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<front>
<journal-meta>
<journal-id journal-id-type="issn">1043-3155</journal-id>
<journal-id journal-id-type="nlm-ta">Pediatr Neurol Briefs</journal-id>
<journal-id journal-id-type="pmc">pedneurbriefs</journal-id>
<journal-id journal-id-type="iso-abbrev">Pediatr Neurol Briefs</journal-id>
<journal-title-group>
<journal-title>Pediatric Neurology Briefs</journal-title>
<abbrev-journal-title>Pediatr Neurol Briefs</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2166-6482</issn>
<issn pub-type="ppub">1043-3155</issn>
<issn-l>2166-3155</issn-l>
<publisher>
<publisher-name>Pediatric Neurology Briefs Publishers</publisher-name>
<publisher-loc>Chicago, IL, USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">PNB-18-12</article-id>
<article-id pub-id-type="doi">10.15844/pedneurbriefs-18-2-4</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Cerebral Palsy</subject>
</subj-group>
<subj-group subj-group-type="Discipline-v2">
<subject>Neurology</subject>
<subject>Pediatrics</subject>
<subject>Nervous System Diseases</subject>
<subject>Child Development</subject>
<subject>Brain Diseases</subject>
<subject>Neurosurgery</subject>
<subject>Child</subject>
<subject>Infant</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Cord Serum Inflammatory Cytokines as Biomarkers of Cerebral Palsy</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" corresp="yes">
<contrib-id contrib-id-type="orcid">http://orcid.org/0000-0002-0173-7931</contrib-id>
<name>
<surname>Millichap</surname>
<given-names>J. Gordon</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="AF0001">1</xref>
<xref ref-type="aff" rid="AF0002">2</xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref>
</contrib>
</contrib-group>
<aff id="AF0001">
<label>1</label>Division of Neurology, Children&#x0027;s Memorial Hospital, Chicago, IL</aff>
<aff id="AF0002">
<label>2</label>Departments of Pediatrics and Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL</aff>
<author-notes>
<corresp id="cor1"><label>&#x002A;</label>Correspondence: Dr. J. Gordon Millichap, E-mail: <email xlink:href="jgmillichap@northwestern.edu">jgmillichap@northwestern.edu</email>
</corresp>
</author-notes>
<pub-date date-type="pub" publication-format="print">
<month>02</month>
<year>2004</year>
</pub-date>
<pub-date date-type="pub" publication-format="electronic">
<day>01</day>
<month>03</month>
<year>2016</year>
</pub-date>
<volume>18</volume>
<issue>2</issue>
<fpage>12</fpage>
<lpage>13</lpage>
<permissions>
<copyright-statement>Copyright: &#x00A9; 2004 The Author(s)</copyright-statement>
<copyright-year>2004</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This work is licensed under the <uri xlink:href="http://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International License</uri>, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<related-article id="R1" related-article-type="commentary-article" ext-link-type="doi" xlink:href="10.1002/ana.10809" vol="55" page="186">
<article-title>Cerebral palsy is characterized by protein mediators in cord serum</article-title>
</related-article>
<abstract abstract-type="web-summary" specific-use="electronic-only">
<p>The relationship between 78 inflammatory protein mediators in cord serum and cerebral palsy (CP) in 41 term and preterm children was determined at the University of Oulu. Finland.</p>
</abstract>
<kwd-group>
<kwd>Cord Serum</kwd>
<kwd>Cerebral Palsy</kwd>
<kwd>Proinflammatory Cytokines</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<p>The relationship between 78 inflammatory protein mediators in cord serum and cerebral palsy (CP) in 41 term and preterm children was determined at the University of Oulu. Finland. Infants were born in the year 1992-1993 at 4 university hospitals, and CP was diagnosed by child neurologists by age 5, according to standard criteria: a persistent abnormality of muscle tone, movement, and posture with functional impairment due to a nonprogressive lesion of the immature brain. Children with congenital cerebral malformation, prenatal viral or protozoal infection, post-neonatal brain damage, or chromosomal abnormality were excluded. Of 41 children with CP in the study group, 22 had spastic diplegia, 12 spastic hemiplegia, 3 spastic quadriplegia, and 4 dystonic quadriplegia. One paired control matched for gestational age and without CP was selected for each case.</p>
<p>In children with CP, the levels of 8 cytokines, 1 growth factor, and 3 chemokines were higher (p&#x003C;0.05) than in controls, findings consistent with an infection or fetal inflammatory response. Infants developing CP had an altered serum profile of specific protein mediators. Prematures had high IL-6 and IL-8 levels, and 9 additional cytokines showed significant changes. Several of these regulatory proteins found in newborns with CP are distinct from those with acute neonatal disease not resulting in CP. Inflammatory mediators and growth factors in cord blood of CP infants are indicative of a fetal response to a pre- or perinatal infection that manifests after birth as permanent brain damage. [<xref ref-type="bibr" rid="CIT0001">1</xref>]</p>
<p>COMMENT. In references cited by the authors, chorioamnionitis is considered a risk factor for cerebral palsy [<xref ref-type="bibr" rid="CIT0002">2</xref>]; and an increase in proinflammatory cytokines in amniotic fluid or cord blood has been associated with the development of CP [<xref ref-type="bibr" rid="CIT0003">3</xref>]. The Finnish investigators propose that susceptible infants have an abnormal pattern of cytokines and growth factors that predispose to CP during perinatal infection and lead to neuronal and neuroglial brain damage. An editorial [<xref ref-type="bibr" rid="CIT0004">4</xref>] cautions that the study group is small, and no appreciable differences are demonstrated between cases and controls in the distribution of the &#x201C;classic&#x201D; proinflammatory cytokines (eg. IL-1B, IL-6, tumor necrosis factor-a). More studies of developmental regulation of biomarkers are required to adjust for gestational age-specific changes.</p>
<p><bold>Cytokines and SIDS</bold>. Pro-inflammatory cytokines are found in the brainstem of infants dying from SIDS, and an increase in IL-6 has been demonstrated in the CSF. The limitations of these findings in the etiology of SIDS is discussed by Waters KA. [<xref ref-type="bibr" rid="CIT0005">5</xref>]</p>
</body>
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