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Key messages

  • Perinatal asphyxia is an important cause of neonatal encephalopathy, for which therapeutic cooling may be applicable.
  • It is important to consider differential diagnoses for neonatal encephalopathy.
  • Infants requiring vigorous resuscitation including an endotracheal tube and positive pressure ventilation beyond five minutes of age may require transfer to a Level 6 neonatal unit. These infants should be discussed with PIPER.
  • Management includes therapeutic cooling, ventilatory support if required, fluid and blood pressure management, treatment of seizures, and other investigations for differential diagnoses.

Please note that all guidance is currently under review and some may be out of date. We recommend that you also refer to more contemporaneous evidence in the interim.

Neonatal encephalopathy is a clinically defined syndrome of disturbed neurologic function in the earliest days of life in an infant born at or beyond 35 weeks of gestation, manifested by a subnormal level of consciousness or seizures, and often accompanied by difficulty with initiating and maintaining respiration and depression of tone and reflexes.

Perinatal asphyxia is an important cause of neonatal encephalopathy, for which therapeutic cooling may be applicable. Treatment is otherwise mostly supportive.

Neurological assessment at two weeks is a good predictor of outcome.

Magnetic resonance imaging (MRI) and spectroscopy can provide information about cause, timing of injury and further refine the prognosis.

Infants requiring vigorous resuscitation including an endotracheal tube and positive pressure ventilation beyond five minutes of age may require transfer to a Level 6 neonatal unit. These infants should be discussed with PIPER.

The term 'birth asphyxia' has been traditionally used to describe infants who present 'flat' at birth (for example, delayed onset of breathing, bradycardia, impaired muscle tone and reflexes) where a period of fetal hypoxia is likely.

However, the clinical presentation is not specific to perinatal asphyxia (see differential diagnosis) and the preferred term is 'neonatal encephalopathy' (NE), where the precise cause is not implied.

Possible antecedents of neonatal encephalopathy

Antecedents of neonatal encephalopathy may include:

  • perinatal hypoxia-ischaemia
  • infection
  • cerebral infarction
  • intracranial haemorrhage
  • congenital brain malformations
  • inborn errors of metabolism
  • genetic syndromes.

Hypoxic-ischaemic encephalopathy (HIE) is reserved for the subgroup of the term NE who have convincing evidence of peripartum or intrapartum hypoxia; and signs and contributing factors of which have been outlined by the American College of Obstetricians and Gynecologists’ Task Force on Neonatal Encephalopathy 2014.

Neonatal Signs Consistent With an Acute Peripartum or Intrapartum hypoxia

  • Apgar score of less than 5 at 5 minutes and 10 minutes
  • Fetal umbilical artery acidaemia with pH< 7.0, or base deficit ≥12 mmol/L
  • Neuroimaging evidence of acute brain injury seen on brain magnetic  resonance imaging (MRI) or magnetic resonance spectroscopy (MRS) consistent with hypoxia– ischaemia
  • Presence of multisystem organ failure consistent with hypoxic–ischemic encephalopathy (HIE)
  • Exclusion of other identifiable etiologies such as trauma, coagulation disorders, infectious conditions or genetic disorders.

Contributing factors consistent with Acute Peripartum or Intrapartum Event

  • Sentinel (signal) hypoxic event occurring immediately before or during labour
  • Sudden and sustained fetal bradycardia or the absence of fetal heart rate variability in the presence of persistent, late or variable decelerations, usually after a hypoxic sentinel event when the pattern was previously normal
  • Timing and type of brain injury patterns based on imaging studies consistent with an etiology of an acute peripartum or intrapartum event. Several well-defined patterns of brain injury on MRI are typical of hypoxic–ischaemic cerebral injury in the newborn, including deep nuclear gray matter or watershed cortical injury. Focal infarction or haemorrhage, porencephaly, or metabolic encephalopathies suggest that peripartum hypoxia–ischaemia was not the cause of the neonatal encephalopathy.  

Management of neonatal encephalopathy

Resuscitation

If the infant requires vigorous resuscitation including an endotracheal tube and positive pressure ventilation beyond five minutes of age, then the infant should be admitted to the special care nursery (SCN) and a blood gas taken before extubation. If the pH is < 7.20 the infant should remain intubated and PIPER contacted with view to transfer to a tertiary neonatal centre. If the pH is > 7.20 but the infant is still in a depressed state then there should be a discussion with PIPER.

Referral to Level 6 neonatal nursery should be considered in any infant with moderate to severe encephalopathy requiring:

Ventilation

Ventilate if there is respiratory depression especially in the setting of:

  • severe encephalopathy
  • frequent seizures
  • post anticonvulsant medication.

Aim for oxygen saturations 91-95 per cent to minimise the risk of pulmonary hypertension.

Avoid hypocapnia (pCO2 < 50 mmHg) as this may worsen cerebral vasoconstriction and further compromise cerebral blood flow. 

Perfusion

Consider crystalloid boluses (10-20 mL/kg of 0.9 per cent saline) if:

  • perfusion is poor
  • lactate is not improving
  • mean BP <40mmHg in a term baby.

Consider a blood transfusion if there has been fetal blood loss and poor perfusion and metabolic/lactic acidosis persist.

If hypotension persists start inotropes:

  • dobutamine (5-20 micrograms/kg/minute)
  • dopamine (5-20 micrograms/kg/minute). 

See the drug calculator

Fluid, electrolyte and acid-base management

Acidosis usually improves with improved ventilation and perfusion. Consider a half bicarbonate correction if severe metabolic acidosis persists. However, persisting acidosis suggests impaired cardiac output and attention should be directed towards treating this.

Restrict fluids to 40 mL/kg/day until urine output (= 1 mL/kg/hour) is established.

