Zheng, M.; Su, Y.; Bao, Y.; Sun, W.; Gao, Y.

This study employed a "one-versus-many" (a single pregnant woman compared with multiple non-pregnant women) urinary proteomic comparative framework to examine whether fetal development-related signals can be captured through changes in the urinary proteome under conditions of limited sample size. The experimental group consisted of urinary proteomic data from three women with normal pregnancies (R6, R15, R16) at three gestational time points (~6-8 weeks, 22-24 weeks, and 32-34 weeks; Wang et al., 2022), while the control group consisted of urinary proteomic data from six healthy non-pregnant women (Bao & Gao, ChinaXiv: 202302.00108v2). A total of nine independent "1 vs. 6" differential protein analyses and DAVID GO Biological Process enrichment analyses (P < 0.05) were performed. The results showed that all three pregnant women exhibited a large number of differentially expressed proteins at each time point, and all enriched GO BP terms highly relevant to concurrent fetal organ development (nervous system, lung, eye, ear, kidney, etc.). This suggests that the pregnancy urinary proteome can reflect fetal development signals, corroborating the findings reported by Wang et al. (2025) in a rat model. This study demonstrates that the one-versus-many comparative approach maintains high sensitivity under small-sample conditions and can provide a methodological reference for personalized pregnancy medicine.