Pregnancy is associated with extensive physiological and biochemical adaptations necessary for maintaining maternal health and fetal development. However, disturbances in these mechanisms may result in obstetric complications, among which hypertensive disorders of pregnancy remain a major cause of maternal and perinatal morbidity and mortality worldwide.[1] Preeclampsia, gestational hypertension, and eclampsia represent important hypertensive disorders, with preeclampsia being particularly significant due to its multisystem involvement and potential for rapid progression to severe disease. Preeclampsia is characterized by the development of hypertension after 20 weeks of gestation with associated proteinuria and/or maternal organ dysfunction involving the renal, hepatic, neurological, hematological, or fetoplacental systems.[2] It affects approximately 5–10% of pregnancies globally and contributes significantly to adverse outcomes, especially in low- and middle-income countries. Severe preeclampsia may lead to complications such as eclampsia, HELLP syndrome (Hemolysis, Elevated Liver Enzymes, and Low Platelet Count), placental abruption, fetal growth restriction, preterm birth, and maternal mortality. Therefore, early prediction of disease severity is essential for timely intervention and improved maternal and fetal outcomes.[3] The pathogenesis of preeclampsia involves abnormal placentation, inadequate trophoblastic invasion, impaired spiral artery remodeling, placental ischemia, endothelial dysfunction, oxidative stress, and systemic inflammatory activation. These pathological processes result in reduced uteroplacental perfusion and widespread vascular endothelial injury.[4] Although clinical parameters such as blood pressure, proteinuria, and symptoms are routinely used for assessment, they may not always accurately predict disease progression. Hence, biochemical markers that can provide early information regarding severity and prognosis have gained considerable clinical interest. [5,6] Lactate dehydrogenase (LDH) is an intracellular enzyme involved in anaerobic glycolysis, converting pyruvate to lactate. Placental hypoxia associated with preeclampsia increases glycolytic activity and LDH expression, leading to enhanced lactate production and cellular stress.[7] Increased maternal serum LDH reflects tissue injury, oxidative stress, hepatic involvement, and hemolysis. Elevated LDH levels have been associated with severe preeclampsia, HELLP syndrome, renal dysfunction, and adverse maternal and neonatal outcomes.[8] Therefore, serum LDH may serve as a useful marker for identifying patients at higher risk of severe disease. Serum uric acid is another important biochemical marker associated with preeclampsia severity. [9,10] Hyperuricemia occurs due to increased oxidative stress, enhanced production from ischemic placental tissue, reduced renal clearance, and altered renal function associated with endothelial dysfunction. Elevated uric acid levels have been correlated with increased blood pressure severity, renal impairment, fetal growth restriction, and adverse pregnancy outcomes. [11,12] Thus, uric acid estimation may provide valuable prognostic information regarding maternal and fetal risk. The combined assessment of maternal serum LDH and uric acid provides a simple, cost-effective, and easily available approach for predicting disease severity. Unlike specialized angiogenic biomarkers, these parameters can be routinely measured in clinical laboratories and may assist in risk stratification, monitoring, and decision-making regarding management and timing of delivery.[13] Considering the significant impact of severe preeclampsia on maternal and perinatal outcomes, the present study was undertaken to evaluate the role of maternal serum LDH and uric acid levels as predictors of severity in preeclampsia and to assess their association with clinical severity indicators and maternal-fetal outcomes.

