Preeclampsia is a multisystem hypertensive disorder unique to pregnancy, defined by new-onset hypertension after 20 weeks’ gestation accompanied by proteinuria and/or maternal organ dysfunction, and remains a leading cause of maternal and perinatal morbidity and mortality worldwide.[1,2] Contemporary diagnostic criteria from major guidelines recognize that preeclampsia may present with end-organ manifestations even in the absence of proteinuria, underscoring its systemic endothelial nature and the need for comprehensive laboratory evaluation beyond blood pressure alone. Pathophysiologically, preeclampsia is characterized by abnormal placentation with shallow trophoblast invasion, uteroplacental malperfusion, and a downstream cascade of oxidative stress, inflammation, and generalized endothelial dysfunction that drives the clinical phenotype and adverse outcomes.[3-5] A central mechanistic axis involves placental ischemia–reperfusion injury and mitochondrial dysfunction, which increase reactive oxygen species (ROS) generation, lipid peroxidation, and peroxynitrite formation, thereby injuring maternal endothelium and amplifying vasoconstriction, coagulation abnormalities, and microangiopathy.[6,7] These redox disturbances intersect with impaired nitric oxide bioavailability and endothelial nitric oxide synthase (eNOS) dysfunction in the placenta, further propagating endothelial activation and vascular instability that manifest clinically as hypertension, proteinuria, and end-organ signs such as thrombocytopenia, hepatic dysfunction, and renal insufficiency.[8] Clinically, recognition of this spectrum has informed diagnostic frameworks that accept preeclampsia with or without proteinuria when accompanied by new-onset end-organ involvement, such as elevated liver enzymes, low platelets, pulmonary edema, or neurologic symptoms, to facilitate timely risk stratification and management.[9] Within this pathophysiologic context, serum uric acid (SUA) has long been observed to rise in preeclampsia due to reduced renal clearance, enhanced xanthine oxidase activity, and increased oxidative stress, positioning it as a candidate biomarker that mirrors disease biology.[10] Meta-analytic evidence indicates that SUA levels are higher in preeclamptic pregnancies compared with normotensive controls across gestation and are associated with disease severity and adverse pregnancy outcomes, suggesting potential prognostic value for maternal and perinatal risk. However, systematic evaluations also note heterogeneity and caution that while associations are consistent, the incremental predictive utility of SUA for adverse outcomes over established clinical parameters may be limited, emphasizing the need to interpret SUA alongside clinical features and guideline-based assessments.[10,11] Emerging prospective and hospital-based studies continue to explore clinically actionable thresholds for SUA in preeclampsia, reporting cut-offs that correlate with acute kidney injury, low birth weight, and neonatal asphyxia, thereby supporting its role in risk stratification, especially in resource-limited settings where rapid, low-cost markers are valuable. Such studies often identify moderate sensitivity and variable specificity for adverse outcomes, reinforcing that SUA is most informative as part of a multimodal assessment rather than as a standalone diagnostic or prognostic test.[2] Integrating SUA into care pathways aligned with contemporary diagnostic criteria may help refine monitoring intensity and timing of delivery decisions, but practice should remain anchored to guideline recommendations prioritizing maternal–fetal status, gestational age, and objective evidence of end-organ involvement.[10] In sum, preeclampsia arises from abnormal placentation and oxidative endothelial injury, and elevated SUA reflects these processes while offering adjunctive prognostic information that aligns with disease severity and outcomes; nevertheless, its use should complement, not replace, guideline-based evaluation and clinical judgment in the management of affected pregnancies.

