Elsevier

Brain and Development

Volume 31, Issue 1, January 2009, Pages 64-68
Brain and Development

Original article
Development of epilepsy in newborns with moderate hypoxic-ischemic encephalopathy and neonatal seizures

https://doi.org/10.1016/j.braindev.2008.04.001Get rights and content

Abstract

Background: Hypoxic-ischemic encephalopathy (HIE) is one of the most frequent causes of neonatal death or neurological handicaps such as cerebral palsy, mental delay, and epilepsy. Moreover, an acute consequence of HIE are neonatal seizures which can cause an additional brain damage. The neurodevelopmental outcome is known in the mild or severe cases of HIE, but in the moderate conditions the predictivity results, to date, unsatisfying. Objective: The purpose of this prospective study was to appraise the development of post-neonatal epilepsy in a cohort of term infants with moderate HIE and neonatal seizures. Methods: This study considered all newborns admitted to Neonatal Intensive Care Unit of the University of Parma between January 2000 and December 2002 for perinatal asphyxia, then followed by Neonatal Neurology Service. In all patients, neonatal variables such as type of delivery, birth weight, gestational age, Apgar scores, the need for resuscitation and assisted ventilation soon after birth, and arterial-blood pH were analyzed. Results: Ninety-two newborns were enrolled in the study because of perinatal asphyxia. Of these, 27 subjects developed mild HIE, 25 moderate, and five severe HIE. Neonatal seizures were present in 13 subjects with moderate HIE and in all newborns with severe HIE. At the last follow-up, only three infants belonging to patients with severe HIE developed epilepsy. Conclusion: Moderate HIE seems not to be related to post-neonatal epilepsy either if associated or not with neonatal seizures.

Introduction

Hypoxic-ischemic encephalopathy (HIE) is one of the most frequent causes of neonatal death and neurological disabilities in children. It is estimated that about 1 to 2 per 1000 live term births [1], [2] suffer from HIE, mainly due to perinatal asphyxia. A percentage between 15% and 20% of the newborns developing HIE die during the neonatal period, whereas about 25% of the survivors will present neurological handicaps such as cerebral palsy, mental delay, and epilepsy [3].

The neurodevelopmental outcome can be predicted on the basis of the degree of HIE according to the Sarnat and Sarnat criteria [4]. However, predictivity of the final outcome based on the neurological features is known in the cases placed at the two extreme sides of the clinical spectrum, like the mild or severe HIE. In moderate conditions this predictivity results, to date, unsatisfying. For this reason and for a most adequate evaluation of the sick newborn, it is necessary to integrate the different clinical and instrumental indicators available.

An important consequence of a moderate or severe HIE are neonatal seizures which can cause an additional brain damage through an increment of the metabolic request by the central nervous system [5], [6], [7]. The exact frequency of neonatal seizures is not known. Some studies report an incidence varying from 0.15% to 0.5% [8], others from 22.7% of the premature newborns to 0.16% of the full-term newborns [9], [10], where HIE results to be the most frequent cause of seizures, accounting for 50–60% of all newborns with convulsions [11], [12].

To our knowledge, only few studies in literature focused on the relationship between moderate HIE and post-neonatal epilepsy [13], [14].

Therefore, the purpose of this prospective study was to appraise the development of post-neonatal epilepsy in a cohort of term infants with neonatal seizures due to moderate HIE.

Section snippets

Methods

This study considered all full-term newborns consecutively admitted to Neonatal Intensive Care Unit (NICU) of the Parma University between 2000 and 2002 for perinatal asphyxia, then followed by Neonatal Neurology Service. Among 1106 newborns admitted, 92 full-term newborns met the following criteria for perinatal asphyxia.

Perinatal asphyxia was defined on the basis of at least three of the following findings: intrapartum distress, as indicated by foetal bradycardia with a heart-rate of less

Results

Of the 92 newborns with perinatal asphyxia, only 57 subjects developed HIE later, 41 males and 16 females. Only 18 subjects (31.6%) presented neonatal seizures as consequence of HIE. Newborns with seizures had significant lower Apgar scores at 5, and 10 min, demonstrating a more difficult neonatal adaptation (p < 0.05). The value of the pH, measured out in 20/39 subjects without seizures and in 17/18 of the subjects with seizures, did not show significant differences between the two groups. The

Discussion

The interest for HIE is due to the still rather high frequency of occurrence and to the fact that it remains one of the most important cause of neonatal mortality and of severe neurological impairment [3], [25]. The prognosis of a hypoxic-ischemic insult to the term newborn depends on the degree of the encephalopathy. However, whether seizures superimposed on a moderate HIE would predispose to the risk of developing epilepsy later in life is still poorly investigated. To our knowledge, only few

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