Early Neurological Outcome in Newborns With Mild Encephalopathy:a Regional Network

This is a multicenter prospective observational study that aims to determine the natural history of patients with early diagnosis (within 6 hours of life) of mild hipoxic ischemic encephalopaty (HIE), who are not candidates for treatment with therapeutic hypothermia. The goal of this study is to learn about the early neurological outcome in babies with mild encephalopathy, as recent studies have shown how there is an increased risk of brain damage with a high incidence of resonance magnetic nuclear (RMN) anomalies and possible neurodevelopmental complications including learning or neuropsychological disorders, epilepsy, visual and sensory deficits. The main question aimed to answer is the identification of early possible predictive factors for an unfavorable outcome in order to undertake early rehabilitation programs and for the future planning of trials on early neuroprotection in the investigated population. Babies with early diagnosis (within 6h of life) of mild grade HIE not candidate for hypothermic treatment are subjected to clinical and instrumental assessments during the neonatal period:

• neurological objective exam according to the modified "Sarnat" score, Thompson score and Hammersmith Neonatal Neurological Examination (HINE) within 6 hours of life, 24 hours of life and before resignation;
• an Amplitude Electroencephalogram (aEEG) study within 6 hours of life, for 6 hours;
• cerebral ultrasound within 6 hours of life, in the third and seventh day of life;
• a brain magnetic resonance imaging study between the seventh and 14th day of life;
• an Electroencephalogram (EEG) evaluation within 7 days.

After resignation, all patients will be included in a minimum duration follow-up program of 12 months, with assessments at 3rd, 6th and 12th month of age:

• Hammersmith Neonatal Neurological Examination (HINE) and evaluation of the General Movements;
• evaluation of psychomotor development through Griffiths/Bayley III scales at the 12th month;
• EEG evaluation at the 6th and 12th month.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypoxic Encephalopathy
• Intervention / Treatment: Diagnostic test: Clinical and instrumental neurological assessment

• Study Type: Observational
• Enrollment (Actual): 27

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00168
    • Fondazione Policlinico Universitario Agostino Gemelli -IRRCS

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

patients with early diagnosis (within 6 hours of life) of mild HIE, who are not candidates for treatment with therapeutic hypothermia

Description

Inclusion Criteria:

• patients born after the 36th week of gestational age, with signs of encephalopathy found between the 10th minute of life and 6h, presenting with one or more of the following signs of intrapartum hypoxia with a potential of hydrogeb (pH) ≤ 7 or an excess of bases (BE) ≥ 12 mmol/l in the first hour of life, measured on cord or arterial blood or an abnormal course of delivery (eg: fetal heart rate abnormalities, cord prolapse, uterine tear, haemorrhage/ trauma/ convulsive seizures/ maternal cardiorespiratory arrest; shoulder dystocia; meconium-dyed amniotic fluid or protracted second stage and the presence of an Apgar at 10 min ≤5 or the need for continuous respiratory support at 10 minutes.

Exclusion Criteria:

• mutes neurological objectivity;
• impossibility of recruitment within 6h;
• major congenital anomalies, brain malformations;
• neonatal abstinence syndrome;
• metabolic encephalopathies and severe growth restriction (birth weight ≤1800g);
• treatment with therapeutic hypothermia;
• refusal of consent.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Patients with early diagnosis (within 6 hours of life) of mild HIE

Diagnostic test: Clinical and instrumental neurological assessment; During the neonatal period: neurological objective exam according to the modified Sarnat score, Thompson score and Hammersmith Neonatal Neurological Examination (HINE) within 6 hours of life, 24 hours of life and before resignation; an AEEG study within 6 hours of life, for 6 hours; cerebral ultrasound within 6 hours of life, in the third and seventh day of life; a brain magnetic resonance imaging study between the seventh and 14th day of life; an EEG evaluation within 7 days. After resignation, all patients will be included in a minimum duration follow-up program of 12 months, with assessments at 3rd, 6th and 12th month of age: Hammersmith Neonatal Neurological Examination (HINE) and evaluation of the General Movements; evaluation of psychomotor development through Griffiths/Bayley III scales at the 12th month; EEG evaluation at the 6th and 12th month.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
early neurological outcome	the percentage of patients with mild asphyxia with evidence of brain damage, defined by MRI	between the seventh and 14th day of life
early neurological outcome	the percentage of patients with mild asphyxia with evidence of brain damage, defined by EEG abnormalities	at the 6th month
early neurological outcome	the percentage of patients with mild asphyxia with evidence of brain damage, defined by EEG abnormalities	at 12th month.
early neurological outcome	the percentage of patients with mild asphyxia with evidence of brain damage, defined by neurological examination	at the 3th month
early neurological outcome	the percentage of patients with mild asphyxia with evidence of brain damage, defined by neurological examination	at the 6th month.
early neurological outcome	the percentage of patients with mild asphyxia with evidence of brain damage, defined by neurological examination	at the 12th month.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Electroencephalographic and epilepsy outcome	percentage of abnormalities at electroencephalographic checks and presence of critical events	between the 6 hours of life and 12th month.
Neurodevelopmental outcome	percentage of abnormalities at Neurodevelopmental evaluation	12th month
Hospitalization	Duration of Hospitalization	between birth until 12th month
adverse events	Death	between birth until 12th month

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): February 27, 2020
• Primary Completion (Actual): November 7, 2022
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: March 2, 2023
• First Submitted That Met QC Criteria: March 14, 2023
• First Posted (Actual): March 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 27, 2023
• Last Update Submitted That Met QC Criteria: March 14, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Mild Hypoxic Encephalopathy
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia; Brain Diseases; Hypoxia, Brain
• Other Study ID Numbers: 2631 (Bern University Hospital)

Drug and device information, study documents

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