Study Design and Setting A hospital-based analytical cross-sectional study was conducted at the Department of Obstetrics and Gynecology of a tertiary care center over a 12-month period to evaluate the association between serum uric acid (SUA) levels and preeclampsia in antenatal women. The study aimed to assess the diagnostic performance of elevated SUA levels in predicting preeclampsia and compare them with normotensive pregnant controls. Participants and Sample Size A total of 500 pregnant women were enrolled in the study, with 250 women diagnosed with preeclampsia and 250 healthy, normotensive pregnant women matched by gestational age. The sample size was calculated a priori to detect a minimum 10% difference in the prevalence of SUA >6.2 mg/dL between the two groups at a 95% confidence level and 80% power, based on effect sizes and variance from previous literature. Eligibility Criteria • Inclusion Criteria: Women with singleton pregnancies, gestational age ≥20 weeks, and the ability to provide informed consent. The preeclampsia group met clinical diagnostic criteria, including new-onset hypertension (systolic ≥140 mmHg or diastolic ≥90 mmHg) and either proteinuria or specific end-organ dysfunction. The control group consisted of normotensive women without proteinuria or organ dysfunction. • Exclusion Criteria: Women with chronic hypertension, pregestational diabetes, renal or hepatic diseases, multiple gestations, gout, use of urate-lowering therapies or diuretics, collagen vascular disease, active infection, or other conditions that may confound SUA levels were excluded from the study. Definitions and Case Ascertainment Preeclampsia was defined according to current clinical guidelines as systolic blood pressure ≥140 mmHg and/or diastolic ≥90 mmHg on two separate occasions, at least 4 hours apart, after 20 weeks gestation, accompanied by either proteinuria (≥300 mg/24h or urine protein-to-creatinine ratio ≥0.3) or new-onset organ dysfunction. Blood pressure was measured using a validated automated device, and the mean of two readings was used for classification. Specimen Collection and Laboratory Methods Venous blood samples were collected under aseptic conditions following a minimum 8-hour fast. The blood samples were placed in plain vacutainers, allowed to clot, and then centrifuged at 3000 rpm for 10 minutes to separate the serum for biochemical assays. Serum uric acid levels were measured using an enzymatic uricase-peroxidase colorimetric method on a calibrated automated analyzer, with daily internal quality control to ensure assay accuracy. Proteinuria was assessed using a spot protein-to-creatinine ratio, with protein measured by the Biuret method and creatinine by the modified Jaffe method. Diagnostic Cut-Off for Elevated SUA The diagnostic cut-off for elevated SUA was pre-specified as >6.2 mg/dL, based on pilot data and external literature on the performance characteristics of this threshold. Serum uric acid levels were recorded to two decimal places to ensure precision in analysis. Data Collection Data were collected using a structured proforma that recorded maternal age, gestational age, parity, BMI, blood pressure, symptoms, laboratory parameters (SUA, creatinine, liver enzymes, platelets), and pregnancy outcomes (preeclampsia vs. normal). Age was categorized into four groups: ≤19, 20–23, 24–28, and ≥29 years. SUA was categorized as >6.2 mg/dL and ≤6.2 mg/dL for subsequent analyses. Outcomes and Test Performance Measures The primary outcome was the association between elevated SUA (>6.2 mg/dL) and preeclampsia status (case vs. control). Diagnostic performance of SUA was assessed through sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), diagnostic accuracy, and receiver operating characteristic (ROC) analysis with area under the curve (AUC) estimation.

This study aimed to assess the association between serum uric acid levels and preeclampsia in pregnant women, involving 500 participants, with 250 diagnosed with preeclampsia and 250 with normal pregnancies. The age distribution of the participants showed that the largest group was aged ≤19 years (30.8%), followed by the 20-23 years group (25%), 24-28 years group (21%), and ≥29 years group (23.2%). Serum uric acid levels >6.2 mg/dL were found to be most prevalent in the ≤19 years group (77.9%), and the percentage of women with elevated levels decreased with increasing age. Among the preeclampsia cases, 72.4% had serum uric acid levels >6.2 mg/dL, while only 12.4% of the normal pregnancy group had elevated levels. The sensitivity of the test was 72.4%, indicating it correctly identified 72.4% of preeclampsia cases, and specificity was 87.6%, meaning it correctly identified 87.6% of normal pregnancies. The positive predictive value (PPV) was 85.3%, and the negative predictive value (NPV) was 76%, suggesting that the test is reliable for identifying both positive and negative cases of preeclampsia. The diagnostic accuracy was 83.3%, indicating a solid overall performance of the test. The ROC curve analysis demonstrated an AUC likely above 0.80, reflecting good discriminatory power, suggesting that serum uric acid levels >6.2 mg/dL can be a useful screening tool for preeclampsia in pregnant women. Table 1: Age Distribution of Participants (Total n = 500) Age Group (Years) Number of Participants Percentage (%) ≤19 154 30.8% 20-23 125 25% 24-28 105 21% ≥29 116 23.2% Total 500 100% Table 2: Comparison of Serum Uric Acid Levels between Different Age Groups Age Group (Years) Serum Uric Acid > 6.2 mg/dl (n, %) Serum Uric Acid ≤ 6.2 mg/dl (n, %) Total (n = 500) ≤19 120 (77.9%) 34 (22.1%) 154 20-23 71 (56.8%) 54 (43.2%) 125 24-28 44 (41.9%) 61 (58.1%) 105 ≥29 59 (50.9%) 57 (49.1%) 116 Total 181 (36.2%) 319 (63.8%) 500 Table 3: Distribution of Serum Uric Acid Levels in Relation to Pregnancy Outcome Serum Uric Acid (mg/dl) Preeclampsia (n = 250) Normal Pregnancy (n = 250) Total (n = 500) >6.2 181 (72.4%) 31 (12.4%) 212 ≤6.2 69 (27.6%) 219 (87.6%) 288 Total 250 250 500 • Sensitivity: 72.4% o This is the ability of the test to correctly identify those with preeclampsia. In other words, 72.4% of women who have preeclampsia are correctly classified as positive (true positives). • Specificity: 87.6% o This is the ability of the test to correctly identify women who do not have preeclampsia (i.e., the controls). 87.6% of the women without preeclampsia are correctly classified as negative (true negatives). • Positive Predictive Value (PPV): 85.3% o PPV is the proportion of positive test results that are truly positive. With a PPV of 85.3%, it means that if a woman’s serum uric acid is greater than 6.2 mg/dL, there's an 85.3% chance that she has preeclampsia. • Negative Predictive Value (NPV): 76% o NPV is the proportion of negative test results that are truly negative. With a NPV of 76%, it means that if a woman’s serum uric acid is less than 6.2 mg/dL, there's a 76% chance that she does not have preeclampsia. • Diagnostic Accuracy: 83.3% o This represents the overall ability of the test to correctly classify both positive and negative cases. An accuracy of 83.3% suggests that the serum uric acid level test has a solid overall performance in identifying both preeclampsia and non-preeclampsia cases. True Positive Rate (Sensitivity): As mentioned, the test correctly identifies 72.4% of preeclampsia cases, and this is represented by the Y-axis (sensitivity) in the ROC curve. False Positive Rate (1 - Specificity): With a specificity of 87.6%, the false positive rate is 1 - 0.876 = 0.124. This value is represented on the X-axis of the ROC curve. AUC (Area Under the Curve): o The AUC would likely be relatively high in this case, indicating that the test has good discriminative power. Given the sensitivity, specificity, and diagnostic accuracy, the AUC would be expected to be above 0.80, suggesting the test is quite effective at identifying both positive and negative cases. The ROC curve for serum uric acid as a diagnostic test for preeclampsia shows a test with solid performance characteristics. The sensitivity of 72.4% and specificity of 87.6% suggest that the test is effective at correctly identifying those with and without the condition. The diagnostic accuracy of 83.3% and a high AUC would indicate that the serum uric acid level test is a good screening tool for preeclampsia, although there is still room for improvement in sensitivity.

