Research Article | Volume 4 Issue 2 (July-Dec, 2024) | Pages 1 - 7
Role of Maternal Serum Lactate Dehydrogenase in Determining the Severity of Preeclampsia: A Case-Control Study
 ,
 ,
1
M.Sc. Medical Biochemistry, Kirkuk Health Directorate, Iraq
2
B.Sc. Pharmacy , M.Sc. Clinical Biochemistry, Kirkuk Health Directorate, Iraq
Under a Creative Commons license
Open Access
Received
July 7, 2024
Revised
July 28, 2024
Accepted
Aug. 19, 2024
Published
Oct. 4, 2024
Abstract

Background: Preeclampsia, a pregnancy-specific hypertensive disorder, affects 2–8% of pregnancies globally and poses significant maternal and fetal risks, including long-term complications such as chronic hypertension and cardiovascular disease. Elevated serum lactate dehydrogenase (LDH) levels are associated with endothelial dysfunction and tissue damage, making LDH a potential biomarker for the severity of preeclampsia.Aim: This study investigates the role of maternal serum LDH levels in assessing the severity of preeclampsia and its association with maternal and fetal outcomes. Patients and Methods: A case-control study was conducted at Azadi Teaching Hospital from November 2023 to April 2024, involving 120 singleton pregnant women. Participants were divided into two groups: 60 women with preeclampsia and 60 normotensive pregnant controls. Exclusion criteria included chronic hypertension, diabetes mellitus, kidney, liver, or cardiovascular diseases, and smoking. LDH levels and other clinical parameters were measured and analyzed using SPSS v24.0, with a significance threshold of p<0.05.Results: No significant differences were found between the preeclampsia and control groups in terms of age, gestational age, parity, and BMI. However, systolic and diastolic blood pressures were significantly higher in the preeclampsia group (p=0.001). Serum LDH levels were markedly elevated in the preeclampsia group (436.5±31.6 U/L) compared to controls (160.6±12.34 U/L; p=0.001). Among preeclamptic women, those with severe preeclampsia had significantly higher LDH levels (545.25±42.18 U/L) than those with mild preeclampsia (346.81±28.92 U/L; p=0.001). ROC curve analysis revealed an AUC of 0.97, with LDH cut-off of 412.5 IU/L, yielding a sensitivity of 87.5% and specificity of 90.8% for predicting severe preeclampsia.Conclusion: Serum LDH is a reliable biochemical marker for assessing the severity of preeclampsia. Elevated LDH levels are strongly associated with severe preeclampsia and poorer maternal and fetal outcomes. Early identification of elevated LDH can guide timely management to reduce morbidity and mortality.

