Comparison of Serum Uric Acid, Iron and Total Iron Binding

Comparison of Serum Uric Acid, Iron and Total Iron Binding
Capacity (TIBC) Levels
Levels in Pre–
Pre–eclamptic and
Normal Pregnant Women
Bita Eslami,
Eslami, M.P.H.1; Ashraf Moeini,
Moeini, M.D.1,2; Reihaneh Hosseini,
Hosseini, M.D.1; Mojtaba Sedaghat,
Sedaghat, M.D.3
1 Department of Gynecology and Obstetrics, Arash Women’s Hospital, Tehran University of Medical
Sciences, Tehran, Iran
2 Department of Endocrinology and Female Infertility, Royan Institute, ACECR, Tehran, Iran
3 Department of community medicine, Tehran University of Medical Sciences, Tehran, Iran
Received June 2010; Revised and accepted July 2010
Objective: The objective of our study was to compare uric acid, iron and TIBC levels in normal and
preeclamptic pregnant women and determine their relations with maternal and fetal complications.
Materials and methods: A case control study was conducted in 200 normal and preeclamptic pregnant
women. At 32–40 weeks of pregnancy (third trimester) a blood test was taken in order to measure the
uric acid, iron and TIBC and their relation with maternal and fetal complications.
Results: Uric acid level showed significant difference (4.58 ± 0.73, 4.87 ± 0.58, p=0.002) between
two groups of pre–eclamptic and normal women. The iron and TIBC level had no significant difference
in either group. The uric acid level and iron had significant differences between two groups with and
without maternal complication, respectively (4.69 ± 0.66, 5.05 ± 0.59, p<0.05) (387.42 ± 82,
405.24 ± 57, p<0.05). There was not any difference in three parameters between groups with and
without fetal complication. The BMI was significantly higher in preeclamptic group and has positive
relation with uric acid level. If we consider 29 as BMI cut–off point; it will be associated with 73%
sensitivity and 67% specificity in preeclampsia determination. Using 4.55 as uric acid cut–off point,
the sensitivity is 76% and specificity is 49%.
Conclusion: Although the higher level of uric acid, higher BMI scale and positive roll–over test are
associated with preeclampsia, but they are not very strong predictors as single test.
Keywords: Serum uric acid, Iron, TIBC, Roll–over test, Preeclampsia
Preeclampsia is a multisystemic obstetric disorder with
unknown etiology (1) and it affects 5 to 10 percent of
all pregnancies (2). It’s the most significant cause of
Ashraf Moini, Arash Women’s Hospital, North Bagheri Ave.,
Resalat Highway, Tehran, Iran
Tel: +98 (21) 77883283 , Fax: +98 (21) 77883196
E–mail: [email protected] , [email protected]
Journal of Family and Reproductive Health
maternal and fetal morbidity and is responsible for
approximately 15% of maternal mortality (3).
Early detection of preeclampsia has been investigated by several biological and biochemical tests.
Although none of them have not enough accuracy in
order to detect preeclampsia as early as possible.
Some studies evaluated serum uric acid levels and
correlation between serum uric acid with maternal and
fetal morbidity (4–6).
In normal pregnancy, serum uric acid concentraVol. 4, No. 4, December 2010
Eslami et al.
considered a positive test result (4).
Five millimeters of venous blood was taken from
these women in 32–40 weeks of pregnancy (third trimester) in order to measure the iron and uric acid (photometric) and TIBC (immunoturbidimetric) by Pars
Azmoon kit (Iran). Serum was prepared from venous
blood collected and stored at –40°C until assayed. The
patients were followed until 48 hours after delivery
and maternal and neonatal outcomes were reported.
The maternal complications included HELLP syndrom, eclampsia and maternal death. Fetal complications were IUGR, preterm labour, low Apgar score and
Statistical analysis was performed with SPSS software (Version 16). The appropriate statistical test including Chi–Square and Student’s t–test were used to
compare the results. A two–tailed p–value of less than
0.05 was considered significant.
