Background
Hypoxic ischemic encephalopathy: Definition, incidence and risk factors
Management of HIE and short and long-term outcomes
Predicting mortality and neurodevelopmental outcomes
Objectives
Methods
Study design
Participants
Neurological signs | • Moderate HIE: lethargy, hyper-reflexia, myosis, bradycardia, seizures, hypotonia with weak suck and poor Moro reflex • Severe HIE: stupor, flaccidity, small to mid-position pupils that react poorly to light, decreased stretch reflexes, hypothermia or absent Moro reflex |
Biological criteria indicating asphyxia during the first hour after birth in a sample of umbilical-cord blood or any other blood sampled | • Severe biological signs: pH ≤7.0 or less or a base deficit ≥16 mmol per liter • Moderate/absent biological signs with additional perinatal events: ○ 7.0 < pH ≤ 7.15, or 10 ≤ a base deficit < 16 mmol per liter, or blood gas measurement unavailable ○ With: - 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 FHR after a period of normal tracing: bradycardia or prolonged deceleration, persistent variable decelerations, persistent late decelerations, and reduced heart variability - or either a 10-min Apgar score of 5 or less or assisted ventilation initiated at birth and continued for at least 10 min. |
Baseline data collection and follow-up organization
Mother and pregnancy characteristics | • Maternal age, parity, educational level, occupation, history of previous pregnancies, medical history and complications of the current pregnancy |
Circumstances of birth | • Labor and delivery mode: onset of labor, mode of delivery, intrapartum complications, fetal heart rate monitoring • Neonatal characteristics: gestational age, birthweight, gender, small for gestational age (<10th percentile), 1, 5 and 10 min Apgar scores, cord or arterial pH, base deficit within the first hour of life, neonatal transfer • Care in delivery room: O2, ventilation, resuscitation • Placental examination and fetal autopsy (if performed) |
Admission in NICU | • Standardized neurological examination: Sarnat classification and Thompson score during the first week of life. • First clinical investigations: Electrophysiological examination (cEEG or aEEG) and neuro-imaging |
Hospital stay in neonatal units | • Clinical investigations Electrophysiological examination (standard or amplitude-integrated), Cerebral ultrasound exams (Doppler and morphological), Brain MRI (diffusion –weighted and standard), Standard blood tests (heart, liver, kidney). • Treatment: analgesia, sedatives, anticonvulsant treatment, cooling or other neuroprotective strategies, ventilation, nutrition • Neonatal morbidity and mortality: pulmonary, cardiac, renal or liver pathologies, multi-organ system failure, neonatal death (date and presumed cause) |
Hospital discharge from neonatal unit | • Standardized neurological examination: Sarnat definition, Thompson score, and Amiel-Tison neurological assessment. • Hospital discharge: discharge home, discharge to another care facility, death • Presumed circumstances or cause of HIE according to the neonatologist: Identified maternal, obstetrical, or neonatal conditions and events |
Organization of care | • Place of birth, level of care of the maternity ward, timing of transfer and admission to NICU, transport conditions, level of care of the first and subsequent neonatal units, length of hospital stay |
Data management and completeness of HIE registration
Study outcomes
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intellectual impairment (mental score > 2sd below the mean or intellectual quotient (IQ) < 70 according to the revised Brunet Lezine Score and ASQ scores),
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or cerebral palsy (GMFCS of 3–5),
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or sensorial impairment (bilateral blindness with vision < 20/200 acuity or deafness requiring amplification > 60 dB),
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or persistent disorder defined as recurrent seizures after discharge from the NICU requiring anti-convulsive therapy.
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intellectual impairment (1 sd < mental score ≤ 2 sd below the mean or 70 ≤ IQ < 85),
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cerebral palsy (GMFCS of 1–2),
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or hearing impairment requiring no amplification.
Sample size calculation
Statistical analysis
Ethics approval and consent to participate
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from the National French data protection authority (Commission Nationale Informatique et Libertés) on March 27, 2015; DR-2015-136
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and from the Regional Ethics committee CPP South-East V (Comité de Protection des Personnes Sud Est; Institutional Review Board n°5891) on July 18, 2014.
