THE ROLE OF SERUM URIC ACID AS A PROGNOSTIC INDICATOR
OF THE SEVERITY OF MATERNAL AND FETAL COMPLICATIONS IN
HYPERTENSIVE PREGNANCIES
Keith P. Williams, MBBS, FRCSC, France Galerneau, MO, FRCSC
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven CT
Abstract
Objective: To examine whether an elevated serum uric acid level
in hypertensive pregnant women is a useful prognostic indica-
tor of severe hypertension; hemolysis, elevated liver enzymes,
low platelets (HELLP) syndrome; and small for gestational age
(SGA) infants.
Methods: A total of 459 women newly diagnosed with hyperten-
sion in pregnancy were categorized into "gestational hyperten-
sion" and "hypertension with proteinuria (preeclampsia)"
groups. Their serum uric acid levels were correlated with the
development of HELLP syndrome, severity of hypertension, and
incidence of SGA newborns « I Oth percentile birth weight).
HELLP syndrome was divided into 3 classes depending on the
severity of the thrombocytopenia. Prior to this study, serum
uric acid levels had been measured in a group of normotensive
women. Mean and standard deviation of serum uric acid levels
for each group were compared using analysis of variance and
student t-tests, where necessary. , pare la moyenne et I'ecart-type des taux d'acide urique
Results: Significant elevation in serum uric acid levels over nor-
motensive pregnant women (285 ± 72 IJmol/L) was observed in
both the gestational hypertensive group (341 ± 83 IJmol/L) and
the preeclamptic group (384 ± 93 IJmol/L) of women (p < 0.00 I
and p < 0.05 respectively). Serum uric acid levels were also sig-
nificantly elevated (p < 0.00 I) in women with gestational hyper-
tension with HELLP syndrome (382 ± 78 IJmol/L) compared to
those without HELLP syndrome (330 ± 80 IJmoI/L).
Preeclamptic women with HELLP syndrome (412 ± 99 IJmol/L)
also demonstrated elevated uric acid levels (p < 0.05) over
those without HELLP syndrome (374 ± 87 IJmoI/L). However,
the level of uric acid did not predict the severity of HELLP syn-
drome. The presence of SGA infants in the gestational hyper-
tensive group was not associated with increased uric acid levels.
Conclusion: Uric acid levels, although significantly elevated in
women with gestational hypertension and preeclampsia as com-
pared to normotensive pregnant women, are not good prog-
nostic indicators of the severity of the maternal or fetal
complications.
KeyWords
Preeclampsia, uric acid levels, HELLP syndrome, gestational age,
gestational hypertension
Competing interests: None declared.
Received on February 4, 2002
Revised and accepted on April 4, 2002
JOGe
Resume
Objectif : Verifier si une concentration elevee d'acide urique
dans Ie sang, chez la femme enceinte faisant de I'hypertension,
est un facteur de pronostic utile d'hypertension grave, d'he-
molyse, d'enzymes hepatiques elevees, du syndrome HELLP et
de cas de nouveau-nes hypotrophiques (SGA).
Methodes: On a classe un total de 459 femmes enceintes, diag-
nostiquees comme faisant de I'hypertension, en deux cate-
gories : {( hypertenSion gestationnelle » et {( hypertension avec
proteinurie (preeclampsie) ». On a fait une correlation entre
les concentrations d'acide urique dans Ie sang avec I'apparition
du syndrome HELLP, la gravite de I'hypertension et I'incidence
de nouveau-nes hypotrophiques (po ids de naissance < I De
percentile). On a divise les cas de syndrome HELLP en 3 cate-
gories selon la gravite de la thrombocytopenie. Avant cette
etude, on avait mesure les concentrations d'acide urique dans
Ie sang chez un groupe de femmes normotensives. On a com-
