Perinatal asphyxia, a common cause of death in neonates, is caused by compromised placental or pulmonary gas exchange and can occur during the antepartum, intrapartum, or perinatal period. Persisting impairment of blood gas exchange results in oxygen deficiency, hypercapnia, and blood acidosis with potential subsequent compromise of cell function in various tissues (e.g., heart, muscle, brain). The brain is the most vulnerable organ in the context of perinatal asphyxia and the development of hypoxic-ischemic encephalopathy is a potential consequence. After rapid evaluation, eligible patients require therapeutic hypothermia over a period of 72 hours to minimize brain damage. Depressed myocardial function can exacerbate ischemia and cause subsequent short-term complications with end-organ damage in other tissues (e.g., kidneys, lung, liver, gastrointestinal tract, bone marrow). Long-term complications of perinatal asphyxia include irreversible neurological damage, cerebral palsy, and periventricular leukomalacia.
- Perinatal asphyxia is a condition characterized by fetal oxygen deprivation that occurs in close temporal proximity to birth. It may lead to impaired cell function in various tissues and result in end-organ damage (e.g., encephalopathy, renal injury).
Neonatal encephalopathy: a syndrome of CNS dysfunction in the early newborn period characterized by an altered level of consciousness/seizures, difficulty initiating/maintaining respiration, poor tone, and/or depressed reflexes
- Several conditions can be the cause (e.g., hypoxic-ischemic encephalopathy, )
- Hypoxic-ischemic encephalopathy (HIE) is a diffuse disruption of brain function and/or structure caused by inadequate tissue oxygenation (e.g., due to cardiac arrest, trauma, drug overdose, perinatal asphyxia). It is the most common subtype of neonatal encephalopathy.
- Perinatal asphyxia accounts for ∼ 900,000 fetal deaths per year (worldwide) and is one of the main causes of early neonatal mortality. 
- Hypoxic-ischemic encephalopathy occurs in ∼ 1.5:1,000 live births in the US. 
Epidemiological data refers to the US, unless otherwise specified.
- Perinatal risk factors
- Antepartum risk factors (play the biggest role)
Intrapartum risk factors
- Traumatic delivery (e.g., cesarean delivery, failed ) , emergency
- Cesarean delivery with general anesthesia
- Impaired placental perfusion (e.g., , abnormal uterine contractions, )
- Abnormal maternal oxygenation (e.g., pulmonary edema in preeclampsia)
- Maternal hemodynamic compromise (e.g., amniotic fluid embolus)
- umbilical cord knot , ,
Pathophysiology of multiorgan damage 
- Hypoxia → ↑ sympathetic activity → circulatory centralization to maintain perfusion of vital organs (e.g., brain, adrenal glands, heart) → reduced oxygen supply to peripheral organs → tissue damage (e.g. kidneys, costal diaphragm, skeletal muscle, liver)
- Prolonged hypoxia → compromised myocardial cell function and ischemia → ↓ myocardial contractility → ↓ cardiac output → worsening of ischemia in peripheral organs
Pathophysiology of brain damage 
- Primary energy failure: antepartum/intrapartum placental dysfunction or postpartum pulmonary gas exchange impairment → insufficient oxygen supply to organ tissue → brain tissue acidosis (due to CNS susceptibility) → osmotic dysregulation in cells → cellular edema → apoptosis
- Latency period (lasting several hours): reperfusion and recovery of some brain cells
- Secondary energy failure (6–48 h after initial injury): distribution of toxic neurotransmitters, oxidative stress, inflammation → widening of affected area
- Brain injury (months to years after initial injury): persistent inflammation, impaired neurogenesis, reduced axonal growth → reduced neural plasticity, myelin deficits, brain cell death
Signs and symptoms of asphyxia
- Short-term asphyxia
- Prolonged asphyxia
- Further course of perinatal asphyxia: varies greatly and depends on the duration of oxygen deficiency
Clinical features of hypoxic-ischemic encephalopathy 
|Clinical stages of neonatal encephalopathy |
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Neonatal assessment 
- Should be performed within the first 6 hours of life, in all newborns showing clinical signs of neonatal encephalopathy (e.g., difficulty initiating and/or maintaining breathing, seizures, abnormal level of consciousness) as neuroprotective treatment is time-sensitive
- Allows estimation of the likelihood that perinatal asphyxia contributed to the development of neonatal encephalopathy
- Neurological damage is the major concern after a hypoxic-ischemic event.
- Neonatal signs: a hypoxic-ischemic etiology of neonatal encephalopathy is most likely if one or more of these signs are present
- Birth-related events that might have lead to hypoxic-ischemic complications:
- Neuroimaging patterns consistent with neonatal hypoxic-ischemic brain injury (e.g., watershed cortical injury in MRI)
- No evidence of other causes for neonatal encephalopathy (e.g., inborn errors of metabolism, genetic disorders)
Further diagnostic measures
- Umbilical : arterial pH, venous pH,
- thrombocytopenia : may show signs of infection, hemorrhage, or
- Electrolytes: monitoring and treatment guidance
- : evaluation of possible damage
- : evaluation of possible damage
- myocardial injury is clinically suspected : if
- : in case of bleeding, to exclude
- neonatal sepsis : to exclude
- meningitis/encephalitis : if there is clinical suspicion of
- Most sensitive tool for detecting hypoxic-ischemic injury in the brain to exclude other causes of neonatal encephalopathy
- Patterns consistent with HIE include deep nuclear gray matter injury, parasagittal injury of the cerebral cortex, and watershed cortical injury
- Magnetic resonance spectroscopy can be performed additionally.
- CNS ultrasound
- Cranial MRI
- Conducted on the first day of life, continued monitoring for at least 24 hours
- Evaluation of seizure activity and background electrical activity
- Biomarkers: Recent studies indicate that VEGF is significantly increased in neonates that subsequently develop encephalopathy. 
Therapeutic hypothermia 
- Eligibility criteria
- Ensure sufficient oxygenation and ventilation (e.g., supplemental oxygen, inhaled nitric oxide, intubation).
- Maintain adequate organ perfusion (e.g., inotropic agents).
- Maintain electrolyte and glucose homeostasis.
- Anticonvulsive treatment of seizures
- Recent studies indicate a neuroprotective effect of erythropoietin in neonates with HIE. 
- (most likely spastic quadriplegia or dyskinetic cerebral palsy)
- PVL) (
- Hearing and/or visual impairment
Other organ complications
- Heart: impaired myocardial contractility
- Hematopoietic: bone marrow suppression, ,
- Liver: elevated transaminase levels, hepatic injury
- Gastrointestinal tract: in case of severe hypoperfusion
- Lungs: ,
We list the most important complications. The selection is not exhaustive.