Relationship of Neonatal Seizure Burden Before Treatment and Response to Initial Antiseizure Medication.

OBJECTIVE: To assess among a cohort of neonates with hypoxic-ischemic encephalopathy (HIE) the association of pretreatment maximal hourly seizure burden and total seizure duration with successful response to initial antiseizure medication (ASM). STUDY DESIGN: This was a retrospective review of data collected from infants enrolled in the HEAL Trial (NCT02811263) between January 25, 2017, and October 9, 2019. We evaluated a cohort of neonates born at ≥36 weeks of gestation with moderate-to-severe HIE who underwent continuous electroencephalogram monitoring and had acute symptomatic seizures. Poisson regression analyzed associations between (1) pretreatment maximal hourly seizure burden, (2) pretreatment total seizure duration, (3) time from first seizure to initial ASM, and (4) successful response to initial ASM. RESULTS: Among 39 neonates meeting inclusion criteria, greater pretreatment maximal hourly seizure burden was associated with lower chance of successful response to initial ASM (adjusted relative risk for each 5-minute increase in seizure burden 0.83, 95% CI 0.69-0.99). There was no association between pretreatment total seizure duration and chance of successful response. Shorter time-to-treatment was paradoxically associated with lower chance of successful response to treatment, although this difference was small in magnitude (relative risk 1.007, 95% CI 1.003-1.010). CONCLUSIONS: Maximal seizure burden may be more important than other, more commonly used measures in predicting response to acute seizure treatments.

Safety of High Dose Erythropoietin Used with Therapeutic Hypothermia as Treatment for Newborn Hypoxic-Ischemic Encephalopathy: Secondary Analysis of the HEAL Randomized Controlled Trial.

OBJECTIVE: To assess whether high dose erythropoietin (Epo) treatment of cooled infants with neonatal hypoxic ischemic encephalopathy results in a higher risk of prespecified serious adverse events (SAEs). STUDY DESIGN: Five hundred infants born at ≥36 weeks of gestation with moderate or severe hypoxic ischemic encephalopathy undergoing therapeutic hypothermia were randomized to Epo or placebo on days 1, 2, 3, 4, and 7. Pretreatment and posttreatment SAEs were compared with adjusted generalized linear models, with posttreatment models adjusted for the presence of a pretreatment SAE. Clinical risk factors and potential mechanisms for SAEs were also examined. RESULTS: The rate of experiencing at least one posttreatment SAE did not significantly differ between groups (adjusted relative risk [aRR], 95% CI: 1.17, 0.92-1.49); however, posttreatment thrombosis was identified more often in the Epo group (n = 6, 2.3%) than the placebo group (n = 1, 0.4%; aRR, 95% CI: 5.09, 1.32-19.64). The rate of posttreatment intracranial hemorrhage identified at the treatment sites by either ultrasound or magnetic resonance imaging was slightly elevated in the Epo group (n = 61, 24%) but not significantly different from the placebo group (n = 46, 19%; aRR, 95% CI: 1.21, 0.85, 1.72). CONCLUSIONS: A small increased risk of major thrombotic events was identified in the Epo treatment group. TRIAL REGISTRATION: NCT02811263.

Decisional Satisfaction, Regret, and Conflict Among Parents of Infants with Neurologic Conditions.

OBJECTIVE: To characterize decisional satisfaction, regret, and conflict among parents of critically ill infants with neurologic conditions. STUDY DESIGN: In this prospective cohort study, we enrolled parents of infants with neurologic conditions in the intensive care unit (ICU). Hospital discharge surveys included the validated Family Satisfaction with the ICU (FS-ICU) decision making subscale, Decision Regret Scale (DRS), and Decisional Conflict Scale (DCS). We defined high satisfaction with decision making as an FS-ICU score ≥75, high decisional regret/conflict as DRS/DCS score >25, and within-couple disagreement as a difference of at least 25 points between scores. RESULTS: We enrolled 61 parents of 40 infants (n = 40 mothers, n = 21 fathers); 35 mothers and 15 fathers completed surveys. Most mothers reported high satisfaction with decision making (27 of 35; 77%) and low decision regret (28 of 35; 80%); 40% (14 of 35) reported high decisional conflict. Mothers and fathers reported higher decisional conflict in the domains of uncertainty and values clarity compared with the domain of effective decision making (Bonferroni-corrected P < .05). There were no differences in decision outcomes between paired mothers and fathers; however, within any given couple, there were numerous instances of disagreement (7 of 15 for decision regret and 5 of 15 for decisional conflict). CONCLUSIONS: Many parents experience decisional conflict even if they ultimately have high satisfaction and low regret, underscoring the need for decision aids targeting uncertainty and values clarity. Couples frequently experience different levels of decisional regret and conflict.