A prospective observational study was conducted to evaluate the role of maternal serum lactate dehydrogenase (LDH) and uric acid levels as predictors of severity in preeclampsia. The study was carried out in the Department of Obstetrics and Gynaecology at a tertiary care teaching hospital. Study Population The study included pregnant women diagnosed with preeclampsia who were admitted to the obstetric unit during the study period. A total of 70 pregnant women fulfilling the eligibility criteria were enrolled in the study. All participants were evaluated clinically and biochemically, and maternal serum LDH and uric acid levels were assessed to determine their association with disease severity and maternal-fetal outcomes. Inclusion Criteria The study included pregnant women who fulfilled the following criteria: • Pregnant women with gestational age ≥20 weeks. • Women diagnosed with preeclampsia according to standard diagnostic criteria. • Singleton pregnancies. • Women willing to participate and provide written informed consent. Exclusion Criteria Patients were excluded if they had: • Chronic hypertension diagnosed before pregnancy or before 20 weeks of gestation. • Pre-existing renal disease, hepatic disease, or cardiovascular disease. • Diabetes mellitus or other significant medical disorders affecting pregnancy. • Multiple pregnancies. • Known cases of autoimmune disorders or infections. • Patients unwilling to participate in the study. Study Procedure and Data Collection After obtaining informed consent, detailed demographic and clinical information was recorded for all enrolled participants. Data regarding maternal age, gestational age, parity, obstetric history, blood pressure measurements, symptoms, and clinical features were collected. Complete physical examination and routine obstetric evaluation were performed. The diagnosis and severity classification of preeclampsia were based on clinical findings, blood pressure levels, laboratory investigations, and evidence of maternal organ involvement. Patients were categorized into mild and severe preeclampsia groups according to standard clinical criteria. Biochemical Assessment Venous blood samples were collected from all participants under aseptic precautions. Serum LDH and uric acid levels were measured using standard laboratory methods. LDH levels were assessed as a marker of cellular injury, tissue hypoxia, and hemolysis, whereas serum uric acid levels were evaluated as an indicator of oxidative stress and renal involvement associated with preeclampsia.The obtained biochemical values were correlated with clinical severity parameters and maternal-fetal outcomes. Assessment of Maternal and Fetal Outcomes Maternal outcomes including progression to severe preeclampsia, development of HELLP syndrome, eclampsia, mode of delivery, and other obstetric complications were recorded. Fetal outcomes including gestational age at delivery, birth weight, Apgar score, neonatal intensive care unit (NICU) admission, and perinatal complications were documented. Statistical Analysis The collected data were entered into a Microsoft Excel spreadsheet and analyzed using SPSS. 25. Continuous variables were expressed as mean ± standard deviation (SD) or median with interquartile range, while categorical variables were presented as frequency and percentage.Comparison of biochemical markers between different severity groups was performed using appropriate statistical tests. The association between serum LDH, uric acid levels, and clinical severity parameters was assessed using correlation analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive ability of LDH and uric acid levels for severe preeclampsia. A p-value of <0.05 was considered statistically significant.

The present prospective observational study included 70 pregnant women diagnosed with preeclampsia. The enrolled participants were evaluated for demographic characteristics, clinical severity parameters, maternal serum lactate dehydrogenase (LDH), serum uric acid levels, and maternal-fetal outcomes. The association between biochemical markers and severity of preeclampsia was analyzed.

The mean age of study participants was 28.6 ± 4.8 years. Majority of women belonged to the age group of 21–30 years (57.1%), followed by >30 years (28.6%). Primigravida women constituted 54.3% of the study population, whereas 45.7% were multigravida. The mean gestational age at presentation was 34.8 ± 2.9 weeks. Most participants presented in the third trimester. The baseline demographic and obstetric characteristics of the study population are summarized in Table 1.

Table 1: Baseline Demographic and Obstetric Characteristics of Study Participants (n=70)

Among the 70 participants, 42 (60.0%) women had severe preeclampsia, while 28 (40.0%) had mild preeclampsia. Severe cases showed significantly higher systolic and diastolic blood pressure values compared with mild cases. The distribution of clinical severity parameters is presented in Table 2.

Table 2: Clinical Severity Characteristics of Preeclampsia Patients (n=70)

The mean serum LDH level was significantly higher among women with severe preeclampsia compared with mild preeclampsia. Similarly, serum uric acid levels were significantly elevated in the severe disease group. The difference in biochemical markers between mild and severe preeclampsia groups is shown in Table 3, Figure 1

Table 3: Comparison of Serum LDH and Uric Acid Levels Between Mild and Severe Preeclampsia (n=70)

Figure 1 Comparison of Serum LDH and Uric Acid Levels Between Mild and Severe Preeclampsia (n=70)

Serum LDH demonstrated a significant positive correlation with systolic blood pressure, diastolic blood pressure, and proteinuria severity. Serum uric acid also showed a significant positive correlation with blood pressure levels and severity of preeclampsia. These findings are summarized in Table 4.

