Perinatal Asphyxia and Hypoxic Ischaemic Encephalopathy

Perinatal asphyxia is a significant impairment of gas exchange in the peripartum period, causing progressive hypoxaemia and metabolic acidosis.

Hypoxic ischaemic encephalopathy is the resulting syndrome of neurological dysfunction in a neonate after a perinatal hypoxic-ischaemic insult. It is an important cause of neonatal mortality and long-term neurodevelopmental morbidity, including cerebral palsy.

Two clinical priorities follow.

• Structured intrapartum surveillance, to identify and address evolving fetal compromise before established injury occurs.
• Prompt therapeutic hypothermia once significant perinatal asphyxia has occurred. It is the single most important evidence-based neuroprotective intervention available.

Pathophysiology and staging

• Interruption of placental or umbilical blood flow, or of maternal-fetal gas exchange, produces progressive fetal hypoxaemia and, if severe or prolonged, metabolic acidosis. Causes include placental abruption, cord prolapse, uterine rupture, prolonged or severe fetal heart rate abnormality during labour, and significant maternal hypoxaemia or hypotension.
• The threshold and duration of insult needed to cause neurological injury vary with the nature and severity of the insult and with underlying fetal reserve.
• Cerebral injury evolves in two phases. Primary neuronal injury occurs during the acute insult itself.
• After a variable latent period (typically several hours), a secondary phase of delayed, progressive neuronal injury follows, driven by excitotoxicity, oxidative stress and inflammation. This secondary phase is the therapeutic window in which therapeutic hypothermia is believed to exert its neuroprotective benefit.
• Hypoxic ischaemic encephalopathy is graded, typically with the Sarnat staging system, into mild, moderate and severe categories according to the pattern and severity of neurological findings. Staging bears directly on prognosis and on eligibility for therapeutic hypothermia.

• Evidence of intrapartum compromise includes a significant fetal heart rate abnormality in labour and meconium-stained liquor.
• At delivery, supportive evidence of significant perinatal asphyxia includes metabolic acidosis on umbilical cord blood gas (cord arterial pH below a defined threshold, generally around 7.0, with a significantly elevated base deficit). A need for significant resuscitation and low Apgar scores persisting beyond the first few minutes also support the diagnosis.
• Mild hypoxic ischaemic encephalopathy presents with hyperalertness, irritability and mild hypertonia, generally without seizures. It typically resolves within the first twenty-four to forty-eight hours and carries a generally favourable prognosis.
• Moderate hypoxic ischaemic encephalopathy presents with lethargy, hypotonia, reduced spontaneous movement and frequently seizures, typically developing within the first day of life. Prognosis varies with severity, evolution and subsequent neuroimaging findings.
• Severe hypoxic ischaemic encephalopathy presents with stupor or coma, significant hypotonia, absent or severely depressed primitive reflexes, and frequent, often refractory seizures. In the most severe cases there is multiorgan dysfunction. Risk of mortality is substantially elevated, and survivors have significant long-term neurodevelopmental morbidity.
• Multiorgan involvement reflects the systemic nature of the insult and frequently accompanies significant encephalopathy. It includes renal impairment, hepatic dysfunction and cardiac dysfunction, so these systems need systematic assessment and monitoring.

• Diagnosis combines evidence of a perinatal hypoxic-ischaemic insult with the characteristic evolving pattern of neonatal encephalopathy.
• Encephalopathy is graded with the Sarnat staging system, which incorporates level of consciousness, tone, primitive reflexes, autonomic function, and the presence and character of any seizure activity.
• Continuous or serial amplitude-integrated electroencephalography (aEEG) gives ongoing assessment of background cerebral electrical activity and seizure detection. It supports characterisation of severity and assessment of eligibility for therapeutic hypothermia, as many treatment protocols incorporate it.
• Magnetic resonance imaging, generally performed once the infant is clinically stable and typically toward the end of the first week of life, gives the most detailed and prognostically valuable assessment of the pattern and extent of cerebral injury.
• The injury pattern informs long-term neurodevelopmental prognosis. Predominant involvement of the basal ganglia and thalami reflects a more acute, profound insult. Watershed cortical involvement reflects a more prolonged, partial insult.
• Assessment for multiorgan involvement is essential, given the frequently systemic nature of significant perinatal asphyxia. It includes renal function, liver function and coagulation studies, with cardiac assessment where clinically indicated.

• Therapeutic hypothermia is the essential evidence-based neuroprotective treatment for moderate to severe hypoxic ischaemic encephalopathy. The infant is cooled to approximately 33 to 34 degrees Celsius for seventy-two hours, followed by gradual, controlled rewarming.
• Robust trial evidence shows a meaningful reduction in the combined outcome of death or significant neurodevelopmental disability when cooling starts within the treatment window, generally within six hours of birth. This window corresponds to the secondary injury phase, so prompt recognition and rapid initiation are essential.
• Eligibility criteria require evidence of significant perinatal asphyxia (including the cord blood gas and resuscitation criteria) and at least moderate encephalopathy on clinical assessment. Treatment is delivered in an appropriately resourced neonatal intensive care setting, given the intensive monitoring and supportive care required.
• Supportive intensive care throughout treatment is integral. It includes careful fluid management, given the risk of both cerebral oedema and fluid overload in the frequent presence of renal impairment.
• It also includes glucose monitoring and management, as both hypoglycaemia and hyperglycaemia bear directly on secondary neuronal injury, and prompt, effective treatment of any seizure activity.
• Long-term neurodevelopmental follow up extends through early childhood and beyond where significant impairment is identified. It includes regular developmental assessment, early proactive intervention and support services, and family support. Where a specific impairment is identified, including cerebral palsy, families are connected to the relevant services.
• Sensitive communication with the family is essential throughout the acute course and follow-up. It should address the inherent uncertainty about eventual outcome, particularly early on, before neuroimaging and developmental assessment findings are available. Family-centred care matters in what is often a profoundly distressing clinical course.