Wharton’s jelly (WJ), the mucoid connective tissue of the umbilical cord, provides essential protection to the umbilical vessels against mechanical stress. While research into WJ-derived stem cells for regenerative medicine has surged, the clinical significance of its in utero pathologies remains less explored. This review synthesizes the current literature on the pathophysiology of WJ abnormalities and their direct impact on fetal and neonatal outcomes. Pathologies are broadly categorized as quantitative (absence/reduction or excess/edema) and structural (pseudocysts, mucoid degeneration). A reduction or segmental absence of WJ critically compromises cord integrity, leading to vascular compression and is a direct cause of stillbirth, fetal growth restriction (FGR), and intrapartum distress. Conversely, excessive WJ or edema is associated with maternal diabetes and fetal hydrops and can also impair hemodynamics. Umbilical cord pseudocysts, arising from focal WJ degeneration, are significant markers for severe chromosomal abnormalities, particularly Trisomy 18 and 13, and other structural defects, especially when persistent or multiple. Sonographic measurement of WJ area shows promise as a surrogate for placental function, with decreased area correlating with placental pathology and FGR. However, significant diagnostic challenges persist, particularly the prenatal detection of segmental WJ absence, a “silent” pathology often discovered only after a catastrophic event. This review highlights the critical role of WJ integrity in determining perinatal outcomes and underscores the urgent need for improved diagnostic modalities and standardized management protocols to mitigate associated risks.
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