Preeclampsia remains one of the most significant obstetric complications worldwide, affecting 2-8% of all pregnancies and contributing to substantial maternal and fetal morbidity and mortality.[1]This hypertensive disorder, characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, is responsible for approximately 46,000 maternal deaths annually and around 500,000 fetal or newborn deaths globally. In developing countries, preeclampsia and eclampsia account for approximately 10% of maternal deaths in Asia and Africa, and up to 25% in Latin America.[2] The pathophysiology of preeclampsia involves complex interactions between maternal constitutional factors, placental dysfunction, and systemic inflammatory responses, leading to widespread endothelial dysfunction and multi-organ involvement.[3] Despite extensive research, the precise mechanisms underlying this condition remain incompletely understood, necessitating the identification of reliable biomarkers for early detection, risk stratification, and monitoring of disease progression.[4]Among various biochemical markers investigated, serum uric acid has emerged as a particularly promising parameter due to its association with disease severity and adverse maternal-fetal outcomes.[1,5] In normal pregnancy, serum uric acid levels undergo characteristic physiological changes that reflect the adaptive maternal response to pregnancy. During early pregnancy, uric acid concentrations decrease significantly by approximately 25-35% due to increased glomerular filtration rate, enhanced renal plasma flow, and the uricosuric effects of estrogen.[6] This reduction is maintained until approximately 16-24 weeks of gestation, after which uric acid levels gradually increase during the third trimester, often reaching or exceeding pre-pregnancy values by term.[7] The normal reference ranges vary by trimester, with first trimester values of 2.0-4.2 mg/dL, second trimester values of 2.4-4.9 mg/dL, and third trimester values of 3.1-6.3 mg/dL.[8,9] In contrast to normal pregnancy, women who develop preeclampsia demonstrate significantly elevated serum uric acid levels, with hyperuricemia often preceding the clinical manifestations of the disease. Multiple studies have reported mean serum uric acid concentrations ranging from 6.7-8.7 mg/dL in preeclamptic women compared to 3.2-4.0 mg/dL in normotensive controls.[10,11] This elevation appears to be related to decreased uric acid clearance due to reduced glomerular filtration, increased tubular reabsorption, and impaired secretion mechanisms. Furthermore, the magnitude of hyperuricemia correlates with disease severity, with more pronounced elevations observed in severe preeclampsia and eclampsia cases. The temporal relationship between uric acid elevation and preeclampsia onset has important clinical implications for disease prediction and monitoring. Research has demonstrated that uric acid levels begin to rise significantly after 20 weeks of gestation in women who subsequently develop early-onset preeclampsia (before 34 weeks), while those who develop late-onset disease show elevation after 30 weeks. The uric acid ratio (UAr), calculated as serum uric acid levels after 20 weeks divided by levels before 20 weeks of gestation, has shown diagnostic utility, with values ≥1.5 demonstrating high negative predictive value (99.5%) for excluding preeclampsia development.[12] Beyond its role as a diagnostic marker, emerging evidence suggests that elevated uric acid may contribute directly to the pathogenesis of preeclampsia rather than merely serving as a consequence of the disease.[13] Experimental studies have shown that uric acid can inhibit endothelial function, induce systemic and glomerular hypertension, promote inflammation and oxidative stress, and impair placental angiogenesis.[14] These mechanisms may explain the strong association between hyperuricemia and adverse maternal outcomes, including acute kidney injury, as well as fetal complications such as intrauterine growth restriction, preterm delivery, and low birth weight.[15,16] The prognostic value of serum uric acid in preeclampsia has been extensively validated across different populations and healthcare settings. Studies have established threshold values ranging from 309-393 μmol/L (5.2-6.6 mg/dL) for predicting adverse outcomes, with sensitivity values of 64-94% and specificity of 48-79%.[15,16] These findings support the utility of serum uric acid measurement as a cost-effective and readily available tool for risk stratification in clinical practice, particularly valuable in resource-limited settings where more sophisticated biomarkers may not be accessible.[12,13,17] Given the significant clinical implications of accurate preeclampsia diagnosis and the potential therapeutic benefits of early intervention, comparative studies examining serum uric acid levels between preeclamptic and normotensive pregnant women are essential for establishing population-specific reference values and optimizing clinical decision-making algorithms. This study aims to provide comprehensive data on serum uric acid concentrations in both groups, contributing to the growing body of evidence supporting its clinical utility in obstetric practice.

