Biol Trace Elem Res (2013) 152:327332

DOI 10.1007/s12011-013-9637-4

Serum Trace Elements Levels in Preeclampsia and Eclampsia:

Correlation with the Pregnancy Disorder
Touhida Ahsan & Salina Banu & Quamrun Nahar &
Monira Ahsan & Md. Nazrul Islam Khan &
Sheikh Nazrul Islam

Received: 15 January 2013 / Accepted: 21 February 2013 / Published online: 23 March 2013
# Springer Science+Business Media New York 2013

Abstract Preeclampsia and eclampsia are fatal medical complications of pregnancy accounting for 2080 % of increased
maternal death in developing countries. Their aetiologies are still
under investigation. Serum trace elements have been suggested
to be involved in the pathogenesis of preeclampsia. Aim of this
study was to address the correlation of serum trace elements
with preeclampsia and eclampsia. It was a comparative crosssectional study conducted on conveniently recruited 44 preeclampsia, 33 eclampsia and 27 normotensive pregnant patients.
Atomic absorption spectrometry was employed to analyse serum concentrations of Ca, Mg, Cu, Zn and Fe. Data were
analysed by Student's t test, one-way analysis of variance and
multinomial logistic and binary regression analyses. p<0.05 was
considered as a level of significance. In preeclampsia, the serum
Ca and Mg were significantly lower than those in eclampsia,
while Cu and Zn values were higher. Significant changes of Ca,
Mg and Cu were noted among preeclampsia, eclampsia and
pregnant control. Serum Ca and Mg indicated a positive
T. Ahsan
Department of Gynaecology and Obstetrics, Ibn Sina Medical
College, Kalanpur,
Dhaka 1212, Bangladesh
S. Banu : M. N. I. Khan : S. N. Islam (*)
Institute of Nutrition and Food Science, University of Dhaka,
Dhaka 1000, Bangladesh
e-mail: sheikhnazrul@du.ac.bd
S. N. Islam
e-mail: sheikhnazrul09@gmail.com
Q. Nahar
Department of Biochemistry and Cell Biology, Biomedical
Research Group, BIRDEM, Dhaka 1000, Bangladesh
M. Ahsan
Department of Pharmaceutical Chemistry, Faculty of Pharmacy,
University of Dhaka, Dhaka 1000, Bangladesh

association, and Cu gave a negative association in preeclampsia.

Cu/Fe ratio was high in eclampsia. Significant correlations of
Mg with Zn in eclampsia and Mg with Fe in preeclampsia and
eclampsia were predicted. Significant changes in serum trace
element levels were present in preeclampsia and eclampsia that
may have a link with the pathogenesis of pregnancy disorder.
Keywords Trace elements . Correlation . Association .
Preeclampsia . Eclampsia

Introduction
Preeclampsia is a fatal medical disorder of pregnancy. It has
been associated with adverse course and outcome of the
pregnancy [1, 2], resulting in increased maternal and infant
mortality and morbidity [3]. Preeclampsia has been described
as a transient, but potentially dangerous complication of pregnancy leading to eclampsia. It affects approximately 510 %
of pregnancies worldwide [46]. Its greatest impact is in the
developing countries accounting for 2080 % of the strikingly
high maternal mortality and 15 % of preterm births or deliveries [7]. However, even in the developed countries, there
have major effects, primarily on the foetus [8].
Preeclampsia is a rapidly progressive pregnancy-induced
hypertension characterised by persistently elevated blood pressure (>140/90 mmHg), proteinuria, platelet aggregation and
oedema of the lower extremities, particularly after midpregnancy [5, 7]. If untreated, preeclampsia can progress rapidly leading to eclampsia, putting the mother at serious health
risk [9]. Eclampsia is a convulsive state. In spite of extensive
pathophysiological and anatomical changes in pregnancy, it
may be local or systemic. Eclampsia is commonly seen in poor
teenage pregnant women who live in slum area devoid of both
home and antenatal cares [10]. In Bangladesh, eclampsia causes

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5 % of total obstetric admission in the health facilities and 16 %

