (stupor/coma, decerebrate posture, spontaneous activity absent, flaccidity, primitive reflexes absent, non-reactive pupils or apnoea).
• Amplitude integrated electroencephalogram( aEEG ) by Cerebral Functional Monitoring (CFM) or electroencephalogram (EEG) for at least 30 minutes, which shows either moderate or severe electroencephalographic anomalies, or the presence of convulsions.

All enrolled infants underwent therapeutic hypothermia according to the international guideline for 72 hours.

Exclusion Criteria:

Infants with:

• gestational age <35 weeks,
• severe foetal growth restriction (body weight <1800 g),
• inability to start therapeutic hypothermia within 6 hours of birth,
• other known causes of encephalopathy (chromosomopathies, brain malformations, metabolic encephalopathies, major congenital anomalies, neonatal withdrawal syndrome), - incoercible bleeding,
• refusal of consent by the parent/guardian/legal representative

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia	Diagnostic test: Clinical and instrumental neurological assessment; Participants will be involved in serial assessment: Neonatal Cranial Ultrasonography; Brain magnetic resonance imaging; Neurological assessment; Neurodevelopmental and cognitive assessment; Electroencephalogram (EEG); Motor performance assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental outcome	the score in Griffiths Mental Development Scales (GMDS)	24th months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurodevelopmental outcome	the score in Wechsler Preschool and Primary Scale of Intelligence (WPPSI)	between 36th and 42th months
Motor coordination outcome	The score in Movement ABC (m-ABC)	between 42th and 48th months.

Collaborators and Investigators

• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
• Investigators: Principal Investigator: Domenico M Romeo, MD,PHD, ChatolicUIT

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2021
• Primary Completion (Anticipated): August 31, 2025
• Study Completion (Anticipated): December 31, 2027

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): March 14, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Body Temperature Changes; Brain Ischemia; Ischemia; Brain Diseases; Hypoxia; Hypothermia; Hypoxia, Brain; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: 3544

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No