Differential expression of ADAM10 in fetal membranes during pregnancy and evaluation as an early blood biomarker for preterm birth.

Spontaneous preterm birth (SPTB) includes two distinct presentations: preterm labor with intact membranes (PTL-IM) and preterm premature rupture of membranes (PPROM), both associated with inflammation. In prior work, we identified first-trimester serum CX3CL1, a membrane-bound chemokine cleaved by the metalloprotease ADAM10, as an independent predictive blood biomarker for PPROM. The present study aimed to characterize the expression of ADAM10 and CX3CL1 in fetal membranes and maternal serum across gestation, and to assess serum ADAM10 as a potential predictive biomarker for SPTB. mRNA and protein expression of CX3CL1 and ADAM10 was assessed in 26 fetal membranes (amnion and choriodecidua). Serum ADAM10 was measured in a prospective cohort of 438 pregnant women with samples collected in the first trimester, second trimester and delivery. CX3CL1 expression increased in the choriodecidua during the second trimester and declined at term. ADAM10 mRNA remained stable in the amnion, while protein levels peaked in the choriodecidua in the second trimester and at term. Serum ADAM10 showed a similar pattern, with significantly higher levels in second-trimester PTL-IM cases versus term deliveries. Second trimester serum ADAM10 significantly enhanced the predictive ability of maternal risk factors for PTL-IM. Area under the ROC curve was 0.73 (95 % confidence interval: 0.65-0.81). This model identified cases with a 72 % (59 %-82 %) sensitivity and a 64 % (55 %-72 %) specificity. ADAM10 and CX3CL1 are expressed in the fetal-maternal interface, and their soluble forms measured in blood may help in the early identification of SPTB.