Postnatal management of newborn infants with hypoxic ischaemic encephalopathy (HIE)

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Authors

Thoresen M, Hellström-Westas L, Zimmermann LJI, Buonocore G, Murray DM, Sabir H, Saliba E, Van Bel F

Click on the image to read the standard in brief.

Target group

Term and near-term infants with hypoxic ischaemic encephalopathy (HIE) and parents

User group

Healthcare professionals, neonatal units, hospitals, and health services

Statement of standard

Newborn infants who have suffered from hypoxia-ischaemia receive early evaluation and appropriate postnatal management and monitoring including therapeutic hypothermia in infants with ‘moderate to severe’ encephalopathy and follow-up.

Rationale

The goal is to reduce long-term effects of hypoxic-ischaemic brain injury. Moderate to severe perinatal asphyxia in term and near-term infants is one of the most important causes of neonatal death and adverse motor and cognitive outcome. The incidence is 2-20 per 1000 live born infants, depending in which part of the world they are born. (1) Based on experimental work and randomised clinical trials therapeutic hypothermia was suggested as the standard of care in 2010. (2,3) The original protocol from 1999; reducing  core body temperature to 33-34°C for 72h is still the only valid therapy which has shown a significant decrease in adverse outcomes (death or substantial disability) after perinatal asphyxia, both at 18 months (4–6) and at school age. (7–9) Since 2018, optimisation studies aimed to cool for longer (120h) or deeper (32°C) or to start cooling later (>6-24h) did not improve outcomes further than therapeutic hypothermia (TH) at 33.5°C, but increased the risk of harm. Outcome after RCT on cooling infants with HIE of 34–35-week gestation is not yet available (NCT01793129). Regarding combination therapies, adding Xenon gas (10) or erythropoietin to TH (11) was ineffective. Currently, alternative substances are being examined in preclinical settings (1) and clinical trials (e.g. allopurinol (NCT03162653), melatonin (NCT02621944) or stem cells (NCT03635450). In low-and middle-income countries one large randomized controlled cooling trial (RCT) failed to show neuroprotective efficacy of TH (12) with a primary outcome being death and disability at 18-24 months of age. In a recent metanalysis, TH improved outcome in survivors globally. (9)

Where infants are born and cared for, staff should be competent in early diagnosis of infants at risk of developing moderate or severe encephalopathy. TH should start as early as possible after diagnosis including either passive or active cooling during transport with continuous core temperature monitoring to a cooling centre. Evidence-based data is only available for efficacy of TH in infants with moderate or severe HIE as no RCT enrolling infants with mild HIE has been completed. Infants with all grades of HIE (including suspected mild HIE) should be fully assessed for TH eligibility, parents should be informed of the diagnosis and decision-making process; and the infant enrolled in long term follow up.

Benefits

Short-term benefits

Long-term benefits

Components of the standard

Component

Grading of evidence

Indicator of meeting the standard

For parents and family

  1. Parents are informed by healthcare professionals about the management and outcome of hypoxic ischaemic encephalopathy (HIE). (7,32–34)

A (Low quality)
B (High quality)
C (Moderate quality)

Patient information sheet1

  1. Parents receive counselling regarding the expected short- and long-term outcome and prognosis related to HIE prior to discharge by healthcare professionals. (34)

B (High quality)
C (Moderate quality)

Clinical records

For healthcare professionals

  1. A unit guideline on management of HIE including criteria for hypothermia treatment is adhered to by all healthcare professionals.

B (High quality)

Guideline

  1. Training in assessment and management of encephalopathic infants is attended by all responsible healthcare professionals. (35–37)

A (Moderate quality)
B (High quality)

Training documentation

  1. Moderate hypothermia treatment is started within 6 hours and continued for 72 hours after birth of eligible infants. (38,39)

A (High quality)

Audit report2 and RCT’s

For neonatal unit

  1. A unit guideline on the management of HIE (22) including monitoring of blood glucose (hypoglycaemia and hyperglycaemia), a-EEG, seizures (24), heart rate (40), oxygen saturation (41,42), PCO2 (24,41), and blood pressure, is available and regularly updated. Other predictive markers of insult severity and outcome are LDH (43), the time it takes for lactate levels to drop to <5 mmol/L, low or high glucose. Important markers available in many units are the time it takes for a-EEG to normalize after birth and MRI severity scoring. (37)

A (Moderate quality)
B (High quality)

Guideline

  1. Infants who require hypothermia treatment are managed in centres with documented expertise and experience including in temperature-monitored transfer and passive or active cooling (see Birth & transfer).

B (Moderate quality)

Guideline

For hospital

  1. Training in assessment and management of encephalopathic infants is ensured.

B (High quality)

Training documentation

  1. At designated units, cooling devices and monitoring equipment are available.

B (High quality)

Audit report2

For health service

  1. A national guideline on management of HIE including criteria for hypothermia treatment is available and regularly updated.

B (High quality)

Not all EU Countries have national guidelines. We aim for that.

  1. Hypothermia treatment including documented follow-up at 2 years (as suggested in national guidelines preferably also later ≥ 5yrs) and necessary educational support is coordinated and organised.

