INTRODUCTION:

Preeclampsia is a pregnancy complication that affects many organs including the liver, kidneys, brain, blood vessels and often the placenta¹. It is diagnosed with hypertension, proteinuria and edema after the 20th gestational week². This problem occurs in approximately 8-10%³of pregnancies in India and is the leading cause of maternal, newborn and infant morbidity and mortality⁴.

According to studies, preeclampsia is responsible for approximately 50,000 maternal deaths worldwide each year⁵. The World Health Organization has determined the prevalence of preeclampsia in developing countries (2.8% of live births) are seven times more common in developing countries (0.4% of live births)⁶.

Pregnant women die from hemorrhage and hypertension disorders especially in developing countries⁷. Hypertension during pregnancy, especially eclampsia, is responsible for approximately 7-10% of all pregnancies⁸. The main features of preeclampsia include placental defects and endothelial dysfunction. Endothelial dysfunction can cause inappropriate vasoconstriction, platelet aggregation, activation of the coagulation system and ultimately reduced blood flow to organs, all of which are early symptoms of hypertension².

Pregnancy and childbirth are considered physiological processes that pose a risk to mother and child. Maternal deaths may result from complications such as bleeding, megaloblastic anemia⁹, gestational hypertension, sepsis, obstructed birth, and abortion complications. Globally, maternal mortality estimate is 400/1,00,00 live births¹⁰. According to the Preeclampsia Foundation, preeclampsia is a pregnancy complication that affects approximately 3 million women worldwide each year and kills one woman every six minutes. This condition is characterized by maternal hypertension, proteinuria and edema after the 20th week of pregnancy and can be fatal for both mother and baby².

Depending on the severity of symptoms, preeclampsia can be classified as mild or severe. Acute preeclampsia is defined as high blood pressure after the 20th week of pregnancy with a systolic blood pressure of 140-160 mmHg or a diastolic blood pressure of 90-110mmHg and proteinuria of 0.3-5 grams per day. A blood pressure of 160mmHg or a diastolic blood pressure of more than 110mmHg with proteinuria of 5g or more per day is diagnosed as severe preeclampsia¹¹. Although the etiology of preeclampsia is unknown, it may be associated with placental hypoxia and endothelial dysfunction, as well as with race, genetics, diet, immune system and increased oxidative stress¹². Eclampsia is a complication of preeclampsia that can seriously affect maternal health, including kidney failure, liver disease, HELLP syndrome, abruptio placentae¹³, DIC, cerebrovascular accident, pulmonary edema, and aspiration pneumonia¹⁴. It may also increase perinatal mortality through preterm delivery, uterine enlargement, low birth weight¹⁵ and birth asphyxia¹⁶.

Lactate dehydrogenase (LDH) is an intracellular, cytosolic enzyme found in all organs, including the heart, kidneys, muscles, and white and red blood cells, that converts lactate to pyruvate. Cellular enzymes in the extracellular space are useful because they can work as indicators of disruption of cellular integrity, pathological diseases and assess cell damage or cell death, even if there is no additional metabolic function in this area. LDH levels have recently been accepted as an important biochemical marker of the severity and outcome of preeclampsia and an indicator of multiorgan involvement. No studies have been done in our institution to correlate the serum LDH increase with the severity of preeclampsia and its association with hypertension and adverse outcomes maternofetal outcome.

Although LDH estimation is not specific, it is a simple, less invasive and inexpensive biochemical test that has been shown to have good sensitivity, reliability, and predictability of adverse fetal outcomes in predicting severity^17,18,19. Preeclampsia and eclampsia are more common in developing countries due to hypoproteinemia, malnutrition, inadequate facilities and ineffective use of antenatal services. Therefore, early detection of this biochemical marker may improve care for these women thereby improving maternal and fetal outcomes²⁰. Therefore, in this study, it was aimed to evaluate serum LDH levels in pregnant women, systolic and diastolic blood pressureand to compare LDH levels with maternal and fetal outcomes in three groups (group 1: normotensive group, group 2: mild preeclampsia, group 3: severe preeclampsia). These diseases can affect almost all pregnant women and require close cooperation, so special attention should be paid to prevention, diagnosis and treatment.

MATERIALS AND METHODS:

The research group comprised of pregnant women with preeclampsia who had sought treatment from the Obstetrics and Gynecology department of a tertiary hospital. The study design was a case-control study, and the sample size was 60. The study was conducted between February and March 2021 and involved measuring the serum LDH levels in a total of 60 antenatal patients who were 28 weeks or more into their pregnancy.