Table 4: Correlation of Serum LDH and Uric Acid with Clinical Severity Parameters

Patients with elevated LDH and uric acid levels had a higher incidence of adverse maternal and fetal outcomes. HELLP syndrome and eclampsia were more frequently observed among women with higher biomarker levels. Similarly, fetal growth restriction, preterm delivery, and NICU admission were more common in patients with severe biochemical abnormalities. The maternal and fetal outcomes are presented in Table 5, Figure 2

Table 5: Maternal and Fetal Outcomes Among Study Participants (n=70)

Figure 2 Maternal and Fetal Outcomes Among Study Participants (n=70)

ROC curve analysis demonstrated that both serum LDH and uric acid had significant predictive ability for identifying severe preeclampsia. LDH showed a higher area under the curve (AUC) compared with uric acid, indicating better discriminatory performance. The diagnostic performance parameters are presented in Table 6, Figure 3

Table 6: ROC Analysis of Serum LDH and Uric Acid for Prediction of Severe Preeclampsia

Figure 3 ROC Analysis of Serum LDH and Uric Acid for Prediction of Severe Preeclampsia

Preeclampsia is a major hypertensive disorder of pregnancy associated with significant maternal and perinatal morbidity and mortality due to its multisystem involvement and variable progression. The present prospective observational study evaluated the role of maternal serum lactate dehydrogenase (LDH) and uric acid as predictors of severity in preeclampsia among 70 pregnant women. The study demonstrated that both biomarkers were significantly elevated in severe preeclampsia and showed significant association with clinical severity parameters and adverse maternal-fetal outcomes. In the present study, the mean age of participants was 28.6 ± 4.8 years, with the majority belonging to the 21–30 years age group (57.1%), and primigravida women constituted 54.3% of cases. Similar demographic trends have been reported in previous studies, where preeclampsia was more frequently observed among younger women and primigravida patients due to altered maternal vascular adaptation and immunological mechanisms associated with first pregnancy. The predominance of third-trimester presentation in the present study is consistent with the usual clinical onset of preeclampsia after mid-pregnancy. In the current study, 42 (60.0%) women had severe preeclampsia, whereas 28 (40.0%) had mild disease. Severe cases showed higher blood pressure levels, increased proteinuria, and more frequent symptoms such as headache and visual disturbances. These findings reflect progressive endothelial dysfunction, placental ischemia, and systemic vascular injury associated with severe disease. Serum LDH levels were significantly higher among women with severe preeclampsia (684.3 ± 152.7 U/L) compared with mild cases (412.6 ± 96.8 U/L; p<0.001). Increased LDH reflects cellular injury, placental hypoxia, oxidative stress, hepatic involvement, and hemolysis. Moharana et al. [14] reported significantly elevated LDH levels in severe preeclampsia and eclampsia, with severe cases showing LDH levels of 1116.94 ± 4.78 U/L, and concluded that LDH was a useful predictor of disease severity and adverse fetomaternal outcomes. Similar findings have been reported in other studies where elevated LDH levels, particularly above 600–800 IU/L, were associated with increased maternal complications and severe disease progression. Serum uric acid also demonstrated a significant association with disease severity. In the present study, severe preeclampsia patients had significantly higher uric acid levels compared with mild cases (7.4 ± 1.5 mg/dL vs 5.8 ± 1.1 mg/dL; p<0.001). Hyperuricemia in preeclampsia occurs due to increased oxidative stress, enhanced production from ischemic placental tissue, and reduced renal clearance secondary to endothelial dysfunction. Previous studies have demonstrated similar findings, with severe preeclampsia patients showing higher uric acid levels (7.3 ± 1.2 mg/dL vs 5.0 ± 0.9 mg/dL; p<0.001) and identifying uric acid as a useful marker for predicting disease severity. In the present study, LDH showed significant positive correlation with systolic blood pressure (r=0.62), diastolic blood pressure (r=0.56), and proteinuria severity (r=0.49). Similarly, uric acid showed significant correlation with systolic blood pressure (r=0.58), diastolic blood pressure (r=0.51), and proteinuria (r=0.46). These findings indicate that increasing biomarker levels parallel worsening clinical severity and support their prognostic value in preeclampsia. The present study also demonstrated increased adverse outcomes among women with elevated LDH and uric acid levels. HELLP syndrome occurred in 11.4%, eclampsia in 7.1%, and NICU admission was required in 34.3% of neonates. Similar associations between elevated LDH, uric acid, and adverse maternal-fetal outcomes have been reported by Moharana et al. [14]. ROC analysis showed that LDH had good predictive ability for severe preeclampsia with an AUC of 0.84, sensitivity of 78.6%, and specificity of 82.1%, whereas uric acid showed an AUC of 0.79, sensitivity of 76.2%, and specificity of 75.0%. These findings suggest that both biomarkers are useful predictors, with LDH demonstrating slightly better discriminatory performance. Overall, the present study confirms that maternal serum LDH and uric acid levels are significantly associated with severity of preeclampsia and adverse maternal-fetal outcomes. Their routine assessment may provide a simple, cost-effective, and accessible method for early identification of high-risk pregnancies and may assist in timely management and improved outcomes.

