Serum Decorin and Biglycan as Potential Biomarkers to Predict PPROM in Early Gestation

Abstract

Preterm birth is a leading cause of neonatal mortality in the US and globally, with preterm premature rupture of fetal membranes (PPROM) accounting for one third of preterm births. Currently no predictive diagnostics are available to precisely assess risk and potentially reduce the incidence of PPROM. Bigycan and decorin, the main proteoglycans present in human fetal membranes, are involved in the physiological maturation of fetal membranes as well as in the pathophysiology of preterm birth. The serum protein sex hormone-binding globulin (SHBG) has recently been identified as a predictor of spontaneous preterm birth. We hypothesize that the balance between serum decorin and biglycan on one hand and SHBG on the other hand may provide insight into the status of the fetal membranes in early pregnancy, thereby predicting PPROM prior to symptoms. Using chart review, 18 patients with confirmed cases of PPROM were identified from 2013-2016. Second trimester residual serum was retreived from freezer storage for these cases along with 5 matched controls for each case. The biomarkers biglycan, decorin and SHBG were analyzed first separately, then in combination to determine their ability to predict PPROM. The predictive score for the combined model displays an AUC ¼ 0.774. The ROC curve of the predicted score has an optimal threshold of 0.238 and a sensitivity and specificity of 0.72 and 0.84 respectively. This prenatal serum panel is a promising serum screening-based biochemical model to predict PPROM in asymptomatic women.

Roles of Two Small Leucine-Rich Proteoglycans Decorin and Biglycan in Pregnancy and Pregnancy-Associated Diseases

“…Through complex interactions involving TLR2/4 and NADPH oxidases (NOX), BGN influenced the synthesis and maturation of IL-1β [ 144 ]. The proinflammatory role of BGN deserves investigation, when considering the impact of inflammation in pregnancy [ 133 , 145 ].…”

“…While serum DCN levels alone could predict PTB before 37th gestational week among preterm labor patients, a combined measurement with cervical length was required to predict PTB within 7 days and before the 34th gestational week [ 161 ]. PPROM was associated with lower DCN serum levels appearing in the second trimester [ 145 ] and a decline in p-Smad-2 [ 134 ]. As a possible cause of PPROM [ 68 , 162 , 163 ], chorioamnionitis was linked to substantial DCN degradation in the amnion [ 160 ].…”

“…Patients diagnosed with PPROM displayed heightened BGN serum levels during the second trimester, which may represent an immune response to early tissue damage in the fetal membranes [ 145 ]. Chorioamnionitis was associated with substantial degradation of BGN, which may account for diminished strength of preterm fetal membranes [ 160 ].…”

Current and Emerging Strategies for Prediction and Diagnosis of Prelabour Rupture of the Membranes: A Narrative Review

“…Underhill et al ( 93 ) recently described a serum panel comprising two proteoglycans, i.e. biglycan and decorin, together with serum protein sex hormone-binding globulin (SHBG) as a promising second-trimester prenatal serum screening-based biochemical model with an ability to predict pPROM in asymptomatic women.…”

“…biglycan and decorin, together with serum protein sex hormone-binding globulin (SHBG) as a promising second-trimester prenatal serum screening-based biochemical model with an ability to predict pPROM in asymptomatic women. They found that the increased serum concentrations of biglycan in conjunction with decreased serum concentrations of decorin and SHBG in the second trimester were observed in asymptomatic patients who developed pPROM later on ( 93 ). However, more scientific research is required to target effective screening strategies for PROM at term and preterm.…”