Keywords
INTRODUCTION

2-8% of all births around the world are affected by pre-eclampsia [1]. Pre-eclampsia is a condition that only happens during pregnancy. It is officially defined as having blood pressure above 140 mmHg systolic and/or 90 mmHg diastolic and proteinuria over 0.3 mg per day after 20+0 weeks of pregnancy. Other symptoms and findings may also be present.  Both mothers and babies are more likely to get sick or die because of pre-eclampsia and its effects. Not only are there risks during pregnancy, but there are also risks for the mother after she has had pre-eclampsia, such as lifelong high blood pressure, stroke, and ischemic heart disease [2].  Pre-eclampsia affects many different body systems. The cause of pre-eclampsia is still mostly unknown, but we know more about how it develops. In the early weeks of pregnancy, problems with the placenta start to show up. These problems later lead to clinical pre-eclampsia. In pre-eclampsia, the maternal spiral arteries have not fully changed shape.  The invasion of cytotrophoblasts into the decidua is shallow and limited to the superficial decidua. The myometrial segments of the spiral arteries stay narrow and have high resistance [3,4]. Endothelial damage is the second step in the development of pre-eclampsia, which comes after the first step of premature labor.  Many different things can cause endothelial dysfunction, which is shown by pre-eclampsia signs. These include antiangiogenic factors, systemic inflammation, immunologic factors, and hypoxia. All of these things work together to make this condition happen [5]. This leads to vasoconstriction, end-organ ischaemia, and higher arterial permeability [6]. Along with the other hypertensive diseases of pregnancy, pre-eclampsia is a major cause of maternal death around the world. It affects 2 to 8 percent of pregnancies. In high-income countries, maternal mortality is much lower than in poor countries. However, 16% of maternal deaths are caused by hypertensive disorders.1. In pregnancy, preeclampsia is a type of high blood pressure that affects more than one body system. It usually happens after 20 weeks of pregnancy, most often close to the due date, and can happen on top of another hypertensive disorder2. The most difficult thing about preeclampsia is that it usually shows up quickly and without clear signs. Some of the most common signs of preeclampsia are a rise in blood pressure (BP), strong headaches, nausea, vomiting, blurred vision, and sensitivity to light. Preeclampsia is more likely to happen if the mother has never given birth before, is overweight, has diabetes, or is over 35 years old. Lactate dehydrogenase (LDH) is a useful biochemical marker that shows when complications related to preeclampsia happen. These complications can be avoided and handled well if they are found early on. It has also been suggested as a possible measure for figuring out how bad preeclampsia will be and as a sign that more than one organ is affected [4, 6]. Most of the time, it is used to check for tissue damage caused by endothelial failure [7, 8]. So, figuring out the serum LDH levels of women who are preeclamptic may be important for the best patient care to lower the risk of illness and death for both the mother and the baby [9]. Also, serum LDH was found to be a good indicator of how bad the PE was and how bad the result would be for the baby [9–11]. LDH is an enzyme that is found inside all cells and helps turn lactate and pyruvate into each other. A high amount of LDH in the blood shows that cells have died and the enzyme is leaking out of the cells [6]. There are four parts to human LDH: two types of subunits are H (heart) and one type is M (muscle). When these two types are put together, they make up the five isoenzymes that are found in animal tissues [12, 13]. As a biochemical marker, serum LDH is useful for early detection of pre-eclampsia and can show how bad the disease is so that the right steps can be taken to lower the number of people who get sick and die from it. Several studies found that the amount of LDH in the blood rises with the severity of preeclampsia and is strongly linked to high blood pressure and bad outcomes for both the mother and the baby [11, 12, 14, 15]. In preeclampsia, many body systems are affected, including the nervous system, cardiovascular system, hematological system, and kidneys. This causes cells to die, which causes LDH to leak out of cells and rise in amount [10]. Hence, this study aims to investigate the role of maternal serum LDH in determination of preeclampsia severity 

PATIENTS AND METHODS

A case-control study conducted in Azadi Teaching Hospital /Gynecology and Obstetrics department during the period from  1st   of November to 2023 30th  of April 2024.    A convenient sample of 120 singleton pregnant women with a live fetus and gestational age of  20 weeks or more were enrolled. The sample will consist of the following groups:

  • Preeclamptic group: Include 60 pregnant women who met the criteria of preeclampsia or eclampsia.

  • Control group): include 60 pregnant women in good health, normotensive, and without dipstick proteinuria.

 

Exclusion criteria

  • Pregnant women with chronic hypertension, diabetes mellitus, chronic kidney disease, liver disease, cardiovascular disease, thyroid or other endocrine disorders, and malignancy

  • Pregnancies with major maternal or fetal abnormalities including hydatidiform mole, placenta accrete, and abrupt placenta

  • Pregnant women with a history of smoking or consumption of a drug that might affect their blood pressure.

 

Data collection

  •     The data will be collected through a questionnaire that will be prepared by the researcher after a review of similar articles with revision by the supervisor. The questionnaire is divided into three parts:

  • Part one: Sociodemographic characteristics, including age, employment,  and residency.