A comparative case-control study was conducted to estimate and compare serum uric acid levels in preeclampsia patients and normotensive pregnant women. The study included 250 randomly selected patients with clinically diagnosed preeclampsia attending the Obstetrics and Gynaecology outpatient department or admitted to Patna Medical College and Hospital. An equal number of 250 apparently healthy pregnant subjects served as controls from the same institution. The study period extended from September 2014 to December 2015. Study Population and Selection Criteria Cases: Pregnant women in the third trimester of gestation (28-40 weeks) diagnosed with preeclampsia based on clinical history, examination, and blood pressure measurements showing systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg. Controls: Apparently healthy pregnant women in the third trimester (28-40 weeks) without hypertensive complications. Exclusion Criteria Subjects were excluded if they presented with multiple gestations, active labor, essential hypertension, acute or chronic liver diseases, coagulation-affecting medications, corticosteroid therapy, diabetes mellitus, gout, chronic inflammatory disorders (rheumatoid arthritis, tuberculosis, osteoarthritis, inflammatory bowel diseases), thyroid disorders, specific medications (diuretics, salicylates, ethambutol, pyrazinamide), magnesium-containing medications, chronic alcoholism, chronic kidney disease, cardiovascular diseases, fetal infections or congenital abnormalities, premature rupture of membranes, active sexually transmitted diseases, or severe anemia (Hb <6 g/dl). Sample Collection and Processing Following comprehensive history taking and clinical examination, the procedure was explained to participants and informed consent obtained. Blood pressure measurements and proteinuria assessment were documented in cases. Fasting venous blood samples were collected from the antecubital vein under aseptic conditions using plain bottles. Blood samples were allowed to clot and subsequently centrifuged for serum separation. Serum uric acid analysis was performed on the same day at the Diagnostic Laboratory of Patna Medical College and Hospital. Laboratory Analysis Serum uric acid estimation was performed using the Uricase-Peroxidase method. The principle involves uricase converting uric acid to allantoin and hydrogen peroxide. The hydrogen peroxide then reacts with phenolic compounds and 4-aminoantipyrine through peroxidase catalytic action, forming a red quinoneimine dye complex with intensity directly proportional to uric acid concentration. Assay Procedure: The working reagent was prepared by combining buffer reagent (L1) and enzyme reagent (L2) in a 4:1 ratio. Test samples (0.02 ml) were mixed with 1.0 ml working reagent and incubated at 37°C for 5 minutes or at room temperature (25°C) for 15 minutes. Absorbance measurements were taken at 520 nm wavelength using a spectrophotometer with 1 cm light path against reagent blank. Statistical Analysis Data were analyzed using appropriate statistical methods including mean calculations, standard deviation, Student's t-test for comparing groups, and Pearson's correlation coefficient to assess relationships between diastolic blood pressure and uric acid levels. Statistical significance was determined at p<0.05 for highly significant results, p=0.1-0.05 for partially significant results, and p>0.1 for non-significant findings. Ethical Considerations The study received approval from the Institutional Research and Ethics Committee of Patna Medical College. Informed consent was obtained from all participants following detailed explanation of study procedures. Participation was voluntary, and all data were maintained with strict confidentiality for research purposes only.