Give 10 per cent glucose in the first 24 hours and monitor blood glucose levels. Once renal function is stable, sodium and potassium additives can be commenced.

If oliguria/anuria, consider:

  • urinary catheterisation
  • fluid challenge (20 mL/kg 0.9 per cent saline over 30 minutes) with diuretic (frusemide 1-2 mg/kg IV)
  • dopamine (renal dose: 2.5-5 micrograms/kg/minute)
  • withholding the second/subsequent aminoglycoside antibiotics; if prescribed, the first dose should be given. 

Therapeutic hypothermia

Whole body hypothermia to 33-34C for 72 hours may be used for infants more than 35 weeks' gestation with moderate or severe HIE who are less than six hours of age. 

Seizure management

Seizures peak in the first 48 hours.

Phenobarbitone - first-line anticonvulsant 
Phenobarbitone is the first-line anticonvulsant. Dosage information:

  • Initial loading dose of 20 mg/kg/dose given IV.
  • If seizures continue, up to 40 mg/kg total can be given safely.

After this dose you will increase side effects with minor additional effective seizure control. It is usual to stop IV use once seizures are controlled; however, if maintenance is required then 5 mg/kg/day once daily should produce good levels.

Phenobarbitone is the drug of choice for maintenance monotherapy in the first six months of life due to its reliable absorption and long safety record.

Phenytoin - second-line anticonvulsant
Phenytoin is the usual second line anticonvulsant. Dosage:

  • loading dose is 15-20 mg/kg/dose IV given slowly.

Phenytoin absorption orally in the newborn is highly unreliable and thus this agent is not continued after the immediate stabilisation period.

Midazolam - third-line agent

Midazolam is the third line agent:

  • can be titrated as a continuous infusion
  • some authors have stated concerns over the continuous infusion in the preterm infant.

Clonazepam is a safe and effective alternative.

Multi-organ involvement

Renal

With renal involvement there are usually signs of:

  • oliguria
  • transient haematuria
  • anuria
  • elevated serum creatinine.

There is usually spontaneous recovery over 48 hours.

Use appropriate fluid and electrolyte management.

Hepatic

Hepatic involvement is indicated by:

  • deranged liver enzymes
  • coagulation disturbances.

Consider FFP, second dose of vitamin K.

Cardiac

Cardiac involvement is indicated by:

  • hypotension management
  • elevated cardiac enzymes difficult to interpret especially if the infant received CPR during acute resuscitation
  • respiratory
  • meconium aspiration
  • infection - antibiotics as per unit policy.

Gastrointestinal

Breast milk is preferable as gut circulation may have been compromised. However, it is recommended that the infant not be fed until the cardiorespiratory status has normalised.

Sepsis

For sepsis management:

  • antibiotics as per unit policy
  • only prescribe one dose of gentamicin until renal function has normalised.

Other investigations

Other investigations for NE include:

  • full blood examination
  • urea, electrolytes, creatinine
  • calcium, magnesium, glucose
  • acid-base
  • serum lactate
  • c-reactive protein
  • blood cultures.

Also consider:

  • lumbar puncture
  • liver function tests
  • coagulation profile
  • serum for chromosome analysis, ammonia, amino acids
  • urine for amino and organic acids, ketones
  • reducing substances if metabolic/genetic disorders suspected.

Prognosis

Clinical assessment (Sarnat staging)

Sarnat stage Clinical Symptoms  Outcome
1 Mild Hyperalert, irritable and hyperreflexic
Sympathetic autonomic symptoms
Normal EEG
Symptoms resolve by two days and neurological examination normal by one to two weeks
Unaffected
2 Moderate Lethargic, mild hypotonia, hyperreflexic
Parasympathetic autonomic symptoms
Seizures and abnormal EEG
Symptoms last two to 14 days
25 per cent develop cerebral palsy
3 Severe Stuporous, flaccid, hypo-/a-reflexic
Depressed autonomic function
Seizures uncommon, suppressed EEG
Symptoms may persist for weeks
Disability or death likely

Severity of the acute encephalopathy and a standardised neurological examination (e.g. Dubowitz score - a method of clinical assessment that includes neurologic criteria for the infants maturity and other physical criteria) at two weeks is predictive of outcome.

Investigations in the Level 6 NICU setting

Neuro-imaging

MRI/MRS should be performed in infants with moderate to severe NE between days 5-14.

Electrophysiology

It has been suggested that cotside amplitude integrated EEG (aEEG) and/or two-channel EEG should become part of the initial evaluation and continued monitoring of infants with HIE, for seizure detection and outcome prediction. However, cotside EEG interpretation is based primarily on pattern recognition, and depends on experience of the user. Caution is also raised against using the cotside aEEG or 2-channel EEG for reliable detection and treatment of neonatal seizures. Between days 4-7 a formal EEG should be done in the setting of moderate to severe NE or seizures.

More information

References

  • Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. The Cochrane database of systematic reviews. 2013;1:CD003311.
  • Executive summary: Neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians and Gynecologists' Task Force on Neonatal Encephalopathy. Obstetrics and gynecology. 2014;123(4):896-901.
  • Shankaran S. Neonatal encephalopathy: treatment with hypothermia. Journal of neurotrauma. 2009;26(3):437-43.
  • Volpe JJ. Hypoxic-Ischaemic Encephalopathy: Biochemical and Physiological Aspects. In: Volpe JJ, editor. Neurology of the Newborn. 5th ed. Philadelphia: Saunders; 2008. p. 245-480.

Get in touch

Centre of Clinical Excellence - Women and Children
Safer Care Victoria

Version history

First published: August 2018

Last web update: October 2018

Review by: August 2019

Uncontrolled when downloaded

Page last updated: 17 Feb 2021

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