General characteristics (age, BMI, parity) of patients
and infants are shown in Table 1.
Table 2 shows the comparison of uric acid, iron
and TIBC level in each group. As it was shown the
iron and TIBC level had no significant difference in
either group. Only uric acid level was significantly
increased in preeclamtic women (4.58 ± 0.73, 4.87 ±
0.58, p= 0.002).
According to the data of table 3 seventeen patients
were known as sever preeclampsia with BP >160/110
and there is no significant difference in uric acid, iron
and TIBC levels between two groups of mild and severe preeclampsia.
As it was evident, maternal complication was manifested in 14 patients of preeclamptic group and 2 persons of normal group. Twenty persons in preeclamptic
group and 5 persons in normal group had fetal complications.
The uric acid level (4.69 ± 0.66, 5.05 ± 0.59, p<0.05)
and iron (387.42 ± 82, 405.24 ± 57, p<0.05) had significant differences between two groups with and without maternal complication. There was no significant
difference in three parameters between groups, with
and without fetal complication.
There was significant relationship between positive
roll– over test and preeclampsia. One person in normal
group and 14 persons in preeclamptic group had positive roll–over test (p<0.001).
tion decreased (7) and concentrations usually are in
the 3–4 mg/dl range (180–240 µmol/l) (7, 8) and then
slowly increase reaching 4–5 mg/dl (240–300 µmol/l)
by term (9).
In preeclamptic women, serum uric acid concentration is increased in compare with normal pregnancy
due to reduction in renal excretion of urate, which is
probably mediated by the systemic vasoconstriction,
reduction in renal blood flow and decrease in glomerular filtration rate that accompany this disease (10).
There are several other potential origins for uric
acid in preeclampsia; increased tissue breakdown, acidosis and increased activity of the enzyme xanthine
oxidase /dehydrogenase (11).
The causes of preeclampsia are complex and not
fully understood, but the condition may be associated
with poor placentation (12). The effect of poor placentation is to leave the spiral arteries smaller than normal
for the second half of pregnancy (12). Iron may arise
in the ischemic placenta by destruction of red blood
cells from thrombotic, necrotic, and hemorrhagic areas
(13), which, if uncontrolled, may result in endothelial
cell damage, as hypothesized by Hubel et al. (14).
Disturbances in iron hemostasis have already been
observed in preeclampsia (15, 16).
Meanwhile, the roll–over test has also been found
useful in identifying patients at risk (4).
Therefore in this study serum uric acid, serum iron
and TIBC and roll–over test are examined as screening
tests in order to compare in preeclamptic cases against
normal pregnant women.
Materials and Methods
A total of two hundreds obstetric patients at Arash hospital were enrolled in an ongoing investigation. The
study was approved by the ethics institutional review
board of Arash Hospital and informed consent was
obtained from all participants. Women were excluded
from the study if they had multiple fetuses, chronic
hypertension, renal disease, any form of anemia, diabetes, and other preexisting medical condition or history of drug use. Neither of mothers had received iron
supplements until 20 weeks of pregnancy and then all
women received 30 mg elemental iron daily.
One hundred women with normal pregnancy and
100 patients with preeclampsia were recruited in this
In the roll–over test, between 32–40 weeks of pregnancy, diastolic BP was recorded while the patient
was at rest and after she turned over on her back. An
increase of more than 20 mm Hg in diastolic BP was
Vol. 4, No. 4, December 2010
The results of our study manifested the theoretical sigJournal of Family and Reproductive Health
Uric acid, Iron and TIBC in pre–eclampsia
Table 1: Characteristics of patients and infants
(n = 100)
28.2 ± 5.6
31.6 ± 6.1
2.2 ± 0.4
37.13 ± 2.8
2980 ± 605
** BMI: Body Mass Index
*** GA: Gestational Age
The iron level shows correlation with maternal complications too. It may be due to a rise in heme catabolism after increased destruction of maternal red blood
cells (17).
