Our Studies

What is known/not known

• About 15-25% of children who had newborn seizures due to brain injury will develop epilepsy (seizures that occur periodically and without a known cause) in early childhood.
• Little is known about why some children develop epilepsy and others do not. We also don’t know why some children develop epilepsy a few months after newborn seizures, while for others, epilepsy develops after several years without any seizures.
• There are several known risk factors for epilepsy after newborn seizures. For example, having several days of seizures on EEG (a test that measures electrical activity in the brain) or particular patterns of brain injury (i.e. newborn stroke, lack of oxygen to the brain) puts a child at higher risk for epilepsy. However, most children with these risk factors do not develop epilepsy.
• The research doctors suspect that genetic causes may play a role in which children develop epilepsy.
• Understanding more about the genetic risk factors for epilepsy can help researchers develop new treatments to prevent epilepsy.

What we are studying

• We seek to identify genetic differences among children with and without epilepsy after newborn seizures.

How we are studying it

• We will perform genetic testing on participating children and their biological parents.
• We will collect DNA (genetic) specimens by collecting saliva or buccal (cheek) swabs.
• The DNA specimen can be collected in the privacy of your own home or during a planned visit to the medical center.

What we expect to learn

• The primary goal of the study is to develop better ways to predict a child’s risk of developing epilepsy using both clinical (e.g. EEGs, MRIs, physical exams) and genetic factors.
• We expect to learn why some children develop epilepsy following newborn seizures while others do not.

What this means for care of children with neonatal seizures

• This study will help doctors of newborns with seizures more accurately predict which children will develop epilepsy.
• This study may also yield information that can help researchers to evaluate new medicines to prevent epilepsy in high-risk children.

Who can participate

• Participants of NSR-II, NSR-DEV and NSR-RISE may enroll in this study. We will also recruit eligible and interested families seen in Neurology or Epilepsy clinics at NSR participating sites.
• We will begin enrolling in 2022. If you are eligible, your local research team will contact you soon!

What is known/not known

• Newborn seizures due to brain injury are related to higher risk of physical and learning challenges.
• Little is known about how these physical and learning challenges manifest in children at school age.
• Little is known about the mental health challenges experienced by parents and how best to support parents of children with early life seizures.

What we are studying

• We are following children previously enrolled in NSR-II during early childhood (ages 3-8).
• We are examining risk factors for developmental challenges after newborn seizures and how these risk factors might be affected by parent well-being.

How we are studying it

• Parents of children enrolled in the study complete online questionnaires and telephone interviews to evaluate their child’s development, behavior, medical conditions, and school progress.
• Children participate in developmental testing at the medical center with a neuropsychologist one time during the study period when they are about 5 or 6 years old.
• Parents of children enrolled in the study complete annual questionnaires to assess their mental health and emotional wellbeing.

What we learned

• Stay tuned! We are still collecting data and anticipate preliminary findings in 2024. We will be sure to include updates in our biannual NSR newsletter.

Expected Outcomes and Future Directions

• We anticipate identifying medical risk factors for developmental challenges in early childhood for children with history of seizures, as well as risk factors related to parent well-being.
• We expect findings will help doctors to better predict the types of physical or learning challenges that a child may face. This will help doctors (1) council families regarding what to expect and (2) prescribe tailored early interventions.

What other opportunities are available for families to get involved?

• We will launch NSR-GENE during the Spring of 2022. If your family is enrolled in NSR-DEV you may be eligible to participate in NSR-GENE. We will reach out with more details in the coming months.

What is known/not known

• Seizures are a common sign of brain injury in the newborn period.
• There is increasing evidence that inflammation, or the body’s immune response to injury or infection, may play a role in the development of epilepsy.
• There are limited data evaluating levels of inflammation in newborns with seizures.

What we studied

• We are measuring inflammation levels in the blood of children with newborn seizures compared with infants who did not have a seizure.
• We will evaluate whether there is a relationship between inflammation and seizure severity, as well as later development of epilepsy.

How we studied it

• We plan to enroll 72 infants who had seizures and 15 infants who received a neurology consultation but did not experience a seizure.
• We are collecting blood 48-96 hours after the first seizure to measure levels of inflammation. For infants with seizures, we are collecting blood again when they are 2-4 months old.
• We will follow participants until they are two years old to examine whether they develop epilepsy.

What we learned

• Stay tuned! We are still collecting data and anticipate preliminary findings in 2022. We will include updates in our biannual NSR newsletter.

What this means for care of children with neonatal seizures

• We expect findings will eventually lead to new treatments to prevent epilepsy after newborn seizures.

What other opportunities are available for families to get involved?

• We will launch NSR-GENE during the Spring of 2022. If your family is enrolled in NSR-RISE, you may be eligible to participate in NSR-GENE. We will reach out with more details in the coming months.

What is known/not known

• Seizures in newborns can be associated with short and long-term developmental challenges.
• Diagnosis and management of seizures in newborns have been limited by several important factors: (1) seizures are difficult to diagnose (2) commonly used medications have limited efficacy; and (3) occurrence of seizures is relatively rare.

