Long Term Prognostic of Neonatal Hypoxic Ischemic Encephalopathy With Hypothermia Treatment

NCT02676063 | Unknown

• 1 other identifier: DCIC1416
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 22

Brief Summary

The primary objective is to evaluate neonatal characteristics, and biological and clinical investigations as predictive factors of death, or of severe and moderate neurodevelopmental disability at 3 years, in a large population-based cohort of full-term and late preterm neonates with moderate or severe HIE. Contrary to most previous studies which have often analyzed the accuracy of one factor among all other clinical investigations, the investigators objective's is to seek a relevant combination of several factors among the following list:

• Neonatal characteristics: gestational age and birthweight, maternal disease, acute intrapartum event, delivery mode, acidosis, neurological examination, place of birth and neonatal transfer
• Laboratory investigations: pH, lactates and new biological markers as detailed below
• Clinical investigations: aEEG, EEG, MRI, diffusion-weighted MRI

Conditions

Ischemic-Hypoxic Encephalopathy

Keywords

predictive factors; neurodevelopmental disabilities

Outcome Measures

Primary Outcomes (1)

• The primary outcome measure is a combined criterion : death, neurodevelopmental disabilities in survivors

  A combined criterion which includes: * Death between birth and 3 years of age * Neurodevelopmental disabilities in survivors, defined as : o Severe disabilities * Intellectual impairment with a mental score \>2SD below the mean or \<70 (ASQ) * Or Cerebral palsy with a Gross Motor Function level of 3-5 according to the GMFCS * Or bilateral blindness (vision \<20/200 acuity) * Or deafness requiring amplification (\>60dB)and/ * Or a persistent disorder defined as recurrent seizures after discharge from neonatal intensive care requiring anti-convulsion therapy at the examination time point o Moderate disabilities * Intellectual impairment with a mental score \>1SD below the mean or 70 to 84 (ASQ) * Cerebral palsy with a Gross Motor Function level of 1 or 2 according to the GMFCS * Or hearing impairment requiring no amplification

  between birth and 3 years of age

Secondary Outcomes (4)

• First secondary objective : The relevance of specific new biomarkers : Protein levels (IL-6, MMP-9, TIMP-1, Albumine modified by hypoxia, troponine I), acylcarnitins and amino acids.

  before H6 and at 3 days

• Second secondary objective: the predictive value of clinical investigations during the first weeks of life and treatments.

  first week, At 18 months and 3 years of age

• Third secondary objective : Number and percentage of participants with cooling.

  birth

• Fourth secondary objective : Number and percentage of various obstetrical conditions leading to the worse outcomes

  birth

Study Arms (1)

neonatal Hypoxic Ischemic encephalopathy

moderate or severe HIE among term and late preterm newborn

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will be performed on all moderate or severe cases of hypoxic ischemic encephalopathyhie, occurring between 34 and 42 completed weeks gestation in newborns admitted to a neonatal intensive care unit of the participating French regions. Children will be followed-up until the age of 3 years.

You may qualify if:

• Infants born at a gestational age of 34 weeks or more;
• Presenting early neurological distress with clinical signs of moderate to severe HIE at a standardized neurologic examination performed by a senior examiner:
• Moderate HIE: lethargy, hyper-reflexia, miosis, bradycardia, seizures, hypotonia with weak suck and Moro reflex
• Severe HIE: stupor, flaccidity, small to mid-position pupils that react poorly to light, reduced stretch reflexes, hypothermia or no Moro reflex
• With criteria for asphyxia:
• pH of 7.0 or less or a base deficit of 16 mmol per liter or more in a sample of umbilical-cord blood or any blood sampled in the first hour after birth.
• If, during this interval, the pH is between 7.01 and 7.15, base deficit is between 10 and 15.9 mmol per liter, or blood gas is not available, additional criteria will be required. These include:
• an acute perinatal event (e.g., late or variable decelerations, cord prolapse, cord rupture, uterine rupture, maternal trauma, hemorrhage, or cardiorespiratory arrest)
• or an abrupt change in fetal heart rate (FHR), defined as a persistent abnormal FHE after a period of normal tracing: bradycardia or prolonged deceleration, persistent variable decelerations, persistent late decelerations, and reduced heart variability
• or either a 10-minute Apgar score of 5 or less or assisted ventilation initiated at birth and continued for at least 10 minutes.
• Written parental informed consent
• Covered by the French social security

You may not qualify if:

• Congenital malformations
• Chromosomal disorders
• Congenital neuromuscular disorders

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (22)

