The Impact of Anticonvulsants on Neurologic Outcomes in Neonatal Seizures

Ji Yoon Han; Jin Hee Lee; Sun Young Park; Chung Joon Moon; Young Ah Youn; In Kyung Sung; In Goo Lee

doi:10.14734/kjp.2014.25.2.83

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Han, Lee, Park, Moon, Youn, Sung, and Lee: The Impact of Anticonvulsants on Neurologic Outcomes in Neonatal Seizures

Original Article

Korean J Perinatol 2014;25(2):83-90.

Published online: 21 June 2014

DOI: https://doi.org/10.14734/kjp.2014.25.2.83

The Impact of Anticonvulsants on Neurologic Outcomes in Neonatal Seizures

Ji Yoon Han, M.D., Jin Hee Lee, M.D., Sun Young Park, M.D., Chung Joon Moon, M.D., Young Ah Youn, M.D., In Kyung Sung, M.D., In Goo Lee, M.D.

Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea

Received 7 May 201415 May 2014 Accepted 15 May 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

Although neonatal seizures can cause epilepsy, neurodevelopmental disability, and mortality with high frequency, the use of anti-epileptic drug is limited and the side effect of the drug is unidentified. Thus, authors investigated the prognosis of the neonatal seizures related with anti-epileptic drugs and electroencephalography.

Methods

Retrospective medical records of 37 infants with neonatal seizures under 44 weeks of gestational age who were hospitalized at neonatal intensive care unit in Seoul St. Mary’ Hospital from January to June 2012 were analyzed.

Result

The mean gestational age was 32.5±1.9 weeks and the mean birth weight was 2,010±82 g. Seizures occurred in 65% in infants within 7 days of birth and subtle seizures were most common type. Hypoxic ischemic encephalopathy was the most common cause of seizures and 62% showed abnormal electrographic findings. Among 37 of patients, seizures of 57% were able to be controlled by levetiracetam, but 19% were controlled by co-administration of more than three anti-epileptic drugs. After 6 months of treatment, epilepsy was diagnosed in 6% and developmental delay occurred in 19% among patients controlled by one antiepileptic drug. Epilepsy and developmental delay occurred in 29% and 86%, respectively, among patients with more than three anti-epileptic drugs. In addition 86% of patients with normal electroencephalographic findings show normal development, but 3 patients with severe abnormalities showed abnormal development.

Conclusion

Neurologic outcome was not good when the number of anti-epileptic drugs were added due to uncontrolled seizures, and the result of electroencephalography showed severe abnormalities.

Keywords: Newborn, Seizures, Levetiracetam

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Table 1.

Demographic and Baseline Characteristics of Subjects (N=37)

Male: Female	18 (49%): 19 (51%)
Gestational age	Mean 33.0±1.9 weeks
	Preterm infants (<37 weeks) 24 (65%)
	Full-term infants (≥37 weeks) 13 (35%)
Birth weight	Mean 2,010±82 g
	< 1,000 g	8 (22%)
	1,000~1,500 g	5 (16%)
	1,500~2,500 g	10 (27%)
	> 2,500 g	14 (38%)

Table 2.

Type of Neonatal Seizures (N=37)

Type		Number of patients (%)
Subtle	Ocular movements	2
	Oral-buccal-lingual movements Progression movements	2 9	19 (51%)
	Autonomic dysfunction	6
Clonic	Focal		4 (11%)
	Generalized		1 (3%)
Tonic	Focal		5 (14%)
	Generalized		2 (5%)
Myoclonic	Focal		1 (3%)
	Generalized		0 (0%)
Subtle + Focal clonic			3 (8%)
Subtle + Focal tonic			2 (5%)
Total			37 (100%)

Table 3.

Electrographic Findings in the Subjects (N=37)

EEG category		Number of patients (%)
Normal			14 (38%)
Moderate abnormalities	Low voltage	4	20 (54%)
	Epileptiform activity with normal background rhythms	13
	Maturationally delayed	3
Major abnormalities	Isoelectric or inactive	1	3 (8%)
	Epileptiiform activity with abnormal background rhythms	1
	Burst suppression	1

Table 4.

Treatment for Controlling Seizures (N=37)

Anticonvulsants	Number of patients (%)
Levetiracetam	21 (57%)
Levetiracetam, Phenobarbital	9 (24%)
Levetiracetam, Phenobarbital, Phenytoin	3 (8%)
Levetiracetam, Phenobarbital, Phenytoin, Midazolam	2 (5%)
Levetiracetam, Phenobarbital, Phenytoin, Topiramate	1 (3%)
Levetiracetam, Phenobarbital, Phenytoin, Midazolam, Valproic acid	1 (3%)

Table 5.

Cessation Time of Neonatal Seizures (N=37)

Cessation time	Number of patients (%)
Within 24 hours	22 (59%)
24 to 48 hours	4 (11%)
48 hours to 7 days	7 (19%)
Over 7 days	4 (11%)
Total	37 (100%)

Table 6.

Duration of Anticonvulsant Treatment

	Monotherapy	Polytherapy	P
Days	24±12	51±32	0.022

Table 7.

Outcome at 6 Months after Treatment (N=37)

Prognosis	One AED (N=21)	Two AEDs (N=9)	More than Three AED (N=7)	s Total (N=37)	P
Normal	15 (71%)	3 (33%)	1 (14%)	19 (51%)	0.021
Post-neonatal epilepsy	2 (6%)	2 (22%)	2 (29%)	6 (16%)	0.082
Developmental delay	4 (19%)	4 (44%)	6 (86%)	14 (35%)	0.076

Abbreviation : AED, anti-epileptic drug

Table 8.

EEG Categories and Outcome after Initiation of Treatment (N=37)

Category of EEG	Normal (N=14)	Moderate abnormalities (N=20)	Severe abnormalities (N=3)	Total (N=37)	P
Normal	12 (86%)	7 (35%)	0	19 (51%)	0.030
Post-neonatal epilepsy	2 (14%)	4 (20%)	2 (67%)	6 (16%)	0.071
Developmental delay	2 (14%)	9 (45%)	3 (100%)	14 (35%)	0.087

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