of maternal death [3]. Preeclampsia is a complex, progressive
and multisystemic disorder that may be caused by series of
genetic, nutritional and environmental factors [11]. In pregnancy, the processes of implantation, proliferation, differentiation
and trophoblast invasion produce reactive oxygen species
(ROS), while in preeclampsia, lipid peroxidation also yielding
ROS is uncontrolled. It is thought that preeclampsia is associated with an imbalance of increased lipid peroxides and decreased antioxidants [12, 13]. Placental oxidative stress has been
shown to be a key feature in the pathogenesis of preeclampsia.
Although many pathophysiological factors have been implicated in the aetiology of preeclampsia, its aetiology is still
under investigation [6, 12, 14, 15]. The role of antioxidant in
the prevention of preeclampsia is still an unresolved issue [16].
The high rate of preeclampsia in developing countries has
insisted some researchers to suggest involvement of nutrition,
especially trace elements in the aetiology of preeclampsia [15,
17]. However, a number of studies, which were conducted to
address the relationship between maternal plasma trace elements level and preeclampsia, have been reported inconsistently [1820]. Some reports concluded with the changes in
concentrations of blood trace elements in preeclampsia (10,
18, 21), but the other did not find any association between
serum trace elements and occurrence of preeclampsia [15].
Some authors reported higher trend of ratio of plasma Cu/Zn
in preeclamptic women, and it has been taken as an index of the
inflammation [18]. The present study has analysed the serum
trace element levels in preeclampsia and eclampsia and has
made an attempt to look into the correlation of the trace
elements with the onset of preeclampsia and eclampsia.

Ahsan et al.

blood pressure of at least 160/110 mmHg measured on two

occasions each 6 h apart and proteinuria of at least >2+ or 3+
on dipstick testing. Preeclampsia was diagnosed with clinical
signs and symptom by consultant gynaecologist as described
elsewhere [3, 5, 7]. Demographic well-matched healthy normotensive pregnant patients of 28 to 42 weeks of singleton
gestation with nil urinary protein were enroled by convenience
as controls for both preeclampsia and eclampsia subjects.
Patients with history of hypertension and proteinuria before
conception or before 20 weeks of gestation, any associated
medical disorders, history of any trace element supplementation during the last 1 year and with history of convulsion were
excluded from the study.
Analysis of Trace Element
A 5 ml venous blood sample was collected from the antecubital
vein from each of the case and control subjects. Serum trace
elements were analysed at the Centre for Advanced Researches, University of Dhaka. It was performed with an atomic
absorption spectrometer equipped with a hollow cathode lamp
and a deuterium background corrector at the respective wavelength of 422.7 nm for calcium, 285.2 nm for magnesium,
324.8 nm for copper, 213.9 nm for zinc and 248.3 nm for iron
with the use of an air-acetylene flame. A series of working
standard solutions of calcium, magnesium, copper, zinc and
iron were prepared from the stock standard solutions, and
appropriate dilutions of the sera were made for absorbance as
described by Hossain et al. [22]. Standard calibration graphs
were constructed for each of the elements for calculation of
their concentrations in the sera.
Statistical Analysis

Methods
Study Population
It was a comparative cross-sectional study conducted on
44 preeclampsia, 33 eclampsia and 27 normotensive
pregnant patients who were demographically well matched.
The case and control subjects were enroled conveniently from
Salimullah Medical College Hospital, Dhaka Medical College
Hospital, and Bangabandhu Sheikh Mujib Medical University,
Dhaka, Bangladesh. Ethical permission was taken from the
departments concerned for enrolment of the patients. All of
the case and control subjects were informed about the nature of
the work, and they agreed to participate voluntarily in the study.
Preeclamptic patients were in 28 to 42 weeks of singleton
gestation with one measurement of diastolic pressure of
110 mmHg or more or two measurements of 90 mmHg or
more on two consecutive occasions 6 h or more apart and
urinary protein 2+ or more (100 mg/dl; dipstick reagent strip,
Boehringer Mannheim, Germany). Eclampsia patients had

The SPSS software package (12.5 version; SPSS, Inc., Chicago, USA) was used for statistical analysis. Data were
presented as meanSD. Comparison of serum trace element
levels between groups was performed by Student's t test
and, among the groups, by one-way analysis of variance.
In order to analyse the association and correlation of the
trace elements with case and control subjects, multinomial
logistic and binary regression analyses were used. p<0.05
was considered as a level of significance.

Results
Demographic Characteristics
Maternal age and clinical profile of the case and pregnant control
subjects are outlined in Table 1. Maternal age, gestational age
and gravida among the case and control subjects were noted
well matched. Proteinuria between preeclampsia and eclampsia

Trace Elements in Preeclampsia and Eclampsia

329

Table 1 Demographic characteristics of preeclampsia, eclampsia and pregnant control

Maternal characteristicsa

Preeclampsia
(n=44)

Eclampsia
(n=33)

Pregnant
(n=27)

Maternal age (year)

Gestational age (week) at sampling
Gravida in no. (%)
Primi
Multi
Proteinuria (mg/dl and no)
Primi
Multi
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)

26.055.41
35.603.85

22.864.87
35.513.47

24.114.93
36.232.64

18 (41)
26 (59)

24 (73)
9 (27)

12 (34)
23 (66)