Table 1: Age Distribution of Cases and Controls Age Group (years) Cases (n = 250) Controls (n = 250) ≤19 92 (36.8%) 62 (24.8%) 20-23 50 (20%) 75 (30%) 24-28 40 (16%) 65 (26%) ≥29 68 (27.2%) 48 (19.2%) Total 250 (100%) 250 (100%) Table 1 presents the age distribution of both the preeclampsia cases and controls. Among the 250 cases, the highest proportion (36.8%) was in the ≤19 years age group, followed by 27.2% in the ≥29 years group. In contrast, the controls had a higher percentage (30%) in the 20-23 years age group. Table 2: Mean Age of Cases and Controls Group Mean Age ± SD P Value Cases 23 ± 4.81 0.93 (NS) Controls 22.1 ± 4.06 Table 2 compares the mean age of the preeclampsia cases (23 ± 4.81 years) with that of the controls (22.1 ± 4.06 years). The mean ages of both groups are very similar, and the statistical analysis shows no significant difference (P = 0.93). Table 3: Serum Uric Acid Comparison between Cases and Controls Serum Uric Acid (mg/dl) Range Mean ± SD P Value Cases 3.98 - 8.61 6.7 ± 1.1 < 0.05 Controls 2.52 - 6.24 4.26 ± 1.03 Table 3 illustrates the comparison of serum uric acid levels between the cases and controls. The mean serum uric acid level in the cases was significantly higher at 6.7 ± 1.1 mg/dl, compared to 4.26 ± 1.03 mg/dl in the controls. The difference in serum uric acid levels between the two groups is statistically significant (P < 0.05), indicating a clear association between higher uric acid levels and preeclampsia. Table 4: Diagnostic Value of Serum Uric Acid in Preeclampsia Serum Uric Acid (mg/dl) Cases (n = 250) Controls (n = 250) Total (n = 500) > 6.2 181 (72.4%) 31 (12.4%) 212 < 6.2 69 (27.6%) 219 (87.6%) 288 P Value < 0.05 Sensitivity 72.4% Specificity 87.6% Positive Predictive Value 85.3% Negative Predictive Value 76% Diagnostic Accuracy 83.3% Table 4 evaluates the diagnostic value of serum uric acid in identifying preeclampsia. A cutoff value of 6.2 mg/dl was used, with 72.4% of preeclampsia cases having serum uric acid levels above this threshold. In contrast, only 12.4% of controls had uric acid levels above 6.2 mg/dl. The sensitivity of this test is 72.4%, specificity is 87.6%, and the diagnostic accuracy is 83.3%, demonstrating that serum uric acid is a useful biomarker for preeclampsia detection. Table 5: Correlation of Serum Uric Acid with Diastolic Blood Pressure in Cases Correlation Between Pearson’s Correlation Coefficient (r) Significance (P Value) Serum Uric Acid and Diastolic BP +0.606 < 0.05 Table 5 highlights the correlation between serum uric acid levels and diastolic blood pressure (BP) in the preeclampsia cases. A positive and significant correlation was observed, with a Pearson's correlation coefficient of +0.606 (P < 0.05).

The primary objective of this study was to evaluate and compare serum uric acid levels between patients with preeclampsia and normotensive pregnant women. The key findings from this study reveal that serum uric acid levels were significantly higher in preeclamptic patients (mean = 6.7 ± 1.1 mg/dl) compared to controls (mean = 4.26 ± 1.03 mg/dl). Additionally, a positive and significant correlation was found between serum uric acid levels and diastolic blood pressure, further supporting the potential role of uric acid as a biomarker in preeclampsia. These findings are consistent with a comprehensive meta-analysis by Bellos et al.,[18] which demonstrated significantly elevated uric acid levels in preeclamptic women across all trimesters, with mean differences of 0.21 mg/dL in the first trimester, 1.41 mg/dL in the second trimester, and 2.26 mg/dL in the third trimester compared to healthy pregnant women. Similarly, Samaha et al.[19] reported serum uric acid levels of 7.65 ± 0.61 mg/dl in severe preeclampsia patients compared to 5.26 ± 0.79 mg/dl in mild preeclampsia cases. The age distribution analysis shows that preeclampsia cases were more prevalent in younger women, particularly in the ≤19 years age group, while the control group had a higher proportion in the 20-23 years age category. Despite these differences, the mean ages between cases and controls were not significantly different (P = 0.93). This suggests that age alone may not be a determining factor in the development of preeclampsia, and other physiological factors, such as serum uric acid levels, may play a more prominent role in disease pathogenesis. This finding aligns with recent research by Nakimuli et al.,[20] who identified younger maternal age as a significant predictor of eclampsia progression in low-middle income countries. However, maternal age shows a complex relationship with preeclampsia risk, as Tyas et al.[21] demonstrated that advanced maternal age (>35 years) represents an independent risk factor with a 4.5-fold increased risk compared to women aged 25-29 years. Interestingly, Basso et al.[22] found an inverse association between mother's age at delivery and daughter's subsequent risk of primiparous preeclampsia, suggesting generational effects on preeclampsia susceptibility. The significant elevation of serum uric acid in preeclampsia cases as compared to the controls aligns with previous research that highlights the role of hyperuricemia in the development of preeclampsia. The study found a cut-off value of 6.2 mg/dl for serum uric acid, with good sensitivity (72.4%) and specificity (87.6%). The diagnostic accuracy of 83.3% suggests that serum uric acid can be a reliable diagnostic marker for identifying preeclampsia. However, it is important to note that while serum uric acid levels can be a useful screening tool, they should be used in conjunction with other clinical parameters to improve diagnostic precision. This cut-off value is higher than several other studies but falls within the reported range in the literature. Pooransari et al.