Clinical trial NCT05767476: Neurodevelopmental Outcome in Newborn With Hypoxic-ischemic Encephalopathy Treated With Therapeutic Hypothermia
Official title: Neurodevelopmental Outcome in Newborn With Hypoxic-ischemic Encephalopathy Treated With Therapeutic Hypothermia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Encephalopathy, Hypoxic Ischemic
Lead sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Sponsor class: OTHER
First posted: 2023-03-14
Enrollment: 70
Sex: ALL
Minimum age (years): 10
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypotermia

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.


Eligibility criteria: 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

Primary outcomes:
measure: Neurodevelopmental outcome
timeFrame: 24th months
Secondary outcomes:
measure: Neurodevelopmental outcome
timeFrame: between 36th and 42th months
measure: Motor coordination outcome
timeFrame: between 42th and 48th months.
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Domenico Marco Romeo
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli -IRRCS
Study officials:
affiliation: ChatolicUIT
name: Domenico M Romeo, MD,PHD
role: PRINCIPAL_INVESTIGATOR
References: