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

Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Other)

Overall Status

Recruiting

CT.gov ID

NCT05767476

Collaborator

(none)

Enrollment

Locations

80.1

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Encephalopathy, Hypoxic Ischemic	Diagnostic Test: Clinical and instrumental neurological assessment

Study Design

Study Type:

Observational

Anticipated Enrollment :

70 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Apr 28, 2021

Anticipated Primary Completion Date :

Aug 31, 2025

Anticipated Study Completion Date :

Dec 31, 2027

Arms and Interventions

Arm	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

Arm

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

Outcome Measures

Primary Outcome Measures

Neurodevelopmental outcome [24th months]
the score in Griffiths Mental Development Scales (GMDS)

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Minutes to 6 Hours

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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