What we studied

• We established a multi-center registry of infants with seizures to identify the causes and characteristics of visible seizures, as well as seizures not visible but captured on EEGs during the newborn period.
• We identified current practices for medical management of seizures during the newborn period and determined whether differences in management affect short-term outcomes of these infants.

How we studied it

• We collected data from 426 infants with seizures at 7 different hospital sites. We collected data regarding the cause of the seizure, the frequency and severity of the seizures and how the seizures were treated.

What we learned

• The most common causes of seizures in in infants are due to acute brain injury (e.g., hypoxic-ischemic encephalopathy (HIE)/neonatal encephalopathy, ischemic stroke, and intracranial hemorrhage).
• Epilepsy (unprovoked seizures) is a rare but important cause of seizures that occur during this window (10-15% of neonatal seizures). Genetic testing has a high yield when no cause of acute seizures is found.
• Children with a higher burden of seizures have a higher risk of short and long-term adverse outcomes and death.
• Preterm newborns are more likely to have seizures that are only detected using an EEG.
• Approximately 2/3 of newborns require additional doses of anti-seizure medications for ongoing seizures. Children with high seizure burden, no hypothermia therapy, and abnormal EEG background are more likely to have ongoing seizures after the first dose of anti-seizure medicine.
• Most infants at participating study hospitals receive the same initial treatment for seizures, but duration of treatment varies by hospital: 75% of infants were maintained on anti-seizure medications at the time of discharge home, however the range across sites was 4% to 91%, indicating inconsistent treatment practice.

What is known/not known

• Infants with acute symptomatic seizures (due to brain injuries like hypoxic-ischemic encephalopathy, stroke or hemorrhage) are typically given medication to treat seizures.
• The length of treatment is not standardized.
• We do not know if longer treatment is necessarily better treatment.

What we studied

• We followed >300 children who had neonatal seizures at birth from birth to 2 years of age at 9 sites across the U.S.
• We collected data during their hospital stay and after they went home.

How we studied it

• We compared outcomes for children whose antiseizure medication was discontinued before discharge from the seizure admission with children whose antiseizure medication was maintained at discharge from seizure admission.
• We looked at how treatment duration affected their neurodevelopmental outcomes, risk of epilepsy, and length of hospital stay.
• We used a method called “propensity score” to adjust for differences in treatment approach that may be associated with the severity of the clinical condition. This method allows us to infer that the results are due to the medication treatment approach even though we did not perform a randomized, controlled study.

What we learned

• The neurodevelopmental outcomes in the group whose antiseizure medications were discontinued was not worse (no harm) and risk of epilepsy were similar between the two treatment groups at 24 months of age.
• The children with stroke as the reason for seizure whose antiseizure medications were discontinued before hospital discharge had a stay that was 36% shorter than children who were prescribed antiseizure medication at discharge.

What this means for care of children with neonatal seizures

• Based on our findings, we concluded that it is safe to discontinue antiseizure medications after resolution of acute symptomatic seizures and recommend that clinicians stop antiseizure medication treatment after the child’s seizures have resolved. 
• We expect the findings from our study to prompt a change in practice at many centers.

What is known/not known

• An infantile spasm (IS) is a type of seizure that occurs most commonly at around 6 months of age
• Early treatment of infantile spasms provides the best chance of seizure remission.
• We aimed to develop a method to accurately predict which neonates with acute symptomatic seizures would develop infantile spasms.

What we studied

• We examined the association between injury found on neonatal brain magnetic resonance imaging (MRIs), abnormal electroencephalography (EEGs), which detects abnormalities in brain activity, and risk of infantile spasms.

How we studied it

• We used data from the Neonatal Seizure Registry study (NSR2), specifically looking at children who received clinical EEGs, MRIs, and were younger than 2 years of age.

What we learned

• About 5% of infants who survive neonatal seizures due to brain injury develop infantile spams.
• The most important risk factors for infantile spasms were (a) severely abnormal EEG or EEG seizures for 3 or more days (b) MRI brain injury to the deep gray matter or brainstem in the and (c) abnormal resistance of muscles detected on a discharge exam (low or high tone).
• No child without these risk factors developed infantile spasms in the study while more than 50% of children with all three risk factors developed infantile spasms.

What this means for care of children with neonatal seizures

• The risk prediction rule can be valuable for clinical counseling.
• These findings may lead to earlier diagnosis and treatment as well as improve outcomes for early life epilepsy.

What is known/not known

• Little is known about the physiological processes that cause some children to develop post-neonatal epilepsy (recurrent, unprovoked seizures) after acute provoked neonatal seizures.
• There are known risk factors for epilepsy after acute symptomatic seizures but not every infant with risk factors will develop epilepsy

What we studied

• We wanted to identify genetic differences among infants with epilepsy following acute symptomatic seizures.

How we studied it

• We performed genetic testing (whole exome sequencing, WES) in 20 trios (child and both parents), including 10 children with epilepsy and 10 children who were epilepsy-free until at least 2 years old following acute symptomatic seizures at UCSF

What we learned

• Children with epilepsy following acute symptomatic seizures had more genetic changes in epilepsy associated genes compared to children without epilepsy

What this means for care of children with neonatal seizures

• Future studies evaluating this association may lead to a better understanding of the risk of epilepsy after acute symptomatic neonatal seizures