serique pour chaque groupe, au moyen de I'analyse de vari-
ance et Ie test t (de Student), si necessaire.
Resultats : On a constate des hausses importantes des taux
d'acide urique serique, par rapport aux femmes enceintes nor-
motensives (285 ± 72 IJmol/l), dans Ie groupe de femmes
atteintes d'hypertension gestationnelie (341 ± 83 IJmol/l) aussi
bien que dans Ie groupe de celles atteintes de preeclampsie
(384 ± 93 IJmol/l) (p < 0,00 I et p < 0,05, respectivement). Les
taux d'acide urique serique etaient aussi plus eleves de
.maniEke importante (p < 0,00 I) chez les femmes atteintes
d'hypertension gestationnelle combinee au syndrome HELLP
(382 ± 78 IJmol/l), par comparaison it celles qui n'avaient pas
Ie syndrome HELLP (330 ± 80 IJmol/l). Les femmes atteintes
de preeclampsie combinee au syndrome HELLP (412 ±
99 IJmolll) ont aussi eu des taux d'acide urique plus eleves
(p < 0,05) que celles qui n'avaient pas Ie syndrome HELLP
(374 ± 87 IJmol/l). Toutefois, Ie taux d'acide urique ne permet-
tait pas de predire la gravite du syndrome HELLP. On n'a pas
constate de lien entre I'incidence des nouveau-nes hypotro-
phiques dans Ie groupe souffrant d'hypertension gestationnelle
et des taux eleves d'acide urique.
Conclusion: Bien que les concentrations d'acide urique soient
plus elevees, de fas;on importante, chez les femmes atteintes
d'hypertension gestationnelle avec preeclampsie que chez les
femmes enceintes normotensives, ces concentrations ne sont
pas de bons facteurs de pronostic de la gravite des complica-
tions maternelles ou fcetales.
J Obstet Gynaecol Can 2002;24(8):628-32.
AUGUST 2002
INTRODUCTION
Hyperuricemia is thought to be a biochemical feature of
preeclampsia caused by early tubular retention of urate. 1,2 Many
authors utilize elevated maternal serum uric acid levels to pre-
dict fetal complications associated with preeclampsia. 3- 5 The
degree of hyperuricemia in preeclamptic women has been
shown to reflect the clinical severity of preeclampsia, to corre-
late with maternal biopsy changes, and to reflect fetal progno-
sis. 6 The role of serum uric acid levels in distinguishing
hypertensive pregnancies likely to be complicated by hemoly-
sis, elevated liver enzymes, low platelets (HELLP) syndrome,
andlor small for gestational age (SGA) infants is not well doc-
umented in the literature. The aim of our study was to assess
the reliability of serum uric acid measurements as a prognostic
indicator of these maternal and fetal complications associated
with hypertensive pregnancies.
SUBJECTS AND METHODS
We evaluated all hypertensive pregnant women who presented for
care at British Columbia (BC) Women's Hospital between 1992
and 1996. BC Women's Hospital is a tertiary care hospital in
which approximately 7500 births occur annually. Of these,
approximately 400 women are transferred in each year with a vari-
ety of medical and fetal complications, including 40 women
(10%) who were transferred in with hypertensive complications
in their pregnancy. All the women in this study had prenatal care
commencing in their physician's office prior to 20 weeks' gesta-
tion. We classified the type of hypertension in pregnancy using
criteria defined by the National High Blood Pressure Education
Program Working Group7 into 5 categories. For this study, we
included only the women who met the criteria for 3 categories:
(1) gestational hypertension, (2) preeclampsia, and (3) eclampsia.
Inclusion criteria for gestational hypertension included a systolic
blood pressure level> 140 mm Hg and a diastolic level> 90 mm
Hg developing after 20 weeks' gestation. Women were considered