2+ (26)
3+ (18)
160.6822.61
109.1615.21

3+ (18)
3+ (15)
153.7021.80
106.6013.83

nil
109.869.27
72.297.81

Descriptive statistics were performed. Data were expressed in meanSD, number (%), value (number)
a

Demographic data of the case and control subjects were well matched. The subjects were conveniently enroled from lower-middle socio-economic
class

were also matched. Both the case and pregnant control were
conveniently enroled from lower-middle socio-economic class.
Serum Trace Element Level
Serum trace element levels in preeclampsia, eclampsia and
normotensive pregnant control are described in the following
Table 2. In preeclampsia, serum concentrations of Ca and Mg
were found significantly (p<0.05) lower than those in the
eclampsia, but slightly higher than those in the pregnant
control. In case of Cu and Zn values, it was reverse where
Cu and Zn levels were significantly (p<0.05) higher in preeclampsia than those in the eclampsia, but it were marginally
lower than those in the pregnant control. Change in Fe value
was also insignificant. One-way analysis of variance showed
significant (p<0.05) changes of Ca, Mg and Cu among preeclampsia, eclampsia and pregnant control.

In multinomial logistic regression, serum Ca and Mg

presented a positive association, and Cu gave a negative
association in the preeclampsia (Table 3). The ratio of serum
Cu/Fe was seen to have a significant (p<0.05) higher trend in
eclampsia only. Binary regression analysis was done to address the correlation of trace elements in preeclampsia and
eclampsia. It indicated that serum Zn was correlated (p<0.06)
with Mg in eclampsia (Fig. 1). When eclampsia and preeclampsia were considered as a single group, the serum Mg
concentrations were significantly (p<0.04) correlated with
serum Fe levels (Fig. 2).

Discussion
Despite several investigations, aetiologies of preeclampsia
and eclampsia have not yet been elucidated [23, 24]. Some

Table 2 Serum trace element level among preeclampsia, eclampsia and pregnant control
Mineral level
mmol/L
Calcium1
Magnesium2
Copper3
Zinc4
Iron5

Preeclampsiaa
(n=44)
2.360.221
0.8170.489
0.0170.002
0.0160.002
0.0190.004

Eclampsiab
(n=33)
2.470.291
0.8470.054
0.0150.002
0.0140.002
0.0210.008

Values were expressed in mean and standard as meanSD

Level of significance (p<0.05) was expressed by Student's t test
1ab t=1.87, p=0.06; 2ab t=2.52, p=0.014; 3ab t=3.39, p=0.001; 4ab t=2.06, p=0.043; 5ab t=0.33, p=0.744
1ac t=0.65, p=0.51; 2ac t=0.15, p=0.88; 3ac t=1.24, p=0.218; 4ac t=0.56, p=0.580; 5ac t=0.40, p=0.694
1bc t=2.18, p=0.03; 2bc t=1.96, p=0.055; 3bc t=2.06, p=0.044; 4bc t=1.20, p=0.236; 5bc t=0.009, p=0.993
Level of significance (p<0.05) was expressed by ANOVA
1abc p<0.05; 2abc p<0.04; 3abc p<0.003; 4abc p<0.14; ; 5abc p<0.92

Pregnant controlc
(n=27)
2.320.244
0.8150.069
0.0160.002
0.0150.002
0.0230.002

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Ahsan et al.

Table 3 Multinomial logistic regression among preeclampsia and eclampsia

Group

Parameter

Preeclampsia

Eclampsia

-coefficient

SE

Level of
significance

Intercept
Calcium
Magnesium
Copper
Zinc

5.070
0.062
0.437
6.451
2.403

6.120
0.030
0.222
2.874
1.892

0.407
0.036
0.049
0.025
0.204

Iron
Intercept
Calcium
Magnesium
Copper
Zinc
Iron

0.526
7.822
0.009
0.095
4.221
1.926
0.705
0.095

1.270
5.839
0.027
0.191
2.558
1.697
1.148
0.191

0.679
0.180
0.740
0.619
0.099
0.256
0.539
0.619

Expected
-coefficient

95 % confidence interval for expected -coefficient

Lower bound

Upper bound

1.064
1.548
0.002
0.090

1.004
1.002
5.648E-06
0.002

1.1
2.3
0.4
3.6

0.591

0.049

7.1

1.009
1.100
68.091
6.860
0.494
1.100

0.957
0.756
0.453
0.247
0.052
0.756

1.0
1.6
10236.2
190.7
4.6
1.6

Level of significance (p<0.05) was expressed by multinomial logistic regression

SE standard error

studies indicated that changes in blood trace element levels

in preeclamptic patients may have implication on the pathogenesis of this disorder [21, 25], while others did not find any
association [19]. Oxidative stress also claims to contribute a
significant role in the development of preeclampsia [26, 27].
Currently, immunologic maladaptation has been suggesting
as a pathogenic mechanism for preeclampsia. Defective regulation of the complement system is also thought to induce
preeclampsia. Pregnancy in women with systemic lupus
erythematosus or antiphospholipid antibodiesautoimmune
condition characterised by complement-mediated injury
has been reported to be associated with increased risk of
preeclampsia and miscarriage. Mutations in membrane cofactor protein, complement factor I and complement factor H
appear to be contributed to the development of preeclampsia
[28].

