You are on page 1of 50

University of Khartoum

Faculty of Medicine
Postgraduate Medical & Health Studies Board
Department of Obstetrics & Gynecology

THE VALUE OF SERUM URIC ACID AS INDICATOR OF


SEVERITY OF PRE-ECLAMPSIA AMONG SUDANESE
PATIENTS

A thesis submitted in partial fulfillment for the requirements of the Degree of


Clinical M.D. in Obstetrics and Gynaecology

By
Dr. Khalid Hussein Bakheit
M.B.B.S (University of Khartoum)

Supervisor
Prof. A.S.M.A Gerais
M.D., FRCOG,
Department of Obstetrics and Gynaecology,
Faculty of Medicine, University of Khartoum

October 2002

Contents
page
Dedication
Acknowledgement i
Abstract (English).. ii
Abstract (Arabic) iii
Abbreviations . iv
List of Tables.... v
List of Figures . vi
Chapter One
Introduction1
Literature review .2
1-1 Indroduction......2
1-2 Definition ...2
1-3 Features of PE .3
1-4 Classification of HELLP syndrome6
1-5 Risk factors of abruptio placentae and eclampsia..7
1-6 Hyperuricaemia and cardiovascular disease...8
1-7 Chronic hyperuricaemia and renal disease..8
1-8 Relevance of plasma uric acid to pregnancy
induced hypertension.9
1-9 Plasma purine turn over in normal

pregnancy

and pregnancy complicated by PIH in relation to fetal well


being indices.10
1-10 Prediction of pregnancy outcome in women with
renal disease and its relation to plasma
uric acid......11
1-11 Plasma urate and serum deoxy cytidylate deaminase
as measures for early diagnosis of pre eclampsia12

1-12 Plasma urate and prediction of fetal death in


hypertensive pregnancies......12
1-13 Uric acid clearance in pre-eclampsia.....13
1-14 Metabolism of uric acid in normal pregnancy
and pregnancy complicated by pre-eclampsia...13
1-15 The relation between serum uric acid and platelet
count changes in patients with chronic hypertension
and superimposed pre-eclampsia..13
1-16 Abnormal umbilical artery Doppler ultrasound and
serum uric acid level14
1-17 Blood lactate level and hyperuricaemia in
pre-eclampsia.....15
Objectives ..16
Chapter Two
Materials & Methods ....17
Chapter Three
Results ...22
Chapter Four
Discussion .... 33
Conclusion. 36
Recommendations... 37
References ... 38
Appendix
Questionnaire ....42

This work is dedicated to


My Father,
To
My dear teachers with whom I spent my training
period,
To
My dear colleagues in the University of Khartoum.
With Best regards
Khalid

Acknowledgement
I would like to thank with great pleasure my honorable supervisor; Prof. A.S.M.A
Gerais, Department of Obstetrics and Gynaecology, University of Khartoum, for
his kind guidance, meticulous supervision with his kind smile all the time during
the hot afternoons, and discussion of all aspects of the thesis. His valuable advice,
comments and criticism are highly appreciated.
Great thanks to pregnant ladies, inpatients and in the antenatal clinic who were
never reluctant to give any information and kindly donated their samples to the
purpose of this study.

My great appreciation to my dear Friends Mubarak , A.Allah


Nasr, Intisar and their colleagues who helped me doing the
laboratory part of the thesis.
My thanks are expressed to my dear friend Omar Osman who
analyzed my data with great interest.

Dr. K.H.B. Ahmed

Abstract
The value of serum uric acid as indicator of severity of preeclampsia among Sudanese patients was studied in the period
1st-May- to end of September 2002.
The study was carried out as a multicentre study in the Khartoum
state in different maternity units, including, Khartoum teaching
Hospital, Omdurman maternity hospital, Khartoum North teaching
hospital, and Omdurman Military hospital.
Informations were collected from the patients by taking history
through a questionnaire, examination and analysis of serum uric
acid and urine for protein. Number of patients admitted with preeclampsia was 50 as the study population compared with 50
ladies with normal pregnancy, both were selected at the third
trimester of pregnancy.
Most of the patients were primigravidae in the age group between
25 and 34 years.
The severity of hypertension was graded according to systolic
hypertension group and diastolic hypertension group.
The average value of serum uric acid among the control group
was 4.5 mg/dl compared to 6.5 mg/dl in those patients admitted
as cases of pre-eclampsia. The rising level of serum uric acid was
well correlated with the severity of hypertension. The level of
serum uric acid in between the groups (as mild, moderate and
severe pre-eclampsia) had a P value of 0.016 which is significant.




2002.




.



:
-1
.
-2
.

.



25 34.
4.5
. 6.5
.
.

Abbreviations

AMP

Adenosine Monophosphate

DBPG

Diastolic Blood Pressure Group

DNA

Deoxy ribonucleic Acid

FHR

Fetal Heart Rate

HELLP

Hemolysis, Elevated liver enzymes and Low Platelet Count

IDDM

Insulin Dependent Diabetes Mellitus

JVP

Jugular Venous Pressure

RNA
SBPG

Ribonucleic Acid
Systolic Blood Pressure Group

List of Tables

Table 1:

Age distribution between patients and control group

24

Table 2:

Distribution of protein uria between patients and control

25

group
Table 3:

Distribution of patients and control group according to


classification of severity of hypertension
26

Table 4:

Shows the significance of uric acid level between groups


according to blood pressure measurements
27

Table 5:

Distribution of protein uria between patients with mild and


severe pre-eclampsia

28

List of Figures
Figure 1:

Parity distribution between patients and control groups in the


study sample

Figure 2:

29

Family history of renal disease between patients and control


groups in the study sample

30

Figure 3:

Family history of hypertension between patients and control

31

Figure 4:

Past history of pregnancy induced hypertension between


patients and control groups in the study sample

32

INTRODUCTION
Uric acid is the end result of purine catabolism in man.
The degradation of purine nucleotides (Adenosine, Guanosine
and

Hypoxanthine

monophospates)

and

bases

(adenine,

guanine, hypoxanthine) funnel through a common pathway


leading to formation of uric acid.(1) The enzymes involved in
degradation of nucleic acids and nucleotides and nucleosides
vary in specificity. Nucleases show specificity towards RNA or
DNA and towards the bases.
Nucleatidases range from those with relatively high specificity such as
the 5'-AMP nucleotidase, to those with broad specificity, such as the
acid and alkaline phosphatases, which will hydrolyze any of the 3' or 5'
nucleotides. AMP deaminase is specific for AMP, Adenosine deaminase
is less specific. Purine nucleoside phosphorylase catalyzes the reversible
reactions:
Inosine + Pi Hypoxanthine + ribose I - P
Guanosine + Pi Guanine + ribose I - P
Xanthosine + Pi Xanthine + ribose 1 - P
Deoxy-adenosine and Deoxy-guanosine are also substrates for
purine nucleoside phosphorylase.
Uric acid is not very soluble in aqueous media. There are
clinical conditions in which elevated levels of Uric acid results in
deposition of sodium urate crystals, primarily in joints. (2)

LITERATURE REVIEW

1-1. Introduction
Pre-eclampsia / eclampsia is an unpredictable multi-organ disorder
unique to human pregnancy. It is associated with significant fetal and
maternal morbidity worldwide. The exact etiology of it is unknown.
Changes such as increased sensitivity to vasopressors, reduced volume,
altered proximal tubular function, and activation of coagulation system
antedate overt hypertension, and suggest that hypertension may not be
central to the pathogenesis of pre-eclampsia.

1-2. Definition
Pre- eclampsia is a syndrome (group of symptoms and signs), which
can be recognized, but not diagnosed because there is no specific
diagnostic test. The presentation is very variable, and although
hypertension and proteinuria are the two signs most easily detected,
they are not central to the pathogenesis of the disorder. No single
feature is consistently present, 20% of women with pre- eclampsia are
normotensive and 30% have no premonitory proteinuria(3).
A number of classifications for hypertensive disorders in pregnancy
have been proposed. The international society for the study of
hypertension in pregnancy (ISSHP) currently define pre- eclampsia as
the occurrence of hypertension in combination with proteinuria after
twenty weeks gestation in a previously normotensive non-proteinuric
patient. (4).

1-3. Features of PE:


1-3-1. Maternal syndrome

1.

P.I.H.

2.

Proteinuria .

3.

Generalized oedema.

4.

Hyperuricaemia.

5.

Increased haematocrit.

6.

Thrombocytopenia

7.

Reduced antithrombin III.

8.

Abnormal liver function tests.

9.

Hypocalciuria

10.

Raised cellular fibronection, Von willebrand factor.

11.

Abnormal uterine artery Doppler wave forms.

12.

Elevated serum uric acid is characteristic of pre- eclampsia, but

found in up to 40% with P.I.H usually precede proteinuria by 1-2


weeks.

1-3-2. Fetal syndrome :


1.

Fetal growth retardation.

2.

Abnormal fetal Doppler wave forms.

3.

Fetal hypoxaemia (5).

1-3-3. The criteria for diagnosis of severe pre- eclampsia are:


1.

Systolic blood pressure greater than 160mmHg or diastolic blood

pressure greater than 110mmHg in more than two occasions, at least


6hours apart.

2.

Proteinuria more than 5gm/24hours.

3.

Oliguria (urine out put below 400ml/day).

4.

Neurological symptoms or signs:

Headache.

Scotomata.

Blurring of vision.

Altered consciousness.

5.

Pulmonary oedema/cyanosis.

6.

Epigastric pain.

7.

Deranged liver function test.

8.

Liver rupture-subcapsular liver haematoma.

9.

Thrombocytopenia below 100.000/mm3.

10.

H ELLP syndrome.

In pregnancy a diastolic blood pressure of 110mmHg or greater


constitutes a hypertensive crisis, as it has been found that young women
may develop encephalopathy with diastolic blood pressure of
120mmHg. Systolic hypertension however, is as dangerous as diastolic,
hypertension, and persistent systolic values greater than 170mmHg are
associated with significant risk of complications.
It is important to emphasize that pre-eclampsia is a multisystem disorder, but which organ system is going to be affected
predominantly, can not be predicted. The hypertension is only
one sign, albeit the commonest one of pre-eclampsia.
The

concept

of

normontensive

pre-eclampsia

is

well

recognized. Approximately 20% of eclamptic patients, and 15%

of patients with haemolysis, elevated liver enzymes and low


p1atelets (HELLP) syndrome are normotensive.
Of the complications of pre-eclampsia is eclampsia which is
defined as the occurrence of generalized convulsions associated
with signs of pre-eclampsia during pregnancy, labour , or within 7
days of delivery, and not caused by epilepsy or other convulsive
disorders. In the absence of a high blood pressure or if the
convulsions occur after 7 days postpartum, the condition is
referred to as atypical eclampsia(3).
1-3-4. Prediction of pre-eclampsia:
1- Family history.
2- Average second trimester MAP > 90 mmHg.
3- Angiotensin infusion test.
4- ROLL-over test.
5- Uterine artery Doppler wave forms.
6- Urinary calcium.
7- Serum AFP/hCG.
8- Plasma fibronectin.
9- Serum inhibin.
10- Serum urate.
11- Haematocrit.
12- Antithrobin III.
13- Plasminogen activator inhibitors. (6)
1-4. Classification of HELLP syndrome:

In a study on the spectrum of severe pre-eclampsia,


comparative analysis by HELLP (hemolysis elevated liver
enzymes, and low platelet count). Syndrome classification into
class .I, H and III in June 1999 in Department of Obstetrics and
Gynaecology and Preventive medicine, University of Mississippi
Medical Center (USA), this study was undertaken to explore the
spectrum of matemal diseases with a triple classification of
HELLP syndrome and compare these, classes with severe preeclampsia without HELLP syndrome. This was a retrospective
study in which 777 pregnancies with class I, II or Ill HELLP
syndrome were compared and contrasted with 193 women with
severe pre-eclampsia but without HELLP syndrome.
Approximately 50% of pregnancies complicated by class I
HELLP syndrome exhibited significant maternal morbidity,
compared with only 11% of those complicated by severe preeclampsia without HELLP syndrome. Although a significant trend
was apparent in increasing levels of lactate dehydrogenase,
aspartate aminotransferase and uric acid as HELLP syndrome
worsened, there was considerable variation within groups. As a
conclusion from this study, both laboratory and clinical indices of
disease severity in patients with severe pre-eclampsia or
eclampsia." generally were highest with class I HELLP syndrome
and were lowest when HELLP syndrome was absent. Class ill
HELLP syndrome is considered a clinically insignificant traditional
group.(7)
1-5. Risk factors of abruption placentae and eclampsia:
In the same year (June 1999) a study on the risk factors of
abruptio placentae and eclampsia, analyzing 445 women with

severe pre-eclampsia and eclampsia (University of Texas, USA).


In this prospective study, the purpose was to characterize the
clinical presentation or laboratory variables, predictive of either
abruptio placentae or eclampsia in women with severe preeclampsia. Uni-variate analysis reveals statistical significance for
the following variables associated with eclampsia, uric acid
concentration > 8.1 mg/dl; deep tendon reflexes >3+, serum
albumin

concentration

<3mg/dl

and

serum

creatinine

concentration > 1.3 mg/dl.(8)


The pathogenesis and consequences of hyperuricaemia in
hypertension, cardiovascular and renal disease was studied in
February1999.
1-6. Hyperuricaemia and cardiovascular disease:
An elevated uric acid level is associated with cardiovascular
disease. Hyperuricaemia is predictive for the development of both
hypertension and coronary artery disease, it is increased in
patients with hypertension, and when present with hypertension,
an elevated uric acid level is associated with increased
cardiovascular morbidity and mortality. Serum uric acid level
should be measured in patients at risk of coronary artery disease
because it carries prognostic information. Hyperuricaemia is
caused by decreased renal excretion. In this article it was
suggested that, this may be mediated by intra-renal ischaemia
with generation of lactate, and inhibition of the secretion of urate
by the anion-exchange transport system. The possibility that
hyperuricaemia directly contributes to cardiovascular or renal
disease needs to be considered. Although hyperuricaemia is
associated with a number of cardiovascular or renal risk factors,

several studies have found uric acid level to be independently


associated with increased mortality by multivariate analysis. If
hyperuricaemia is toxic, the most likely site is the kidney.(9,10)
1-7. Chronic hyperuricaemia and renal disease:
Chronic hyperuricaemia is strongly associated with chronic
tubulointerstitial disease, and many of these patients have
decreased renal function. Although it is possible that the
hyperuricaemia could simply be the-Consequences of the renal
disease, further studies are necessary to rule out a pathogenic
role for uric acid in the development of renal disease, and salt
dependent hypertension.(11)
1-8. Relevance of plasma uric acid to pregnancy induced
hypertension:
In a study carried in the period from September to December
1999,

at Lagos University Teaching Hospital in Nigeria the

relevance of plasma uric acid to pregnancy induced hypertension


was carried out; plasma uric acid-creatinine were estimated at
each visit of 59 consenting women attending antenatal clinic,
result in the third trimester of pregnancy, confirmed that the
plasma uric acid was able to differentiate between normal
pregnancy and those with PIH at P<0.002. The results of those
with ordinary hypertension and the women who developed preeclampsia

were

similar,

plasma

creatinine

was

able

to

differentiate between women with ordinary hypertension and


those with pre-eclampsia at P<0.01.
For patients with pre-eclampsia who developed convulsions,
there invariably was a further rise in plasma uric acid levels.