Project governance
Discussion
Acknowledgements
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LyTONEPAL Writing Group: Pierre-Yves Ancel, Olivier Baud, Nathalie Bednareck, Marie-Laure Charkaluk, Clothilde Desrobert, Thierry Debillon, Catherine de Launay du Couedic, Anne Ego, Cyril Flamant, Pierre Gressens, Gilles Kayem, Stephane Marret, Juliana Patkail, Loic Senthiles, Elie Saliba
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LyTONEPAL Study Group: Alsace: D Astruc, (Strasbourg), J Nakhleh (Mulhouse); Aquitaine: O Brissaud (Bordeaux), P Jouvencel (Bayonne), T Mansir, K Norbert (Pau); Auvergne: G Gremerand (Clermont-Ferrand); Basse-Normandie: A Cénéric (Caen); Bourgogne: C Chantegret, Dr. Kaletas (Dijon); Bretagne: J-M Roué (Brest), M Gromand (Rennes), E Boutaric, J Chauvel, A Busnel (St-Brieuc), A Sevestre (Vannes); Centre: E Saliba, A Bouissou, E Lopez, G Favrais (Tours), J Guerreiro, E Werner (Orléans); Champagne-Ardenne: N Bednarek, P Venot (Reims), I Arnault, B Kassis-Makhoul (Troyes); Franche-Comté: G Thiriez, T Dabudyk (Besançon); Haute-Normandie: A Chadie, T Blanc (Rouen), J Mourdie (Le Havre); Ile-de-France: C Huon (Colombes), F Decobert, C Jung G Dassieu, C Danan, X Durrmeyer (Créteil), M Granier (Evry), O Baud, S Soudee, V BIRAN (Robert Debré), I Guellec (Trousseau), N Yousef (Bicêtre), G Ciarlo, A DURANDY (Poissy), J Patkai (Port-Royal), A Lapillonne, C Elie (Necker), V Zupan, R Ben Ammar, Y Soreze (Clamart), P Daoud, B Heller Roussin (Montreuil), D Mellah, L Karaoui (Meaux), D Brault (Argenteuil), P Boize, S Merbouche, M Saad, P Boize, C Miler (Pontoise), F Goudjil (St Denis); Languedoc-Roussillon: G Cambonie, M Badr (Montpellier), R Salloum (Perpignan), M Di Maio (Nîmes); Limousin: F Mons (Limoges); Midi-Pyrénées: MO Marcoux (Toulouse); Poitou-Charentes: K Husseini, A Parizel, E Ruiz Nord-Pas-de-Calais: F Flamein, S Joriot (Lille), S Klosowski (Lens), F Lapeyre C Dewitte (Valenciennes), J Ghesquiere, I Guilhoto, L Dusol (Arras), L Egreteau (Calais), Z Osman, M Raqbi (Creil); PACA et Corse: C Desrobert, V Brevaut (Marseille), J Oertel, C Dageville, S Desmet, F Casagrande (Nice); Pays de Loire: C Flamant (Nantes), G Gascoin S le Bouedec (Angers), Y Montcho (Le Mans); Picardie: G Ghostine (Amiens); Rhône-Alpes: N Bouchon (Chambéry), O Claris, JC Picaud, P Vo Van, CM Loys (Lyon), A Ego, T Debillon (Grenoble), H Patural (Saint-Etienne); Martinique: SK Martinon (Fort de France); La Réunion: JB Gouyon (Saint-Pierre), S Samperiz, D Ramful (Saint-Denis).
Funding
Availability of data and materials
Ethics approval and consent to participate
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from the National French data protection authority (Commission Nationale Informatique et Libertés) on March 27, 2015; DR-2015-136
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and from the Regional Ethics committee CPP South-East V (Comité de Protection des Personnes Sud Est; Institutional Review Board n°5891) on July 18, 2014.