Beyond transition, identifying perinatal factors associated with Seizure Risk in Hypoxic-Ischemic Encephalopathy Affected Infants.

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Background:Hypoxic ischemic encephalopathy (HIE) is a disease that affects 1-6 out of 1000 live births in the United States annually with seizures further exacerbating brain injury.  Early identification of infants at risk for HIE related seizures could lead to early treatment with potential decreased morbidity. The goals of this study were to identify perinatal factors associated with seizure risk in infants with HIE. 

Methods:Study is a retrospective medical record review of inborn HIE infants ≥ 35 weeks gestation admitted to the Children's Hospital of Richmond NICU between 2010-2019. Data collected included patient demographics (gestational age, birth weight, sex, race), maternal medical history and perinatal factors, diagnostic HIE criteria (APGAR score, cord blood values, 1stgas values, Sarnat score), identification of seizures and treatment course as well as MRI results. Hypothermia parameters collected included initiation of cooling, time to temperature achievement, and time for achievement of rewarming. Seizure time of onset, treatment and long-term neurodevelopmental outcomes were collected through TIMP, Bayley scales, or follow-up clinical functional examinations up to 2 years of age. Statistical analysis included chi-square, two-tailed T-test, and ANOVA, where appropriate with values considered significant if p<0.05. 

Results:Of the 86 infants with HIE, 21 (24%) had seizures. Of the 65 non-seizure HIE patients, 6 (9%) expired and 41(70%) received follow up care. Of the 21 HIE patients with seizures, 2 (10%) expired and 19 (90%) received follow-up care. Maternal diabetes, p<0.027 and placental pathology p<0.017 as well as delivery by cesarean section were associated with seizure risk, p<0.009. Gestational maturity, maternal hypertension and maternal race were not associated with seizure risk. APGAR Score at 5 min was associated with greater mortality but not seizure risk. Degree of abnormal Sarnat scores(Figure 1) as well as low cord blood pH <7.20(Figure 2) and bicarbonate levels <17 mmol/L(Figure 3) had significant association of seizure risk, p<0.026 and 0.001, respectively. Of the 19 neonates with seizures, 11(60%) MRIs were abnormal compared to those without seizures. All infants with seizures were treated with Keppra initial monotherapy with 6/19 (31%) treated with Keppra and Phenobarbital dual therapy for cessation of seizures. Normal, mild and severe neurodevelopmental outcomes were not significantly different in those with or without seizures. 

Conclusions: Maternal diabetes and placental pathology in the face of HIE were associated with seizure risk. Infants requiring cesarean delivery with low cord blood pH <7.20 and bicarbonate initial levels <17 presented with greater seizure risk. Keppra monotherapy or with Phenobarbital was effective in cessation of seizures and may have been associated with decreased risk of severe neurodevelopmental outcomes in the affected infants. 

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Children's Hospital of Richmond at VCU
Children's Hospital of Richmond
Virginia Commonwealth University

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