Abstract
Pregnancy involves complex maternal–fetal adaptations largely driven by placental function. Placental disorders affect up to 15% of pregnancies and can lead to serious complications such as preeclampsia, underscoring the need for early, accessible diagnostic tools. This study used LC-MS/MS proteomics to characterize longitudinal urinary proteome changes during pregnancy, evaluating urine as a non-invasive monitoring medium. Urine samples from 87 healthy pregnancies, collected at three gestational time points, revealed dynamic proteomic changes linked to immune regulation, coagulation, tissue remodeling, and metabolic processes. Several placental proteins were detected in urine with temporal variation consistent with gestational progression. As proof of concept, comparison with preeclamptic pregnancies identified distinct urinary proteomic signatures, with dysregulated proteins detectable as early as the first trimester. These findings support urinary proteomics as a scalable, non-invasive approach for pregnancy monitoring and early detection of obstetrical complications.