Identification of Putative Biomarkers in Cerebral Palsy: A Meta-Analysis and Meta-Regression

IF 3.2 3区医学 Q2 CLINICAL NEUROLOGY Pediatric neurology Pub Date : 2024-08-02 DOI:10.1016/j.pediatrneurol.2024.07.016

Vinay Suresh MBBS , Shiva Gupta MBBS , Yashita Khulbe MBBS , Muhammad Aaqib Shamim MD, PhD , Vaibhav Jain MBBS , Malavika Jayan MBBS , Madeeha Subhan Waleed MBBS , Neha Joe MBBS , Vivek Sanker MBBS , Aravind P. Gandhi MD , Areesha Alam MD (Pediatrics) , Hardeep Singh Malhotra MD, DM , Ravindra K. Garg MD, DM , Sheffali Gulati MD, DM , Priyanka Roy MD, MPH, PhD , Mainak Bardhan MD

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Abstract

Background

Cerebral palsy (CP) is a neurological disorder that impairs motor abilities. Identifying maternal biomarker derangements can facilitate further evaluation for early diagnosis, potentially leading to improved clinical outcomes. This study investigates the association between maternal biomarker derangements and CP development during the antenatal period.

Methods

A systematic search was conducted in MEDLINE, EMBASE, and Cochrane databases, following MOOSE guidelines. Data on participants exceeding biomarker thresholds (95th and 5th percentiles) were extracted for combined odds ratio estimation. Geometric mean differences, reported as multiples of the median (MoMs), were used to analyze changes in marker levels. Trimesterwise subgroup analysis and metaregression assessed the impact of variables on outcomes.

Results

Five observational studies (1552 cases, 484,985 controls) revealed lower maternal pregnancy-associated plasma protein A levels were associated with CP (pooled odds ratio [OR] = 1.60, 95% confidence interval [CI] = 1.22 to 2.09; I = 0%), with a −0.04 MoM geometric mean difference. Lower maternal beta-human chorionic gonadotropin (HCG) levels in first and second trimesters indicated a pooled OR = 1.18 (95% CI = 0.85 to 1.63; I = 57%). Sensitivity analysis showed an OR = 1.40 (95% CI = 1.08 to 1.82; I = 0%), with a −0.07 MoM geometric mean difference. Metaregression identified primigravida status as negatively influencing beta-HCG levels. Elevated nuchal translucency values and CP presented a pooled OR = 1.06 (95% CI = 0.77 to 1.44; I = 0%).

Conclusion

Lower maternal pregnancy-associated plasma protein A levels during the first trimester and lower beta-HCG levels in the first and second trimesters are associated with CP development in children. Future research should validate the predictive utility of these biomarkers and explore novel ones through large-scale cohort studies.

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鉴定脑瘫的假定生物标志物：元分析和元回归

背景脑瘫（CP）是一种损害运动能力的神经系统疾病。识别母体生物标志物失常有助于进一步评估以进行早期诊断，从而改善临床预后。本研究调查了产前母体生物标志物失常与 CP 发育之间的关系。方法按照 MOOSE 指南在 MEDLINE、EMBASE 和 Cochrane 数据库中进行了系统检索。提取超过生物标志物阈值（第 95 个百分位数和第 5 个百分位数）的参与者数据，以估算合并几率比例。几何平均差异以中位数的倍数（MoMs）报告，用于分析标记物水平的变化。结果五项观察性研究（1552 例病例，484985 例对照）显示，较低的母体妊娠相关血浆蛋白 A 水平与 CP 相关（合计比值比 [OR] = 1.60，95% 置信区间 [CI] = 1.22 至 2.09；I = 0%），几何平均差异为-0.04MoM。妊娠头三个月和后三个月母体β-人绒毛膜促性腺激素（HCG）水平较低的汇总 OR = 1.18（95% CI = 0.85 至 1.63；I = 57%）。敏感性分析显示 OR = 1.40（95% CI = 1.08 至 1.82；I = 0%），几何平均差异为-0.07 MoM。元回归发现，初产妇状态对β-HCG水平有负面影响。结论妊娠头三个月母体相关血浆蛋白 A 水平较低以及妊娠头三个月和后三个月的β-HCG 水平较低与儿童的 CP 发育有关。未来的研究应验证这些生物标志物的预测效用，并通过大规模队列研究探索新的生物标志物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pediatric neurology 医学-临床神经学

CiteScore

4.80

自引率

2.60%

发文量

176

审稿时长

78 days

期刊介绍： Pediatric Neurology publishes timely peer-reviewed clinical and research articles covering all aspects of the developing nervous system. Pediatric Neurology features up-to-the-minute publication of the latest advances in the diagnosis, management, and treatment of pediatric neurologic disorders. The journal''s editor, E. Steve Roach, in conjunction with the team of Associate Editors, heads an internationally recognized editorial board, ensuring the most authoritative and extensive coverage of the field. Among the topics covered are: epilepsy, mitochondrial diseases, congenital malformations, chromosomopathies, peripheral neuropathies, perinatal and childhood stroke, cerebral palsy, as well as other diseases affecting the developing nervous system.