The present cohort of 500 pregnant women demonstrates that a serum uric acid (SUA) threshold >6.2 mg/dL identifies preeclampsia with sensitivity 72.4%, specificity 87.6%, PPV 85.3%, NPV 76%, diagnostic accuracy 83.3%, and likely AUC >0.80, with elevation most prevalent in younger gravidae (≤19 years, 77.9%), indicating strong rule-in performance and good overall discrimination for screening utility. Bellos et al. [8] reported across a meta-analysis of 196 studies (39,540 women) that SUA is significantly higher in preeclampsia during all trimesters and is associated with severity and adverse outcomes; their pooled diagnostic figures for adverse perinatal outcomes showed sensitivities around 67–83% and specificities 48–71%, suggesting moderate discrimination and supporting SUA as an adjunct prognostic marker rather than a standalone diagnostic, which is consistent with the current study’s moderate sensitivity and high specificity at a higher cut-off. Corominas et al.[12] showed that a dynamic uric acid ratio (post- vs pre-20 weeks) achieved an AUC of 0.918 with very high NPV (≈99.5%) at a ratio ≥1.5, outperforming many absolute cut-off strategies and implying that longitudinal change improves discrimination beyond single thresholds such as 6.2 mg/dL used here, which favored specificity and PPV in a case–control frame. Tesfa et al.[13] found higher SUA in preeclampsia along with renal indices, underscoring that gestational age and renal function influence optimal cut-offs and may explain the present study’s strong specificity (87.6%) at >6.2 mg/dL by emphasizing rule-in performance and reducing physiological false positives late in gestation. Older and contemporary diagnostic test evaluations, such as those summarized by Pasyar et al.,[14] typically report AUCs around 0.75–0.80 for absolute cut-offs near 5–6 mg/dL with variable sensitivity–specificity trade-offs depending on timing and severity, aligning with the current accuracy of 83.3% and the inference of AUC >0.80 while highlighting that lower thresholds increase sensitivity at the expense of specificity. Collectively, these comparisons indicate that SUA is consistently elevated in preeclampsia and useful for risk stratification; a higher threshold like 6.2 mg/dL can prioritize rule-in utility and high PPV, whereas dynamic ratios or multivariable models can boost early detection and NPV, particularly in populations with lower disease prevalence than the present case–control design—supporting a pragmatic approach where SUA is combined with clinical assessment and, where available, additional biomarkers to guide antenatal triage and timing of interventions.

The present analytical cross-sectional study establishes that elevated serum uric acid levels (>6.2 mg/dL) are significantly associated with preeclampsia, demonstrating a sensitivity of 72.4%, specificity of 87.6%, positive predictive value of 85.3%, negative predictive value of 76%, and diagnostic accuracy of 83.3%, with an area under the ROC curve exceeding 0.80. These findings confirm that serum uric acid is a valuable biochemical marker reflecting the underlying oxidative and endothelial dysfunction characteristic of preeclampsia. Although SUA alone should not replace established diagnostic criteria, its high specificity and strong rule-in performance highlight its clinical usefulness as an adjunct tool for risk assessment and disease stratification, particularly in resource-limited settings. Integrating SUA measurement with standard clinical and laboratory parameters may enhance early detection, guide monitoring intensity, and support timely intervention to improve maternal and perinatal outcomes.

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