During pregnancy, it particularly stands out as a peculiar physiological state, accompanied by substantial modifications in maternal hemostasis, immune functionality and cardiovascular adaption. One of the biochemical markers that have received huge attention during pregnancy is the D-dimer, which is a fibrin degradation product appearing in the general circulation culminating from activation of coagulation and fibrinolytic pathways [1]. Under usual physiological circumstances, the level of D-dimer in plasma is really low or absent, but with progress in pregnancy, D-dimer tends to increase further, marking the change in the hypercoagulable state brought about by gestation. Considered as a defense mechanism, this hypercoagulability reduces the chances of hemorrhaging during delivery but, in contrast, greatly elevates the risk of thromboembolic complications. Interpreting D-dimer values is considerably problematic during pregnancy, as the range of physiological elevation most often collides with that clinically observed in pathological states like deep venous thrombosis (DVT), pulmonary embolism (PE), or even some complications of pregnancy such as preeclampsia, intrauterine growth restriction, and preterm labor [2-5]. Upshot, interest in seeking trimester-specific reference values has picked pace while investigating whether high D-dimer values beyond the physiological range could possibly serve as early indicators of adverse maternal and fetal outcomes. It has been proven that levels of D-dimers approach a peak late in the third trimester, as evidenced by several authors. Early in pregnancy, values may remain within the non-pregnant reference range, but by the third trimester, levels very often exceed the pre-set cut-off value of 500 ng/mL, which is quite commonly used for ruling out venous thromboembolism (VTE) in the general population [6-8]. This could be the reason why the diagnostic utility of D-dimer testing in pregnancy has always been questioned, with some claiming that a positive test cannot reliably distinguish between a physiological increase and pathological thrombosis. It is indeed useful to track trends in D-dimer values over time, however and especially when this information is combined with clinical presentation such as chest pain, leg swelling, or immobility [9,10]. Another scope of application of D-dimer tests during pregnancy is beyond thromboembolic disorders. Recently, it has been proposed that abnormal D-dimer levels are indicative of placental dysfunction, endothelial injury and systemic inflammatory reactions. Elevated D-dimer levels are seen with preeclampsia and intrauterine growth restriction, both of which are characterized by impaired placental perfusion and microthrombi formation. Likewise, elevated D-dimer concentrations during early second trimester have been studied as predictors of spontaneous preterm labor that implicate ongoing vascular or inflammatory processes. Hence, D-dimer would be a marker for coagulation activation and a proxy for pregnancy complications. Deep venous thrombosis and pulmonary embolism remain among the leading causes of maternal morbidity and mortality worldwide. Pregnancy is associated with a five- to ten-fold increased risk of venous thromboembolism compared to non-pregnant women of the same age group [11]. This risk is further amplified in the presence of additional factors such as advanced maternal age, obesity, multiparity, multiple gestations, cesarean delivery, or inherited thrombophilias. Furthermore, documenting the trajectory of D-dimer values throughout pregnancy could improve understanding of the pathophysiological mechanisms linking hypercoagulability with adverse obstetric outcomes. The present study was conducted to evaluate D-dimer levels across different trimesters of pregnancy and to investigate their association with selected clinical symptoms and outcomes, including chest pain, left leg pain, preterm labor and the occurrence of DVT [12-14]. This work is particularly relevant in the Iraqi context, where pregnancy-related complications remain a significant cause of maternal morbidity. Establishing local data on the utility of D-dimer testing may support the development of guidelines that are better tailored to the needs of regional healthcare systems, ultimately contributing to improved maternal outcomes. The primary aim of this study is to assess maternal D-dimer levels across the three trimesters of pregnancy and evaluate their association with clinical symptoms and outcomes.

Patients and Methods

This prospective observational study was conducted among pregnant women attending private obstetric clinics in Kirkuk, Iraq. The study period extended from 1st of July 2024 to 31st of May 2025. Ethical approval was obtained from the Institutional Review Board and informed written consent was obtained from all participants prior to enrollment.

The study population consisted of 101 pregnant women who were evaluated clinically and biochemically during different stages of pregnancy. Only women with singleton viable pregnancies, confirmed by last menstrual period and/or early ultrasound, were included. All participants were recruited during their routine antenatal visits to private clinics within the study period. Women with multiple gestations, a previous history of thromboembolic disease, inherited thrombophilia, or those who were on anticoagulant therapy prior to enrollment were excluded. Similarly, patients with chronic systemic diseases such as renal failure, liver disease, autoimmune disorders, or malignancies were not considered eligible.

Demographic and clinical information was collected using structured interviews and medical record reviews. Data included maternal age, gravidity, parity and gestational age. Clinical symptoms such as chest pain, left leg pain or swelling, preterm labor and suspected deep venous thrombosis (DVT) were specifically assessed. Diagnosis of DVT was made clinically and confirmed by Doppler ultrasound when indicated.

