SERUM LACTIC DEHYDROGENASE : A BIOCHEMICAL MARKER IN PRE-

ECLAMPSIA AND ECLAMPSIA.

Presenter: Dr Amulya Swati3rd Year PG Student,

MS Obst/Gynae, PMCH,Patna,Bihar.

Guide: Dr Professor Pushpa RoyMBBS,MS,DGO,FICOG,

Dept of Obst/GynaePMCH,Patna,Bihar.

INTRODUCTION

• Hypertensive disorders in pregnancy and their complications rank as one of the major cause of maternal mortality and morbidity in the world. (5-10%)

• Preeclampsia complicates 2-8% of pregnancies. • It accounts for approximately a quarter of all antenatal admissions. • In addition, as it is strongly associated with fetal growth retardation and

prematurity, it also contributes largely to perinatal mortality and morbidity.• Pre-eclampsia is a multi-system disorder of unknown etiology, unique to pregnancy,

with onset after 20 weeks of gestation. • Eclampsia is the occurrence of convulsions in association with the signs and

symptoms of pre-eclampsia

Lactate Dehydrogenase (LDH) : an intracellular enzyme

• In the scenario of increased cell leakiness, hemolysis and cell death, LDH levels are increased in the serum.

• There is enormous vasculo-endothelial cell damage and cellular death in preeclampsia.

• Serum LDH levels can be used to assess the extent of cellular death and thereby the severity of disease.

The Global Burden of Hypertensive Disorders In Pregnancy

• Worldwide Hypertensive Disorders in Pregnancy is the second leading cause of maternal mortality; following haemorrhage , according to WHO systematic analysis published in 2014.

Fig 1. Global causes of maternal deaths : a WHO systematic analysis [ The Lancet Global Health , June 2014 ; Vol 2 , issue 6 ]

27%

14%11%9%

8%3%

28%

GLOBAL MMR (2003 - 2009 )

Haemorrhage 27%HDP 14%Infection 11%obstructed labour 9%unsafe abortions 8%embolism 3%other causes 28%

Common causes of Maternal deaths in PMCH , PATNA ( 2013 )

• During this study, I found that in our institute Patna Medical College and Hospital, Patna, Hypertensive disorders in pregnancy is the leading cause of maternal mortality and morbidity with worse fetal outcomes. This may be accounted to the reason that Patna Medical College being a tertiary centre, is a hub of all referred cases from urban and rural areas of Bihar.

30%

23%11%

10%

26%

MATERNAL MORTALITY IN PMCH

HDP 30%Haemorrhage 23%Anaemia 11%Sepsis 10%Others 26%

AIMS AND OBJECTIVES

• To evaluate the correlation of high serum LDH levels in pre-eclampsia and eclampsia to predict the severity of the disease.

• To improve the feto-maternal outcome in these patients.

MATERIAL AND METHODS• The study was conducted in the department of Obstetrics and Gynaecology, Patna

Medical College and Hospital, Patna, Bihar, India from October 2012 to September 2014.

• Total 100 pregnant women were selected from outpatient department and labour room emergency. All women were in their 3rd trimester of pregnancy.

• The cases were studied in the following groups.• Group A (Mild pre-eclampsia) 25 pregnant women having Singleton

pregnancy,Gestational age 28-40 wks,Blood pressure systolic ≥ 140mmHg,Diastolic ≥ 90 mmHg ,Proteinuria >300mg/ 24 hr or 1+ by dipstick.

• Group B (Severe pre-eclampsia) 25 pregnant women having Singleton pregnancy,Gestational age 28-40 wks,Blood pressure Systolic >160 mmHg,Diastolic > 110 mmHg,Proteinuria >3+

• Group C (Eclampsia) 25 pregnant women having Singleton pregnancy,Gestational age 28-40wks, Convulsions

• Group D (Normal control group) 25 pregnant women having Singleton pregnancy Gestational age 28-40 wk, Normotensive

• The Subjects were also divided according to the S.LDH levels into following groups.

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

• NORMAL SERUM LDH VALUES– Non pregnant women115 to 211 IU/L– First Trimester 78 to 433 IU/L, Second Trimester 80 to 447 IU/L , Third Trimester 82 to 524 IU/L .

• Serum LDH value above the reference range was taken as raised. • Plain blood sample on empty stomach was collected for analysis of LDH which was

done in fully automated biochemistry analyzer.• Exclusion criteria• Medical disorders : liver disorders, diabetes, renal disease, chronic hypertension,

cardiovascular illness, epilepsy, thyroid disorders, hemolytic diseases, Urinary tract infections.

• Obstetric complications e.g. Twin pregnancy.

No. of cases(100)

This study included 100 patients and was divided in 4 groups each with 25 patients. 25 of these were taken as control. 75 cases were divided according to the severity of hypertensive disorders in mild pre-eclampsia, severe pre-eclampsia and eclampsia.

25

2525

25

CASE DISTRIBUTION

A -MILD PRE ECLAMPSIA

B - SEVERE PRE ECLAMPSIA

C - ECLAMPSIA

D - CONTROL

Age distribution.

