Association of Maternal D-Dimer Levels Across Pregnancy Trimesters with Clinical Symptoms and Thromboembolic Events
Background: Pregnancy is associated with profound physiological changes in the coagulation system, reflected by a progressive rise in plasma D-dimer concentrations. Although this elevation complicates the diagnostic use of D-dimer for venous thromboembolism (VTE), its trimester-specific dynamics and potential associations with maternal symptoms and outcomes remain clinically relevant. Materials and Methods: A cross-sectional observational study was conducted on pregnant women attending private clinics in Kirkuk, Iraq, between July 1, 2024 and May 31, 2025. Maternal age, gravidity and type of pregnancy were recorded, alongside D-dimer levels measured during the first, second and third trimesters. Clinical symptoms including chest pain, leg pain, preterm labor and confirmed deep vein thrombosis (DVT) were documented. Statistical analyses included ANOVA, t-tests, correlation and logistic regression to evaluate associations between D-dimer levels and maternal outcomes. Results: The mean maternal age was 28.84±5.91 years, with a median gravidity of 2 (range 1–7) and only one case (0.99%) of twin pregnancy. D-dimer levels increased significantly across trimesters (397.58±217.47 ng/mL in the first, 611.32±233.94 ng/mL in the second and 1185.09±602.73 ng/mL in the third; ANOVA p <0.0001). Clinical symptoms were uncommon: chest pain in 0.99%, left leg pain in 2.97%, preterm labor in 0.99% and DVT in 0.99%. Women with chest pain, leg pain, preterm labor, or DVT had significantly higher third-trimester D-dimer levels (p <0.05 for all comparisons). Logistic regression identified third-trimester D-dimer as an independent predictor of clinical symptoms (coefficient = 0.0027, p = 0.0010). Stratification showed that 84.78% of women with D-dimer>1000 ng/mL developed symptoms compared to none in those ≤500 ng/mL (p <0.0001). Conclusion: This study confirms the physiological rise of D-dimer throughout pregnancy and demonstrates strong associations between elevated third-trimester levels and maternal symptoms, including DVT and preterm labor. While trimester-specific thresholds improve interpretation, elevated D-dimer remains a useful adjunctive marker when combined with clinical assessment. The findings highlight the need for locally validated reference intervals to enhance diagnostic accuracy and risk stratification in pregnant women.