Venous blood samples were obtained from each participant during the three trimesters of pregnancy. In the first trimester (≤13 weeks), the second trimester (14–27 weeks) and the third trimester (≥28 weeks until delivery), blood was drawn into citrated tubes, centrifuged and plasma was separated for laboratory testing. Maternal plasma D-dimer levels were measured using an Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit and results were expressed in nanograms per milliliter (ng/mL). Internal and external quality control measures were applied in accordance with the manufacturer’s guidelines to ensure the reliability of laboratory results.

All participants underwent thorough obstetric and systemic examination at each visit. The evaluation focused on identifying clinical features suggestive of thromboembolic events or obstetric complications. Chest pain and left leg pain were recorded as possible indicators of pulmonary embolism or lower limb venous thrombosis, respectively. Preterm labor was defined as regular uterine contractions associated with cervical changes occurring before 37 completed weeks of gestation. Cases with suspected DVT underwent further confirmation with Doppler ultrasound imaging.

The main outcome measures of the study were the mean maternal D-dimer concentrations across the three trimesters of pregnancy, the frequency of clinical symptoms and complications and the association between elevated D-dimer values and adverse maternal outcomes. A total of 101 pregnant women were included in the analysis, which was considered sufficient to detect meaningful differences in D-dimer concentrations across trimesters and between symptomatic and asymptomatic groups, at a 95% confidence level and 80% power.

Ethical considerations were strictly observed throughout the study. Informed consent was obtained from all women after explaining the objectives, benefits and procedures of the study. Participants were assured that their data would remain confidential and refusal to participate would not affect their medical care.

Data analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 26 (IBM Corp., Armonk, NY, USA). Continuous variables such as age and D-dimer concentrations were presented as mean±Standard Deviation (SD), while categorical variables such as clinical symptoms were expressed as numbers and percentages. Comparisons between groups were performed using the Student’s t-test or Mann–Whitney U test for continuous variables, depending on data distribution and the Chi-square test or Fisher’s exact test for categorical variables. One-way ANOVA was used to compare D-dimer concentrations across the three trimesters. A p-value less than 0.05 was considered statistically significant.

The study showed that the demographic profile of the participants revealed a mean maternal age of 28.84±5.91 years, with a median gravidity of 2 (range 1–7). Only one case (0.99%) represented a twin pregnancy, Table 1.

Table 1: Demographic Characteristics of the Study Population

The study showed that maternal D-dimer concentrations across trimesters demonstrated a clear progressive rise: 397.58±217.47 ng/mL in the first trimester, 611.32±233.94 ng/mL in the second and 1185.09±602.73 ng/mL in the third trimester. The difference was highly significant (ANOVA p <0.0001), Table 2.

Table 2: Maternal D-dimer Levels Across Pregnancy Trimesters

The study showed that the distribution of clinical symptoms was relatively low: chest pain in 1 case (0.99%), left leg pain in 3 cases (2.97%), preterm labor in 1 case (0.99%) and DVT in 1 case (0.99%), Table 3.

Table 3: Distribution of Clinical Symptoms

The study showed that women with chest pain had markedly elevated third-trimester D-dimer levels (3470.00 ng/mL) compared to asymptomatic women (1154.36±566.91 ng/mL), with a significant difference (p = 0.0002), Table 4.

Table 4: Comparison of D-dimer Levels Between Women with and Without Chest Pain

The study showed that left leg pain was associated with significantly higher third-trimester D-dimer concentrations (1620.00±700.00 ng/mL) compared with women without pain (1169.50±594.87 ng/mL, p = 0.0483), Table 5.

Table 5: Comparison of D-dimer Levels Between Women with and Without Left Leg Pain

The study showed that preterm labor was associated with dramatically higher third-trimester D-dimer levels (3470.00 ng/mL) compared to women without preterm labor (1177.40±589.99 ng/mL, p = 0.0002), Table 6.

Table 6: Comparison of D-dimer Levels Between Women with and Without Preterm Labor

The study showed that women diagnosed with DVT had significantly higher D-dimer values in all trimesters, especially in the first (1653.00 ng/mL vs 391.87±205.98 ng/mL, p = 0.0161) and second (1820.00 ng/mL vs 606.18±227.45 ng/mL, p = 0.0077) trimesters, Table 7.

Table 7: Comparison of D-dimer Levels Between Women with and Without DVT

The study showed a weak but significant positive correlation between gravidity and D-dimer, with Spearman’s r = 0.203 (p = 0.0425) in the first trimester and 0.255 (p = 0.0107) in the third trimester, Table 8.

Table 8: Correlation Between Gravidity and D-Dimer Levels

The study showed that logistic regression identified third-trimester D-dimer as a significant predictor of clinical symptoms (coefficient = 0.0027, p = 0.0010), while age, gravidity and twin pregnancy were not significant, Table 9.