Monitoring of plasma creatinine level among patients with PIH will


help to predict those at risk to develop eclampsia. In the same
way monitoring of plasma uric acid level in those with preeclampsia, will help to predict those that will develop eclampsia.
These tests are sensitive and not expensive.(12)

1-9. Plasma purine turn over in normal pregnancy and


pregnancy complicated by PIH in relation to fetal well being
indices:
Uric acid is the end product of purine catabolism. The plasma
purine turnover metabolites in women with normal pregnancy,
and pregnancy complicated by PIH was compared to fetal
wellbeing indices, in a recent study in 2000 in Poznan, Poland.
The research included,
pregnant women of the two groups between 32nd and 41st
week of pregnancy.
To characterize the patients, their age, number of gestations,
and blood pressure values were used. The condition of the fetus
was evaluated by biophysical profile values FHR tracing. The
purine

bases

(hypoxanthine,

xanthine

and

uric

acid)

concentrations in plasma were determined.


Hypoxanthine level, oxypurine pool, hypoxanthine to Xanthine
molar ratio, and the ratio of uric acid to oxypurine pool, were
significantly different in patients with PIH in comparison with
women with physiologic pregnancy.

It was found that increased adenylnucleotide catabolism in the


PIH group, can be related to fetal wellbeing indices, particularly
FHR tracing.
Increased percentages of suspected and pathologic FHR
tracings were found in patients with PIH in comparison with
physiologic pregnancy. (13)
1-10. Prdiction of pregnancy outcome in women with renal
disease and its relation to plasma uric acid:
A recent study in Israel (June 2000) evaluated the prediction of
pregnancy outcome in subgroups of women with, renal disease;
the study, analyzed the types and frequencies of short and longterm(2years after delivery), maternal and neonatal complications
in 38 patients with primary renal disease (46 pregnancies), 24
IDDM patients with diabetic, nephropathy (24pregnancies), 27
patients with a functioning renal allograft (42 pregnancies), most
of them with mild renal insufficiency.
The results were successful pregnancy outcome (live healthy
infants, without severe handicap 2 years after delivery was
observed in 98% of the patients with primary renal disease, 96%
of the ill DM group with diabetic nephropathy and 89% of the
patients with a functioning renal allograft.
Factors found to be significantly predictive of successful
outcome were absence of pre-existing hypertension in all groups,
in addition to low pre-conception serum uric acid level in the
primary

renal

disease

patients,

and

long

interval

from

transplantation to conception and use of low dose prednisolone in


the renal transplant patients.(14)

1-11. Plasma urate and serum deoxy cytidylate deaminase as


measures for early diagnosis of pre eclampsia:
In a study in the late seventies, the plasma urate and serum
deoxycytidylate deaminase were used as measures for the early
diagnosis of pre-eclampsia.
The study sample number was 45 patients .In 19 of them there
was combination of increased blood pressure and plasma urate,
and this was associated with high incidence of fetal and maternal
morbidity ascribable to pre-eclampsia. Seventeen of the 19
patients

also

had

an

increased

serum

deoxycytidylate

deaminase.
With serial antenatal observations both serum urate and
deoxycytidylate deaminase increased together as early changes
in the development of pre-eclampsia (1977) (15)
1-12. Plasma urate and

prediction of fetal death in

hypertensive pregnancies:
In the year 1976, plasma urate measurements were used as
predictors of fetal death in hypertensive pregnancies. This
relation of plasma urate concentration and blood pressure was
studied in 332 pregnant patients with hypertension. Perinatal
mortality was markedly increased when maternal plasma urate
concentrations were raised(16). generally in association with
severe pre-eclampsia of early onset. Plasma urate was a better
indicator than blood pressure of prognosis for the fetus. Maternal
hypertension, even severe, with out hyperuricaemia, was
associated with an excellent prognosis for the fetus. Conversely

when maternal hypertension was mild and, hyperuricaemia was


severe, the prognosis for the fetus was poor. These findings
suggest that, in terms of fetal death, changes in renal handling of
urate may be amore important feature of pre-eclampsia than
hypertension.

(17)

1-13. Uric acid clearance in pre-eclampsia:


Serum uric acid was found to be elevated and uric acid
clearance was found to be impaired in pre-eclampsia in a study
carried

out

among

seventeen

pre-eclamptic

patients,

22

hypertensive patient, and 13 normal pregnant women in 1976. (18)


1-14. Metabolism of uric acid in normal pregnancy and
pregnancy complicated by pre-eclampsia:
The metabolism of uric acid in normal and toxaemic pregnancy
was studied in 1978, the formation, measurement and excretion
of uric acid were reviewed. Alterations in renal handling of uric
acid were responsible for the pronounced. decrease in serum uric
acid over the first 20 weeks of gestation.(19,20) Its gradual increase
in the latter part of pregnancy and its further increase in
pregnancy induced hypertension, generally the level of uric acid
correlates with the severity of pre-eclampsia. (21)
1-15. The relation between serum uric acid and platelet count
changes

in

patients

with

chronic

hypertension

and

superimposed pre-eclampsia:
The relation ship of serum urate and plate let count changes in
patients with chronic hypertension who developed superimposed
pre-eclampsia was studied in 1978 in 131 patients. Both urate
and plate let count were measured serially during pregnancy.

