Serum lactate dehydrogenase : a biochemical marker in pre-eclampsia and eclampsia.
1.
2. 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
3. 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.
4. 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%
5. 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%
6. 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.
7. 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
8. • 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.
9. 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
10. Age distribution.
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.
0
5
10
15
20
25
30
35
40
A- mild pre
eclampsia B -severe pre
eclampsia C -eclampsia
D -control
24
36
40
20
24
24
24
28
28
20
12
2824
20
24
24
No.ofpatients(%distribution)
18-21yrs
22-25yrs
26-29yrs
30-33yrs
11. Distribution according to parity
Majority of patients with severe pre eclampsia (40%) and eclampsia (48%) were
primi-gravida
0
10
20
30
40
50
A-mild pre
eclampsia B-severe pre-
eclampsia C-eclampsia
D-control
28
40
48
24
24
16
24
28
24
20
8
24
24
24
20
24
No.ofpatients(%distribution)
G1
G2
G3
G4 & more
12. 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.
0
5
10
15
20
25
A-mild
preeclampsia B-severe
preeclampsia C-eclampsia
D-control
1
7
7
0
3
10
12
0
21
8
6
25
No.ofpatients
29-32 weeks
33-36weeks
37-40weeks
13. 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.
0.0
200.0
400.0
600.0
800.0
1000.0
1200.0
600.3
1074.0 1154.2
292.2
S. LDH levels in
IU/L
0
5
10
15
20
25
Group A Group B Group C Group D
14
1
0
25
9
4
7
0
2
20
18
0
No.ofpatients
S.LDH groups
<600
600-800
>800
14. 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
148
177 178
113
99
118
111
75
600.3
1074.0
1154.2
292.2
0.0
200.0
400.0
600.0
800.0
1000.0
1200.0
1400.0
60
80
100
120
140
160
180
200
Group A Group B Group C Group D
BP Distribution of Means LDH
Systolic BP Diastolic BP
0
20
40
60
80
100
120
140
160
180
<600
600-800 >800
100.8 105 114.45
149.2
160.5
178.3
S.LDH (IU/L)
DIASTOLIC
BP(mmHg)
SYSTOLIC
BP(mmHg)
15. Mean urea and creatinine levels correlated
with high LDH levels.
Mean S. Transaminases and bilirubin were
highest in eclampsia group
29.6
36.4
33.7
20.8
1.0 1.5 1.6 0.7
600.3
1074.0
1154.2
292.2
0.0
200.0
400.0
600.0
800.0
1000.0
1200.0
0.0
5.0
10.0
15.0
20.0
25.0
30.0
35.0
40.0
Group A Group B Group C Group D
Distribution of Means
Blood Urea (mg/dl)
Serum Creatinine (mg/dl)
LDH (IU/ L)
25.8
35.6
43.2
24.2
27.9
36.7
50.2
27.0
0.8
1.3
2.2
0.7
0.0
0.5
1.0
1.5
2.0
2.5
20.0
25.0
30.0
35.0
40.0
45.0
50.0
55.0
Group A Group B Group C Group D
Transaminases Distribution of Means Bilirubin
SGPT (IU/L) SGOT (IU/L) S.bilirubin (mg/dl)
16. 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 20
17
25
4 5
7
0
Still birth
Alive
39
16
28
1
4
11
0
5
10
15
20
25
30
35
40
45
<600 600-800 >800
S.LDH in IU/L
alive
stillbirth
17. 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.
31
32
33
34
35
36
37
38
39
<600
600-800 >800
38.4
36.9
33.6
Gestational age at birth (in weeks)
gestational age at
birth (in weeks)
0
1
2
3
4
5
6
7
8
9
<600 600-800 >800
7.1
5.6
3.6
8.4
6.9
4.9
S.LDH in IU/L)
APGAR scores vs LDH
APGAR (1 min)
APGAR (5 min)
18. 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
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
<600
600-800
>800
2.9
2.6
1.9
LDH in IU/L
Birth weight in kg
0
2
4
6
8
10
12
14
16
18
20
1
5
6
0
13
17
10
5
11
3
8
20
<1.5kg
1.5-2.5kg
>2.5kg
19. Maximum morbidity was found in women
with S.LDH above 800IU/L.
Women with severe preeclampsia and
eclampsia had most complications.
1 1
3
0
2
4
0 0
1
0 0
4
0 0
1
0 0
1
0 0
2
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
<600 600-800 >800
abruptio placenta
pulmonary
oedema
cerebro vascular
accidents
post partum
eclampsia
HELLP
ARF
sec sut
0
1
2
3
4
5
6
7
8
1
2 2
0
1
2
3
0
0
0
1
0
1
3
0
0
0
1
0
ARF
HELLP
post partum
eclampsia
cerebro vascular
accidents
pulmonary oedema
abruptio placenta
20. 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.
21. 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 <0.001
Diastolic BP (mmHg) 100.8±7.99 105±13.6 114.45± 9.69 74.96±7.77
P Value <0.001
Gestational age
(weeks)
38.4±1.4 36.9±1.62 33.55±2.74 38.84±1.11
P Value 0.155 <0.001
Baby Wt. (Kg) 2.94±0.48 2.63±0.47 1.9±0.65 3.14±0.47
P Value 0.106 <0.001
APGAR Score
(1min.)
7.07±2.02 5.6±3.08 3.56±2.6 7.16±0.9
P Value 0.43 0.02 <0.001
APGAR 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
22. 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)
23. • 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.
24. 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.
25. Pregnancy is nature’s precious
gift which has to be nurtured
during its entire nine months to
achieve good maternal and fetal
outcome