Characteristics of Neonates with Cardiopulmonary Disease Who Experience Seizures: A Multicenter Study.

OBJECTIVE: To compare key seizure and outcome characteristics between neonates with and without cardiopulmonary disease. STUDY DESIGN: The Neonatal Seizure Registry is a multicenter, prospectively acquired cohort of neonates with clinical or electroencephalographic (EEG)-confirmed seizures. Cardiopulmonary disease was defined as congenital heart disease, congenital diaphragmatic hernia, and exposure to extracorporeal membrane oxygenation. We assessed continuous EEG monitoring strategy, seizure characteristics, seizure management, and outcomes for neonates with and without cardiopulmonary disease. RESULTS: We evaluated 83 neonates with cardiopulmonary disease and 271 neonates without cardiopulmonary disease. Neonates with cardiopulmonary disease were more likely to have EEG-only seizures (40% vs 21%, P < .001) and experience their first seizure later than those without cardiopulmonary disease (174 vs 21 hours of age, P < .001), but they had similar seizure exposure (many-recurrent electrographic seizures 39% vs 43%, P = .27). Phenobarbital was the primary initial antiseizure medication for both groups (90%), and both groups had similarly high rates of incomplete response to initial antiseizure medication administration (66% vs 68%, P = .75). Neonates with cardiopulmonary disease were discharged from the hospital later (hazard ratio 0.34, 95% CI 0.25-0.45, P < .001), although rates of in-hospital mortality were similar between the groups (hazard ratio 1.13, 95% CI 0.66-1.94, P = .64). CONCLUSION: Neonates with and without cardiopulmonary disease had a similarly high seizure exposure, but neonates with cardiopulmonary disease were more likely to experience EEG-only seizures and had seizure onset later in the clinical course. Phenobarbital was the most common seizure treatment, but seizures were often refractory to initial antiseizure medication. These data support guidelines recommending continuous EEG in neonates with cardiopulmonary disease and indicate a need for optimized therapeutic strategies.

Seizure Severity and Treatment Response in Newborn Infants with Seizures Attributed to Intracranial Hemorrhage.

OBJECTIVE: We sought to characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born term and preterm. For infants born term, we sought to compare seizure severity and treatment response for multisite vs single-site ICH and hypoxic-ischemic encephalopathy (HIE) with vs without ICH. STUDY DESIGN: We studied 112 newborn infants with seizures attributed to ICH and 201 infants born at term with seizures attributed to HIE, using a cohort of consecutive infants with clinically diagnosed and/or electrographic seizures prospectively enrolled in the multicenter Neonatal Seizure Registry. We compared seizure severity and treatment response among infants with complicated ICH, defined as multisite vs single-site ICH and HIE with vs without ICH. RESULTS: ICH was a more common seizure etiology in infants born preterm vs term (27% vs 10%, P < .001). Most infants had subclinical seizures (74%) and an incomplete response to initial antiseizure medication (ASM) (68%). In infants born term, multisite ICH was associated with more subclinical seizures than single-site ICH (93% vs 66%, P = .05) and an incomplete response to the initial ASM (100% vs 66%, P = .02). Status epilepticus was more common in HIE with ICH vs HIE alone (38% vs 17%, P = .05). CONCLUSIONS: Seizure severity was greater and treatment response was lower among infants born term with complicated ICH. These data support the use of continuous video electroencephalogram monitoring to accurately detect seizures and a multistep treatment plan that considers early use of multiple ASMs, particularly with parenchymal and high-grade intraventricular hemorrhage and complicated ICH.

Early Magnetic Resonance Imaging Predicts 30-Month Outcomes after Therapeutic Hypothermia for Neonatal Encephalopathy.