Twenty-seven women developed a sustained rise in plasma urate


concentrations which began at about 28 weeks gestation and
which is characteristic of pre-eclampsia.
The mean plate let count was already significantly reduced, and
continued to fall until delivery

(22)

, a smaller decrease in plate let

count was seen in 55 women who had border line but consistent
increase in plasma urate concentrations.In 49 women whose
plasma urate concentration remained steady, the plate let count
did not change significantly before delivery. (23).
1-16. Abnormal umbilical artery Doppler ultrasound and serum uric
acid level:
In a study in October 1995, the value of doppler study of the umbilical
artery was assessed in predicting outcome in, pre-eclamptic patients.
Fetal well-being was assessed in 113 women with pre-eclampsia by
weekly performed biophysical profile score and doppler study of the
umbilical artery starting early in the third trimester till delivery.

Last

doppler result was normal in 82 cases and abnormal in 31 cases. The


group with abnormal doppler had significantly higher blood pressure
and serum uric acid level, and significantly lower platelet count than the
group with normal doppler (24)

1-17.

Blood

lactate

level

and

hyperuricaemia

in

pre-

eclampsia:
The relationship of blood lactate to the hyper uricaemia
characteristic of pre-eclampsia was studied in 17 pre-eclamptic,
22 hypertensive , and 13 normal pregnant women, all in the third
trimester. Results showed that serum uric acid is elevated,

creatinine clearance is impaired in pre-eclamptic women, lactate


was lower in pre-eclampsia than in the control subjects (25).

OBJECTIVES
1. To determine the average level of serum uric acid among the
study population
2. To determine the value of serum uric acid as an indicator of
severity of pre-eclampsia among the study population.

MATERIAL & METHODS


2-1. STUDY AREA:
This is a multicentre study, carried in different maternity units, in
different hospitals including Khartoum teaching hospital; the
national reference hospital in Sudan, Omdurman maternity
hospital; the main separate maternity unit in Sudan, Omdurman
Military hospital; the main center for military hospitals in different
parts of the country and Khartoum North hospital.
2-2. SUBJECTS:
Total number of 50 patients were Randomly selected for the
purpose of this study from those admitted in these different

maternity units as cases of pre-eclampsia with different ranges of


severity. The Study was carried out in the period from the 1st of
May to the end of September 2002. The test samples were taken
in the third trimester of gestation. They were compared with
another group of 50 cases of normal pregnancy also in the third
trimester attending the antenatal clinic at Fath Elrahman Elbashir
complex of Antenatal clinics of Khartoum Teaching Hospital.
2-3. INVESTIGATIONS:
1- Estimation of Serum Uric Acid.
2- Urine for Protein.

2-4. Technique:
1- Estimation of Serum Uric Acid.
Serum Uric acid was estimated using colorimetry, the test
sample was obtained as venous blood from the study and control
groups after proper explanation and consent from both groups.
2-4-1. Estimation of Uric acid in blood:Enzymatic colorimetric test: Uricase method
Principle:(26,27,28,29)Uric acid is the end product of purine
metabolism, its quantitation aids in the diagnosis of renal
dysfunction.
Uricase catalyzes the oxidation of uric acid to allantoin
and H202 in the presence of peroxidase (POD), H202 reacts
with

4-minoantipyrine

(4AA)

and

3,5

dichloro

2-hydroxybenzensulphonate (DHBS) to form aquinoneimine

dye, the concentration of which at 546nm is directly proportional


to the uric acid concentration.
Uric acid + O2 + 2H2O + Uricaseallantoin +CO2 + H2O2
2H202 + DHBS + 4AA + POD quinoneimine + 4 H20

2-4-2. PROCEDURE:
Three test tubes were prepared test, standard and blank. To
each the following were added
TEST

STANDARD

BLANK

0.02

STANDARD 8MG/DL

0.02

DISTILLED WATER

0.02

URIC ACIDREAGENT

SERUM

Then each tube was mixed and incubated at 37o C for 5


minutes, the absorbance of the test and standard were measured
against blank at 546nm.
2-4-3. CALCULATION:
Serum Uric acid in mg /dl:
(absorbance of the test / Absorbance of standard) X

concentration of Standard
(A test / A STD) X 8
Reference value: male: 3.4 - 7.0 mg /dl
females: 2.4-5.7 mg/dl
4-5.Urine for Protein:Urine for protein: was estimated using sulphosalicylic acid
+,++,+++ according to the intensity of protein coagulation in,
urine following the addition of sulphosalicylic acid.
2-6. Data Collection
Data was collected from in patients and control groups (sample
size was 50 for each group). Using a questionnaire and direct
interview.
Data

include:

Personal

History,

name,

age,

residence,

occupation, duration of marriage.


