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Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy



Neonatal seizures are associated with adverse neurologic sequelae including epilepsy in childhood. Here we aim to determine whether levels of cytokines in neonates with brain injury are associated with acute symptomatic seizures or remote epilepsy.


This is a cohort study of term newborns with encephalopathy at UCSF between 10/1993 and 1/2000 who had dried blood spots. Maternal, perinatal/postnatal, neuroimaging, and epilepsy variables were abstracted by chart review. Logistic regression was used to compare levels of cytokines with acute seizures and the development of epilepsy.


In a cohort of 26 newborns with neonatal encephalopathy at risk for hypoxic ischemic encephalopathy with blood spots for analysis, diffuse alterations in both pro- and anti-inflammatory cytokine levels were observed between those with (11/28, 39%) and without acute symptomatic seizures. Seventeen of the 26 (63%) patients had >2 years of follow-up and 4/17 (24%) developed epilepsy. Higher levels of pro-inflammatory cytokines IL-6 and TNF-α within the IL-1β pathway were significantly associated with epilepsy.


Elevations in pro-inflammatory cytokines in the IL-1β pathway were associated with later onset of epilepsy. Larger cohort studies are needed to confirm the predictive value of these circulating biomarkers.

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The authors thank Dr. Agnes Bartha for providing the groundwork for this dataset This work was supported by the National Institutes of Health Grants RR 01271, NS 35902, NS 40117, L40 NS094060, and the American Academy of Neurology Clinical Research Training Fellowship in Epilepsy.

Author information

Conception and design of the study: A.L.N., D.M.F., H.C.G. Acquisition and analysis of data: A.L.N., X.D., E.E.R., A.J.B., D.M.F., H.C.G. Drafting of manuscript: A.L.N., H.C.G. Critical revision and final approval of the version to be published: all the authors.

Correspondence to Adam L. Numis.

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