OBJECTIVE: To evaluate the association of therapeutic hypothermia with magnetic resonance imaging (MRI) findings and 30-month neurodevelopment in term neonatal encephalopathy. STUDY DESIGN: Cross-sectional analysis of 30-month neurodevelopment (IQR 19.0-31.4) in a prospective cohort of mild-to-severe neonatal encephalopathy imaged on day 4 (1993-2017 with institutional implementation of therapeutic hypothermia in 2007). MRI injury was classified as normal, watershed, or basal ganglia/thalamus. Abnormal motor outcome was defined as Bayley-II psychomotor developmental index <70, Bayley-III motor score <85 or functional motor deficit. Abnormal cognitive outcome was defined as Bayley-II mental developmental index <70 or Bayley-III cognitive score <85. Abnormal composite outcome was defined as abnormal motor and/or cognitive outcome, or death. The association of therapeutic hypothermia with MRI and outcomes was evaluated with multivariable logistic regression adjusted for propensity to receive therapeutic hypothermia. RESULTS: Follow-up was available in 317 (78%) surviving children, of whom 155 (49%) received therapeutic hypothermia. Adjusting for propensity, therapeutic hypothermia was independently associated with decreased odds of abnormal motor (OR 0.15, 95% CI 0.06-0.40, P < .001) and cognitive (OR 0.11, 95% CI 0.04-0.33, P < .001) outcomes. This association remained statistically significant after adjustment for injury pattern. The predictive accuracy of MRI pattern for abnormal composite outcome was unchanged between therapeutic hypothermia-treated (area under the receiver operating curve 0.76; 95% CI 0.61-0.91) and untreated (area under the receiver operating curve 0.74; 95% CI 0.67-0.81) infants. The negative predictive value of normal MRI was high in therapeutic hypothermia-treated and untreated infants (motor 96% vs 90%; cognitive 99% vs 95%). CONCLUSIONS: Therapeutic hypothermia is associated with lower rates of brain injury and adverse 30-month outcomes after neonatal encephalopathy. The predictive accuracy of MRI in the first week of life is unchanged by therapeutic hypothermia. Normal MRI remains reassuring for normal 30-month outcome after therapeutic hypothermia.

Associations between Infant and Parent Characteristics and Measures of Family Well-Being in Neonates with Seizures: A Cohort Study.

OBJECTIVE: To characterize and determine risk factors for key dimensions of well-being at hospital discharge in families of neonates with acute symptomatic seizures. STUDY DESIGN: This prospective, observational cohort study enrolled 144 parent-infant dyads among neonates with acute symptomatic seizures from 9 pediatric hospitals in the Neonatal Seizure Registry. One parent per family completed a discharge survey, which included measures of anxiety and depression, health-related quality of life, and impact on the family. Multivariable regression analyses adjusted for site were constructed to examine parent and infant characteristics associated with well-being. RESULTS: At discharge, 54% of parents reported symptoms of anxiety and 32% reported symptoms of depression. Parents of infants with hypoxic-ischemic encephalopathy reported more depression and worse quality of life than parents of infants with other seizure etiologies. Parental quality of life was also lower with greater infant age at discharge. A higher level of maternal education was associated with greater impact on the family. All these differences were medium to large effect sizes, ranging from 0.52 to 0.78. CONCLUSIONS: Symptoms of anxiety and depression are common in parents of infants with neonatal seizures, and several parent and infant characteristics are associated with poorer parental quality of life and family well-being. These findings are a call to action to improve mental health screening and services for parents of infants with neonatal seizures.

Treatment Duration After Acute Symptomatic Seizures in Neonates: A Multicenter Cohort Study.

We aimed to define determinants of duration of treatment for acute symptomatic neonatal seizures in a contemporary multicenter observational cohort study. After adjustment for potential confounders, only study site and seizure etiology remained significantly associated with the chance of continuing antiseizure medication after discharge to home.

Antenatal Exposure to Magnesium Sulfate Is Associated with Reduced Cerebellar Hemorrhage in Preterm Newborns.