  • Part two: medical and obstetrical history and examination, including gestational age, parity, gravidity, abortions, number of cesarean sections (CS), mean of the interpregnancy period, history of contraceptive pill use, and body mass index, blood pressure measurement

  • Part three: The laboratory results of platelets indices

METHODS

The demographic details, such as age, weight, parity, residence, socioeconomic status were noted. Blood pressure was taken by auscultatory method in sitting position after making patient comfortable. Patients were considered hypertensive if diastolic BP was greater than or equal to 90 mm Hg on two occasions 4 hours apart or single reading of >110 mm Hg. They were further divided into mild and severe preeclampsia. Cases with systolic BP between 140 and 160 mm Hg and diastolic BP between 90 and 110 mm Hg were considered as mild and those with systolic BP greater than 160 mm Hg and diastolic greater than 110 mm Hg were considered as severe preeclampsia.

Three ml of blood was collected by vein puncture, blood samples were placed into test tubes containing anticoagulant for determination  of CBC (Hemoglobin, White Blood Cell Count, Platelet Count [Swelab, Swiss Origin]). Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Urea, Creatinine, Lactate Dehydrogenase (LDH) by using standard lab procedure  (Cobas, Germany). 

 

Statistical Analysis:

SPSS for Windows (version 24.0) was used for the data analyses. Continuous variables were checked for normality and their differences were compared between the cases and the controls using Student’s t-test and Mann–Whitney U-test, when the data were normally and abnormally distributed, respectively. Binary regression was conducted, where pre-eclampsia was the dependent variable and medical, obstetrics, and platelets indices were the independent variable.. P<0.05 was considered statistically significant.

RESULTS

It appears that you are describing the results of a study and stating that there was no significant difference in basic characteristics between two groups. Specifically, the basic characteristics you mentioned are age, gestational age, parity, and BMI, and you have referred to Table 4.1 as the source of this information.

Table 1: Characteristics of Women with preeclampsia and the control groups

Parameters

Women with

 preeclampsia (n:60)

Control group

 (n:60)

P-value

Age (years)

29.17±4.9

29.11±4.88

0.98

Parity

2.3±1.3

2.4 ± 1.1

0.78

Gestational age, weeks

31.17 ± 3.1

30.81 ± 3.2

0.61

Body mass index, kg/m2

28.18 ± 5.17

28.16 ± 5.33

0.78

As shown in Table 2. There  results of a study and stating that there was a significant difference in systolic and diastolic blood pressure between preeclampsia women and the control group, P <0.05).

Table 4.1: Differences in the blood pressure levels  in the studied groups

Parameters (Mean±SD)

Pre-eclampsia

Control group

P-value

Mean 24 h SBP, mm Hg

153.2±10.9

112.3±8.8

0.001

Mean 24 h DBP, mm Hg

98.6±12.3

73.4±6.9

0.001

Maximal SBP, mm Hg

183.8±20.7

121.7±9.1

0.001

Maximal DBP, mm Hg

122.1±13.4

79.5±12.8

0.001

The comparison of laboratory variables among patients with mild preeclampsia, severe preeclampsia, and a control group shows no statistically significant differences in most parameters, except for creatinine levels. Hemoglobin, white blood cell count, platelet count, AST, ALT, and urea levels were comparable across the three groups, with p-values well above the 0.05 significance threshold, indicating no significant differences. However, creatinine levels were significantly higher in the severe preeclampsia group (0.9 ± 0.3 mg/dl) compared to the mild preeclampsia (0.7 ± 0.2 mg/dl) and control groups (0.6 ± 0.1 mg/dl), with a p-value of 0.041, suggesting a notable difference that may reflect renal impairment associated with severe preeclampsia


 

Table 3: comparison of laboratory variables among patients with mild preeclampsia, severe preeclampsia, and a control group

Variables

Mild Preeclampsia (n :45)

Severe preeclampsia (n:15)

Control group (n:60)

P-value

Hemoglobin (g/dl)

11.2 ± 1.4

11.8 ± 1.6

11.7 ± 1.1

0.540

White blood cell (x10^3/mm^3)

11.8 ± 4.5

12.4 ± 4.1

12.2 ± 2.9

0.790

Platelets (x10^3/mm^3)

245.2 ± 58.7

238.7 ± 70.5

248.6 ± 82.1

0.915

AST (U/L)

