Volume 17 Issue 3

Table of Content - Volume 17 Issue 3 - March 2021

Comparative study of serum LDH levels in pregnant women with non-severe preeclampsia and in severe preeclampsia/eclampsia

Guruprasad Hosamani

Assistant Professor, Department of OBGYN, Raichur Institute of Medical Sciences, Raichur, INDIA.

Email: guruhosmani@yahoo.com

Abstract Background: Lactate Dehydrogenase (LDH) levels are increased in the scenario of increased cell leakiness, hemolysis and cell death. PIH is associated with increased cell death and cell leakiness. Hence increased levels of LDH are often seen in PIH.This study aims to determine whether a correlation exists between maternal and perinatal outcomes and severity of the disease with serum LDH levels. Material and Methods: Present study was prospective, comparative study, conducted in the Pregnant women between 18-35 years, singleton pregnancy, ≥20weeks of gestation with pregnancy induced hypertension. Patients were divided into Group A (patients of non-severe preeclampsia) and Group B (patients of severe preeclampsia and eclampsia). Results: In present study serum LDH in group A was <600 in 51%, 600-800 in 29% and >800 in 20% whereas in group B serum LDH was <600 in 99% and >800 in 1%. p value is <0.001 which is statistically significant. In our study mean serum LDH is 570.5 in group A as compared to group B was mean serum LDH is 201.5. p value was <0.001 which is statistically significant. In our study mean serum LDH in eclampsia is 725 and in controls it is 565.5, p value is 0.221 which is statistically not significant. In our study serum LDH <600 had abruption with PPH, DIC, eclampsia and PPH in 2% each, with serum LDH 600-800 had PPH in 6.9% and with serum LDH >800 had PPH in 5% cases. p value is 0.85 which is statistically not significant. In our study serum LDH<600 underwent elective LSCS in 47.1%, NVD in 47.1%, emergency LSCS in 3.9% and forceps assisted vaginal delivery in 2%. In our study serum LDH <600 had a IUGR in 7.8%, fetal distress in 5.9%, neonatal death and stillbirth in 3.9% each, IUD, LBW, MSL and premature births in 2% each. Serum LDH between 600-800 had IUGR and LBW in 3.4% each. Serum LDH with >800 had IUGR in 15% and neonatal death and stillbirth in 5% each which is clinically significant. p value is 0.585 which is statistically not significant. Conclusion: Higher serum LDH levels more than 500 IU/L to 600 to 800 IU/L have closer association with severe preeclampsia. LDH can be used as a laboratory-based evidence of endothelial damage in preeclampsia.

Keywords: Preeclampsia, eclampsia, LDH(lactate dehydrogenase), pregnancy induced hypertension

INTRODUCTION

Pregnancy is a physiological state associated with many alterations in metabolic, biochemical, physiological, hematological and immunological processes. If there are no complications, all these changes are reversible following a few days to a few months after delivery.¹ Hypertensive disorders of pregnancy are responsible for 8-9% of maternal deaths in India and 15 - 20% of maternal deaths in western world.² Overall they complicate 5-10% of pregnancies in India.^2,3PIH is defined as development of high BP i.e., systolic blood pressure level of 140 mmHg or higher and/or diastolic blood pressure of 90 mmHg or higher, on at least two occasions 6 hrs apart but within a maximum of a week period after 20 weeks of gestation or during labour or during the first 24 hrs after delivery in a previously normotensive, non-proteinuric woman and the blood pressure resolves within 3 months post-partum.⁴It can be divided into non-severe and severe types. Lactate Dehydrogenase (LDH) is mainly an intracellular enzyme. It is responsible for the interconversion of lactate to pyruvate in the cells. Its levels are several times greater inside the cells than in the plasma. Its levels are increased in the scenario of increased cell leakiness, hemolysis and cell death. PIH is associated with increased cell death and cell leakiness. Hence increased levels of LDH are often seen in PIH.⁵ This study aims to determine whether a correlation exists between maternal and perinatal outcomes and severity of the disease with serum LDH levels. This can be further used as a marker in making decisions, regarding the management strategies to improve the maternal and foetal outcomes as well as for prognostic counselling.

MATERIAL AND METHODS

Present study was prospective, comparative study, conducted in the Obstetrics and Gynaecology Department, Raichur Institute of Medical sciences, Raichur which is a tertiary care centre, catering to both low risk and high-risk antenatal patients. Study duration was of 1 year (1^st January 2018 to 31^st December 2018). Study was approved by institutional ethics committee.

Inclusion criteria:

Pregnant women between 18-35 years, singleton pregnancy, ≥20weeks of gestation with pregnancy induced hypertension.

Exclusion Criteria:

Pregnant women with essential hypertension or hypertension <20 weeks gestation;
Pregnant women with pre-existing diabetes mellitus,
Pregnant women with renal disease, liver disorder,
Pregnant women with hyperthyroidism, epilepsy, urinary tract infection, cardiovascular disease, smokers, alcoholics, Rh negative pregnancy, multiple gestation.
Not willing to participate / follow up

All women eligible for the study were explained about the study. An informed consent was taken from all the patients for inclusion in the study.

Study sample was divided into following groups:

Group A- Patients of non-severe preeclampsia⁶

Defined as Pregnant female of ≥20 weeks of gestation with blood pressure ≥140/90 mm of Hg and<160/110 mm of Hg noted first time during pregnancy on ≥2 occasions at least 6 hours apart with proteinuria of ≥1+ (≥30mg/dl) by dipstick method in a random urine sample would be considered as having mild preeclampsia after excluding urinary tract infection.

Group B- Patients of severe preeclampsia and eclampsia.⁶

Defined as the presence of 1 of the following symptoms or signs:

SBP of 160 mm Hg or higher or DBP of 110 mm Hg or higher on 2 occasions at least 6 hours apart while the patient is in bed rest
Proteinuria of 5g or higher in a 24-hour urine specimen or 3+ or greater on two random urine samples collected at least 4 hours apart 3+ on 2 random urine samples collected at least 4 hours apart
Oliguria of less than 500ml in 24 hours
Cerebral or visual disturbances
Pulmonary oedema or cyanosis
Epigastric or right upper quadrant pain
Impaired Liver function
Thrombocytopenia ( platelets <100000)
Intrauterine growth restriction

Blood was collected for analysis along with routine blood investigations. LDH levels was estimated in Erba biochemical fully automated analyzer by using Kinetic UV test.

Normal Serum LDH Values

Non-pregnant

women

First

Trimester

Second

Trimester

Third

Trimester

115 to 211 IU/L

78 to 433 IU/L

80 to 447 IU/L

82 to 524 IU/L

Serum LDH value above the reference range is taken as raised.

All women included in the study were followed until delivery. LDH levels was done after inclusion in the study and patients were followed up till delivery. Management was done according to hospital protocol. All maternal complications like abruption, eclampsia, renal failure, hepatic failure, cerebrovascular accidents, HELLP syndrome [hemolysis, elevated liver enzymes, and low platelet count], pulmonary oedema, shock, postpartum haemorrhage, Disseminated intravascular coagulation are noted down. All perinatal complications including gestational age at the time of delivery, birth weight, APGAR at 1 and 5 min, Intra uterine death, Neonatal ICU admission , Hypoxic ischemic encephalopathy and perinatal mortality are noted down. If patient with non-severe preeclampsia develops severe preeclampsia, LDH levels were repeated and followed up as group 2 patients. All non-severe preeclampsia women included in the study, LDH levels was done and followed till delivery. If patient of non-severe preeclampsia changed to severe preeclampsia LDH levels was done again and followed as severe preeclampsia. Data was analyzed using SPSS software v.23.0. and Microsoft office 2007. All characteristics were summarized descriptively. For continuous variables, the summary statistics of mean± standard deviation (SD) were used. For categorical data, the number and percentage were used in the data summaries and diagrammatic presentation. Chi-square (χ²) test was used for association between two categorical variables. If the p-value was < 0.05, then the results were considered to be statistically significant otherwise it was considered as not statistically significant.

RESULTS

In present study 100 patients were studied in each group. In group A, maximum number of patients were between the age group 20-24 years (53%), next being 25-29 years (27%). While in group B majority i.e., 50%, were between 20-24years followed by 35%, were between 25-29 years, p value was not statistically significant(p=0.365)

Table 1: Age distribution

Age(yrs.)	GROUP A		GROUP B		p value
Age(yrs.)	N	%	N	%
<20	12	12	6	6	0.365
20-24	53	53	50	50
25-29	27	27	35	35
≥30	8	8	9	9

In present study maximum number of patients in group A were primigravida (49%), G2 were (32%). In group B maximum number patients were primigravida (53%), G2 were (32%). Hence p value is 0.447 which is statistically not significant

Table 2: Gravida status distribution

Gravida status	GROUP A		GROUP B		p value
Gravida status	N	%	N	%
Primi	49	49	53	53	0.447
G2	32	32	32	32
G3	14	14	8	8
≥G4	4	4	7	7

In group A maximum number of cases were > 38 weeks of gestation (55%), 36-38 weeks were (27%) and 32-34 weeks were 10%. As compared to group B 42% were >38weeks, 27% were 34-36 weeks and 16% were 32-34 weeks. p value is 0.147 which not statistically significant.