OBJECTIVE: To determine the association of antenatal magnesium sulfate with cerebellar hemorrhage in a prospective cohort of premature newborns evaluated by magnetic resonance imaging (MRI). STUDY DESIGN: Cross-sectional analysis of baseline characteristics from a prospective cohort of preterm newborns (<33 weeks gestation) evaluated with 3T-MRI shortly after birth. Exclusion criteria were clinical evidence of a congenital syndrome, congenital infection, or clinical status too unstable for transport to MRI. Antenatal magnesium sulfate exposure was abstracted from the medical records and the indication was classified as obstetric or neuroprotection. Two pediatric neuroradiologists, blinded to the clinical history, scored axial T2-weighted and iron susceptibility MRI sequences for cerebellar hemorrhage. The association of antenatal magnesium sulfate with cerebellar hemorrhage was evaluated using multivariable logistic regression, adjusting for postmenstrual age at MRI and known predictors of cerebellar hemorrhage. RESULTS: Cerebellar hemorrhage was present in 27 of 73 newborns (37%) imaged at a mean ± SD postmenstrual age of 32.4 ± 2 weeks. Antenatal magnesium sulfate exposure was associated with a significantly reduced risk of cerebellar hemorrhage. Adjusting for postmenstrual age at MRI, and predictors of cerebellar hemorrhage, antenatal magnesium sulfate was independently associated in our cohort with decreased cerebellar hemorrhage (OR, 0.18; 95% CI, 0.049-0.65; P = .009). CONCLUSION: Antenatal magnesium sulfate exposure is independently associated with a decreased risk of MRI-detected cerebellar hemorrhage in premature newborns, which could explain some of the reported neuroprotective effects of magnesium sulfate.

Contemporary Profile of Seizures in Neonates: A Prospective Cohort Study.

OBJECTIVE: To determine the contemporary etiology, burden, and short-term outcomes of seizures in neonates monitored with continuous video-electroencephalogram (cEEG). STUDY DESIGN: We prospectively collected data from 426 consecutive neonates (56% male, 88% term) ≤44 weeks' postmenstrual age with clinically suspected seizures and/or electrographic seizures. Subjects were assessed between January 2013 and April 2015 at 7 US tertiary care pediatric centers following the guidelines of the American Clinical Neurophysiology Society for cEEG for at-risk neonates. Seizure etiology, burden, management, and outcome were determined by chart review by the use of a case report form designed at study onset. RESULTS: The most common seizure etiologies were hypoxic-ischemic encephalopathy (38%), ischemic stroke (18%), and intracranial hemorrhage (11%). Seizure burden was high, with 59% having ≥7 electrographic seizures and 16% having status epilepticus; 52% received ≥2 antiseizure medications. During the neonatal admission, 17% died; 49% of survivors had abnormal neurologic examination at hospital discharge. In an adjusted analysis, high seizure burden was a significant risk factor for mortality, length of hospital stay, and abnormal neurological examination at discharge. CONCLUSIONS: In this large contemporary profile of consecutively enrolled newborns with seizures treated at centers that use cEEG per the guidelines of the American Clinical Neurophysiology Society, about one-half had high seizure burden, received ≥2 antiseizure medications, and/or died or had abnormal examination at discharge. Greater seizure burden was associated with increased morbidity and mortality. These findings underscore the importance of accurate determination of neonatal seizure frequency and etiology and a potential for improved outcome if seizure burden is reduced.

Diminished white matter injury over time in a cohort of premature newborns.

OBJECTIVES: To determine the rate of magnetic resonance imaging (MRI)-detected noncystic white matter injury (WMI) in a prospective cohort of premature newborns, and to evaluate its associations with changes in clinical predictors of WMI over the study period. STUDY DESIGN: A prospective cohort of premature newborns (<33 weeks gestational age) was studied with MRI within 4 weeks of birth and near term-equivalent age. A pediatric neuroradiologist scored the severity of WMI on T1-weighted MRI according to published criteria. WMI was classified as none/mild or moderate/severe. Subjects with severe cystic WMI, periventricular hemorrhagic infarction, or motion artifact on MRI were excluded. Changes in clinical characteristics and predictors of WMI over the study period (1998-2011) were evaluated. Predictors of moderate/severe WMI, including birth year, were evaluated using multivariate logistic regression. RESULTS: Among 267 newborns, 45 (17%) had moderate/severe WMI. The rate of moderate/severe WMI decreased over the study period (P = .002, χ(2) test for trends). On multivariate logistic regression, the odds of moderate/severe WMI decreased by 11% for each birth year of the cohort (OR, 0.89; 95% CI, 0.81-0.98; P = .02). Prolonged exposure to indomethacin also was independently associated with reduced odds of moderate/severe WMI. CONCLUSION: The decreasing burden of MRI-detected moderate/severe noncystic WMI in our cohort of premature newborns is independent over time of changes in the known clinical predictors of WMI. Prolonged exposure to indomethacin is associated with reduced WMI.

Hypoglycemia is associated with increased risk for brain injury and adverse neurodevelopmental outcome in neonates at risk for encephalopathy.

