Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period

Abstract Background Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs). Objective To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. Des...

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Veröffentlicht in:Early human development 2012-01, Vol.88 (1), p.33-38
Hauptverfasser: van der Heide, Mariska J, Roze, Elise, van der Veere, Christa N, ter Horst, Hendrik J, Brouwer, Oebele F, Bos, Arend F
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container_end_page 38
container_issue 1
container_start_page 33
container_title Early human development
container_volume 88
creator van der Heide, Mariska J
Roze, Elise
van der Veere, Christa N
ter Horst, Hendrik J
Brouwer, Oebele F
Bos, Arend F
description Abstract Background Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs). Objective To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. Design/methods We included 82 children (born 1998–2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP). Results Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e. , death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98–7.69; P = .055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42–32.82, P = .016. Persistently severely abnormal aEEG background patterns also increased this risk, OR 3.19; 95%-CI 1.90–5.36; P < .001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99–32.97, P = .051. We found no association between seizure aetiology and outcome. Conclusions In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value.
doi_str_mv 10.1016/j.earlhumdev.2011.06.012
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Objective To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. Design/methods We included 82 children (born 1998–2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP). Results Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e. , death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98–7.69; P = .055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42–32.82, P = .016. Persistently severely abnormal aEEG background patterns also increased this risk, OR 3.19; 95%-CI 1.90–5.36; P &lt; .001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99–32.97, P = .051. We found no association between seizure aetiology and outcome. Conclusions In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value.</description><identifier>ISSN: 0378-3782</identifier><identifier>EISSN: 1872-6232</identifier><identifier>DOI: 10.1016/j.earlhumdev.2011.06.012</identifier><identifier>PMID: 21835564</identifier><identifier>CODEN: EHDEDN</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ireland Ltd</publisher><subject>Advanced Basic Science ; Anti-epileptic drugs ; Anticonvulsants - administration &amp; dosage ; Anticonvulsants - therapeutic use ; Apgar Score ; Biological and medical sciences ; Child ; Child, Preschool ; Children ; Convulsions ; Drugs ; Electroencephalography - methods ; Embryology: invertebrates and vertebrates. Teratology ; Epilepsy ; Epilepsy - diagnosis ; Epilepsy - drug therapy ; Epilepsy - etiology ; Female ; Follow-up ; Follow-Up Studies ; Fundamental and applied biological sciences. Psychology ; Humans ; Infant ; Infant, Newborn ; Infants ; Intensive Care Units, Neonatal ; Lidocaine - administration &amp; dosage ; Lidocaine - therapeutic use ; Logistic Models ; Male ; Midazolam - administration &amp; dosage ; Midazolam - therapeutic use ; Mortality ; Neonatal and Perinatal Medicine ; Neonatal seizures ; Neonates ; Neurological dysfunction ; Paralysis ; Phenobarbital - administration &amp; dosage ; Phenobarbital - therapeutic use ; Prognosis ; Risk Factors ; Seizure control ; Seizures ; Treatment Outcome</subject><ispartof>Early human development, 2012-01, Vol.88 (1), p.33-38</ispartof><rights>Elsevier Ltd</rights><rights>2011 Elsevier Ltd</rights><rights>2015 INIST-CNRS</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c491t-4721c04294cba4bd9d08d74386d274f45977e642f3683d2449a9c39fdf9b13713</citedby><cites>FETCH-LOGICAL-c491t-4721c04294cba4bd9d08d74386d274f45977e642f3683d2449a9c39fdf9b13713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.earlhumdev.2011.06.