B (High quality)

Audit report2

  1. Support services for families of infants with HIE are available.

B (High quality)

Audit report2

1The indicator “patient information sheet” is an example for written, detailed information, in which digital solutions are included, such as web-based systems, apps, brochures, information leaflets, and booklets.

2The indicator “audit report” can also be defined as a benchmarking report.

Where to go

Further development

Grading of evidence

For parents and family

  • Use routine health service and education data for long-term follow-up programmes.

B (Moderate quality)

For healthcare professionals

N/A

For neonatal unit

  • Develop regional training programmes on early assessment and management of hypoxic ischaemic encephalopathy (HIE).

B (High quality)

  • Research on improved interventions, monitoring care and outcome predictors.

B (Moderate quality)

For hospital

N/A

For health service

  • Develop an asphyxia registry service including outcome at 2 years (24,33) and also later for those centres who do ≥5 year assessment including cognitive assessment, or access to school assessments, need for support etc. For UK that is year 2 and 6.
  • Develop databases for comparison between regions and countries.

B (Moderate quality)

Getting started

Initial steps

For parents and family

  • Parents are verbally informed by healthcare professionals about the management and outcome of hypoxic ischaemic encephalopathy (HIE) by healthcare professionals.

For healthcare professionals

  • Attend training in the assessment and management of encephalopathic infants. This includes knowledge on the physiological effects of hypothermia on all organ systems.
  • Use and gain further knowledge of common biochemical markers *which are associated with HIE severity. (19,37,44)
  • Join post-graduate education with respect to hypothermia and a-EEG or EEG monitoring and interpretation technique/knowledge.
  • Develop appropriate neurodevelopmental follow-up expertise.

For neonatal unit

  • Develop and implement a unit guideline on management of HIE including criteria for hypothermia treatment.
  • Develop information material on management and outcome of HIE for parents.
  • Provide appropriate devices and knowledge on how to use device(s). (35)

For hospital

  • Support healthcare professionals to participate in training assessment and management of encephalopathic infants.
  • Provide appropriate budget and technical support for training and equipment.

For health service

  • Develop and implement a national guideline on management of HIE including entry- criteria for hypothermia treatment and plan for short- and long-term follow-up.
  • Recognise that therapies discussed in this statement are mandatory.

Apart from supportive therapies such as haemodynamic stabilisation, respiratory support, avoiding hyperthermia during resuscitation, monitoring of physiological parameters and metabolism (e.g. glucose metabolism, electrolytes, liver function, kidney function, cardiac function) and treatment of coagulation disorders, hypotension and seizures, moderate hypothermia (target; 33-34°C) should be initiated as soon as possible and not later than six hours after birth (within the so-called therapeutic window). Passive cooling locally and during transport is acceptable with continuous core temperature monitoring. TH should be  continued for 72 hours, with appropriate discomfort and pain assessment, sedation and pain management. (36,38,39) It is important to be aware of rare side effects of induced hypothermia like thrombocytopenia; increased bleeding tendency if there are lacerations, hypotension and arrhythmia/bradycardia. High creatinine and TH reduces drug metabolism, and  increased gentamicin levels  increases the risk of hearing loss. (28,45)If sepsis or infection is suspected, antibiotic treatment should be considered. Being cold per se  increases CRP to around 30 units. (46) Appropriate multiorgan, including brain, monitoring is mandatory. Depression of background amplitude on early amplitude-integrated EEG (a-EEG) or abnormal multi-channel EEG activity is an excellent indicator of HIE severity, and is used as an entry criterion in many protocols. (4,6,47) Continuous a-EEG/EEG monitoring with or without video monitoring is essential to detect electrographic seizures and the effect of anticonvulsant treatment. (48) Serial documentation of brain injury, including serial neurological examination (cranial ultrasound; MRI, preferably with diffusion sequences and spectroscopy) as well as biochemical markers in blood/serum or plasma are important to determine the prognosis in the days or first week of life. Be aware of the effect of hypothermia per se on biochemical markers (46,49) and physiological variables. (50) Systematic neurobehavioral testing and documentation at discharge (e.g. Hammersmith Neonatal Neurological Examination (51,52) at two years follow-up in survivors (e.g. Bayley III (53) or Griffiths(54) as well as at early school age for long term, e.g. 5-8 years (see Follow-up & continuing care). (33)

  1. General measures (hemodynamic/respiratory stabilisation; treatment of convulsions; metabolic/haematological and electrolyte surveillance
  2. Optimal neonatal care, normocapnia, normotension, pain assessment, contact with parents (holding the baby if possible) (55)
  3. Moderate whole-body hypothermia (33.5±0.5˚C)
  4. Currently pharmacology/noble gasses or repair with umbilical cord stem cells have not proven effective (21,56–58). Other substances are currently under experimental and clinical investigation (56–58)

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Second edition, December 2024. Previous edition reviewed by Associate Prof Subhabrata Mitra.

Lifecycle

5 years/next revision: 2029

Recommended citation

GFCNI, Thoresen M et al., European Standards of Care for Newborn Health: Postnatal management of newborn infants with hypoxic ischaemic encephalopathy (HIE). 2024.

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