Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity.
<h4>Objective</h4>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...
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| Format: | Article |
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0247749 |
| _version_ | 1830199849020030976 |
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| author | David D Limbrick Diego M Morales Chevis N Shannon John C Wellons Abhaya V Kulkarni Jessica S Alvey Ron W Reeder Volker Freimann Richard Holubkov Jay K Riva-Cambrin William E Whitehead Curtis J Rozzelle Mandeep Tamber W Jerry Oakes James M Drake Ian F Pollack Robert P Naftel Terrie E Inder John R Kestle Hydrocephalus Clinical Research Network |
| author_facet | David D Limbrick Diego M Morales Chevis N Shannon John C Wellons Abhaya V Kulkarni Jessica S Alvey Ron W Reeder Volker Freimann Richard Holubkov Jay K Riva-Cambrin William E Whitehead Curtis J Rozzelle Mandeep Tamber W Jerry Oakes James M Drake Ian F Pollack Robert P Naftel Terrie E Inder John R Kestle Hydrocephalus Clinical Research Network |
| author_sort | David D Limbrick |
| collection | DOAJ |
| description | <h4>Objective</h4>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.<h4>Study design</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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. |
| first_indexed | 2024-12-18T02:21:54Z |
| format | Article |
| id | doaj.art-525875fc8f0546748ad2effdf0167c31 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-18T02:21:54Z |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-525875fc8f0546748ad2effdf0167c312022-12-21T21:24:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01163e024774910.1371/journal.pone.0247749Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity.David D LimbrickDiego M MoralesChevis N ShannonJohn C WellonsAbhaya V KulkarniJessica S AlveyRon W ReederVolker FreimannRichard HolubkovJay K Riva-CambrinWilliam E WhiteheadCurtis J RozzelleMandeep TamberW Jerry OakesJames M DrakeIan F PollackRobert P NaftelTerrie E InderJohn R KestleHydrocephalus Clinical Research Network<h4>Objective</h4>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.<h4>Study design</h4>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.<h4>Results</h4>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).<h4>Conclusion</h4>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.https://doi.org/10.1371/journal.pone.0247749 |
| spellingShingle | David D Limbrick Diego M Morales Chevis N Shannon John C Wellons Abhaya V Kulkarni Jessica S Alvey Ron W Reeder Volker Freimann Richard Holubkov Jay K Riva-Cambrin William E Whitehead Curtis J Rozzelle Mandeep Tamber W Jerry Oakes James M Drake Ian F Pollack Robert P Naftel Terrie E Inder John R Kestle Hydrocephalus Clinical Research Network Cerebrospinal fluid NCAM-1 concentration is associated with neurodevelopmental outcome in post-hemorrhagic hydrocephalus of prematurity. PLoS ONE |
| 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 |
| url | https://doi.org/10.1371/journal.pone.0247749 |
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