Table 3: Distribution of Gestational age

Gestational age (wks.)	GROUP A		GROUP B		p value
Gestational age (wks.)	N	%	N	%
≤32	0	0	2	2	0.147
32-34	10	10	13	13
34-36	8	8	16	16
36-38	27	27	27	27
>38	55	55	42	42

In present study serum LDH in group A was <600 in 51%, 600-800 in 29% and >800 in 20% whereas in group B serum LDH was <600 in 99% and >800 in 1%. p value is <0.001 which is statistically significant. In our study mean serum LDH is 570.5 in group A as compared to group B was mean serum LDH is 201.5. p value was <0.001 which is statistically significant.

Table 4: Distribution of LDH

LDH (IU/l)	GROUP A		GROUP B		p value
LDH (IU/l)	N	%	N	%
< 600	51	51	99	99	<0.001*
600 to 800	29	29	0	0
> 800	20	20	1	1
Mean ± SD	570.5 ± 270.9		201.9 ± 125.9		<0.001*

Note: * significant at 5% level of significance (p<0.05)

In our study mean serum LDH in eclampsia is 725 and in con

trols it is 565.5, p value is 0.221 which is statistically not significant.

Table 5: Mean LDH according to eclampsia and severe pre-eclampsia

Parameters	ECCLAMPSIA		SEVERE PRE-ECLAMPSIA		p value
Parameters	Mean	SD	Mean	SD	p value
LDH(IU/l)	725.0	226.1	565.5	301.1	0.221

In our study serum LDH <600 had abruption with PPH, DIC, eclampsia and PPH in 2% each, with serum LDH 600-800 had PPH in 6.9% and with serum LDH >800 had PPH in 5% cases. p value is 0.85 which is statistically not significant.

Table 6: Maternal Outcome According To LDH

Maternal Outcome	LDH(IU/l)< 600		LDH(IU/l) 600 to 800		LDH(IU/l)> 800		p value
Maternal Outcome	N	%	N	%	N	%	p value
Abruption WITH PPH	1	2.0%	0	0.0%	0	0.0%	0.85
DIC	1	2.0%	0	0.0%	0	0.0%
Eclampsia	1	2.0%	0	0.0%	0	0.0%
PPH	1	2.0%	2	6.9%	1	5.0%

In our study serum LDH<600 underwent elective LSCS in 47.1%, NVD in 47.1%, emergency LSCS in 3.9% and forceps assisted vaginal delivery in 2%. Serum LDH 600-800 underwent NVD in 72.4%, elective LSCS in 24.1% and emergency LSCS in 3.4%. serum LDH >800 underwent elective LSCS in 55%, NVD in 40% and emergency LSCS in 5%. p value is 0.286 which is statistically not significant.

Table 7: Mode of delivery according to LDH

Mode of Delivery	LDH(IU/l)< 600		LDH(IU/l) 600 to 800		LDH(IU/l)> 800		p value
Mode of Delivery	N	%	N	%	N	%
EM.LSCS	2	3.9%	1	3.4%	1	5.0%	0.286
Forceps assisted VD	1	2.0%	0	0.0%	0	0.0%
Elective LSCS	24	47.1%	7	24.1%	11	55.0%
NVD	24	47.1%	21	72.4%	8	40.0%

In our study mean APGAR 1 mins with serum LDH 600-800 is 7.7, >800 is 7.5, <600 is 7.2 respectively. mean APGAR 5 mins with serum LDH 600-800 is 8.7, >800 is 8.5, <600 is 8.3. p value is 0.083 and 0.217 APGAR 1min and APGAR 5mins, hence statistically not significant.

Table 8: Mean APGAR according to LDH

Parameters	LDH(IU/l)< 600	LDH(IU/l) 600 to 800	LDH(IU/l)> 800	p value
APGAR 1MIN	7.2±1.2	7.7±0.6	7.5±0.7	0.083
APGAR 5MIN	8.3±1	8.7±0.6	8.5±0.6	0.217

In our study serum LDH <600 had a IUGR in 7.8%, fetal distress in 5.9%, neonatal death and stillbirth in 3.9% each, IUD, LBW, MSL and premature births in 2% each. Serum LDH between 600-800 had IUGR and LBW in 3.4% each. Serum LDH with >800 had IUGR in 15% and neonatal death and stillbirth in 5% each which is clinically significant. p value is 0.585 which is statistically not significant.

