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Serum Lactate Dehydrogenase (LDH) Level as a Predictor of Severity of Preeclampsia

Dr. Zainab Abd Alkathem Fatnan 1, Dr. Murtadha Abdilkadhim Kareem, 2 Dr. Qusay abul Zahraa alaubaidy

1. Assist professor kufa medical school, Specialist OBG at Al-Zahraa Teaching Hospital 2. Pediatric Surgery Specialist at Al-Zahraa teaching hospital, Lecturer at kufa medical

school

3. Specialist in general surgery in Al-Sader teaching hospital Corresponding author: Dr. Zainab Abd Alkathem Fatnan. Email:

[email protected] Phone number: +9647800789894.

ORCID ID: https://orcid.org/0000-0001-7716-081X

Abstract:

Background: Preeclampsia is a disorder of the human pregnancy and is the leading cause of maternal death and morbidity of growing fetus. Is characterized by extensive endothelial dysfunction that produces hypertension, proteinuria and edema. Objective of the study: to compare the level of lactate dehydrogenase between normal and preeclamptic pregnant women and to assess the role of LDH as a predictor of severity of preeclampsia. Patients and method: Prospective study was carried in Gynecology and Obstetrical Department at Al- Zahra' a Teaching Hospital for Maternity and Pediatrics/ Najaf governorate/Iraq from the beginning of March 2019 to the end of August of the same year. The study population consists of 50 normotensive pregnant women and 50 preeclamptic pregnant women seen for their perinatal care in the third trimester of pregnancy. Results: the mean proteinuria in control and preeclamptic group are 0.04±0.1 and 2.3±0.6 respectively, and highly significant increase in preeclampsia than that in healthy women (P<0.001). The mean of plasma LDH activity for control and preeclamptic groups are 3.14±0.46 U/L and 6.5±2 U/L respectively with highly significant increase in plasma LDH among case groups than that for control (P value <0.001). Conclusion: Significant increase in plasma LDH in patients with preeclampsia than normal pregnant women

Keyword: Preeclampsia, lactate dehydrogenase, pregnancy Introduction

Preeclampsia is a pregnancy- specific syndrome that can affect virtually every organ

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system. (1) It is an idiopathic disorder in which many genetic, environmental and immunological factors interact. (2)

The disorder affects about 4 percent of pregnancies and it is a significant cause of maternal and fetal morbidity and mortality. (3)

Preeclampsia is defined as new onset hypertension (a systolic blood pressure level of 140 mmHg or higher or a diastolic blood pressure level of 90 mmHg or higher) with a proteinuria (≥ 300 mg of protein in a 24-hour urine collection which correlates a 1+ reading in dipstick in a random urine specimen) that starts after 20 weeks of gestation in previously normal blood pressure women. (4, 5) Preeclampsia when arises in early second trimester (14-20) weeks, a molar pregnancy, choriocarcinoma or higher order pregnancies should be considered. (1)

While protein in urine is an important sign of preeclampsia, it may not present in approximately 10-20 percent of women with severe preeclampsia or eclampsia "atypical preeclampsia". (7, 8)

 High risk factors: (9-11)

1.

Previous pregnancy affected by preeclampsia or eclampsia.

2.

Autoimmune disordres like systemic lupus erythematosus (SLE), thrombophilia and antiphospholipid antibody syndrome .

3.Chronic diseases such as (diabetes type I or II, nephrological disorders, or chronic hypertension).

 Moderate risk factors (two or more): (9-11)

1. Higher order pregnancies.

2. Obesity (BMI ≥ 35 Kg/m²).

3. History of preeclampsia or eclampsia in her first-degree relatives.

4. Maternal age < 20 years or >40 years or older.

5. Inter pregnancy interval of more than 10 years.

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6. primiparity/ Nulliparity.

It has been proposed that enzyme profiles vary according to the particular metabolic needs of different tissues and that this variation may occur in response to ischemia, inflammation, necrosis, or malignant neoplasms. (12) Enzyme values considered normal are due to cell renewal, so that an increase in serum values always responds to cell damage or necrosis. (13) The multi-organ condition seen in pre-eclampsia can be evaluated by determining serum enzymes to determine the degree of severity and involvement of different systems. (14) Different laboratory tests have been used in search of an indicator for the diagnosis of preeclampsia. Among the laboratory indicators, lactic dehydrogenase (DHL) stands out. This is an enzyme of intermediate metabolism, present in all cells.

DHL is a cytoplasmic enzyme that contains zinc and is found in different locations in mammals. It is a tetramer that has a molecular weight of about 140 kDa. For a molecule of this size to be released into the extracellular space through the cytoplasmic membrane, it is due to normal cellular exchange such as apoptosis or cell destruction such as acute myocardial infarction. When DHL's isozyme separation techniques were developed, many researchers tried to link alterations in the isoenzyme pattern with damage to certain tissues such as the liver or skeletal muscle. (15) In the myocardium, isoenzyme 1 contributes about 60% of the total activity of lactin dehydrogenase; in the erythrocyte the contribution is about 40%. (16) Isoenzyme 1 predominates in tissues rich in oxygen supply that undergo oxidative metabolism, while 5 is the main form found in skeletal muscle, as it is a tissue that undergoes anaerobic glycolysis with accumulation of lactate and pyruvate. (17)

Aim of study

This study is aims to compare the level of lactate dehydrogenase between normal and preeclamptic pregnant women and to assess the role of LDH as a predictor of severity of preeclampsia.

Patients and Methods

Prospective study was carried in Gynecology and Obstetrical Department at Al-Zahra' a Teaching Hospital for Maternity and Pediatrics/ Najaf governorate/Iraq from the beginning of

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March 2019 to the end of August of the same year.

All pregnant women who had participated in the present expressed their verbal oral consent and cooperation during a period of research. All participants were chosen according to the clinical signs, symptoms and the investigations.

Patients:

The study population consists of 50 normotensive pregnant women and 50 preeclamptic pregnant women seen for their perinatal care in the third trimester of pregnancy.

Preeclampsia is diagnosed when

1. Blood pressure ≥ 140/90 mmHg in two or more repeated readings within 4-6 hours apart with using the proper way of blood pressure measurement as mentioned previously and 2. Albumin were detected ≥ one times (30 mg) on dipstick on a random clean-catch mid- stream urine sample.

Women with multiple pregnancies, chronic hypertension, diabetes mellitus, cardiac, renal disease or other significant metabolic disorder, or a history of rupture membrane or urinary tract infection were excluded.

The women with preeclampsia were subdivided into two groups, mild preeclampsia (n= 18, blood pressure ≥140/90 mmHg and <160/110 mmHg and > 1+ proteinuria) and severe preeclampsia (n= 32, blood pressure of ≥ 160/110 with a proteinuria ≥ 2+).

The gestational age was determined depending on the first day of last menstrual period (LMP) then confirmed by first trimester ultrasound while in women with irregular menstrual cycle we depend on the early trimester scan.

Samples

At the time of admission, 5 cc of venous blood were drawn from each patient, and blood collected in a polyethylene tube without anticoagulants, left for half hour at room temperature, and then centrifuged at (3000×g) for 10 minutes. Sera (should be absolutely free from hemolysis) were aspirated and stored at -20 °C until time of use.

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Statistical analysis

By using SPSS version 21 the analysis were done. Data were presented as (mean ± S.D) so ANOVA were used to measure the variance and comparison of data. And the association between two variants were measured by Pearson correlation coefficient. P value at ≤0.05 were considered significant.

Results:

Table 1: Shows association between the studied groups and demographic factors P value Control

N=50 PE

N=50 Parameter

<0.001 23.4±5.3

29.5±7.4 Age

0.027 1.3±1.4

2.1±2.2 Parity

0.077 37.58±1.2

37±1.8 Gestational age

<0.001 25.9±2

30.1±4 BMI

<0.001 123.2±6.7

168.2±23.5 Systolic BP

<0.001 80.7±7.2

110.6±11.2 Diastolic BP

The mean maternal age in control and preeclamptic group are 23.4±5.3 years and 29±7.4 years, respectively. There is a statistically significant difference between the study groups (p value <0.001).

The mean of parity in control group and preeclamptic group are 1.3±1.4 and 2.1±2.2 respectively. Results showed an insignificant statistical difference between both groups (P value >0.05).

Regarding the data of systolic and diastolic blood pressure there is a statistically significant increase of blood pressure among the study groups as P value <0.001. The results of control versus preeclamptic group were (123.2±6.7, 168.2±23.5) and (80.7±7.2, 110.6±11.2) consecutively.

The mean of gestational age in control and preeclamptic group are 37.58±1.2wks and 37±1.8wks respectively with no significant difference between the studied groups (p value

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>0.05).