According to our results there was no relation between uric acid, iron and TIBC and fetal complication
as reported in Williams and Galerneau and also Thangaratinam et al studies (4, 5). Considering the uric acid
level which is related with maternal complication as
we reported above it seems to be paradox with previous
BMI also is higher in preeclamptic group and also
has significant relationship with uric acid level. Rajasingam et al believe that plasma uric acid level is related to body mass index as a biomarker of oxidative
stress (18).
Delić and Stefanović also reported correctly classified 79.6% patients using uric acid and urea (19). Kaypour and coworkers revealed 54.76% sensitivity and
96% specificity for uric acid 40.47% and 90.90% for
BMI (20).
It seems that no single test can predict preeclamp-
nificant differences of uric acid level between normal
and preeclamptic women. Although preeclampsia is
theoretically associated with iron disturbance metabolism, there is no significant difference in iron and TIBC
levels. It may be due to low power of study or perhaps
some more items (such as ferritin or transferrin) must
be introduced. On the other hand, the disturbance of
iron metabolism is in placental level and may has no
systemic effects. However, Rayman et al have reported significantly higher serum iron (68%) and lower
TIBC (12%) in preeclamptic subjects (16). It should
be mentioned their study sample size was 40 and the
mean gestational age was 33 weeks. However in our
study the sample size is higher and the mean gestational age was 38 weeks which may explain the results'
Although Williams and Galerneau and also Thangaratinam et al have reported that uric acid level is a
poor predictor of maternal and fetal complications,
but our study revealed a correlation between uric acid
levels and maternal complications which supports Koopmans et al study's results (4–6).
* P–value refers to t-test.
Age (years)
BMI** (kg/m2)
GA*** (weeks)
Infant's birth weight (gr)
(n =100)
25.8 ± 4.7
27.8 ± 3.9
2.3 ± 0.4
39.66 ± 1.1
3231 ± 336
Table 2: Comparison of biochemical parameters between two groups
Uric acid (mg/dl)
Serum iron (mg/dl)
TIBC** (mg/dl)
* P–value refers to t-test.
4.87 ± 0.58
107.74 ± 23
384.70 ± 77
4.58 ± 0.73
107.34 ± 32
393.17 ± 84
** TIBC: Total Iron Binding Capacity
Table 3: Comparison of data between mild and severe preeclampsia
Mild preeclampsia
(n =83)
4.71 ± 0.63
107.27 ± 28
387.36 ± 79
Uric acid (mg/dl)
Serum iron (mg/dl)
TIBC** (mg/dl)
* P–value refers to t-test.
Severe preeclampsia
(n = 17 )
4.89 ± 0.64
110.41 ± 30
405.88 ± 100
** TIBC: Total Iron Binding Capacity
Journal of Family and Reproductive Health
Vol. 4, No. 4, December 2010
Eslami et al.
Financial Support
1. Roberts JM, Cooper DW. Pathogenesis and genetics of
preeclampsia. Lancet 2001; 357: 53–6.
2. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC,.
Rouse DJ, Spong CY. Pregnancy Hypertension.
Williams Obstetrics 23 rd edition. USA McGraw–Hill;
2010: 706–56.
3. Habli M, Sibai BM. Hypertensive disorders of pregnancy. In: Gibbs RS, Karlan BY, Haney AF, Nygaard
IE. Danforth,s Obstetrics & Gynecology; Lippincott
Williams & Wilkins. 10th edition; 2008: 257–76.
4. Williams KP, Galerneau F. The role of serum uric acid
as a prognostic indicator of the severity of maternal
and fetal complications in hypertensive pregnancies.
J Obstet Gynaecol Can 2002; 24: 628–32.
5. Thangaratinam S, Ismail K, Sharp S, Coomarasamy
A, Khan K. Accuracy of serum uric acid in predicting
complications of preeclampcia: Tests in Prediction of
Pre–eclampsia Severity review group. BJOG 2006;
113: 369–78.