OBJECTIVE: To investigate the contribution of hypoglycemia in the first 24 hours after birth to brain injury in term newborns at risk for neonatal encephalopathy. STUDY DESIGN: A prospective cohort of 94 term neonates born between 1994 and 2010 with early postnatal brain magnetic resonance imaging studies were analyzed for regions of brain injury. Neurodevelopmental outcome was assessed at 1 year of age. RESULTS: Hypoglycemia (glucose <46 mg/dL) in the first 24 hours after birth was detected in 16% of the cohort. Adjusting for potential confounders of early perinatal distress and need for resuscitation, neonatal hypoglycemia was associated with a 3.72-fold increased odds of corticospinal tract injury (P=.047). Hypoglycemia was also associated with 4.82-fold increased odds of 1-point worsened neuromotor score (P=.038) and a 15-point lower cognitive and language score on the Bayley Scales of Infant Development (P=.015). CONCLUSION: Neonatal hypoglycemia is associated with additional risks in the setting of neonatal encephalopathy with increased corticospinal tract injury and adverse motor and cognitive outcomes.

Seizures and magnetic resonance imaging-detected brain injury in newborns cooled for hypoxic-ischemic encephalopathy.

OBJECTIVE: To describe the association between electrographically detected seizures and brain injury evaluated by magnetic resonance imaging in newborns treated with hypothermia. STUDY DESIGN: A total of 56 newborns treated with hypothermia were monitored using video electroencephalography through cooling and rewarming, and then imaged at a median of 5 days. The electroencephalograms were reviewed for indications of seizure and status epilepticus. Moderate-severe injury detected on magnetic resonance imaging was measured using a classification scheme similar to one predicting abnormal outcome in an analogous population. RESULTS: Seizures were recorded in 17 newborns (30%), 5 with status epilepticus. Moderate-severe injury was more common in newborns with seizures (relative risk, 2.9; 95% CI, 1.2-4.5; P=.02), and was present in all 5 newborns with status epilepticus. Newborns with moderate-severe injury had seizures that were multifocal and of later onset, and they were more likely to experience recurrent seizures after treatment with 20 mg/kg phenobarbital. Newborns with only subclinical seizures were as likely to have injury as those with seizures with a clinical correlate (57% vs 60%). CONCLUSION: Seizures represent a risk factor for brain injury in the setting of therapeutic hypothermia, especially in neonates with status epilepticus, multifocal-onset seizures, and a need for multiple medications. However, 40% of our neonates were spared from brain injury, suggesting that the outcome after seizures is not uniformly poor in children treated with therapeutic hypothermia.

Cerebellar hemorrhage on magnetic resonance imaging in preterm newborns associated with abnormal neurologic outcome.

OBJECTIVE: To investigate the relationship between cerebellar hemorrhage in preterm infants seen on magnetic resonance imaging (MRI), but not on ultrasonography, and neurodevelopmental outcome. STUDY DESIGN: Images from a cohort study of MRI in preterm newborns were reviewed for cerebellar hemorrhage. The children were assessed at a mean age of 4.8 years with neurologic examination and developmental testing using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. RESULTS: Cerebellar hemorrhage was detected on both ultrasonography and MRI in 3 of the 131 preterm newborns evaluated, whereas smaller hemorrhages were seen only on MRI in 10 newborns (total incidence, 10%). Adjusting for gestational age at birth, intraventricular hemorrhage, and white matter injury, cerebellar hemorrhage detectable solely by MRI was associated with a 5-fold increased odds of abnormal neurologic examination compared with newborns without cerebellar hemorrhage (outcome data in 74%). No association with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition score was found. CONCLUSIONS: Cerebellar hemorrhage is not uncommon in preterm newborns. Although associated with neurologic abnormalities, hemorrhage seen only on MRI is associated with much more optimistic outcomes than that visible on ultrasonography.

Perinatal events and early magnetic resonance imaging in therapeutic hypothermia.