Chu Amiens

Amiens, 80000, France

Location

Chu Besancon

Besançon, 25000, France

Location

Chu Bordeaux

Bordeaux, 33000, France

Location

Chu Brest

Brest, 29200, France

Location

CHU CAEN

Caen, 14000, France

Location

CHU Clermond-Ferrand

Clermont-Ferrand, 63000, France

Location

Chi Creteil

Créteil, 94000, France

Location

Chu Dijon

Dijon, 21000, France

Location

CHU FORT de France

Fort de France, 97200, France

Location

Chu Grenoble

Grenoble, 38000, France

Location

Chru Lille

Lille, 59000, France

Location

Chu Limoges

Limoges, 87000, France

Location

Chu Marseille

Marseille, 13000, France

Location

CHU Montpellier

Montpellier, 34000, France

Location

Chu La Miletrie

Poitiers, 86000, France

Location

Chu Reims

Reims, 51100, France

Location

Chu Rouen

Rouen, 76000, France

Location

CHU St Denis

Saint-Denis de La Réunion, 97400, France

Location

CHU St Pierre

Saint-Pierre, 97410, France

Location

Chu Strasbourg

Strasbourg, 67000, France

Location

Chu Toulouse

Toulouse, 31000, France

Location

Chu Tours

Tours, 37000, France

Location

Related Publications (10)

• Volpe JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol. 2012 Aug;72(2):156-66. doi: 10.1002/ana.23647.

  PMID: 22926849 BACKGROUND

• Use and abuse of the Apgar score. Committee on Fetus and Newborn, American Academy of Pediatrics, and Committee on Obstetric Practice, American College of Obstetricians and Gynecologists. Pediatrics. 1996 Jul;98(1):141-2.

  PMID: 8668389 BACKGROUND

• Fenichel GM. Hypoxic-ischemic encephalopathy in the newborn. Arch Neurol. 1983 May;40(5):261-6. doi: 10.1001/archneur.1983.04050050029002.

  PMID: 6405725 BACKGROUND

• Levene ML, Kornberg J, Williams TH. The incidence and severity of post-asphyxial encephalopathy in full-term infants. Early Hum Dev. 1985 May;11(1):21-6. doi: 10.1016/0378-3782(85)90115-x.

  PMID: 4006822 BACKGROUND

• Binet L, Debillon T, Beck J, Vilotitch A, Guellec I, Ego A, Chevallier M; LYTONEPAL research group. Effect of gestational age on cerebral lesions in neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2024 Aug 16;109(5):562-568. doi: 10.1136/archdischild-2023-326131.

  PMID: 38418209 DERIVED

• Guellec I, Ancel PY, Beck J, Loron G, Chevallier M, Pierrat V, Kayem G, Vilotitch A, Baud O, Ego A, Debillon T. Glycemia and Neonatal Encephalopathy: Outcomes in the LyTONEPAL (Long-Term Outcome of Neonatal Hypoxic EncePhALopathy in the Era of Neuroprotective Treatment With Hypothermia) Cohort. J Pediatr. 2023 Jun;257:113350. doi: 10.1016/j.jpeds.2023.02.003. Epub 2023 Feb 23.

  PMID: 36828343 DERIVED

• Debillon T, Sentilhes L, Kayem G, Chevallier M, Zeitlin J, Baud O, Vilotitch A, Pierrat V, Guellec I, Ancel PY, Bednarek N, Ego A. Risk factors for unfavorable outcome at discharge of newborns with hypoxic-ischemic encephalopathy in the era of hypothermia. Pediatr Res. 2023 Jun;93(7):1975-1982. doi: 10.1038/s41390-022-02352-w. Epub 2022 Oct 22.

  PMID: 36272997 DERIVED

• Beck J, Debillon T, Guellec I, Vilotitch A, Loron G, Bednarek N, Ancel PY, Pierrat V, Ego A. Healthcare organizational factors associated with delayed therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: the LyTONEPAL cohort. Eur J Pediatr. 2023 Jan;182(1):181-190. doi: 10.1007/s00431-022-04666-7. Epub 2022 Oct 21.

  PMID: 36269426 DERIVED

• Beck J, Bednarek N, Pierrat V, Vilotitch A, Loron G, Alison M, Guellec I, Hertz-Pannier L, de Launay C, Ego A, Vo-Van P, Ancel PY, Debillon T. Cerebral injuries in neonatal encephalopathy treated with hypothermia: French LyTONEPAL cohort. Pediatr Res. 2022 Sep;92(3):880-887. doi: 10.1038/s41390-021-01846-3. Epub 2021 Nov 20.

  PMID: 34802036 DERIVED

• Debillon T, Bednarek N, Ego A; LyTONEPAL Writing Group. LyTONEPAL: long term outcome of neonatal hypoxic encephalopathy in the era of neuroprotective treatment with hypothermia: a French population-based cohort. BMC Pediatr. 2018 Aug 1;18(1):255. doi: 10.1186/s12887-018-1232-6.

  PMID: 30068301 DERIVED

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain

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

Study Officials

• Thierry DEBILLON, MD PhD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 28, 2015
• First Posted: February 8, 2016
• Study Start: September 1, 2015
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2021
• Last Updated: June 6, 2018

Record last verified: 2018-06

Locations

FR (22)