Clinical significance of plasma SERPINA3 in patients with missed miscarriage

Missed miscarriage is a frequent form of early pregnancy loss, yet its pathophysiology remains incompletely understood and sensitive blood-based biomarkers for detection of established missed miscarriage are limited.

In this single-center case-control study, we enrolled women with ultrasound-confirmed first-trimester missed miscarriage, women with viable intrauterine pregnancies undergoing elective induced abortion, and non-pregnant women of reproductive age. Circulating serine protease inhibitor A3 (SERPINA3) was quantified by ELISA. Routine hematological, biochemical, and coagulation parameters were collected. Associations with SERPINA3 were assessed using Spearman correlation and multivariable regression, and diagnostic performance was evaluated by receiver operating characteristic (ROC) analysis.

Circulating SERPINA3 differed significantly across the three groups (missed miscarriage, n = 91; normal pregnancy, n = 83; non-pregnant controls, n = 66; Kruskal-Wallis P < 0.001), with the highest levels in missed miscarriage, intermediate levels in the normal pregnancy group, and the lowest levels in non-pregnant controls. Compared with missed miscarriage, the normal pregnancy group showed higher systolic blood pressure (P = 0.022) and AST/ALT ratio (P = 0.001), but lower ALT and GGT levels (both P = 0.001), and eosinophil percentage and absolute eosinophil count also differed (P = 0.003 and P = 0.014). After adjustment for age, BMI, systolic blood pressure, ALT, GGT, and eosinophil count, SERPINA3 remained independently associated with pregnancy outcome (adjusted OR = 1.018, 95% CI: 1.010-1.025, P < 0.001).Within the missed miscarriage group, higher SERPINA3 (above median) was associated with higher lymphocyte counts (P = 0.042) and fibrinogen concentrations (P = 0.014) after adjustment for age and BMI. SERPINA3 correlated positively with GGT, white blood cell count, eosinophil indices, and lymphocyte count; GGT and eosinophil count remained independently associated with SERPINA3 in linear regression.SERPINA3 discriminated missed miscarriage from normal pregnancy controls with an AUC of 0.8751 (95% CI: 0.7641 to 0.9153, P < 0.0001), yielding 85.54% sensitivity and 72.53% specificity.

SERPINA3 is markedly elevated in missed miscarriage and serves as an indicator of established missed miscarriage, and its predictive value for future loss remains to be confirmed in prospective studies. Prospective multicenter validation and mechanistic studies are warranted.