The role of D-dimer changes in predicting delivery time in preterm premature rupture of membranes: a retrospective analysis

Archives of Gynecology and Obstetrics https://doi.org/10.1007/s00404-025-07940-9 MATERNAL-FETAL MEDICINE The role of D‑dimer changes in predicting delivery time in preterm premature rupture of membranes: a retrospective analysis Gizem Aktemur1 · Betül Tokgöz Çakır1 · Gülşan Karabay1 · Can Ozan Ulusoy1 Serap Topkara Sucu2 · Nazan Vanlı Tonyalı1 · Can Tekin İskender1 · Zeynep Seyhanlı1 · Received: 10 July 2024 / Accepted: 7 January 2025 © The Author(s) 2025 Abstract Introduction Pregnancy induces a hypercoagulable state, characterized by increased coagulation factors and decreased anticoagulants, alongside ongoing fibrinolysis marked by elevated D-dimer (DD) levels. Reference values for DD in pregnancy often exceed the non-pregnant cutoff due to these changes. Elevated DD levels are common in late pregnancy and may correlate with complications such as gestational diabetes, hypertension, and preterm delivery, particularly in cases of preterm premature rupture of membranes (PPROM). This study investigates the association between DD levels, the duration from PPROM diagnosis to delivery, and neonatal outcomes. Methods This retrospective study was conducted at the Department of Perinatology, Etlik City Hospital, Ankara, Turkey, from October 2022 to May 2023. Eighty patients with PPROM between 24 and 36 weeks of gestation were included. Routine blood tests and coagulation parameters, including DD, were monitored every other day for 2 weeks. Patients were classified into two subgroups based on whether labor occurred within 7 days of PPROM diagnosis. Statistical analyses included the Mann–Whitney U test, Student’s t test, Chi-square test, Friedman test, Durbin–Conover test, generalized estimating equations (GEE), and ROC analysis. Results Gestational age at admission was significantly lower in patients who delivered later than 7 days post-PPROM. Significant differences were observed in ultrasonographic measurements, with larger fetal parameters in the early delivery group. Higher DD levels at the third follow-up correlated with shorter durations to delivery (p = 0.021). Longitudinal analysis showed significant fluctuations in DD levels over time, particularly near delivery. The GEE analysis demonstrated a strong inverse relationship between DD levels and time to delivery (p = 0.004), supported by ROC analysis (AUROC = 0.811). Conclusions Elevated DD levels are associated with shorter durations from PPROM diagnosis to delivery, indicating their potential utility in predicting labor onset. Monitoring DD levels may help in clinical decision-making for managing PPROM, including planning neonatal care and timing of interventions. Keywords D-dimer (DD) · Hypercoagulable state · Prediction of labor onset · Preterm premature rupture of membranes (PPROM) * Gizem Aktemur Nazan Vanlı Tonyalı nazanvanlı@gmail.com Betül Tokgöz Çakır Can Tekin İskender Gülşan Karabay 1 Can Ozan Ulusoy Department of Obstetrics and Gynecology, Division of Perinatology, Ankara Etlik City Hospital, Ankara, Turkey 2 Department of Obstetrics and Gynecology , Ankara Etlik City Hospital , Ankara, Turkey Zeynep Seyhanlı Serap Topkara Sucu Vol.:(0123456789) Archives of Gynecology and Obstetrics Abbreviations PPROM Preterm premature rupture of membranes aPTT Activated partial thromboplastin time PT Prothrombin time TF Tissue factor TFPI Tissue factor pathway inhibitor TAT Thrombin anti thrombin DD D-dimer GDM Gestational diabetes GHT Gestational hypertension WBC White blood cell count ALT Alanine aminotransferase AST Aspartate aminotransferase CRP C-reactive protein BPD Biparietal diameter HC Head circumference AC Abdominal circumference FL Femur length EFW Estimated fetal weight MVP Maximum vertical pouch What does this study add to the clinical work D-dimer levels and labor onset: This study demonstrates a relationship between elevated D-dimer levels and the time to delivery in PPROM cases. Higher D-dimer levels at the third follow-up were significantly correlated with shorter durations from diagnosis to delivery, suggesting the potential of DD as a predictive marker for labor onset. Clinical Implications for PPROM management: Monitoring D-dimer levels in pregnant women with PPROM could enhance clinical decision-making by providing insights into the timing of delivery. This can aid in planning neonatal care and interventions, ultimately improving outcomes for both mothers and infants. Introduction Pregnancy is characterized by an increase in coagulation factors and a decrease in anticoagulants, which is widely recognized. This situation, characterized by reduced fibrinolysis, is in contrast to elevated levels of D-dimers (DD). Nevertheless, it is clear that fibrinolysis continues to be an ongoing process. [1, 2]. DD is the smallest part of fibrin degradation products [3]. The reference values for DD during pregnancy were derived from the reference values of healthy, nonpregnant adults. Nevertheless, because of the established knowledge of the rise in clotting factors during pregnancy, it is appropriate to regard the reference value above the usual cutoff of 0.5 mg/mL [4–6]. Multiple studies have consistently demonstrated that around 78% of pregnant women in the second trimester and close to 100% of pregnant women in the third trimester have elevated levels of DD compared to women in the first trimester [7, 8]. Research has indicated that gestational diabetes (GDM), gestational hypertension (GHT), preeclampsia, preterm delivery, and preterm premature rupture of membranes (PPROM) may be caused by alterations in the hemostatic system during pregnancy [9, 10]. Studies have shown that the increase in DD during pregnancy is significant, especially for GHT and GDM, and that it may be associated with pregnancy complications [11, 12]. Thrombin is believed to have a significant impact on the development of preterm delivery by initiating uterine contractions. Additionally, hypercoagulation may contribute to the development of PPROM [13]. Studies have demonstrated that DD serves not only as a marker for coagulation, but also as an indicator of inflammation and as a prognostic tool for significant disorders. Multiple investigations on COVID-19 patients have consistently demonstrated a correlation between elevated levels of DD and increased rates of both mortality and morbidity [14, 15]. Our study aimed to determine if there is an association between the duration from diagnosis to delivery, changes in DD, and other coagulation markers in individuals diagnosed with PPROM. We examined if there is a correlation between the variation in DD and the timing of birth. Materials and methods Study setting and approval This retrospective study was conducted at the Department of Perinatology, Etlik City Hospital in Ankara, Turkey, from October 2022 to May 2023. The study received approval from the hospital’s ethics committee and adhered to the universal standards outlined in the Declaration of (...truncated)