Click icon to add picture

This graph shows that 40% of patients with eclampsia (i.e.10 in 25)and 36% of patients with severe pre-eclampsia (i.e. 9 in 25) belong to age group 18-21 years.

A- mild pre eclampsia B -severe pre

eclampsia C -eclampsiaD -control

0

5

10

15

20

25

30

35

40

24

3640

20

2424

2428

28

20

12

2824

2024

2418-21yrs22-25yrs26-29yrs30-33yrsNo

. of p

atien

ts (%

dist

ributi

on)

Distribution according to parity

Majority of patients with severe pre eclampsia (40%) and eclampsia (48%) were primi-gravida

05

101520253035404550

28

40

48

24

24

1624 28

24

20

8

24

2424

20 24 G1 G2

G3 G4 & more

No. o

f pati

ents

(% d

istrib

ution

)

Gestational age at delivery.

76% cases of eclampsia and 68% cases of severe pre eclampsia delivered before term i.e. at <37 weeks. 84% cases of mild pre-eclampsia delivered at term. Whereas all patients in control group delivered at term.

A-mild preeclampsia B-severe

preeclampsia C-eclampsiaD-control

0

5

10

15

20

25

1

77

0

3

10 12

0

21

8

6

25

29-32 weeks33-36weeks37-40weeksNo

. of p

atien

ts

S. LDH LEVELS

This graph shows mean ldh levels in all groups. Highest level was found in eclampsia patients.

40 women had ldh below 600, 20 had ldh b/w 600-800 and 40 had ldh above 800.

All controls had ldh below 600 IU/ml.

A- mild

preecla

mpsia

B- sev

ere pre

eclam

psia

C- ecla

mpsia

D- contro

l

0.0

200.0

400.0

600.0

800.0

1000.0

1200.0

600.3

1074.01154.2

292.2S. LDH levels in IU/L

Group A Group B Group C Group D0

5

10

15

20

25

14

10

25

9

4

7

0

2

20

18

0

<600600-800>800

S.LDH groups

No.

of p

atien

ts

RELATION OF S. LDH LEVELS WITH BP

This graph shows the mean systolic and diastolic BP of women in relation to the mean S.LDH levels. (distribution group wise)

This graph shows higher systolic and diastolic BP in women with rising S.LDH levels. Levels above 800IU/L were associated with significantly higher BP

Group A Group B Group C Group D60

80

100

120

140

160

180

200

0.0

200.0

400.0

600.0

800.0

1000.0

1200.0

1400.0

148

177 178

113

99

118111

75

600.3

1074.0

1154.2

292.2

BP Distribution of Means LDH

Systolic BP Diastolic BP

<600 600-800 >800

0

20

40

60

80

100

120

140

160

180

100.8 105114.45

149.2160.5

178.3

DIASTOLIC BP(mmHg)

SYSTOLIC BP(mmHg)

S.LDH (IU/L)

S.LDH VS. BLOOD UREA, S.CREATININE, BILIRUBIN, SGPT, SGOT

Mean urea and creatinine levels correlated with high LDH levels.

Mean S. Transaminases and bilirubin were highest in eclampsia group

Group A Group B Group C Group D0.0

5.0

10.0

15.0

20.0

25.0

30.0

35.0

40.0

0.0

200.0

400.0

600.0

800.0

1000.0

1200.0

29.6

36.433.7

20.8

1.0 1.5 1.6 0.7

600.3

1074.0

1154.2

292.2

Distribution of Means

Blood Urea (mg/dl) Serum Creatinine (mg/dl)

LDH (IU/ L)

Group A Group B Group C Group D20.0

25.0

30.0

35.0

40.0

45.0

50.0

55.0

0.0

0.5

1.0

1.5

2.0

2.5

25.8

35.6

43.2

24.2

27.9

36.7

50.2

27.0

0.8

1.3

2.2

0.7

Transaminases Distribution of Means Bi-lirubin

SGPT (IU/L) SGOT (IU/L) S.bilirubin (mg/dl)

NEONATAL OUTCOME

Rate of still births was higher in cases with pre-eclampsia and eclampsia group. There was no still birth in the control group in this study.

11 out of total 16 still births (68.75%) were in the group with S.LDH above 800IU/L.

0

5

10

15

20

25

21 2017

25

4 57

0

Still birthAlive

<600 600-800 >8000

5

10

15

20

25

30

35

40

45

39

16

28

14

11

alivestillbirth

S.LDH in IU/L

It was found that as the LDH increased, mean gestational weeks at birth decreased, and at >800 IU/L mean GA was 33.6wks.

It was found that as S.LDH level increased mean APGAR score decreased.

<600 600-800 >800

31

32

33

34

35

36

37

38

39 38.4

36.9

33.6

Gestational age at birth (in weeks)

gestational age at birth (in weeks)

<600 600-800 >8000

1

2

3

4

5

6

7

8

9

7.1

5.6

3.6

8.4

6.9

4.9

APGAR scores vs LDH

APGAR (1 min)APGAR (5 min)

S.LDH in IU/L)

BIRTH WEIGHT

22 babies (88%) delivered by women with severe pre-eclampsia and 16 babies (64%) of eclamptic mothers were low birth weight.