Obstetric History: detailed past obstetric history including past
history of pre-eclampsia or pregnancy induced hypertension or
eclampsia.
History also included symptoms related to the severity of preeclampsia such as blurring of vision, Epigastric pain or severe
headache and urine output (which was a subjective estimation,
output was not measured).
Clinical examination was performed looking for signs of
anaemia, jaundice, blood pressure and pulse, JVP, presence or
absence of ascites and Oedema (in face, abdominal wall, lower
limbs).
According to blood pressure readings cases were classified as

mild pre-eclampsia when the diastolic and blood pressure was


less than 100, moderate pre-eclampsia when the diastolic blood
pressure between 100 110, severe when it is more than 110
mm/Hg. Regarding the systolic blood pressure, mild less than
150, moderate between 150 160, severe more than 160mmHg.
Data collected was analyzed, then it underwent interpretation in
accordance with the objectives and internationally reported
findings (see discussion). Lastly a conclusion was made from
which recommendations were delivered.

RESULTS
Figure (1) Shows the distribution of parity among both control
group and study sample. The majority of patients were
primigravidae. In the control group majority of cases with more
than two previous deliveries followed by primigravidae.
Figure (2) Shows the family history of renal disease among
both groups, the majority of both had no family history of renal
diseases. Those with positive family history were 7 in the study
sample and 6 in the control group.
Figure (3) shows the family history of hypertension in both
groups. The majority in both groups had no family history of
hypertension. Those with positive family history were 17 in the
control group and 20 in the study sample.
Figure (4) shows the past history of pregnancy induced,
hypertension (PIH) between patient and control groups. In both
groups the majority had no past history of PIH. Those with
positive past history were 4 in the control group and 15 in the
study sample.
The study sample and control group were distributed according
to their age into below 25 years (18 in the control group 11 in
study sample), between 25 -34 years (27 control group, 26 study
sample), 35 years and above (5 control, 13 study sample) Table
(1).
Table (2) shows the distribution of proteinuria between the two

groups. In the control group non of them had significant


proteinurea. In the study sample 40 cases had mild proteinuria
(<=+2) and 10 cases had severe protein urea (>= +3)
Table (3) shows the distribution of study sample according to
the severity of hypertension (systolic or diastolic hypertension). 7
cases had mild systolic hypertension, 28 moderate and 15 had
severe systolic hypertension. 16 cases had mild diastolic
hypertension,

17

moderate,

and

17had

severe

diastolic

hypertension.
Table (4) The level of Uric acid between groups according to
severity of the blood pressure. P value was found to be
significant 0.016.
Table (5) shows systolic blood group for cross tabulation of
protein in urine.
Those with mild systolic hypertension 7 had mild proteinuria,
those with moderate systolic hypertension; 25 had mild
proteinuria and 3 of them had severe proteinuria. Those with
sever systolic hypertension; 8 had mild proteinuria and 7 had
severe proteinuria.

Table (1):

Age distribution between


patients and control group
Below 25

25 34

35 and
above

Type of control age groups

18

27

Subject patient age groups

11

26

13

Table (2):

Distribution of protein uria


between patients and control
group
No

Mild

Severe

Type control protein in urine

50

Subject patient protein in

40

10

urine

Table (3):
Distribution of patients and control group according to classification of severity of hypertension

Type of subject
Control

Patient

SBP groups

DBP groups

SBP groups

DBP groups

Count

Count

Count

Count

Mild

50

50

16

Moderate

28

17

Severe

15

17

Table (4):

Shows the significance of uric acid level between groups according to blood pressure measurements

Some of

df

squares

Mean

Sig.

4.553

.016

square

Between groups

20.623

10.312

Within groups

106.457

47

2.265

Total

127.081

49

Table (5):
Distribution of protein uria between patients with mild and
severe pre-eclampsia
Protein in urine

Total

Mild

Severe

SBP mild

Groups moderate

25

28

Severe

15

Total

40

10

50

DISCUSSION
Pre-eclampsia is a disease which has a significant impact on
both fetal and maternal well being and accounts for a
considerable cause of hospital admission in current obstetric
practice. It is principally a disease of primigravidae at the
extremes of reproductive age. This age distribution is well
correlated with the number of patients in the study sample, as
most of them were primigravidae between the age of 25 -34
years.
This disease which is unique to human pregnancy is a real
dilemma as yet its aetiology is unknown as hypertensive disease
of pregnancy which has led to clinical signs such as hypertension
and protienuria, not merely diagnosing disease but defining it.
in the study sample 17cases had severe systolic hypertension 8
cases of those with severe hypertension had mild proteinuria
(<=+2) and 7 cases had severe proteinuria (>=+3) Table (3) and

this might show a correlation between severity of hypertension


and the amount of proteinuria but these might not be well
correlated

in

clinical

practice;

some

cases

with

severe

hypertension may not show gross proteinuria and vice versa.


This really reflects the fact that, the exact nature of this disease is
unknown and why is it common in primigravidae is yet to be
identified as is shown in figure (1) most of the cases in the study
are primigravidae and this correlates well with the already
established fact.
Again there was no strong evidence suggesting the role of renal
disease or hypertension present in their families and this is
shown in figures (2) and (3) that the majority of patients had no
family history of neither renal disease nor hypertension.
Concerning the importance of past history of PIH among the
control and study groups only 15 cases had past medical history
of PIH compared to 4 cases in the control group figure (4).
The importance of clinical history is in the relative risk of preeclampsia; in the first pregnancy the risk is 7-10, for daughter of
women with pre-eclampsia is 4, for sisters of women with preeclampsia is 7 and for women with chronic hypertension is 3-7
(30)

Concerning the value of serum uric acid among both groups the
average level of serum uric acid among the control group was 4.5
mg/dl compared to 6.5 mg/dl among those with pre-eclampsia as
the study sample. Those with severe hypertension had elevated
levels of serum uric acid compared to those with mild and
moderate hypertension, and this is well correlated with the known
association of hyperuricaemia with pr-eclampsia (5).

