Glycosylated Fibronectin in Fetal Growth Restriction: An Emerging Biomarker of Placental Dysfunction.

Fetal growth restriction (FGR) is a major placenta-mediated pregnancy complication associated with perinatal morbidity, stillbirth, neonatal complications, and long-term cardiometabolic and neurodevelopmental consequences. Its diagnosis remains challenging because fetal smallness alone cannot reliably distinguish constitutionally small fetuses from pathological growth restriction caused by placental insufficiency. Glycosylated fibronectin (GlyFn), a modified extracellular matrix glycoprotein involved in cell adhesion, angiogenesis, endothelial function, and tissue remodeling, has emerged as a promising biomarker of placenta-mediated disease. This review summarizes the biological rationale and current evidence regarding GlyFn in FGR, with emphasis on placental dysfunction, trophoblast invasion, spiral artery remodeling, oxidative stress, endothelial activation, altered angiogenic signaling, and extracellular matrix remodeling. Current data suggest that GlyFn is most consistently associated with preeclampsia, where elevated maternal serum levels have shown diagnostic and prognostic potential. However, direct evidence supporting GlyFn as an independent biomarker of isolated FGR remains limited. Most available findings are derived from preeclampsia cohorts or studies of broader adverse pregnancy outcomes, making it unclear whether GlyFn reflects FGR itself, preeclampsia-related endothelial injury, or general placental stress. GlyFn may be particularly relevant in early-onset placental FGR, where severe malperfusion and endothelial dysfunction are prominent. Its greatest future value may lie in multimarker models combining GlyFn with placental growth factor, soluble fms-like tyrosine kinase-1/placental growth factor ratio, fetal biometry, Doppler indices, and placental histopathology. Prospective longitudinal studies using standardized FGR definitions are required before GlyFn can be translated into clinical practice.