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

Abstract

BackgroundCerebral 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. MethodologyA 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 MoMs, were used to analyze changes in marker levels. Trimester-wise subgroup analysis and meta-regression assessed the impact of variables on outcomes. ResultsFive observational studies (1,552 cases, 484,985 controls) revealed lower maternal PAPP-A levels were associated with CP (pooled OR = 1.60, 95% CI = 1.22-2.09; I = 0%), with a -0.04 MoM geometric mean difference. Lower maternal beta-HCG levels in 1st and 2nd trimesters indicated a pooled OR = 1.18 (95% CI = 0.85-1.63; I=57%). Sensitivity analysis showed an OR = 1.40 (95% CI = 1.08-1.82; I=0%), with a -0.07 MoM geometric mean difference. Meta-regression identified primigravida status as negatively influencing beta-HCG levels. Elevated nuchal translucency values and CP presented a pooled OR = 1.06 (95% CI = 0.77-1.44; I = 0%). ConclusionLower maternal PAPP-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.