Markers of collagen metabolism during pregnancy with undifferentiated connective tissue dysplasia

Aim: to assess the features of collagen metabolism and extracellular matrix markers, namely hydroxyproline, sulfated glycosaminoglycans, and MMP-9, in pregnant women with undifferentiated connective tissue dysplasia and to analyze their relationship with clinical manifestations of the dysplastic phenotype and pregnancy course. Materials and methods. A prospective single-center cohort study included 175 pregnant women with singleton pregnancy. The main group consisted of 92 pregnant women with clinical signs of undifferentiated connective tissue dysplasia, and the control group included 83 women without signs of a dysplastic phenotype. Serum levels of hydroxyproline, sulfated glycosaminoglycans, MMP-9, magnesium, and total calcium were measured at 16-18 and 30–32 weeks of gestation; cervical length was assessed by ultrasound cervicometry at 18–22 weeks. Results. Pregnant women with undifferentiated connective tissue dysplasia demonstrated higher levels of hydroxyproline, sulfated glycosaminoglycans, and MMP-9 than controls, with the most pronounced differences observed at 30–32 weeks of gestation: hydroxyproline was 22.7±4.8 μmol/L versus 18.9±4.3 μmol/L, sulfated glycosaminoglycans were 15.8±3.1 μg/mL versus 13.7±2.8 μg/mL, and MMP-9 was 349 [298; 403] ng/mL versus 291 [249; 345] ng/mL. Positive correlations were found between these markers and the severity of phenotypic signs of connective tissue dysplasia, while inverse correlations were observed with cervical length. Complicated pregnancy occurred more often in the main group than in the control group (41.3% vs 21.7%). Independent predictors of adverse pregnancy course were MMP-9 above 340 ng/mL (OR 2.74; 95% CI 1.37–5.49), cervical length below 32 mm (OR 3.11; 95% CI 1.49–6.47), and the presence of undifferentiated connective tissue dysplasia itself (OR 1.98; 95% CI 1.01–3.91). Conclusions. Pregnant women with undifferentiated connective tissue dysplasia exhibit more intensive collagen degradation and extracellular matrix remodeling than women without a dysplastic phenotype. MMP-9, combined with cervical assessment and clinical phenotyping, showed the greatest clinical and prognostic value. Integrated evaluation of these indicators may be useful for early obstetric risk stratification.

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