Hemogram-Derived Inflammatory and Oxidative Stress-Related Indices in Second-Trimester Pregnancy Loss

Abstract

OBJECTIVES: To investigate hemogram-derived inflammatory indices in women with spontaneous second-trimester pregnancy loss and to compare these parameters with those of the women who achieved term delivery.

STUDY DESIGN: This retrospective case–control study included women aged 18–35 years. There were two groups: women who experienced spontaneous second-trimester pregnancy loss between 14+0 and 23+6 gestational weeks (Group A), and women who achieved term delivery (≥37 weeks) (Group B). We excluded pregnancies terminated for medical or fetal indications, multiple gestations, chronic systemic or blood (hematological) diseases, active infection, and pregnancy complications. Complete blood count (CBC) parameters, which are laboratory measurements of different types of blood cells—such as white blood cells (WBCs), red blood cells, and platelets—were obtained during the second trimester. We calculated hemogram-derived indices, including the neutrophil-to-lymphocyte ratio (NLR, the ratio of neutrophils to lymphocytes) and the systemic immune-inflammation index (SII, calculated as platelet count multiplied by neutrophil count, then divided by lymphocyte count). Multivariable logistic regression models—statistical analyses that account for several influencing factors at once—were adjusted for maternal age, parity (number of previous pregnancies), previous abortion history, and gestational age at sampling. An additional adjustment for total white blood cell (WBC) count was done in hierarchical analyses. Receiver operating characteristic (ROC) curve analysis, a statistical method to evaluate how well a test distinguishes between groups, was performed to assess discriminative performance.

RESULTS: A total of 439 women were included—218 with spontaneous second-trimester pregnancy loss and 221 with term delivery. Women in the pregnancy loss group were older and more often had a history of previous abortion (p<0.001). White blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) values were significantly higher in the pregnancy loss group (all p<0.001). In a multivariable analysis adjusted for maternal age, parity (number of pregnancies), previous abortion history, and gestational age at sampling, both NLR and SII were significantly associated with second-trimester pregnancy loss. However, after additional adjustment for total WBC, these associations were reduced (attenuated). ROC (receiver operating characteristic) curve analysis, which assesses how well a test differentiates between groups, showed limited discriminative performance with area under the curve (AUC) values ranging from 0.61 to 0.63. SII had the highest AUC.

CONCLUSION: Hemogram-derived inflammatory indices, particularly NLR and SII, are elevated in women with spontaneous second-trimester pregnancy loss. These indices are associated with this outcome after adjustment for key clinical factors. However, their discriminative performance is modest. These parameters are readily available. They should be considered adjunctive markers rather than standalone predictive tools in this clinically heterogeneous setting.