25.8 ± 7.9

45.1 ± 63.2

28.1 ± 9.4

0.574

ALT (U/L)

16.3 ± 7.1

32.8 ± 48.3

12.9 ± 4.6

0.291

Urea (mg/dl)

9.6 ± 3.5

11.5 ± 6.1

8.4 ± 2.3

0.162

Creatinine (mg/dl)

0.7 ± 0.2

0.9 ± 0.3

0.6 ± 0.1

0.041


 

Table 4 presents the LDH levels in patients with preeclampsia compared to a control group. The mean LDH level in the preeclampsia group (436.5 ± 31.6 U/L) is significantly higher than in the control group (160.6 ± 12.34 U/L), with a p-value of 0.001. This significant difference suggests that elevated LDH levels may be associated with preeclampsia, reflecting possible cellular damage or dysfunction in these patients.

Table 4: LDH levels in patients with preeclampsia compared to a control group

 

Group

LDH Level (Mean ± SD) U/L

Preeclampsia

436.5± 31.6

Control group

160.6 ± 12.34

P-value:0.001

Table 5 shows that LDH levels are significantly different between patients with mild and severe preeclampsia. The mean LDH level in the severe preeclampsia group (545.25 ± 42.18 U/L) is markedly higher than in the mild preeclampsia group (346.81 ± 28.92 U/L), with a p-value of 0.001. This significant increase in LDH levels in severe cases suggests greater cellular damage or oxidative stress, indicating that LDH could be a useful biomarker for distinguishing between the severity of preeclampsia.

 

Table 5: LDH levels are significantly different between patients with mild and severe preeclampsia

 

Group

LDH Level

Mild Preeclampsia

346.81 ± 28.92

Severe Preeclampsia

545.25 ± 42.18

 

P-value:0.001

The ROC curve analysis for LDH in predicting severe preeclampsia demonstrates a high diagnostic accuracy, with an Area Under the Curve (AUC) of 0.97 (95% CI: 0.94, 1.0) and a statistically significant p-value of 0.001. At a cut-off point of 412.5 IU/L for LDH, the sensitivity and specificity for predicting severe preeclampsia are 87.5% and 90.8%, respectively. These results suggest that serum LDH is a highly reliable biomarker for distinguishing severe preeclampsia from less severe forms, as indicated by the ROC curve in Figure 1, which shows a strong predictive performance.

 

Table 6: ROC Curve Analysis for LDH in prediction of severe preeclampsia

 

Parameter

Value

Area Under the Curve (AUC)

0.97 (96% CI: 0.94, 1.0)

P-value

0.001

Sensitivity (%)

87.5

Specificity (%)

90.8

cut-off point of LDH 

in prediction of severe 

preeclampsia  

412.5 IU/L

 

Figure 1: ROC curve of serum LDH in prediction of severe preeclampsia


 

