[Association between umbilical cord blood proteome and early infant neurodevelopmental risk]

To systematically investigate the associations between umbilical cord blood protein expression profiles and early infant neurodevelopment using a prospective birth cohort, to identify potential early biomarkers through high-throughput proteomics, and to explore underlying biological mechanisms, thereby providing scientific evidence for early identification of neurodevelopmental risks and understanding the molecular basis of neurodevelopmental deviations in general populations.

Based on the Peking University Birth Cohort in Tongzhou, this study enrolled 96 children who completed ages and stages questionnaires, third edition (ASQ-3) assessments at 1 and 3 years of age. Participants were classified into an abnormal group (n=42) and a control group (n=54) according to ASQ-3 screening results. Non-targeted quantitative proteomics was performed on cryopreserved umbilical cord blood plasma samples collected at birth. Differential expression analysis, principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA), and weighted gene co-expression network analysis (WGCNA) were conducted to identify differentially expressed proteins, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. The fold change (FC) was calculated. Independent samples t-test was used for statistical comparison, with Benjamini-Hochberg method applied to calculate false discovery rate (FDR) for multiple testing correction.

Proteomic analysis identified 8 214 common proteins, among which 385 proteins were differentially expressed (P < 0.05, |log₂FC| >0.585), including 189 proteins upregulated and 196 proteins downregulated in the abnormal group. PCA and OPLS-DA revealed systematic differences in protein expression patterns between the two groups. WGCN A identified 10 co-expression modules, with the yellow module showing significant negative correlation with ASQ-3 abnormal grouping (r=-0.233, P=0.024) and the pink module positively correlating with communication domain scores (r=0.342, P=0.003). Enrichment analyses demonstrated that differential proteins and key modules were primarily enriched in two functional categories: (1) genetic information processing pathways, including ribosome, spliceosome, and mRNA processing; and (2) cytoskeleton organization and Wnt signaling pathways. These pathways held significant biological relevance in the pathogenesis of neurodevelopmental disorders.

Perturbations in proteins associated with genetic information processing and cytoskeleton/Wnt signaling pathways in umbilical cord blood may represent important molecular characteristics of early neurodevelopmental screening abnormalities in infants. This study provides potential peripheral blood biomarker combinations for early identification of neurodevelopmental risks in general populations and offers novel insights into the biological mechanisms underlying neurodevelopmental deviations. Future research should validate these findings in larger-scale cohorts and elucidate specific functional mechanisms of key proteins through experimental studies.