Neonatal seizures are the most common neurological emergency occurring in the first 28 days of life. These episodes are not a final diagnosis but a symptom of an underlying disruption in the newborn’s developing brain function. A seizure represents an abnormal, uncontrolled electrical discharge of neurons, which can manifest in subtle ways, such as brief stiffening, rhythmic eye fluttering, or bicycling movements of the limbs. Identifying the root cause is a time-sensitive process that requires immediate investigation by medical professionals. This disruption can stem from physical injury, chemical imbalances, infection, or inherent developmental problems.
Oxygen Deprivation and Physical Injury
The most frequent cause of acute symptomatic seizures in term newborns is a lack of oxygen or blood flow to the brain, often occurring just before or during birth. This condition, known as Hypoxic-Ischemic Encephalopathy (HIE), accounts for a large percentage of cases. Oxygen loss damages brain cells by compromising the energy-dependent pumps that maintain the electrical balance of neurons. This cellular stress causes excessive depolarization, making the brain’s electrical activity unstable.
Physical injury to the brain tissue, often associated with difficult labor, can also trigger seizures. Intracranial hemorrhage (bleeding within the skull) is another leading cause, accounting for around 12% of seizures in term infants. Hemorrhage can include subdural bleeding or intraventricular hemorrhage (IVH), which is common in premature infants. The presence of blood irritates the surrounding brain tissue, leading to electrical instability.
A perinatal stroke, a disruption of blood supply to a specific brain area, is the second most common cause of symptomatic seizures. This event, such as an arterial ischemic stroke or venous thrombosis, creates a focal area of injury that acts as a seizure focus. Stroke-related seizures often present 24 to 48 hours after birth and typically involve focal movements affecting one side of the body. The damaged tissue in these areas is prone to generating abnormal electrical signals.
Metabolic and Electrolyte Imbalances
Seizures can be provoked by systemic chemical problems where brain structure is intact but function is impaired by an improper balance of substances in the blood. Hypoglycemia (abnormally low blood sugar) is a common metabolic issue contributing to seizures, especially in stressed infants. Since the newborn brain relies heavily on glucose for energy, a significant drop in blood sugar rapidly compromises neuronal function and stability.
Electrolyte disturbances can destabilize the electrical environment of brain cells. Hypocalcemia (low blood calcium) is the most frequently identified primary metabolic cause of newborn seizures. Calcium regulates neurotransmitter release, and insufficient levels increase central nervous system excitability. Low magnesium levels (hypomagnesemia) often accompany hypocalcemia and contribute to overall CNS irritability, leading to seizures.
Inborn Errors of Metabolism (IEMs) are rarer genetic conditions that prevent the body from properly processing certain chemicals, leading to a toxic buildup that affects the brain. These disorders, such as urea cycle defects, typically manifest after the first 72 hours of life once the infant has begun feeding. The accumulated toxic metabolites interfere with normal brain signaling, causing a secondary encephalopathy that results in seizures.
Infections of the Central Nervous System
Infectious agents can cause seizures by directly invading the central nervous system (CNS) or by triggering a massive inflammatory response. Meningitis is an infection of the protective membranes surrounding the brain, while encephalitis is an infection of the brain tissue itself. These infections cause inflammation, swelling, and direct damage to neurons, creating a focus for seizure activity.
Sepsis, a severe systemic infection in the bloodstream, can also lead to seizures due to widespread inflammation and disruption of normal functions, including brain perfusion. Infections may be acquired before birth, during the birth canal passage, or after birth. Common bacterial culprits include Group B Streptococcus (GBS) and Escherichia coli.
Viral infections that cross the blood-brain barrier and cause encephalitis must also be considered. The Herpes Simplex Virus (HSV) is a recognized cause of severe neonatal encephalitis and seizures that can manifest early or several weeks after birth. Prompt identification of a CNS infection is necessary, as specific antimicrobial or antiviral treatment minimizes permanent neurological injury.
Congenital Brain Malformations and Genetic Syndromes
Issues rooted in prenatal brain development or inherited conditions can predispose a newborn to seizures. Structural brain malformations occur when the brain does not form correctly during gestation, often due to abnormal neuronal migration. Conditions like cortical dysplasia or lissencephaly involve areas of disorganized cerebral cortex that are inherently epileptogenic. These abnormal areas act as a consistent source of erratic electrical signals.
Genetic epilepsy syndromes involve inherent instability in the brain’s electrical wiring, even without an obvious structural defect. These conditions are caused by mutations in specific genes, often those that code for ion channels like KCNQ2 and KCNQ3. These genetic changes directly affect the flow of ions across the neuronal membrane, making the brain hypersensitive to excitation.
These genetic causes range from self-limited neonatal epilepsies, which resolve spontaneously, to more severe conditions known as developmental and epileptic encephalopathies (DEEs). A rare but treatable cause is Pyridoxine-dependent epilepsy, where a genetic defect leads to a deficiency in a specific form of Vitamin B6. Identifying these causes is important because some, like Pyridoxine-dependent epilepsy, can be managed with targeted nutritional therapies that improve the long-term outlook.