The level of uric acid between groups as shown in table (4) to be


of P. value of 0.016 is a highly significant value indicating the
value of uric acid as a sensor of severity of pre-eclampsia.
But there were few patients with severe hypertension having a
serum uric acid level of 6 mg /dl which is not that high when
compared to the control group, this is again a good explanation
that pre-eclampsia is a multifactorial disorder and no one single
test would be highly sensitive indicator of severity but when
combined with other indices such as platelet count, serum
creatinine, Hb estimation and fetal well being indices, it would
then be a good marker of severity.

CONCLUSION

Pre-eclampsia is a real nightmare in current obstetric practice,


creating a really difficult balance between maternal and fetal well
being and a considerable worry to the doctor , the patient and her
family in spite of the wide range at present available of modern
ways to assess foetal well being.
The mystery about its' aetiology confers a real difficulty to
obstetricians in the antenatal clinics in its prediction, an area that
needs further research to be established.
In spite of the many hidden facts about this disease improved
perinatal outcome, maternal well being can be achieved to a
satisfactory level by establishing specialized referral centers fully
equipped with facilities for proper neonatal and maternal
handling, antenatally, during labour and further follow up
afterwards.
The value of serum uric acid was found to have a good
correlation with severity of hypertension but yet it is not the sole
marker that is much reliable in the severity of this multifactorial
disease.

RECOMMENDATIONS
Pre-eclampsia is a multiorgan disorder whose severity is better assessed
through its effect on target organs.
Assessment include renal and liver function tests and good
fetal monitoring , rather than doing a single test alone.
Estimation of serum uric acid in patients admitted with preeclampsia should be part of the tests done for renal function done
for these patients because it showed a significant value in this
study.

REFERENCES
1.

W.R. Montfort. Biosynthesis of nucleotides. In : Lubert stryer

(editor). Biochemistry - 4th edition. New York : W.H. Freeman and


company; 1995. P ( 756).
2.

Joseph G. Cory. Purine and pyrimidine nucleotide metabolism. In:

Thomas M. Devlin (editor). Text book of Biochemistry with clinical


correlations. 4th edition. New York: Wiley Liss, inc.; 1997. P 501503.
3.

Faphima Paruk and Jack Moodley. Management of severe

preeclampsia and eclampsia. In : John Studd (editor). Progress in


Obstetrics and Gynaecology. 14th edition. London : Churchill
Livingstone; 2001. P (101-119).
4.

Davey DA and Macgillivray. The classification and definition of the

hypertensive disorders of pregnancy. In : John M. Perry (editor).


High risk pregnancy. 4th edition. New York : Black well Science, inc.;
1986 P (97 133).
5.

S. C Robson. Hypertension and renal disease in pregnancy. In :

D. Keith Edmonds (editor). Dewhursts Text book of Obstetrics and


Gynaecology. 6th edition. London : Blackwell Science Ltd.; 1999
p (166).
6.

Kaulhausen -H ; Oney - T - New aspects of the pathophysiology

of pre-eclampsia . Z-Geburtshilte' - Pernatol- 1979 Aug 183(4) : 23948


7.

Martin - JN Jr, Rinehart - BK, May -WL, Magann - EF; Terrone -

DA ; Blake- PG -; The Spectrum of Severe pre-eclampsia:


Comparative analysis by HELLP (Hemolysis , elevated liver

enzymes , and low platelet count ). Am - J - Obst gynecol, 1999


Jun; 77 (7): 717-21.
8.

Witlin - AG; Saade - GR ; Mattar -f ; Sibai -BM -: Risk factors for

abruptio placentae and eclampsia : analysis of 445 consecutively


managed women with severe pre-eclampsia and eclampsia . Am J- Obst - gynecol . 1999 June; 22 (8) : 1006-11.
9.

Wannamethee - SG: Is serum Uric acid a risk factor for coronary

heart disease ? J- Hum- Hypertens , 1999 Mar; 70 (6) : 220-23.


10. Wang -JG , Staessen - JA; Fagard -RH ; Birkenhager -WH ; Gong
-L; Liu L.The prognostic significant of serum creatinine and uric
acid in the older chinese patients with isolated systolic hypertension
- Hypertension 2001 Apr ; 37(4) : 1069-74 .
11. Johnson - Rj; Kivlighn - SD ; Kim - YG ; Suga - S; Foso - AB.:
Reappraisal

of

the

pathogenesis

and

consequences

of

hyperuricaemia in hypertension , cardiovascular disease , and renal


disease. Am -J-Kidney-Dis., 1999 Feb; 92 (3) : 257-63.
12. Wakwe- VC , Abudu -OO : Estimation of plasma uric acid in
pregnancy induced hypertension (PIH) is the test still relevant . AfrJ Med-Med-Sci - 1999 Sep-Dec ; 28 (3-4) :155-8
13. Klejewski - A ; Szczesniak , Chmielecka - A; Sermoska Cancellaro , - M; Urbaniak ,-T . Plasma Purine turn over metabolites
in women with normal pregnancy and pregnancy complicated with
pregnancy induced hypertension as compared to foetal well being
indices - J- Pernat- med 2000 April; 28(5) : 399-406.
14. Bar , -J ; Ben - Rafael , -Z ; Padoas, - A; Orvieto , -R ; Boner ,- G;
Hod ,-M. Prediction of pregnancy outcome in subgroups of women
with renal disease. Clin Nehprol . 2000 June . 53 (6) : 437-44.