As LDH increased, baby birth weight decreased. Above 800 IU/L mean birth weight was 1.9kg

<600600-800

>800

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5 2.9

2.6

1.9

Birth weight in kg

LDH in IU/L

0

2

4

6

8

10

12

14

16

18

20

1

5 6

0

13

17

10

5

11

3

8

20

<1.5kg1.5-2.5kg>2.5kg

MATERNAL MORBIDITY

Maximum morbidity was found in women with S.LDH above 800IU/L.

Women with severe preeclampsia and eclampsia had most complications.

<600 600-800 >8000

0.5

1

1.5

2

2.5

3

3.5

4

4.5

1 1

3

0

2

4

0 0

1

0 0

4

0 0

1

0 0

1

0 0

2

abruptio placenta

pulmonary oedema

cerebro vascular accidents

post partum eclampsia

HELLP

ARF

sec sut

A- mild

preeclampsia

B- seve

re preeclampsia

C -ecla

mpsia

D -contro

l0

1

2

3

4

5

6

7

8

12 2

0

1

23

0

0

0

1

0

1

30

0

01

0

ARF

HELLP

post partum eclampsia

cerebro vascular accidents

pulmonary oedema

abruptio placenta

DISCUSSION• Preeclampsia and eclampsia was found to be more common in young women who

were primi-gravida from lower socioeconomic group.• S. LDH increased as the severity of disease increased.• The mean blood pressure was found higher.• Blood investigations shown higher levels of urea, creatinine, bilirubin, SGPT, SGOT

and uric acid.• Highest morbidity was found in women with S .LDH >800IU/L. Complications

included abruption, pulmonary oedema, acute renal failure, HELLP syndrome, Cerebrovascular accidents, post partum eclampsia.

• There were 2 maternal mortalities, both with S.LDH >800 IU/L.• Perinatal morbidity was highest in women with S.LDH >600IU/L.• There were preterm births, low birth weight babies, low APGAR scores, more NICU

admissions of babies.• Still birth rates were highest in women with S.LDH>800IU/L.

Statistical analysis of the present study was done using “2 sample T-test” and the p-values were calculated. We compared systolic BP, diastolic BP of patients and gestational age, baby weight, APGAR scores at one and five minutes of babies in all the cases of group A,B,C with control group D.

LDH <600 IU/L 600-800 IU/L >800 IU/L Control (<600IU/L) Systolic BP (mmHg) 149.20±9.65 160.5±16.8 178.3±21.1 112.72±9.78

P Value <0.001Diastolic BP (mmHg) 100.8±7.99 105±13.6 114.45± 9.69 74.96±7.77

P Value <0.001Gestational age

(weeks)38.4±1.4 36.9±1.62 33.55±2.74 38.84±1.11

P Value 0.155 <0.001Baby Wt. (Kg) 2.94±0.48 2.63±0.47 1.9±0.65 3.14±0.47

P Value 0.106 <0.001APGAR Score

(1min.)7.07±2.02 5.6±3.08 3.56±2.6 7.16±0.9

P Value 0.43 0.02 <0.001APGAR Score

(5min.)8.40±2.32 6.9±3.58 4.85±3.29 8.8±0.5

P Value 0.261 0.015 <0.001

The analysis showed that- The systolic BP and diastolic BP was significantly higher in patients of all the 3 groups with

S.LDH <600, 600-800 and >800 IU/L when compared against control group. (p value <0.001) The gestational age at birth of babies was significantly lower in 2 groups with S.LDH 600-800

and >800 IU/L (p value <0.001). The difference was not significant in babies in <600 IU/L group. (p value 0.155)

The birth weight of babies was significantly lower in 2 groups with S.LDH 600-800 and >800 IU/L (p value <0.001). The difference was not significant in babies in <600 IU/L group.(p value 0.106)

The APGAR scores at one minute and five minutes of babies was significantly lower in >800 IU/L (p value <0.001). The difference was not significant in babies in <600 IU/L group. (p value 0.43 at one minute and 0.261 at five minutes) and 600-800 group (p value 0.02 and 0.015 at one and five minutes respectively)

• All cases were followed in hospital for at least seven days and discharged

• For further management of their blood pressures they were advised medical checkup after two weeks, and then four to six weeks later.

• Preconception counselling and Regular ANC during subsequent pregnancy was advised.

• They were also advised for medical supervision at intervals to rule out chronic diseases like chronic hypertension, cardiovascular diseases and diabetes in future.

CONCLUSION• Serum lactic dehydrogenase as a biochemical marker is cheap, easily available

test which can be offered to all the patients with hypertensive disorders in pregnancy.

• Identification of high-risk patients with elevated levels of lactic dehydrogenase, their close monitoring and prompt and correct management may prevent or at least reduce the complications .

• Hence , S.LDH along with other severity markers can be used in making decision, regarding the management strategies to improve the maternal and fetal outcome.

• This would lead to a decrease in the global burden of maternal and perinatal morbidity and mortality.

Pregnancy is nature’s precious gift which has to be nurtured

during its entire nine months to achieve good maternal and fetal

outcome

THANK YOU