OBJECTIVE: To compare the association between perinatal events and the pattern and extent of brain injury on early magnetic resonance imaging in newborn infants with and without therapeutic hypothermia for hypoxic-ischemic encephalopathy. STUDY DESIGN: We performed a cohort study of 35 treated and 25 nontreated neonates who underwent magnetic resonance imaging. The injury patterns were defined a priori as: normal, watershed, or basal ganglia/thalamus-predominant, as well as a dichotomous outcome of moderate-to-severe versus mild-no injury. RESULTS: Neonates with hypothermia had less extensive watershed and basal ganglia/thalamus injuries and a greater proportion had normal imaging. Therapeutic hypothermia was associated with a decreased risk of both basal ganglia/thalamus injury (relative risk, 0.29; 95% CI, 0.10 to 0.81, P = .01) and moderate-severe injury. Neonates with sentinel events showed a decrease in basal ganglia/thalamus-predominant injury and an increase in normal imaging. All neonates with decreased fetal movements had injury, predominantly watershed, regardless of therapeutic hypothermia. CONCLUSIONS: These results validate reports of reduced brain injury after therapeutic hypothermia and suggest that perinatal factors are important indicators of response to treatment.

Extreme premature birth is not associated with impaired development of brain microstructure.

OBJECTIVE: To assess whether birth at <26 weeks gestation is an important predictor of brain microstructure maturation as determined by using diffusion tensor imaging. STUDY DESIGN: We performed serial magnetic resonance imaging and diffusion tensor imaging in 176 infants born at <33 weeks gestation. Diffusion parameters were calculated for white and gray matter regions. Linear regression for repeated measures was used to assess the effect of extremely premature birth on brain maturation. RESULTS: In white matter, fractional anisotropy increased by 0.008 per week (95% CI, 0.007-0.009; P < .0001) and mean diffusivity decreased by 0.021 mm(2)/sec per week, (95% CI, -0.24-0.018; P < .0001). Birth at <26 weeks was associated with lower white matter fractional anisotropy (-0.01; 95% CI, -0.018-0.003; P = .008), but this effect was eliminated when co-morbid conditions were added to the model. Moderate-severe brain injury was associated with decreased mean white matter fractional anisotropy (-0.012; 95% CI, -0.02-0.004; P = .002). CONCLUSION: Brain microstructure maturation as measured serially in premature infants is independent of extremely premature birth. Brain injury and co-morbid conditions may be the important determinants of microstructure maturation.

Clinical Neonatal Seizures are Independently Associated with Outcome in Infants at Risk for Hypoxic-Ischemic Brain Injury.

OBJECTIVE: To examine whether neonatal seizures are associated with neurodevelopmental outcomes in infants with hypoxia-ischemia independent of the presence and severity of brain injury seen on magnetic resonance imaging (MRI). STUDY DESIGN: We used multivariate regression to examine the independent effect of clinical neonatal seizures and their treatment on neurodevelopment in 77 term newborns at risk for hypoxic-ischemic brain injury. Clinical seizures were recorded prospectively, and high-resolution newborn MRI measured the severity of brain injury. The outcome measure was the Full-Scale Intelligence Quotient (FSIQ) of the Wechsler Preschool and Primary Scale of Intelligence-Revised and neuromotor score at age 4 years. RESULTS: After controlling for severity of injury on MRI, the children with neonatal seizures had worse motor and cognitive outcomes compared with those without seizures. The magnitude of effect varied with seizure severity; children with severe seizures had a lower FSIQ than those with mild/moderate seizures (P < .0001). CONCLUSIONS: Clinical neonatal seizures in the setting of birth asphyxia are associated with worse neurodevelopmental outcome, independent of the severity of hypoxic-ischemic brain injury. Randomized controlled trials are needed to determine whether differences in seizure treatment can improve outcome.

Antenatal and intrapartum risk factors for seizures in term newborns: a population-based study, California 1998-2002.

OBJECTIVE: To assess antenatal and intrapartum risk factors for seizures occurring during the birth admission. STUDY DESIGN: Using multivariable logistic regression analysis, we evaluated the association between maternal characteristics and birth admission seizures in a cohort of 2.3 million California children born at >or=36 weeks' gestation between 1998 and 2002 using the California Office of Statewide Planning and Development database containing birth certificates linked to infant and maternal hospital discharge abstracts. RESULTS: The incidence of seizures during the birth admission was 0.95/1000 live births. In an adjusted analysis, infants of women age 40 years and older who were nulliparous; had diabetes mellitus, intrapartum fever, or infection or delivered at >or=42 weeks had an increased risk of seizures. Infants of Hispanic and Asian mothers had a lower risk compared with infants of Caucasian mothers. CONCLUSIONS: Several maternal antenatal and intrapartum factors increased the risk of seizures during the birth admission. Identifying and avoiding risks for neonatal seizures may lead to lower infant neurologic morbidity and mortality.