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

Hypoxic-ischemic encephalopathy (HIE) is a rare neonatal condition affecting about 1‰ births and with a high rate of death and severe neurological disability despite significant improvement of the management of this illness in the last ten years. During the first hours and days of life, different examinations are made by neonatologists to guide decisions about the management of HIE and to provide information to families. Nevertheless, better knowledge about the early and late predictive factors of long-term severe and moderate neurodevelopmental outcomes is badly needed.

This study is a prospective national observational population-based study involving all level III intensive care units in France.

This population-based cohort study will be performed including all moderate or severe cases of HIE, 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.

Participating centers will be invited to adhere to current HIE management guidelines and/or clinical investigations considered optimal to date, to ensure standardize clinical practice. The study will ensure high quality data collection.

About indications, timing and characteristics of treatments and investigations will be elaborated by the scientific committee during the preparation stage of the cohort study. This professional advice will have the double advantage of enabling us to record more homogeneous and high-quality data, and to standardize and improve clinical management and investigations among newborns with HIE.

Within this main study, an ancillary study will be performed by 21 centers to address the first secondary objective (predictive value of very early - first 6 hours of life - neurological examination and biological investigations, including specific new biomarkers such as Interleukin-6, Metalloproteinase-9, TIMP-1, Albumin modified by hypoxia, troponin I, acylcarnitins and amino acids).

Inclusion Criteria:

• 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

Exclusion Criteria:

• Congenital malformations
• Chromosomal disorders
• Congenital neuromuscular disorders

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.