The present study demonstrated that maternal serum LDH and uric acid levels were significantly elevated among women with severe preeclampsia and showed a strong association with clinical severity parameters and adverse maternal-fetal outcomes. Both biomarkers showed good predictive ability for identifying severe disease, with LDH demonstrating slightly superior discriminatory performance. Measurement of serum LDH and uric acid provides a simple, cost-effective, and readily available approach for risk stratification of preeclamptic pregnancies. These biomarkers may assist clinicians in early identification of high-risk patients, timely intervention, and improved maternal and neonatal outcomes.

Limitations

The present study had a relatively small sample size of 70 participants and was conducted at a single tertiary care centre, which may limit the generalizability of the findings. The observational study design did not allow assessment of long-term maternal and neonatal outcomes. Additionally, other potential biomarkers and confounding factors influencing disease severity were not evaluated. Further multicentric studies with larger sample sizes are required to validate the predictive role of LDH and uric acid in preeclampsia.

1. Craici I, Wagner S, Garovic VD. Pre-eclampsia and future cardiovascular risk: formal risk factor or failed stress test? Ther Adv Cardiovasc Dis. 2008;2(4):249-259.
2. Cunningham FC, Leveno KJ, Bloom SL, Dashe JS, Hoffman BL, Casey BM, et al. Williams Obstetrics. 23rd ed. New York: McGraw-Hill; 2010. p.706.
3. Tsoi SCM, Zheng J, Xu F, Kay HH, Tsoi S. Differential expression of lactate dehydrogenase isozymes (LDH) in human placenta with high expression of LDH-A4 isozyme in the endothelial cells of pre-eclampsia villi. Placenta. 2001;22:317-322.
4. Kay HH, Zhu S, Tsoi S. Hypoxia and lactate production in trophoblast cells. Placenta. 2007;28(8-9):854-860.
5. Burd LI, Simmons MA, Makowski EL, Meschia G, Battaglia FC. Placental production and foetal utilization of lactate and pyruvate. Nature. 1975;254:710-711.
6. Bougneres PF, Rocchiccioli F, Nurjhan N, Bier DM, Haymond MW. Stable isotope determination of plasma lactate conversion into glucose in fasting infants. Am J Physiol. 1995;268:E652-E660.
7. Markert CL, Shaklee JB, Whitt GS. Evolution of a gene: multiple genes for LDH isozymes provide a model of the evolution of gene structure, function and regulation. Science. 1975;189:102-500.
8. Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J Biol Chem. 1994;269:23757-23763.
9. Hofmeyr GJ, Belfort M. Proteinuria as a predictor of complications of pre-eclampsia. BMC Med. 2009;7:11.
10. Tompkins MJ, Thiagarajah S. HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome: the benefit of corticosteroids. Am J Obstet Gynecol. 1999;181:304-309.
11. O’Brien JM, Milligan DA, Barton JR. Impact of high-dose corticosteroid therapy for patients with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Am J Obstet Gynecol. 2000;183(4):921-924.
12. O’Brien JM, Shumate SA, Satchwell SL, Milligan DA, Barton JR. Maternal benefit to corticosteroid therapy in patients with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome: impact on the rate of regional anesthesia. Am J Obstet Gynecol. 2002;186:475-479.
13. Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol. 2004;103(5):981-991.

14. Moharana JJ, Mishra R, Nayak AK. A study on serum lactate dehydrogenase and uric acid in preeclampsia and eclampsia: can they predict adverse fetomaternal outcome? Int J Appl Basic Med Res. 2023;13(2):95-100.