Department of Neurosurgery, Washington University St. Louis, St. Louis, MO, United States of America.
Department of Neurosurgery, Vanderbilt University Medical Center, Nashville, TN, United States of America.
PLoS One. 2021 Mar 10;16(3):e0247749. doi: 10.1371/journal.pone.0247749. eCollection 2021.
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.
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.
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).
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.
针对伴有脑室内出血（IVH）和出血后脑积水（PHH）的早产儿，减轻神经功能障碍的努力受到缺乏能够预测长期结局的可量化指标的限制。本研究的目的是探讨行神经外科治疗 PHH 的婴儿的候选脑脊液（CSF）PHH 生物标志物与神经发育结局之间的关系。
PHH 早产儿在脑积水临床研究网络中入组。在临时神经外科手术时采集 CSF 样本（n=98）。比较 PHH 与对照组 CSF 中的淀粉样前体蛋白（APP）、L1CAM、NCAM-1 和总蛋白（TP）。其中 54 例 PHH 受试者在 15-30 个月校正年龄时接受贝利婴幼儿发展量表第三版（Bayley-III）测试。控制假发现率（FDR），并调整胎龄（PMA）和 IVH 分级，采用 Pearson 偏相关系数检验 CSF 蛋白与 Bayley-III 复合认知、语言和运动评分之间的关系。
临时手术时 PHH 的 CSF APP、L1CAM、NCAM-1 和 TP 高于对照组。CSF NCAM-1 与 Bayley-III 运动评分相关（R=-0.422，p=0.007，FDR Q=0.089），与认知（R=-0.335，p=0.030，FDR Q=0.182）和语言（R=-0.314，p=0.048，FDR Q=0.194）评分有中度关系。CSF APP、L1CAM 或 TP 与 Bayley-III 评分无相关性。临时手术时 FOHR 与 Bayley-III 评分无相关性，但与 Bayley-III 运动（p=0.0647，R=-0.2912）和认知评分（p=0.0506，R=-0.2966）有趋势。
本多机构 PHH 队列的 CSF NCAM-1 与神经发育相关。这是首个将特定 CSF 蛋白 NCAM-1 与 PHH 相关神经功能障碍相关的报告。未来的工作将进一步研究 NCAM-1 作为 PHH 相关神经功能障碍的生物标志物的可能作用。
