Most Common Cause of Neonatal Seizures
Perinatal asphyxia (hypoxic-ischemic encephalopathy) is by far the most common cause of neonatal seizures, accounting for 46-65% of cases in both term and preterm infants. 1
Evidence-Based Answer: c. Perinatal asphyxia
Epidemiologic Hierarchy of Neonatal Seizure Etiologies
The American College of Radiology guidelines clearly establish the following frequency distribution for neonatal seizures 1:
Primary causes (in order of frequency):
- Hypoxic-ischemic injury: 46-65% - This is the dominant etiology, representing nearly half to two-thirds of all neonatal seizures 1
- Intracranial hemorrhage and perinatal ischemic stroke: 10-12% - These combined represent the second most common category 1
- Infection, genetic disorders, and malformations of cortical development - These become more likely when seizures occur beyond the seventh day of life 1
Clinical Timing Patterns
Early-onset seizures (within 2 days of birth):
- Approximately 90% of infants with hypoxic-ischemic encephalopathy experience seizure onset within the first 2 days after birth 1, 2
- This early timing strongly suggests perinatal asphyxia as the underlying etiology 2
Late-onset seizures (beyond day 7):
- More likely related to infection (meningitis), genetic disorders, or malformations of cortical development 1
- This shifts the differential away from perinatal asphyxia 1
Why Other Options Are Less Common
Intracranial hemorrhage (option a):
- Accounts for only 10-12% of neonatal seizures when combined with perinatal ischemic stroke 1
- While important, it is significantly less common than hypoxic-ischemic injury 1
Kernicterus (option b):
- Not mentioned as a leading cause in current guidelines 1
- With modern bilirubin monitoring and phototherapy, this has become a rare cause of neonatal seizures
Meningitis (option d):
- More commonly presents with seizures occurring beyond the seventh day of life 1
- Not among the top etiologies in the acute neonatal period 1
Supporting Research Evidence
Multiple studies confirm perinatal asphyxia as the predominant etiology:
- A 2012 study found perinatal asphyxia was the most common cause at 28.6%, followed by intracranial hemorrhage at 17% 3
- A 2024 review confirmed hypoxic-ischemic encephalopathy remains the most common cause of neonatal seizures 4
- Historical data from 1981 established that hypoxic-ischemic encephalopathy was the predominant etiological process for neonatal seizures, a finding that remains consistent today 5
Clinical Pitfall to Avoid
Do not assume all neonatal seizures presenting in the first week are due to asphyxia. While perinatal asphyxia is most common, an underlying cause can be identified in approximately 95% of neonatal seizures, requiring systematic evaluation including neuroimaging, laboratory studies, and consideration of metabolic and genetic causes when the clinical picture is atypical 1, 6.