preeclamptic if they met the blood pressure criteria and also devel-
oped significant proteinuria defined as 1+ in dipstick or >300 mg
on a 24 h urine collection. Women who were preeclamptic and
had seizures were classified as eclamptic. We excluded all women
with diabetes, chronic hypertension, or multiple gestations. Final
classification of the type of hypertension was assigned after the
physicians' offices were contacted for follow-up information about
postpartum blood pressure and proteinuria.
On admission to hospital with a diagnosis of hypertensive dis-
ease in pregnancy, the women's serum uric acid levels were mea-
sured by the L peroxidase colorimetric method using a Beckman
Colorimetric C X-7 chemical analyzer. Complications of hyper-
tensive pregnancies were classified in the following manner:
HELLP syndrome was diagnosed in women with a combina-
tion of red blood cell hemolysis, elevated liver enzymes, and throm-
JOGC
bocytopenia, and placed into 3 levels of severity based
on platelet count levels: Class I: platelet count ~ 50 x 10 9IL;
Class II: platelet counts between 50 x 109 /L and 100 x 109IL;
and Class III: platelet counts between 100 x 10 9IL and
150 x 10 9 IL. Elevated liver enzymes were identified by an
SGOT (AST) of> 40 IU/L, and hemolysis was identified on
blood film or lactic dehydrogenase 2:: 600 IU/L. SGA infants were
defined as being less than the 10th percentile based on the Cana-
dian birth weight percentile figures. s Women were considered to
have severe hypertension if their blood pressure on two occasions
was 2:: 160 mm Hg systolic andlor 2:: 11 0 mm Hg diastolic. Previ-
ously, as part of an investigation of the normal biochemistry of
pregnancy; serum uric acid levels had been measured at four week-
ly intervals throughout pregnancy in a group of 29 normoten-
sive women who delivered at term,9 and, subsequently, these
gestational age specific serum uric acid levels were available for
comparison with the hypertensive groups studied here. 9
Results are reported as mean plus or minus standard devia-
tion. Mean values between the groups of continuous variables were
compared by using analysis ofvariance, and pair-wise comparisons
were done using the Tukey test. Student t-tests were used when
indicated. To determine if serum uric acid levels were a prognos-
tic indicator of the severity of hypertension and HELLP syndrome,
as well as the incidence of SGA newborns, two cut-off levels set at
1 standard deviation above the mean, at 540 )lmollL, were devel-
oped. Using these cut-off levels, we assessed the sensitivity, speci-
ficity, positive and negative predictive values, and relative risk with
95% confidence intervals of the value of uric acid as a prognostic
indicator. Significance was set at the p < 0.05 level.
RESULTS
From Table 1, it can be noted that serum uric acid levels in
women with gestational hypertension (341 ± 83 )lmoI/L) and
preeclampsia (384 ± 93 )lmoI/L) are significantly increased
above the level documented in the normotensive group (285 ±
72 )lmollL, p < 0.01). Eclampsia and preeclampsia are associ-
ated with the highest increases in uric acid levels. The develop-
ment of HELLP syndrome is associated with a significant
increase in uric acid levels over the non-HELLP women in both
the gestational hypertensive (382 ± 78 vs. 330 ± 80 )lmollL,
p < 0.001) and preeclamptic (412 ± 99 vs. 374 ± 87 )lmollL,
p < 0.05) groups (Table 2). However, the increasing severity of
HELLP syndrome as defined by decreasing platelet count lev-
els was not associated with a significant difference in uric acid