15. Redman - Cw ; Williams - GF ; Jones DD ; Wilkinson - RH :

Plasma Urate and serum deoxycytidylate deaminase measurements


for the early diagnosis of pre-eclampsia . Br- J- Obstet - Gynaecol
1977 Dec ; 84 (12):904-8.
16. Anasuya -a ; Raman - L . Significance of hyperuricaemia in
pregnancy . Indian - J- Med - Res. 1979 Nove ; 70 : 767-70.
17. Redman - CW ; Beil in -LJ ; Bonnar - J ; Wilkinson -RH: Plasma
urate measurements in predicting fetal deaths in hypertensive
pregnancy . Lancet . 1976 Jun 26 ; (7974) : 1370-3.
18. Redman - Cw ; Beilin -LJ ; bonnar J : Renal Function in preeclampsia. J-Clin-Pathol-Suppl- R-Coll-Pathol 1976(10) 91-94.
19. Dunlop - W; Davison - JM : The effect of normal pregnancy upon
the renal handling of uric acid . Br- J- Obstet - Gynaecol 1977 Jan ;
84(1):13-21
20. Hill - LM. Metabolism of uric acid in normal and toxaemic
pregnancy . Mayo - Clin - Proc . 1978 Nov ; 53 (11) : 743-51.
21. Redman - CW ; Bonnar - J Plasma urate changes in preeclampsia . Br - Med - J 1978 Jun 3 ; 1 (6125):1484-5.
22. Redman - CW ; Bonnar - J ; Beilin - L - Early platelet consumption
in pre-eclampsia . Br - Med - J 1978 , Feb 25;1(6111): 467-9
23. Calvert -SM , Tuffnell -DJ ; Haley-J . Poor predictive value of
platelet count , mean platelet volume and serum urate in
hypertension with pregnancy . Eur - J- Obstet - Gynecol - Reprod Biol . 1996 Feb ; 64(2): 179-84.

24. Rocca- MM ; Said - MS ; Khamis - MY; Ghanem -IA ; Karkour TA . The value of doppler study of the umbilical artery in predicting
perinatal outcome in preeclamptic patients. J - obstet -- Gynaecol .
1995 , Oct ; 21 (5) : 427-31.

25. Fadel - HE ; Northrop - G; Misenhimer - HR : Hyperuricaemia in


pre-eclampsia . A reaapraisal . Am- J-Obstet-Gynaecol . 1976 Jul 1;
125(5): 6407.
26. Ruth Haslam. Organic Constituents and Function tests. In : I.D.P
Wootton (editor). Micro analysis in Medical biochemistry. 5th edition.
London : Churchill Livingstone; 1974 P (87-91).
27. Feichtmeir and Wrenn. Deremination of serum uric acid. In :
Varley (editor). Practical clinical biochemistry. 5th edition. London :
William Heinemann Limited; 1984 P (476).
28. Willard R. Faulkner. Estimation of serum uric acid. In : Norbert W.
Teitz (editor). Fundamentals of clinical chemistry. 6th edition.
Philadephia : W.B.Saunders company; 1982 P (593).
29. Henry, Sobel and Kim. Determination of serum uric acid by
reaction with alkaline phospho-tungstate. In : Richard J-Henry
(editor). Clinical chemistry principles and techniques. 4th edition.
California : Hoeber Medical Division; 1964 P (278 280).
30. P. Baker, F. Broughtan Pikin. Screening tests for pregnancy
induced hypertension. In John stud (editor). Progress in Obstetrics
and Gynaecology. 10th edition. London : Churchill Livingstone; 1999
P (78).

The value of serum uric acid as indicator


of severity of pre-eclampsia among Sudanese patients

Name: . Age:..
Residence:. Occupation:..
Married for:.
G Par+.
LMP EDDGA..
BP: Pre-pregnancy 1st trimester..
Now: BP..
Symptoms:
1. Headache:

Yes..

No..

2. Epigastric pain:

Yes..

No..

3. Blurring of vision:

Yes..

No..

4. Oedema-face:

Yes..

No..

Yes..

No..

L.Limbs:

5. Urine out put: Normal.. Reduced..


F.H. of hypertension:

Yes..

No..

F.H. of renal disease:

Yes..

No..

1. P.I.H

Yes..

No..

2. Eclampsia

Yes..

No..

1. Pale

Yes..

No..

2. Jaundiced

Yes..

No..

P.H. of:

O/E:

Pulse BP. RR..


JVP: Raised..Normal
Oedema:

Face:

Yes..

No..

Abdominal wall: Yes..

No..

Ascitis:

Yes..

No..

L. Limbs:

Yes..

No..

FL..
Investigation:

1. S. Uric acid.
2. Urine for protein + ++.. >++.

You might also like