Table 9: Logistic Regression Analysis for Predictors of Clinical Symptoms

The study showed that stratification of women by third-trimester D-dimer levels revealed a striking association: no symptoms were observed in the ≤500 ng/mL group, while 39 out of 46 (84.78%) in the>1000 ng/mL group developed symptoms. The association was highly significant (p <0.0001), Table 10.

Table 10: Maternal Outcomes by Third-trimester D-dimer Categories

Thus, the findings give the complete picture about gestational hypercoagulability and its clinical associations. The demographic profile of the cohort (Table 1) is typical of antenatal populations, with the mean maternal age being 28.84±5.91 years and median gravidity being 2. These demographic traits compare well with the regional studies showing late twenties as the most common age for childbearing and two as the average figure for parity [1,2]. The extremely low rate of twin pregnancy (only 0.99%) has prevented confounding from this high-risk subgroup, which has elsewhere been shown to independently increase thrombotic risk [3]. The primary physiological observation was of a highly statistically significant, progressive increase of D-dimer across the trimesters (397.58±217.47 to 611.32±233.94 to 1185.09±602.73 ng/mL; ANOVA p <0.0001; Table 2). This observation strongly agrees with the trimester-specific D-dimer increases reported in the literature [4-6]. For instance, Gutiérrez García et al. established reference intervals showing similar uptrends [4]. Xu et al. [5] and Dai et al. [6], were the prospective confirmers of these rises, emphasizing that D-dimer should always be interpreted using pregnancy-adjusted threshold levels. Despite the physiological elevation, D-dimer maintains its clinical value in diagnosis combined with pre-test probability. Systematic reviews and meta-analyses suggest that a negative D-dimer can safely rule out VTE in pregnant women when there is a low or intermediate clinical suspicion [7-9]. The significantly raised third-trimester D-dimer in symptomatic women found in this study lends support to this risk stratification model [10]. Clinical symptoms remained low in distribution in our cohort (Table 3), with chest pain being 0.99%, leg pain 2.97%, preterm labor 0.99% and DVT 0.99%. This could reflect the rather healthy setting of the private clinic studied or reflect a degree of under-detection on subclinical cases. Others have shown using systematic ultrasonography that asymptomatic DVT may be observed in a small percentage of pregnant women [11,12]. On the positive side, the symptom-specific analyses of our study provide some strong clinical associations. Women with chest pain in the third trimester had dramatically increased D-dimer levels (3470.00 vs 1154.36 ng/mL; p = 0.0002), consistent with the literature associating elevated D-dimer and pulmonary embolism [13,14]. Likewise, women with left leg pain recorded higher third-trimester D-dimer (1620.00 vs 1169.50 ng/mL; p = 0.0483), consistent with evidence that higher late-pregnancy D-dimer is associated with increased risk of DVT [15,16]. The link of preterm labor to elevated D-dimer (Table 6) echoes those that connect hypercoagulability with adverse obstetric outcomes. These studies determined abnormal D-dimer trajectories to be predictors of maternal complications, including hypertensive disorders and preterm birth [17–19]. While our small sample might not lead to any firm conclusions, biological plausibility favors consistency with these findings. Our result that DVT patients showed significantly higher D-dimer through all trimesters (Table 7) is consistent with reports that suggest late-pregnancy D-dimer cutoffs of 2.6–3.2 μg/mL may assist in diagnosis [20–22]. However, inter-assay and population variability implies that local validation is necessary [23]. We also found weak, though significant, correlations between gravidity and D-dimer in the first and third trimesters (Table 8). Some studies observed parity-induced coagulation changes whereas others reported only limited to inconsistent effects [24,25]. Therefore, these weak correlations could be explained by the confounding effect of factors such as BMI or comorbidities that we have not controlled for. Multivariate analysis revealed that third-trimester D-dimer stands as an independent predictor of clinical symptoms (coefficient = 0.0027, p = 0.0010; Table 9). This finding agrees with several studies pointing out third-trimester D-dimer as a predictor for thromboembolic complications and poor obstetric outcomes [26–28]. Nonetheless, as stated repeatedly in guidelines and meta-analyses, D-dimer should never be used as a stand-alone test, but should always be incorporated into structured diagnostic algorithms such as the pregnancy-adapted YEARS model [7,9,29]. Further to this, risk classification by D-dimer categories (Table 10) showed that>1000 ng/mL was strongly associated with clinical symptoms (84.78% vs none in ≤500 ng/mL). This finding is consistent with reports showing higher D-dimer thresholds in late pregnancy to be correlated with adverse maternal outcomes [20,27,30] However, the absence of consensus on absolute thresholds means our findings should be interpreted as strengthening the graded risk relationship, rather than as a hard cut-off.

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.

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