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Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity
OBJECTIVE: Efforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946285/ https://www.ncbi.nlm.nih.gov/pubmed/33690655 http://dx.doi.org/10.1371/journal.pone.0247749 |
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author | Limbrick, David D. Morales, Diego M. Shannon, Chevis N. Wellons, John C. Kulkarni, Abhaya V. Alvey, Jessica S. Reeder, Ron W. Freimann, Volker Holubkov, Richard Riva-Cambrin, Jay K. Whitehead, William E. Rozzelle, Curtis J. Tamber, Mandeep Oakes, W. Jerry Drake, James M. Pollack, Ian F. Naftel, Robert P. Inder, Terrie E. Kestle, John R. |
author_facet | Limbrick, David D. Morales, Diego M. Shannon, Chevis N. Wellons, John C. Kulkarni, Abhaya V. Alvey, Jessica S. Reeder, Ron W. Freimann, Volker Holubkov, Richard Riva-Cambrin, Jay K. Whitehead, William E. Rozzelle, Curtis J. Tamber, Mandeep Oakes, W. Jerry Drake, James M. Pollack, Ian F. Naftel, Robert P. Inder, Terrie E. Kestle, John R. |
author_sort | Limbrick, David D. |
collection | PubMed |
description | OBJECTIVE: Efforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the relationships between candidate cerebrospinal fluid (CSF) biomarkers of PHH and neurodevelopmental outcomes in infants undergoing neurosurgical treatment for PHH. STUDY DESIGN: Preterm infants with PHH were enrolled across the Hydrocephalus Clinical Research Network. CSF samples were collected at the time of temporizing neurosurgical procedure (n = 98). Amyloid precursor protein (APP), L1CAM, NCAM-1, and total protein (TP) were compared in PHH versus control CSF. Fifty-four of these PHH subjects underwent Bayley Scales of Infant Development-III (Bayley-III) testing at 15–30 months corrected age. Controlling for false discovery rate (FDR) and adjusting for post-menstrual age (PMA) and IVH grade, Pearson’s partial correlation coefficients were used to examine relationships between CSF proteins and Bayley-III composite cognitive, language, and motor scores. RESULTS: CSF APP, L1CAM, NCAM-1, and TP were elevated in PHH over control at temporizing surgery. CSF NCAM-1 was associated with Bayley-III motor score (R = -0.422, p = 0.007, FDR Q = 0.089), with modest relationships noted with cognition (R = -0.335, p = 0.030, FDR Q = 0.182) and language (R = -0.314, p = 0.048, FDR Q = 0.194) scores. No relationships were observed between CSF APP, L1CAM, or TP and Bayley-III scores. FOHR at the time of temporization did not correlate with Bayley-III scores, though trends were observed with Bayley-III motor (p = 0.0647 and R = -0.2912) and cognitive scores (p = 0.0506 and R = -0.2966). CONCLUSION: CSF NCAM-1 was associated with neurodevelopment in this multi-institutional PHH cohort. This is the first report relating a specific CSF protein, NCAM-1, to neurodevelopment in PHH. Future work will further investigate a possible role for NCAM-1 as a biomarker of PHH-associated neurological disability. |
format | Online Article Text |
id | pubmed-7946285 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-79462852021-03-19 Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity Limbrick, David D. Morales, Diego M. Shannon, Chevis N. Wellons, John C. Kulkarni, Abhaya V. Alvey, Jessica S. Reeder, Ron W. Freimann, Volker Holubkov, Richard Riva-Cambrin, Jay K. Whitehead, William E. Rozzelle, Curtis J. Tamber, Mandeep Oakes, W. Jerry Drake, James M. Pollack, Ian F. Naftel, Robert P. Inder, Terrie E. Kestle, John R. PLoS One Research Article OBJECTIVE: Efforts directed at mitigating neurological disability in preterm infants with intraventricular hemorrhage (IVH) and post hemorrhagic hydrocephalus (PHH) are limited by a dearth of quantifiable metrics capable of predicting long-term outcome. The objective of this study was to examine the relationships between candidate cerebrospinal fluid (CSF) biomarkers of PHH and neurodevelopmental outcomes in infants undergoing neurosurgical treatment for PHH. STUDY DESIGN: Preterm infants with PHH were enrolled across the Hydrocephalus Clinical Research Network. CSF samples were collected at the time of temporizing neurosurgical procedure (n = 98). Amyloid precursor protein (APP), L1CAM, NCAM-1, and total protein (TP) were compared in PHH versus control CSF. Fifty-four of these PHH subjects underwent Bayley Scales of Infant Development-III (Bayley-III) testing at 15–30 months corrected age. Controlling for false discovery rate (FDR) and adjusting for post-menstrual age (PMA) and IVH grade, Pearson’s partial correlation coefficients were used to examine relationships between CSF proteins and Bayley-III composite cognitive, language, and motor scores. RESULTS: CSF APP, L1CAM, NCAM-1, and TP were elevated in PHH over control at temporizing surgery. CSF NCAM-1 was associated with Bayley-III motor score (R = -0.422, p = 0.007, FDR Q = 0.089), with modest relationships noted with cognition (R = -0.335, p = 0.030, FDR Q = 0.182) and language (R = -0.314, p = 0.048, FDR Q = 0.194) scores. No relationships were observed between CSF APP, L1CAM, or TP and Bayley-III scores. FOHR at the time of temporization did not correlate with Bayley-III scores, though trends were observed with Bayley-III motor (p = 0.0647 and R = -0.2912) and cognitive scores (p = 0.0506 and R = -0.2966). CONCLUSION: CSF NCAM-1 was associated with neurodevelopment in this multi-institutional PHH cohort. This is the first report relating a specific CSF protein, NCAM-1, to neurodevelopment in PHH. Future work will further investigate a possible role for NCAM-1 as a biomarker of PHH-associated neurological disability. Public Library of Science 2021-03-10 /pmc/articles/PMC7946285/ /pubmed/33690655 http://dx.doi.org/10.1371/journal.pone.0247749 Text en © 2021 Limbrick et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Limbrick, David D. Morales, Diego M. Shannon, Chevis N. Wellons, John C. Kulkarni, Abhaya V. Alvey, Jessica S. Reeder, Ron W. Freimann, Volker Holubkov, Richard Riva-Cambrin, Jay K. Whitehead, William E. Rozzelle, Curtis J. Tamber, Mandeep Oakes, W. Jerry Drake, James M. Pollack, Ian F. Naftel, Robert P. Inder, Terrie E. Kestle, John R. Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity |
title | Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity |
title_full | Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity |
title_fullStr | Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity |
title_full_unstemmed | Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity |
title_short | Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity |
title_sort | cerebrospinal fluid ncam-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946285/ https://www.ncbi.nlm.nih.gov/pubmed/33690655 http://dx.doi.org/10.1371/journal.pone.0247749 |
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