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=25372930$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21835564$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>van der Heide, Mariska J</creatorcontrib><creatorcontrib>Roze, Elise</creatorcontrib><creatorcontrib>van der Veere, Christa N</creatorcontrib><creatorcontrib>ter Horst, Hendrik J</creatorcontrib><creatorcontrib>Brouwer, Oebele F</creatorcontrib><creatorcontrib>Bos, Arend F</creatorcontrib><title>Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period</title><title>Early human development</title><addtitle>Early Hum Dev</addtitle><description>Abstract Background Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs). Objective To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. Design/methods We included 82 children (born 1998–2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP). Results Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e. , death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98–7.69; P = .055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42–32.82, P = .016. Persistently severely abnormal aEEG background patterns also increased this risk, OR 3.19; 95%-CI 1.90–5.36; P &lt; .001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99–32.97, P = .051. We found no association between seizure aetiology and outcome. Conclusions In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value.</description><subject>Advanced Basic Science</subject><subject>Anti-epileptic drugs</subject><subject>Anticonvulsants - administration &amp; dosage</subject><subject>Anticonvulsants - therapeutic use</subject><subject>Apgar Score</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Convulsions</subject><subject>Drugs</subject><subject>Electroencephalography - methods</subject><subject>Embryology: invertebrates and vertebrates. Teratology</subject><subject>Epilepsy</subject><subject>Epilepsy - diagnosis</subject><subject>Epilepsy - drug therapy</subject><subject>Epilepsy - etiology</subject><subject>Female</subject><subject>Follow-up</subject><subject>Follow-Up Studies</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Infants</subject><subject>Intensive Care Units, Neonatal</subject><subject>Lidocaine - administration &amp; dosage</subject><subject>Lidocaine - therapeutic use</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Midazolam - administration &amp; dosage</subject><subject>Midazolam - therapeutic use</subject><subject>Mortality</subject><subject>Neonatal and Perinatal Medicine</subject><subject>Neonatal seizures</subject><subject>Neonates</subject><subject>Neurological dysfunction</subject><subject>Paralysis</subject><subject>Phenobarbital - administration &amp; dosage</subject><subject>Phenobarbital - therapeutic use</subject><subject>Prognosis</subject><subject>Risk Factors</subject><subject>Seizure control</subject><subject>Seizures</subject><subject>Treatment Outcome</subject><issn>0378-3782</issn><issn>1872-6232</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkk2PFCEQhjtG446rf8FwMXrpkQL6g4uJu_ErmcSDeiYMVM8wdsMI9G724H-Xzoxu4sF4IBx46q0KT1UVAboGCu3rwxp1HPfzZPFmzSjAmrZrCuxBtYK-Y3XLOHtYrSjv-rocdlE9SelAKW16SR9XFwx63jStWFU_N8Hv6oxxIh7nGMawc0aPJMzZhAlJGMjyWG9D9MTs3WgjepIj6oyW3Lq8J_k2kBDJFCIS7bOr8ehGPGZniI3zLhE7R-d3JO-x9Ahe55J_xOiCfVo9GvSY8Nn5vqy-vX_39fpjvfn84dP1201thIRci46BoYJJYbZabK20tLed4H1rWScG0ciuw1awgbc9t0wIqaXhcrCD3ALvgF9WL0-5xxh-zJiymlwyOI66DDQnJYF1spG8KeSrf5LAGIBoGeMF7U-oiSGliIM6RjfpeKeAqkWTOqh7TWrRpGiriqZS-vzcZd5OaP8U_vZSgBdnQKeiY4jaG5fuuYZ3THJauKsTh-X3bhxGlYxDb9C6iCYrG9z_TPPmrxAzOr-swXe8w3QIc_TFjgKVmKLqy7JWy1YBUMqgafgvgvPLlw</recordid><startdate>20120101</startdate><enddate>20120101</enddate><creator>van der Heide, Mariska J</creator><creator>Roze, Elise</creator><creator>van der Veere, Christa N</creator><creator>ter Horst, Hendrik J</creator><creator>Brouwer, Oebele F</creator><creator>Bos, Arend F</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7X8</scope></search><sort><creationdate>20120101</creationdate><title>Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period</title><author>van der Heide, Mariska J ; Roze, Elise ; van der Veere, Christa N ; ter Horst, Hendrik J ; Brouwer, Oebele F ; Bos, Arend F</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c491t-4721c04294cba4bd9d08d74386d274f45977e642f3683d2449a9c39fdf9b13713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Advanced Basic Science</topic><topic>Anti-epileptic drugs</topic><topic>Anticonvulsants - administration &amp; dosage</topic><topic>Anticonvulsants - therapeutic use</topic><topic>Apgar Score</topic><topic>Biological and medical sciences</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Convulsions</topic><topic>Drugs</topic><topic>Electroencephalography - methods</topic><topic>Embryology: invertebrates and vertebrates. Teratology</topic><topic>Epilepsy</topic><topic>Epilepsy - diagnosis</topic><topic>Epilepsy - drug therapy</topic><topic>Epilepsy - etiology</topic><topic>Female</topic><topic>Follow-up</topic><topic>Follow-Up Studies</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Humans</topic><topic>Infant</topic><topic>Infant, Newborn</topic><topic>Infants</topic><topic>Intensive Care Units, Neonatal</topic><topic>Lidocaine - administration &amp; dosage</topic><topic>Lidocaine - therapeutic use</topic><topic>Logistic Models</topic><topic>Male</topic><topic>Midazolam - administration &amp; dosage</topic><topic>Midazolam - therapeutic use</topic><topic>Mortality</topic><topic>Neonatal and Perinatal Medicine</topic><topic>Neonatal seizures</topic><topic>Neonates</topic><topic>Neurological dysfunction</topic><topic>Paralysis</topic><topic>Phenobarbital - administration &amp; dosage</topic><topic>Phenobarbital - therapeutic use</topic><topic>Prognosis</topic><topic>Risk Factors</topic><topic>Seizure control</topic><topic>Seizures</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>van der Heide, Mariska J</creatorcontrib><creatorcontrib>Roze, Elise</creatorcontrib><creatorcontrib>van der Veere, Christa N</creatorcontrib><creatorcontrib>ter Horst, Hendrik J</creatorcontrib><creatorcontrib>Brouwer, Oebele F</creatorcontrib><creatorcontrib>Bos, Arend F</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Early human development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>van der Heide, Mariska J</au><au>Roze, Elise</au><au>van der Veere, Christa N</au><au>ter Horst, Hendrik J</au><au>Brouwer, Oebele F</au><au>Bos, Arend F</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period</atitle><jtitle>Early human development</jtitle><addtitle>Early Hum Dev</addtitle><date>2012-01-01</date><risdate>2012</risdate><volume>88</volume><issue>1</issue><spage>33</spage><epage>38</epage><pages>33-38</pages><issn>0378-3782</issn><eissn>1872-6232</eissn><coden>EHDEDN</coden><abstract>Abstract Background Neonatal seizures may persist despite treatment with multiple anti-epileptic drugs (AEDs). Objective To determine in term-born infants with seizures that required two or more AEDs, whether treatment efficacy and/or the underlying disorder were related to neurological outcome. Design/methods We included 82 children (born 1998–2006) treated for neonatal seizures. We recorded mortality, aetiology of seizures, the number of AEDs required, achievement of seizure control, and amplitude-integrated-EEG (aEEG) background patterns. Follow-up consisted of an age-adequate neurological examination. Surviving children were classified as normal, having mild neurological abnormalities, or cerebral palsy (CP). Results Forty-seven infants (57%) had status epilepticus. The number of AEDs was not related to neurological outcome. Treatment with three or four AEDs as opposed to two showed a trend towards an increased risk of a poor outcome, i.e. , death or CP, odds ratio (OR) 2.74; 95% confidence interval (CI) 0.98–7.69; P = .055. Failure to achieve seizure control increased the risk of poor outcome, OR 6.77; 95%-CI 1.42–32.82, P = .016. Persistently severely abnormal aEEG background patterns also increased this risk, OR 3.19; 95%-CI 1.90–5.36; P &lt; .001. In a multivariate model including abnormal aEEG background patterns, failure to achieve seizure control nearly reached significance towards an increased risk of poor outcome, OR 5.72, 95%-CI 0.99–32.97, P = .051. We found no association between seizure aetiology and outcome. Conclusions In term-born infants with seizures that required two or more AEDs outcome was poorer if seizure control failed. The number of AEDs required to reach seizure control and seizure aetiology had limited prognostic value.</abstract><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>21835564</pmid><doi>10.1016/j.earlhumdev.2011.06.012</doi><tpages>6</tpages></addata></record>
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subjects Advanced Basic Science
Anti-epileptic drugs
Anticonvulsants - administration & dosage
Anticonvulsants - therapeutic use
Apgar Score
Biological and medical sciences
Child
Child, Preschool
Children
Convulsions
Drugs
Electroencephalography - methods
Embryology: invertebrates and vertebrates. Teratology
Epilepsy
Epilepsy - diagnosis
Epilepsy - drug therapy
Epilepsy - etiology
Female
Follow-up
Follow-Up Studies
Fundamental and applied biological sciences. Psychology
Humans
Infant
Infant, Newborn
Infants
Intensive Care Units, Neonatal
Lidocaine - administration & dosage
Lidocaine - therapeutic use
Logistic Models
Male
Midazolam - administration & dosage
Midazolam - therapeutic use
Mortality
Neonatal and Perinatal Medicine
Neonatal seizures
Neonates
Neurological dysfunction
Paralysis
Phenobarbital - administration & dosage
Phenobarbital - therapeutic use
Prognosis
Risk Factors
Seizure control
Seizures
Treatment Outcome
title Long-term neurological outcome of term-born children treated with two or more anti-epileptic drugs during the neonatal period
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