6. Koopmans CM, van Pampus MG, Groen H, Aarnoudse
JG, van den Berg PP, Mol BW. Accuracy of serum uric
acid as a predictive test for maternal complications in
pre–eclampsia: bivariate meta–analysis and decision
analysis. Eur J Obstet Gynecol Reprod Biol 2009; 146:
7. Carter J, Child A. Serum uric acid levels in normal
pregnancy. Aust NZ J Obstet Gynaecol 1989; 29:
313– 4.
8. Chappel LC, Seed PT, Briley A, Kelly FJ, Hunt BJ,
Charnock–Jones DS, et al. A longitudinal study of
biochemical variables in women at risk of preeclampsia. Am J Obstet Gynecol 2002; 187: 127–36.
Edelstam G, Lowbeer C, Kral G, Gustafsson SA,
Venge P. new reference values for routine blood
samples and human neutrophilic lipocalcin during
third–trimester pregnancy. Scand J Clin Lab Invest
2001; 61: 583–92.
Sibai BM. Hypertension in pregnancy In:Gabbe SG,
Niebyl JR, Simpson JL. Obstetrics normal and problem
pregnancies; Churchill Livingtone. 5th edition .2007,
Johnson RJ, Kang DH, Feig D, Kivlighn S, Kanellis J,
Watanabe S, et al. Is there a pathogenetic role for uric
acid in hypertension and cardiovascular and renal
disease? Hypertension 2003; 41: 1183–90.
Brosens IA, Robertson WB, Dixon HG. The role of the
spiral arteries in the pathogenesis of preeclampsia.
Obstet Gynecol Annu 1972; 1: 177–91.
Balla J, Jacob HS, Balla G, Nath K, Eaton JW, Vercelloti GM. Endothelial–cell heme uptake from heme
proteins: induction of sensitization and desensitization
to oxidant damage. Proc Natl Acad Sci USA 1993;
90: 9285–9.
Hubel CA, Roberts JM, Taylor RN, Musci TJ, Rogers
JM, McLaughlin MK. Lipid peroxidation in preeclampsia: new perspectives on preeclampsia. Am J Obstet
Gynecol 1989; 161: 1025–34.
Hubel CA, Kozlov AV, Kagan EV, Evans RW, Davidge
ST, McLaughlin MK, et al. Decreased transferring
and increased transferrin saturation in sera of women
with preeclampsia: Implications for oxidative stress.
Am J Obstet Gynecol 1996; 175: 692–700.
Rayman MP, Barlis J, Evans RW, Redman CW, King
LJ. Abnormal iron parameters in the pregnancy syndrome preeclampsia. Am J Obstet Gynecol 2002; 187:
Samuels P, Main EK, Mennuti MT, Gabbe SG. The
origin of increased serum iron in pregnancy–induced
hypertension. Am J Obstet Gynecol 1987; 157: 721–5.
Rajasingam D, Seed PT, Briley AL, Shennan AH,
Poston L. A prospective study of pregnancy outcome
and biomarkers of oxidative stress in nulliparous obese
woman. Am J Obstet Gynecol 2009; 200: 395.
Delić R, Stefanović M. Optimal laboratory panel for
predicting preeclampsia. J Matern Fetal Neonatal Med
2010; 23: 96–102.
Kaypour F, Masomi Rad H, Ranjbar Novin N. The
predictive value of serum uric acid, roll–over test and
body mass index in preeclampsia. International
J Gynecol Obstet 2006; 92: 133–4.
sia correctly. The combination of uric acid level, roll–
over test and BMI may improve the predictive value.
The primary outcome of our study was comparison
of uric acid level between two groups of pre eclamptic and normal pregnant women (4.58 ± 0.73, 4.87 ±
0.58 respectively). Based on our result the power of
our study will be 87.5% by using the Epi Info Web
site ( However by considering the other outcomes the power will be low.
So, further studies at the first or second trimesters
with larger sample size are suggested to find a specific
marker in preeclampsia and focus on it to reduce maternal and fetal complications.
Vol. 4, No. 4, December 2010
Journal of Family and Reproductive Health