levels. For use of serum uric acid levels of 450 )lmollL in dis-
tinguishing women with HELLP syndrome from non-HELLP
women in the preeclamptic group, the positive predictive value
was 38% with a relative risk with 95% confidence interval of
1.6 (0.87-2.97) (Table 3). Positive predictive values for serum
uric acid levels of 450 )lmollL in the setting of gestational hyper-
tension to distinguish HELLP syndrome from non-HELLP
AUGUST 2002
 TABLE I ,DISCUSSION
HYPERTENSIVE DISORDERS OF PREGNANCY
AND SERUM URIC ACID LEVELS Uric acid is filtered by the renal glomeruli, absorbed by the first
N Serum Uric Acid part of the proximal convoluted tubule, with a further secretion
(jJmollL) and reabsorption phase. 10 Ten percent of the filtered urate is
Mean ± SD excreted in the urine. II During pregnancy, uric acid clearance
Gestational hypertension 258 341 ± 83* increases from 6 to 12 mLlmin to 12 to 20 mLlmin, with a
25% decrease in blood concentration. 1,2,12
Gestational hypertension 194 384 ± 93*
In our present study, we have documented that serum uric
and proteinuria (preeclampsia)
acid levels are not sufficiently elevated in women with
Eclampsia 7 410 ± 98t preeclampsia or pregnancy-induced hypertension to be good
Normotensive 29 285 ± 72 prognostic indicators of maternal and fetal complications.
N: number
Management in our study was not based on uric acid levels.
*p < 0.0 I compared to normotensive Serum uric acid levels, as a marker of kidney dysfunction, do
tp < 0.00 I compared to normotensive not correlate significantly with either decreased placental func-
tion (as suggested by SGA infants) or vascular responsiveness
(as evidenced by blood pressure changes in preeclampsia).
syndrome was 35% and with a relative risk with 95% confi- Serum uric acid levels are significantly increased in women with
dence interval of 1.93 (0.81-4.6). HELLP syndrome but not enough to distinguish the class of
Severe hypertension diagnosed by a blood pressure the HELLP syndrome.
,2: 160/110 mm Hg on two occasions was associated with a sig- Plouin et aI. 13 documented a poor perinatal outcome
nificant increase in uric acid levels compared to the mild hyper- (including stillbirths and neonatal deaths) in pregnancies com-
tension in the gestational hypertensive group (365 ± 89 vs. plicated by preeclampsia and predicted by serum uric acid lev-
333 ± 78 flmollL, p < 0.01) (Table 4). Although uric acid levels els. In their study, 59% of women had serum uric acid levels
of 450 flmollL in preeclamptic women were associated with a ,2: 360 flmoIlL in the group with poor perinatal outcome com-
relative risk of 1.72 (0.94-3.15) and a 44% positive predictive pared to 20.3% in the group with good outcome. We used
value for the prediction of severe hypertension, this was not sig- higher serum uric acid levels (450 flmol/L and 540 flmol/L) in
nificant. Increasing the uric acid cut-off to 540 flmol/L did not an attempt to predict maternal and fetal complications and
change the predictive capability. Uric acid levels were higher in were still not able to distinguish these complications on uric
women who delivered SGA infants (398 ± 13 flmollL) com- acid levels alone.
pared to those with non-SGA infants (385 ± 7 flmollL) in the Redman and colleagues l4 showed that serum uric acid lev-
preeclamptic group (Table 5). The positive predictive value was els,2: 420 flillol/L were associated with significant perinatal mor-
30% with a relative risk of2.36 (0.96-5.77) (Table 3). tality and maternal morbidity, including severe hypertension,
and were of great value when the diagnosis of preeclampsia was