Changes of serum trace element concentrations like Ca and

Mg can lead to alteration of blood pressure. Magnesium is an
essential cofactor for many enzyme systems and also plays an
important role in neurochemical transmission and peripheral
vasodilatation. Also, change of plasma Ca can induce elevation of blood pressure in the gestational hypertensionpreeclampsia. It is documented that blood Ca and Mg have a
relaxant effect on the blood vessels of pregnant women [4].
Serum Mg may have significant effect on cardiac excitability
and, on vascular tone, contractility and reactivity. Low serum
concentrations of Ca and/or Mg induce constriction of vascular smooth muscles and increase vascular resistance and thus
increase blood pressure [11, 29].
In the present study, the concentrations of serum Ca and
Mg were found lower in preeclampsia than those in the
eclampsia, but it was insignificant. Similar finding was also
1.0

.9

r=0.24
p= 0.04

r= 0.35
p=0.06

.9

.8

Mg
(mmol/l)

Mg
(mmol/l)

.8

.7

.6
.010

.012

.014

.016

.018

Zinc (mmol/L)

Fig. 1 Correlation between magnesium and zinc in eclampsia

.020

.7
.01

.02

.03

.04

Fe (mmol/l)

Fig. 2 Correlation between Mg and Fe in preeclampsia and eclampsia

Trace Elements in Preeclampsia and Eclampsia

reported by others [21, 30]. The lower levels of serum Ca

and Mg may be responsible for the pathogenesis of preeclampsia. Some studies indicated contrary finding with
higher serum Mg in the preeclamptic patients than that in
the pregnant patients [31, 32], while others obtained no
alteration, particularly for Mg [33]. However, Cu and Zn
concentrations obtained in this study were found high in
preeclampsia as compared to those in the eclampsia and
pregnant control where it was significant in respect of
eclampsia, but insignificant in respect of the control. However, the finding for Cu and Zn is contrary to the report
made by James et al. [21]. It was further observed that trace
element values among preeclampsia and eclampsia were
found within the normal range as noted by Young [34],
but serum Mg value was in the lowest limit, indicating
insufficient blood Mg that may be the cause of the development of preeclampsia. The significant higher trend of Cu/Fe
ratio obtained in eclampsia may be an index for pathogenesis of this disorder [18]. One-way analysis of variance
showed significant changes in Ca, Mg and Cu among the
case and control subjects. Multinomial logistic regression
predicted a positive association of serum Ca and Mg and a
negative association of Cu in preeclampsia. Binary regression analysis indicated a higher trend of correlation of Mg
with Zn in eclampsia and Mg with iron in both eclampsia
and preeclampsia. All of these findings obtained in this
study suggest that the changes of serum trace elements
may have an association or correlation with the pathogenesis of preeclampsia and eclampsia.

Conclusion
Changes of serum trace elements were manifested in preeclampsia and eclampsia. A higher trend of Cu/Fe ratio was
obtained in eclampsia. Serum Ca and Mg presented a positive association, and Cu gave a negative association in
preeclampsia. Magnesium was found to correlate with Zn
in eclampsia and with Fe in eclampsia and preeclampsia. It
is, thus, apparent that serum trace elements level may have
important function in the development of preeclampsia
and/or eclampsia and probable link with the pathogenesis
of these disorders. Revealing the aetiologies of preeclampsia
and eclampsia would help in the prevention and management of preeclampsia and eclampsia, and this would support
the health care facilities.

Limitation
There have been some limitations in this study. It investigated only four serum trace elements. Analysis of more trace
elements would enrich the finding. In addition to analysed

331

trace element profile, investigation into more aetiological

factors like oxidative stress, antioxidant level and immunological aspect in larger population of both preeclampsia and
eclampsia would be a better way to address a conclusive
comment on the pathogenesis of this pregnancy disorder.
Acknowledgments Authors thank the Ministry of Science, Information and Communication Technology, Government of Bangladesh, for
their financial support. Authors are also grateful to Dr. Sagarmay Barua,
Professor of the Institute of Nutrition and Food Science, University of
Dhaka, for his kind input in editing this manuscript.
Conflict of Interest Authors do not have any conflict of interest.

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