Evaluation of Inflammatory Markers, First‐Trimester Biochemical Tests, and Gelsolin Levels in Patients With Second‐Trimester Pregnancy Loss

OBJECTIVE: The pathophysiological mechanisms underlying second trimester pregnancy loss are not yet fully elucidated. This study aimed to evaluate whether maternal serum gelsolin levels, together with hematological inflammatory indices and pregnancy related hormones, are associated with second trimester pregnancy loss. METHODS: A total of 912 pregnant women were prospectively enrolled, and a nested matched case-control analysis was subsequently conducted including 112 participants (40 cases and 72 matched controls). The study was conducted at Ankara Etlik City Hospital between January and December 2024. The pregnancy loss group comprised 40 women who experienced second-trimester pregnancy loss, whereas the control group included 72 age- and body mass index-matched women with ongoing pregnancies. Maternal inflammatory markers-including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and aggregate index of systemic inflammation (AISI)-were evaluated. In addition, serum levels of human chorionic gonadotropin (hCG), pregnancy-associated plasma protein-A (PAPP-A), and gelsolin were measured and compared between groups. RESULTS: Most hematological inflammatory indices, including NLR, PLR, MLR, SII, SIRI, and AISI, did not differ significantly between the groups. However, maternal serum PAPP-A levels were significantly lower in the pregnancy loss group (p = 0.012), whereas gelsolin levels were significantly higher (p = 0.034). Receiver operating characteristic (ROC) analysis demonstrated limited discriminatory performance for both markers. PAPP-A MoM showed an AUC of 0.644 (95% CI: 0.533-0.755, p = 0.012), with a cut-off value of <0.46 yielding a sensitivity of 77.5% and specificity of 91.7%. Despite its high specificity at the selected cut-off, overall discriminatory performance was limited. Gelsolin exhibited modest diagnostic performance with an AUC of 0.621 (95% CI: 0.501-0.741, p = 0.034), with a sensitivity of 57.5% and specificity of 44% at a threshold of >0.893 ng/mL. CONCLUSION: Maternal serum gelsolin levels were elevated and PAPP-A levels were reduced in pregnancies affected by second-trimester pregnancy loss. While gelsolin remained independently associated with pregnancy loss after adjustment, neither marker demonstrated sufficient discriminatory performance to be used as a standalone predictive tool. These findings may reflect underlying placental dysfunction and inflammatory dysregulation rather than overt systemic inflammation, and should be considered hypothesis-generating pending validation in larger prospective studies.