TABLE 2
SEVERITY OF HELLP SYNDROME AND SERUM URIC ACID LEVELS IN VARIOUS HYPERTENSIVE DISORDERS
Gestational Hypertension Preeclampsia

N Serum Uric Acid (jJmoIlL) N Serum Uric Acid (jJmoI/L)

Mean ± SD Mean ± SD

Non-HELLP 201 330 ± 80* 139 374 ± 87t

All HELLP 57 382 ± 78 55 412 ± 99

Class III HELLP 46 390 ± 79 36 418 ± 96

Class II HELLP 5 356 ± 69 15 393 ± 122

Class I HELLP 6 340 ± 90 4 434 ± 86

N: number; HELLP: hemolysis, elevated liver enzymes, low platelets syndrome

*p < 0.00 I compared to Class III HELLP and all HELLP syndrome women
tp < 0.05 compared to all HELLP syndrome women

JOGC AUGUST 2002

 TABLE 3
PERFORMANCE OF SERUM URIC ACID LEVELS IN PREDICTING MATERNAL AND
FETAL COMPLICATIONS IN HYPERTENSIVE DISORDERS OF PREGNANCY
Diagnosis Maternal Cut-off Level Sensitivity Specificity Positive Predictive Relative Risk
Complications Serum Uric Acid % % Value % (95% CI)
(~moI/L)

Preeclampsia HELLP 450 24 85 38 1.6 (0.87-2.97)

540 17 91 41 1.79 (0.82-3.95)

Severe 450 25 86 44 1.72 (0.94-3.15)

hypertension 540 16 91 45 1.72 (0.83-3.97)
BP;::: 160/110 mm Hg

Small for 450 16 81 20 0.89 (0.42-1.89)

gestational age 540 9 88 18 0.76 (0.27-2.13)

Gestational HELLP 450 12 94 35 1.93 (0.81-4.60)

hypertension 540 9 97 45 2.98 (0.94-9.42)

Severe hypertension 450 13 94 45 2.37 (1.03-5.41)

BP >160/110 mm Hg 540 7 97 45 2.41 (0.76-7.65)

Small for 450 15 94 30 2.36 (0.96-5.77)

gestational age 540 10 97 36 3.14 (0.96-10.20)

HELLP: hemolysis, elevated liver enzymes, low platelets syndrome

BP: blood pressure

in doubt. In Redman's study,14 the best correlation to predict
perinatal mortality was the serum uric acid level at 28 to 32
weeks' gestation. With term pregnancies, a serum uric acid level
of ~ 420 /lmollL only predicted a perinatal mortality of 6%
to 9% in their group. 14
Koike et al. 15 reported that the elevation of serum uric acid
levels occurs earlier in twin gestations than singletons and may
serve as a useful early predictor of the development of
preeclampsia. Lim et al. 16 recently documented that mean
serum uric acid levels were significantly higher in women with
transient hypertension, preeclampsia, and superimposed
preeclampsia. However, the clinical utility in differentiating
these states was limited. Our study agreed with Lim's conclu-
sions and also showed that elevated serum uric acid levels were
not specific for maternal or fetal complications.

TABLE 4
VARIATION OF SERUM URIC ACID LEVELS WITH THE SEVERITY OF HYPERTENSION
Gestational Hypertension Preeclampsia

N Serum Uric Acid (~moI/L) N Serum Uric Acid (~moI/L)

Mean ± SD Mean ± SD

Severe hypertension 65 365 ± 89* 67 393 ± 96 t

(BP ;:::160/110 mm Hg)

Mild hypertension 193 333 ± 78 127 383 ± 85 t

(BP < 1601110 mm Hg,
> 140/90 mm Hg)
N: number; BP: blood pressure
*p < 0.0 I compared to mild hypertension
tp < 0.05 compared to gestational hypertension

JOGe AUGUST 2002

 TABLE 5
VARIATION OF SERUM URIC LEVELS WITH BIRTH WEIGHT
Gestational Hypertension
N Serum Uric Acid (IJmoI/L)
Mean ± SO
SGA 40 350 ± 13
Non-SGA 218 339 ± 6
N: number; SGA: small for gestational age infants
,
p < 0.000 I compared to non-SGA
CONCLUSION
This study confirms previous reports \6-20 that significant eleva-
tion of serum uric acid occurs in pregnancies complicated by
preeclampsia, eclampsia, and pregnancy-induced hypertension
compared with normotensive pregnancies. However, the values
overlap too much to be useful to discriminate between these
hypertensive pregnant conditions, or between the pregnancies
likely to be associated with maternal complications or SGA
newborns. Although uric acid levels are higher in women with
HELLP syndrome, the severity of the HELLP syndrome does
not correlate with the serum uric acid level. Thus the measure-
ments of serum uric acid levels in hypertensive pregnant women
can support the diagnosis of a new hypertensive disorder, but
has a poor predictive value for the development ofHELLP syn-
drome and SGA infants.
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