The finding of BMI of control and preeclamptic groups were (25.9±2) and (30.1±4). There is a statistically significant increase in BMI between control and preeclamptic group (P value

<0.001).

Table 2: Show the differences between control and preeclamptic group in mild and severe cases

P value Range

Control N=50 Rang

e Mild PE N=18 Rang

e Severe PE

N=32 Characteristics

(Plasma)

0.001(1),<

0.001(2), 0.565(3) 15-35

23.4±5.3 18-37

28.7±6.6 17-42

30±7.8 Age

0.079(1), 0.044(2), 0.871(3) 0-6

1.3±1.2 0-7

2.1±1.8 0-8

2.2±2.4 Parity

0.417(1), 0.051(2), 0.459(3) 33-40

37.5±1.2 33-40

37.2±1.5 32-41

36.8±1.9 GA

<0.001(1), 0.001,(2) 0.001(3) 110-140

123.2±6.

7 140- 155 199.3±4.

3 160- 280 178.9±23.3

Systolic blood pressure

0.001(1), 0.001(2), 0.001(3) 60-100

80.7±7.2 95-

105 149.3±4.

3 110- 140 117±8.5

Diastolic blood pressure

0.001(1), 0.001(2), 0.644(3) 21-32.1

25.9±2 2308-

3901 29.8±3.8

23- 40.4 30.3±4.1

BMI

1. Control vs. mild 2. Control vs. severe. 3. Mild vs. severe.

The mean maternal age for control and mild PE is 23.4±5.3 and 28.7±6.6 years, respectively while between control and severe PE are 23.4±5.3 and 30±7.8 years, consecutively. There is a statistically significant difference (P value 0.001). While, there is no

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significant difference between mild and severe PE regarding maternal age (P value >0.05).

3.2. Protein urea for study groups

Table 3 shows that the mean proteinuria in control and preeclamptic group are 0.04±0.1 and 2.3±0.6 respectively, and highly significant increase in preeclampsia than that in healthy women (P<0.001)

Table 3: Shows the comparison between study groups in relation to proteinuria.

P value Control(n=50)

Preeclamptic (50) Parameter

<0.001 0.04±0.1

2.3±0.6 Proteinuria

Table 4: The relation between proteinuria in control, mild and severe preeclamptic pregnant women.

P value Control

group(n=50) Mean± SD Preeclamptic group(n=50)

Mean± SD 2.3±0.6 Parameter

Mild PE(n=18) Mean ± SD Severe(n=32)

Mean ±SD

<0.001(1),

<0.001(2), 0.003(3) 0.04±0.19

2.05±0.53 2.56±0.56

Proteinuria

The table 4 shows a statistically significant differences among control, mild, and severe PE regarding the proteinuria P values <0.001, 0.001, and 0.003 respectively.

Serum LDH activity

The mean of plasma LDH activity for control and preeclamptic groups are 3.14±0.46 U/L and 6.5±2 U/L. There is a significant increase in plasma LDH among study groups (P value

<0.001).

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Table 5: The relation between plasma LDH U/L in the studied groups

P value Control group(n=50)

Mean± SD Preeclamptic group(n=50)

Mean ±SD 6.5±2 Parameter

Mild PE (n=18) Mean ± SD Severe (n=32)

Mean ±SD

<0.001 3.14±0.46

4.86±0.58 7.51±2.01

Plasma LDH U/L

Discussion

Pre-eclampsia is considered an idiopathic multisystem disorder. Early diagnosis of preeclampsia is very important to prevent any other complications. In the present study, authors observed a significant rise in the LDH levels in preeclampsia patients as compared to control group and that there is an increase in LDH value with increasing severity of preeclampsia (p <0.01). this is similar to that found by

Qublan et al, study (18) confirmed that there is significant association of LDH levels with severe preeclampsia. Moreover, similar results were depicted in studies conducted by Jaiswar et al Hazari et al and Gandhi et al. (19-21)

This study demonstrates that the mean value of plasma LDH level in all preeclamptic groups (6.5±2U/L) higher than that of the control (3.1±0.46U/L) P value<0.001 as shown in table 4.

These findings were similar to those of Demir et al and Sarkar et al. (22,23)

In the present study, it was observed that systolic blood pressure (SBP) and diastolic blood pressure (DBP) was significantly higher with higher serum LDH levels. Regarding the data of systolic and diastolic blood pressure there is a statistically significant increase of blood pressure among the study groups as P value <0.001. The results of control versus preeclamptic group were (123.2±6.7, 168.2±23.5) and (80.7±7.2, 110.6±11.2) consecutively.