Table 9: Perinatal outcome according to LDH

Perinatal Outcome	LDH(IU/l)< 600		LDH(IU/l) 600 to 800		LDH(IU/l)> 800		p value
Perinatal Outcome	N	%	N	%	N	%	p value
Fetal Distress	3	5.9%	0	0.0%	0	0.0%	0.585
IUD	1	2.0%	0	0.0%	0	0.0%
IUGR	4	7.8%	1	3.4%	3	15.0%
LBW	1	2.0%	1	3.4%	0	0.0%
MSL	1	2.0%	0	0.0%	0	0.0%
Neonatal death	2	3.9%	0	0.0%	1	5.0%
Premature	1	2.0%	0	0.0%	0	0.0%
Still Birth	2	3.9%	0	0.0%	1	5.0%

DISCUSSION

Preeclampsia is an important disease of pregnancy with potentially sever consequences for mother and child. It’s progression differs among patients. Severe preeclampsia can lead to grave complications like eclampsia, HELLP syndrome, abruption and even perinatal mortality and morbidity. All these correlate with distinct activity of LDH. Hence LDH is a useful biochemical marker that reflects the severity of preeclampsia. In our study, the study age of most pregnancies occurred in age group 20-24years followed by 25-29 years. Similar findings were noted by Jaiswar et al.⁷ and Pallavi Singh et al.⁸ In our study, most of the patients were primigravida. Similar findings were noted by Pallavi Singh et al.,⁸ In present study mean LDH in severe pre-eclampsia and eclampsia patients were 570.5 IU/L. Rubina Aziz et al.⁹ and Metin Ingec et al.¹⁰ noted mean LDH in severe pre-eclampsia and eclampsia patients as 348.34 IU/L and 1118 IU/L respectively. The mean LDH levels in the severe preeclampsia group were significantly higher compared to non-severe pre-eclampsia patients. Similar findings were noted by Metin Ingec et al.¹⁰ In the study post-partum haemorrhage, DIC, abruption, eclampsia were noted as maternal complications. They were significantly seen with raised LDH levels. Kiren K Malik et al.¹¹ reported that in severe preeclampsia patients with LDH>800 IU/L had significant increase in all the complications, eclampsia being the most frequent one. This was consistent with the findings of Qublan Hussein S et al.¹². Similarly, James N Martin et al. reported that LDH>1400IU/L have the strongest predictive value for the morbidity of the patients with severe preeclampsia.¹³ He S, Brenne K et al.¹⁴ studied the increased concentrations of lactate dehydrogenase in pregnancy with preeclampsia as a predictor for the birth of small for gestational age infants. They found that preeclamptic women with small for gestational age infants had significantly higher LDH concentrations than those in the appropriate for gestational age group, but ALT and AST concentrations did not increase significantly. This showed that increase in LDH levels were due to cell damage subsequent to chronic anoxemia and not due to liver damage in preeclampsia. A prospective study conducted by Sreelatha S et al.¹⁵, 80 PIH cases was participated in the study. Serum LDH, Serum Uric acid were analysed in these women. In their study they concluded that increased LDH level correlate with severity of PIH and has got poor perinatal outcome. So, it can be considered as one of the biochemical marker. A prospective comparative case control study was conducted by Y.Umasatyasri et al.¹⁶, 150 pregnant women were included in the study. In this study they assess the prognostic significance of the values of serum LDH as a marker of preeclampsia –eclampsia and severity. Mean LDH levels in normotensive (n=50) 159.06 ± 41.93 Mild preeclampsia (n = 30) 323.30 ±77.40 Severe preeclampsia (n =20) 636.20 ± 132.29 Eclampsia (n = 50) 649.32 ± 153.53 are founded. Higher serum LDH levels were associated with increased incidence of maternal complications like abruption placenta, renal failure, HELLP syndrome, cerebrovascular accidents etc. There was an increase in maternal morbidity with increasing serum LDH levels. In the study neonatal complications like IUD, IUGR, Preterm, Fetal distress, Stillbirth, APGAR at 1 min and 5 mins were not significantly higher in the abnormal LDH group. Qublan Hussein S et al.¹⁰⁸ reported that perinatal mortality were increased significantly in patients with LDH>800U/L compared with those who had lower levels. Serum LDH is the earliest marker in blood during hypoxia and oxidative stress. It is raised in cases of pre-eclampsia and eclampsia. Detection of high-risk patients with increased levels of LDH mandates close monitoring, prompt and correct management to decrease both maternal and foetal morbidity and mortality. Estimation of serum Lactate Dehydrogenase can be used as a prognostic marker for preeclampsia and eclampsia.

Limitations of present study were sample size studied was small and a smaller number of eclampsia patients. Larger studies are required to document findings.

CONCLUSION

Higher serum LDH levels more than 500 IU/L to 600 to 800 IU/L have closer association with severe preeclampsia. Thus, LDH can be used as a laboratory-based evidence of endothelial damage in preeclampsia. Hence serum LDH can be used as a good biochemical marker in for maternal and perinatal outcome in pre-eclampsia.

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