Inclusion Criteria:

· Singleton Pregnancy

· Age 19-35

· Normotensive preeclamptic women in the first 20 weeks of pregnancy

· No history of hypertension

· All diseases in late pregnancy (> 28 weeks gestation).

Exclusion criteria: Patients with history of liver disease, diabetes, renal failure, heart disease, lung disease multiple pregnancy, gestational diabetes, hypertension, epilepsy or history of hepatotoxic drug use were excluded. Sixty pregnant women in the third trimester were enrolled in this study and was divided depending upon the classification given by ACOG into following groups:

Group 1: 30 healthy normotensive pregnant women (controls);

Group 2: 15 patients with clinical features of mild preeclampsia (subjects): BP of >140/90 to<160/110mmHg

Group 3: 15 patients with clinical features of severe preeclampsia (subjects): BP ≥ 160/110mmHg

Method of Lactate dehydrogenase (LDH) estimation:

At the third-trimester hospital visit, under aseptic conditions, approximately 1ml of venous blood was collected in a plain vial from all three groups of women before the initiation of medical treatment. The blood sample was allowed to clot and then centrifuged to estimate the serum LDH levels. The estimation was performed using the International Federation of Clinical Chemistry method (IFCC method)²¹ on a VITROS 5600 analyzer.

Principle:

Total LDH is tested by reaction of serum sample with lactate and NAD.The reaction is catalysed by LDH

Pyruvate + NADH+H⁺ Lactate dehydrogenase Lactate + NAD⁺

The rate at which NADH falls is directly proportional to LDH activity.Normal serum LDH values: -non pregnant women 115-211 IU/l -first trimester 78-433IU/IL, second trimester 80 – 447 IU/lL, third trimester 82 -524 IU/L²². The patients were divided according to the serum LDH levels into following groups:

(a) < 600 IU/L (b)600–800 IU/L (c) >800 IU/L

All women will be followed up until delivery and early postpartum period and babies till early neonatal period.

RESULTS:

Statistical analysis was performed using version 25 of the Statistical Package for the Social Sciences (SPSS).Continuous variables was expressed as Mean and Standard Deviation(SD). Chi-square and Student’s t-test were utilized to compare the differences between the study and control groups. ANOVA (Analysis of Variance) was performed to determine the correlation between variables.All P value of 0.01 or less was considered statistically significant and no significance for p-values greater than 0.05

The study consisted of 60 patients, of whom 30 were normal pregnant women. The remaining 15 included pregnant women with mild preeclampsia and 15 with severe preeclampsia. The maximum number of patients in the control and test groups were between the ages of 19 and 35 years (Table 1).

Table 1: Distribution of patients based on age and gravidity

Variables	Groups			p Value
Variables	Normal (n=30)	Mild preeclampsia (n=15)	Severe preeclampsia (n=15)	p Value
Age (Mean ± SD)	26.33 ± 4.25	28.67± 4.12	27.00± 4.46	0.232
Gravidity
Primi - n(%)	15 (50.0)	5 (33.3)	4 (26.7)	0.267
Multi- n(%)	15 (50.0)	10 (66.7)	11 (73.3)	0.267

When the data were analyzed, an increase in LDH levels was observed with increasing disease severity (Table 2).

Table 2: Distribution of LDH levels among study groups

LDH Range

Control

(n=30)

Mild preeclampsia

(n=15)

Severe preeclampsia

(n=15)

Total

(n=60)

p Value

<600

n (%)

(100.0)

(86.7)

(80.0)

(91.7)

0.05

600-800

n (%)

(0.0)

(6.7)

(0.0)

(1.7)

>800

n (%)

(0.0)

(6.7)

(20.0)

(6.7)

The mean LDH levels in the various study groups are presented in Table 3, and the p-value of the data is highly significant.

Table 3: Association of LDH levels in various groups

Variables	LDH level (Mean ±SD)	LDH level Range	p Value
Control (n=30)	186.43±38.02	125-270	0.01
Mild Preeclampsia (n=15)	340.00±221.78	125-913
Severe Preeclampsia (n=15)	514.73±359.59	183-1367
Total (n=60)	306.90±248.40	125-1367

Further analysis revealed that higher systolic and diastolic blood pressures were associated with higher serum LDH levels (Table 4).A p value of 0.05 was considered significant for the available data.

