Abstracts

Rationale: Neonatal seizures are known as an acute symptomatic manifestation and mostly an ominous sign of underlying cerebral pathology. The etiology of neonatal seizures is considered as the most significant determinant of the outcomes later in life. However, it is unclear if neonatal seizures have an adverse impact on the developing brain, resulting epilepsy and neurocognitive outcomes, regardless of underlying etiology of seizures. Methods: We performed a retrospective observational study over 6 years (Jan 1, 2009-Dec 31, 2014), using U.S. nationwide commercial claims data from Truven MarketScan® database. Subjects who were born and enrolled in 2009 were analyzed. Neonatal seizures were defined using the International Classification of Diseases, Ninth Revision, Clinical Modification codes and anti-epileptic drugs (AEDs) claims as follows: (a) =1 code 779.0 and =1 code electroencephalogram, (b) =1 code 779.0 and =1 code brain imaging, including ultrasound, computed tomography, or magnetic resonance imaging, (c) =1 code 779.0 and =1 code therapeutic AEDs assays, or (d) =1 code 779.0 and AEDs prescription. Epilepsy cases were identified among subjects having: (a) =2 codes 345.xx, (b) =1 code 345.xx and =1 code 780.39, (c) =1 code 345.xx and AEDs, or (d) =2 codes 780.39 and AEDs. We measured 12 neurocognitive disorders, such as intellectual disabilities, psychiatric & behavioral disorders, and headache. Cox regression analysis estimated hazards ratios, controlling for sex, birth weight, gestational age, and underlying etiology of seizures including perinatal morbidity, congenital infection, brain malformation, metabolic disturbances, central nervous system infection, stroke or cerebrovascular disease, and hydrocephalus. Results: Out of 490071 newborns (male=251850), 823 neonatal seizures cases were identified (2 per 1000 live births). During follow-up, 2438 and 57213 subjects developed epilepsy and =1 neurocognitive disorders, respectively. The most frequent etiology of neonatal seizures was perinatal morbidity (604/823, 73.4%), including hypoxic brain injury, intracranial hemorrhage, and respiratory difficulty. After controlling for sex, birth weight, gestational age, and the underlying etiology of seizures, subjects with neonatal seizures were more likely to develop epilepsy compared to those without neonatal seizures (hazard ratio, 30.3; 95% confidence interval (CI), 25.7-35.9; p < .001). Compared to those without neonatal seizures, an increased risk for intellectual disabilities was observed in those with neonatal seizures, especially mental retardation (hazard ratio, 1.5; 95% CI, 1.2-1.9; p=.001), specific delay in development (hazard ratio, 2.1; 95% CI, 1.8-2.4; p < .001), and delayed milestones (hazard ratio, 2.2; 95% CI, 1.9-2.6; p < .001). Conclusions: Newborns with neonatal seizures had an increased risk of developing epilepsy and intellectual disabilities irrespective of the underlying etiology of seizures. Further long-term outcomes study is warranted. Funding: Children’s Healthcare of Atlanta research grant funded by the Goizueta Foundation.