[23] identified a cut-off of 4.65 mg/dL with sensitivity of 96.9% and specificity of 78% for predicting preeclampsia development in women with gestational hypertension. Bellomo et al.[24] established a lower cut-off of 309 μmol/L (5.2 mg/dL) with area under the curve of 0.75 for predicting preeclampsia progression. The variation in cut-off values may reflect population differences, gestational age at assessment, and severity of preeclampsia cases included in different studies. Thangaratinam et al.[25] conducted a systematic review and found that sensitivity ranged from 0.0% to 55.6% and specificity from 76.9% to 94.9% for various uric acid thresholds. The significant positive correlation between serum uric acid and diastolic blood pressure (r = +0.606, P < 0.05) suggests that elevated serum uric acid levels may contribute to the pathophysiology of preeclampsia through mechanisms that affect vascular tone and blood pressure regulation. This finding is consistent with the hypothesis that uric acid, as a pro-inflammatory and vasoactive molecule, can lead to endothelial dysfunction, a hallmark of preeclampsia. Further studies investigating the molecular mechanisms by which uric acid affects blood pressure regulation in preeclampsia could provide valuable insights into potential therapeutic interventions. Animal studies by Lüscher et al. [26]demonstrated that hyperuricemia during pregnancy leads to increased blood pressure levels and loss of circadian blood pressure dipping in mice, with the highest differences of up to 20 mmHg observed around birth. The temporal relationship between uric acid elevation and blood pressure changes has been well documented by Corominas et al.,[27] who showed that uric acid levels begin rising after 20 weeks of gestation in women who subsequently develop early-onset preeclampsia. This correlation supports the potential mechanistic role of uric acid in preeclampsia pathogenesis beyond its function as a mere biomarker. Our findings are consistent with several studies that have demonstrated elevated serum uric acid levels in preeclampsia patients. Elevated uric acid levels have been implicated in the oxidative stress and inflammatory pathways that contribute to endothelial dysfunction in preeclampsia. However, there is still debate in the literature about whether serum uric acid is a causative factor or merely a marker of the condition. Some studies suggest that while uric acid levels may correlate with disease severity, they may not directly contribute to the onset of preeclampsia. Therefore, future research is needed to explore whether lowering uric acid levels can mitigate the risk of preeclampsia. Colmenares-Mejia et al. [28]conducted one of the largest studies on this topic and found that elevated uric acid levels were associated with increased odds of preeclampsia in a linear relationship without an observable threshold, but concluded that hyperuricemia might represent a disease marker rather than a causal factor. The debate between causative versus marker roles is further complicated by findings from Corominas et al.,[27] who demonstrated that uric acid ratio (UAr) ≥1.5 had a negative predictive value of 99.5% for excluding preeclampsia development, suggesting its utility as a predictive tool regardless of causative mechanisms. Johnson et al.[29] provided evidence supporting the pathogenic role of uric acid, demonstrating that it can inhibit endothelial function, induce hypertension, and promote inflammation. Recent therapeutic studies investigating allopurinol, a uric acid-lowering medication, in preeclamptic women have shown promising results in reducing blood pressure and improving renal function, providing indirect evidence for a causative relationship. This ongoing debate emphasizes the need for well-designed interventional studies to definitively establish whether uric acid represents a therapeutic target or simply a prognostic indicator in preeclampsia management.

This study demonstrates that serum uric acid levels are significantly elevated in preeclampsia patients compared to normotensive pregnant women, with excellent diagnostic performance characteristics including 87.6% specificity and 83.3% overall accuracy. The strong positive correlation between serum uric acid and diastolic blood pressure provides evidence for its potential pathophysiological role beyond being merely a disease marker. These findings support the clinical utility of serum uric acid measurement as a reliable, cost-effective biomarker for preeclampsia screening and risk stratification. The established cut-off value of 6.2 mg/dL can serve as a practical threshold for clinical decision-making, particularly in resource-limited settings where sophisticated biomarkers may not be readily available. Further research investigating the temporal relationship and therapeutic implications of uric acid modulation could enhance our understanding of preeclampsia pathogenesis and improve patient management strategies.

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