Table 4: Association of systolic and diastolic Blood pressure (BP) with LDH levels in various groups

Variabes	<600 IU/L (n= 55)	600-800 IU/L (n= 1)	>800 IU/L (n=4)	Total (n= 60)	p Value
Systolic BP (mmHg)
90- <140	30	0	0	30	0.05
140-<160	13	1	1	15
≥160	12	0	3	15
Diastolic BP (mmHg)
Variabes	<600 IU/L (n=55)	600-800 IU/L (n=1)	>800 IU/L (n=4)	Total (n= 60)	0.26
60- <90	25	0	0	25
90-<110	17	1	2	20
≥110	13	0	2	15

In this study, the relationship between neonatal outcomes and birth weight (kg) was compared with serum LDH levels.

Table 5: Comparison of neonatalbirth weight depending on LDH levels

Serum LDH IU/L	<600 IU/L	600-800 IU/L	>800 IU/L	p Value
Mean neonatal birth weight (Kg)	2.64±0.50	1.78±0.56	1.67±0.68	0.01

This analysis shows that neonates with higher LDH had a higher body weight (Table 5).

Table 6: Comparison of foetal outcome depending on LDH levels

Serum LDH IU/L	<600 IU/L (n=43)	600-800 IU/L (n=1)	>800 IU/L (n=7)	p Value
Neonatal compications	19	0	2	0.63
Neonatal death	2	0	1	0.16
NICU Admission	22	1	4	0.04

The study also compared fetal outcome based on LDH (Table 6). Maternal outcomes also correlated with increasing LDH levels (p = 0.01) (Table 7).

Table 7: Comparison of adverse maternal outcome depending on LDH levels

Serum LDH IU/L	<600 IU/L	600-800 IU/L	>800 IU/L	p Value
HELLP syndrome	8	0	2	0.16
Abruptio placenta	0	0	1	0.01
DIC	0	0	0	-
Acute kidney injury	0	0	1	0.01
Renal failure	0	0	0	-
Postpartum hemorrhage	0	0	1	0.01
Transfusion of blood products	0	0	1	0.01
Cerebrovascular accidents	0	0	0	-
Posterior reversible encephalopathy	1	0	0	0.96
Eclampsia	1	0	1	0.04

DISCUSSION:

Preeclampsia is a multisystem disorder specific to human pregnancy, and its cause is unknown. Early detection is crucial in preventing complications. This disorder can cause dysfunction in the mother's heart, kidneys, lungs, nervous system, and coagulation system, leading to excess fluid production, LDH elevation, and high blood pressure. The findings of Qublan et al¹⁷ and Jain et al²³ support this. Thepresent study hasevaluated that LDH can be used as a biochemical marker of preeclampsia. An increase in LDH levels indicates cell death and enzyme leakage from the cell. The study found that preeclamptic women had higher serum LDH levels than normal pregnant women. These findings matches with the resultsof other authors.

In mild preeclampsia, 86.7% of patients had LDH levels <600 IU/l, whereas in severe preeclampsia, 80% of patients had LDH levels <600 IU/l. LDH levels were significantly higher in severe preeclampsia than in mild preeclampsia. These results are similar to those of Demir et al²⁴.The study also found that higher LDH levels were associated with an increase in systolic and diastolic blood pressure. However, only systolic blood pressure showed statistical significance. Jaiswar et al. also observed similar results¹⁹.

High LDH levels were linked to an increased incidence of neonatal complications, and the average birth weight of babies was lower in mothers with higher LDH levels. These findings were also reported in the study conducted by Jaiswar et al.

The study concluded that higher serum LDH levels were associated with an increased risk of maternal complications such as placental abruption, acute kidney injury, HELLP syndrome, and postpartum hemorrhage. Similar observations were made by Jain etal andJaiswar et al. LDH is a good predictor of the severity of gestational hypertension and adverse fetal outcomes, according to the study conducted by Bera et al. In summary, serum LDH levels have a significant association with various maternal and fetal outcomes in patients with mild and severe preeclampsia.

CONCLUSION:

Preeclampsia is a pregnancy-specific disease characterized by elevated LDH levels in mild to severe cases compared to normal pregnancies. This indicates cellular damage and dysfunction. High LDH levels are associated with maternal and fetal complications. Hence, the assessment of LDH levels can serve as a biochemical indicator of the severity of preeclampsia and the likelihood of complications. Regular monitoring of LDH levels in high-risk pregnancies can aid in early diagnosis and intervention, thereby preventing adverse outcomes for both the mother and fetus.

ACKNOWLEDGEMENT:

We thank Indian council of medical research(ICMR) for funding the research through short term studentship program (STS).

CONFLICT OF INTEREST:

There is no conflict of interest.

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Received on 13.05.2023 Modified on 23.09.2023

Research J. Pharm. and Tech 2024; 17(5):2109-2113.

DOI: 10.52711/0974-360X.2024.00334