These results correlate with the studies conducted by Umasatyashri et al, Bhave et al and Jaiswar et al. (19,22,24)

Elevated serum LDH levels in preeclamptic pregnant women could clarify the rise in systolic and diastolic blood pressure as MPO has an constraining effect on nitric oxide and aggravating action on endothelin-1 and prostaglandins. This is directly contributing to

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endothelial dysfunction. (25)

Conclusion: Significant increase in plasma LDH in patients with preeclampsia than normal pregnant women.

No conflicts of interest Source of funding: self

Ethical clearance: was taken from the scientific committee of the Iraqi Ministry of health

References:

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Hypertensive disorder in pregnancy, Williams Obstetrics, 23rd edition, McGraw-Hill publishing, chapter 34, 2010; 706-756.

2. Cunningham FG. , Haut JC., Leveno KJ. , Gilstrap L., Bloom SL. and Wenstrom KD. ; Hypertensive disorder in pregnancy, Williams Obstetrics, 22nd edition, McGraw-Hill publishing, chapter 34, 2005; 428-437.

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308(5728): 1592-4.

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8. Sibai BM, Stella CL. Diagnosis and management of atypical preeclampsia-eclampsia. Am J Obestet Gynecol 2009; 200. 481l-7.

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10. Bailis A. and Witter FR., Hypertensive Disorders of Pregnancy, Fortner KB. , Szymanski LM., Fox HE., and Wallach EE. , et al., The Johns Hopkins Manual of Gynecology and Obstetrics, 3rd Edition, Lippincott Williams and Wilkins Publishing, chapter 14, 2007; 181- 191.

11. S. Tahmasebi, M.A. El-Esawi, Z.H. Mahmoud, A. Timoshin, H. Valizadeh, L.

Roshangar, M. Varshoch, A. Vaez, S. Aslani, J.G. Navashenaq, L. Aghebati-Maleki, M.

Ahmadi. Immunomodulatory effects of nanocurcumin on Th17 cell responses in mild and severe COVID-19 patients. J. Cell. Physiol. (2020), pp. 1-14

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Bioimpacts. 2013; 3: 101-4.

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17. Vargas-García A. Serum lactic dehydrogenase in preeclamptic patients and normotensive pregnant women. Avances en Biomedicina. 2016 May 1;5(2).

18. Qublan HS, Amarun V, Bateinen O, Al-Shraideh Z, Tahat Y, Awamleh I, et al. LDH as biochemical marker of adverse pregnancy outcome in severe preeclampsia. Med Sci Monit 2005;11(8):393-7.

19. Jaiswar SP, Amrit G, Rekha S, Natu SN, Mohan S. Lactic dehydrogenase: A biochemical marker for preeclampsia–eclampsia. J Obstet Gynaecol India 2011;61(6):645-8.

20. Hazari NR, Hatolkar VS, Munde SM. Study of serum hepatic enzymes in preeclampsia.

Int J Curr Med Appl Sci 2014;2(1):1-8.

21. Gandhi M, Chavda R, Saini HB. Comparative study of serum LDH and uric acid in hypertensive versus normotensive pregnant woman. Int J Biomed Res 2015;6(1):25-8.

22. Demir C, Evruke C, Ozgunen FT, Urunsak IF, Candan E, Kadayifci O. Factors that influence morbidity and mortality in severe preeclampsia, eclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Saudi Med J. 2006;27(7):1015-8.

23. Sarkar PD, Sogani S. Evaluation of serum lactate dehydrogenase and gamma glutamyl transferase in preeclamptic pregnancy and its comparison with normal pregnancy in third trimester. Int J Res Med Sci. 2013;1(4):365-8.

24. Umasatyasri Y, Vani I, Shamita P. Role of LDH (lactate dehydrogenase) in preeclampsia eclampsia as a prognostic marker: An observational study. IAIM. 2015;2(9):88-93

25. Redman CWG, Sargent IL, Roberts JM. Immunology of normal pregnancy and preeclampsia. In: Lindheimer MD, Roberts JM, Cunningham FG, eds. Chesley's hypertensive disorders in pregnancy. Amsterdam: Academic press, Elsevier, 2009: 129- 42.

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