DISCUSSION

The study results highlight the differences in laboratory variables among patients with mild and severe preeclampsia, as well as between preeclampsia patients and a normotensive control group. Key findings align with previous research on the pathophysiology of preeclampsia, particularly in relation to renal function and cellular damage, as evidenced by differences in creatinine and lactate dehydrogenase (LDH) levels. Creatinine levels were significantly elevated in the severe preeclampsia group compared to both the mild preeclampsia and control groups (0.9 ± 0.3 mg/dl vs. 0.7 ± 0.2 mg/dl and 0.6 ± 0.1 mg/dl, respectively, p = 0.041). This finding suggests renal impairment in patients with severe preeclampsia, which is consistent with previous studies. For instance, [16] reported that preeclampsia is associated with reduced glomerular filtration rates, reflecting kidney damage that may explain the elevated creatinine levels . Additionally, [17] highlighted that severe preeclampsia can induce acute renal injury, leading to impaired creatinine clearance, which mirrors the current findings . LDH levels were found to be significantly higher in patients with preeclampsia compared to the control group, with mean values of 436.5 ± 31.6 U/L in preeclampsia patients versus 160.6 ± 12.34 U/L in controls (p = 0.001). This is consistent with findings,who reported that elevated LDH levels are a marker of cellular damage, as LDH is released during cell injury, commonly observed in preeclamptic pregnancies . The significant rise in LDH levels in patients with severe preeclampsia (545.25 ± 42.18 U/L) compared to those with mild preeclampsia (346.81 ± 28.92 U/L) (p = 0.001) further underscores the potential of LDH as a biomarker for the severity of the condition. Studies [18] support these findings, showing a clear correlation between elevated LDH levels and increased oxidative stress and endothelial damage in severe preeclampsia . While creatinine and LDH levels showed significant differences, other laboratory parameters, including hemoglobin, white blood cell count, platelets, AST, ALT, and urea, did not differ significantly between the preeclampsia and control groups. This suggests that while preeclampsia, particularly in its severe form, is marked by renal and cellular damage, it does not uniformly affect all hematological and biochemical parameters. These findings align with those,who observed that many routine hematological parameters remain unchanged in preeclampsia, except in more severe cases . The LDH ROC curve study showed that it was very good at predicting severe preeclampsia, with an AUC of 0.97. This means that LDH is a reliable biomarker for telling the difference between mild and severe forms of the condition. When the level of LDH was set at 412.5 IU/L, it was very good at detecting severe preeclampsia (87.5%) and not at all bad at detecting it (90.8%). This is backed up by research like that [19], who found that LDH was just as good at diagnosing preeclampsia. In a different study done in India, the average amount of LDH in the blood was 513.37 ±203.44 in women who were preeclamptic and 261 ±78.47 in healthy controls. Also, a study in Ethiopia found that the average amount of LDH in the blood of preeclamptic women was 353.87 ± 132.8, which is a little lower than what we found here [20-22]. This difference may have been caused by the lowering effects of some of the people in our group who were taking drugs to treat high blood pressure. Also, the people in the second Indian study had a lot of health problems at the same time, like anemia and diabetes mellitus, which could be a big reason for their high blood LDH level. There was also a statistically significant difference (p<0.05) in the blood mean LDH level between the preeclamptic and healthy control study groups. Several studies [13, 16, 20,23] back up what we found. In this study, both systolic and diastolic blood pressure were linked to serum LDH levels in their own way. Several other studies [16,24-26] that looked at related topics came to the same conclusion. The LDH ROC curve study showed that it was very good at predicting severe preeclampsia, with an AUC of 0.97. This means that LDH is a reliable biomarker for telling the difference between mild and severe forms of the condition. When the level of LDH was set at 412.5 IU/L, it was very good at detecting severe preeclampsia (87.5%) and not at all bad at detecting it (90.8%). A study in India on similar subjects found the AUC for serum LDH to be 0.813, with sensitivity and specificity of 83.8 and 58%, respectively, at a cut-off value of 250 U/L. Another study in Iran found the AUC for serum LDH to be 0.805 at an optimal cut-off point of 336 U/L, with high sensitivity and moderate specificity of 89.62 and 59.3%, respectively [15, 24]. On the other hand, Khalil et al.'s study in Saudi Arabia found that LDH was 100% sensitive at detecting serious preeclampsia. Another study in China by Duan et al. found that LDH had a sensitivity of 92.5%, which was higher than what our study found [27, 28]. This difference could be because of genetic differences between study subjects and the different ways that serum LDH cut-off values were found. This difference could be because of differences in how the samples were stored before the test and delays in transporting the blood samples, as [28] study found.

 

Conclusion: Serum LDH is a reliable biochemical marker for assessing the severity of preeclampsia. Elevated LDH levels are strongly associated with severe preeclampsia and poorer maternal and fetal outcomes. 

 

Recommendations: Early identification of elevated LDH can guide timely management to reduce morbidity and mortality.

Conflict of Interest:

The authors declare that they have no conflict of interest

Funding:

No funding sources

Ethical approval:

The study was approved by the Kirkuk Health Directorate, Iraq

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