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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 com-

plications of pregnancy accounting for 20

80 % of increasedmaternal 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 cross-

sectional study conducted on conveniently recruited 44 pre-

eclampsia, 33 eclampsia and 27 normotensive pregnant patients.

Atomic absorption spectrometry was employed to analyse se-

rum 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.p140/90 mmHg), proteinuria, platelet aggregation and

oedema of the lower extremities, particularly after mid-

pregnancy [5,7]. If untreated, preeclampsia can progress rap-

idly 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

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, Bangladeshe-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

Biol Trace Elem Res (2013) 152:327332

DOI 10.1007/s12011-013-9637-4

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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 pregnan-

cy, 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 associ-ated with an imbalance of increased lipid peroxides and de-

creased 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 im-

plicated 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 ele-ments level and preeclampsia, have been reported inconsistent-

ly [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.

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

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 nor-

motensive 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 supplementa-

tion 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 Re-

searches, University of Dhaka. It was performed with an atomicabsorption spectrometer equipped with a hollow cathode lamp

and a deuterium background corrector at the respective wave-

length 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

The SPSS software package (12.5 version; SPSS, Inc., Chi-

cago, USA) was used for statistical analysis. Data were

presented as mean SD. 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

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were also matched. Both the case and pregnant control wereconveniently 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

Table2. In preeclampsia, serum concentrations of Ca and Mg

were found significantly (p

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studies indicated that changes in blood trace element levels

in preeclamptic patients may have implication on the patho-

genesis 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 reg-

ulation of the complement system is also thought to induce

preeclampsia. Pregnancy in women with systemic lupus

erythematosus or antiphospholipid antibodies

autoimmune

condition characterised by complement-mediated injury

has been reported to be associated with increased risk of

preeclampsia and miscarriage. Mutations in membrane co-

factor 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 eleva-

tion of blood pressure in the gestational hypertensionpre-

eclampsia. 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 vascu-

lar 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

.020.018.016.014.012.010

.9

.8

.7

.6

Zinc (mmol/L)

r= 0.35p=0.06

Mg(mmol/l)

Fig. 1 Correlation between magnesium and zinc in eclampsia

Table 3 Multinomial logistic regression among preeclampsia and eclampsia

Group Parameter -coefficient SE Level of

significance

Expected

-coefficient

95 % confidence interval for expected -coefficient

Lower bound Upper bound

Preeclampsia Intercept 5.070 6.120 0.407

Calcium 0.062 0.030 0.036 1.064 1.004 1.1

Magnesium 0.437 0.222 0.049 1.548 1.002 2.3Copper 6.451 2.874 0.025 0.002 5.648E-06 0.4

Zinc 2.403 1.892 0.204 0.090 0.002 3.6

Iron 0.526 1.270 0.679 0.591 0.049 7.1

Eclampsia Intercept 7.822 5.839 0.180

Calcium 0.009 0.027 0.740 1.009 0.957 1.0

Magnesium 0.095 0.191 0.619 1.100 0.756 1.6

Copper 4.221 2.558 0.099 68.091 0.453 10236.2

Zinc 1.926 1.697 0.256 6.860 0.247 190.7

Iron 0.705 1.148 0.539 0.494 0.052 4.6

0.095 0.191 0.619 1.100 0.756 1.6

Level of significance (p

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

and Mg may be responsible for the pathogenesis of pre-

eclampsia. 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 andpregnant control where it was significant in respect of

eclampsia, but insignificant in respect of the control. How-

ever, 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 develop-

ment of preeclampsia. The significant higher trend of Cu/Fe

ratio obtained in eclampsia may be an index for pathogen-

esis of this disorder [18]. One-way analysis of variance

showed significant changes in Ca, Mg and Cu among thecase and control subjects. Multinomial logistic regression

predicted a positive association of serum Ca and Mg and a

negative association of Cu in preeclampsia. Binary regres-

sion 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 pathogene-

sis of preeclampsia and eclampsia.

Conclusion

Changes of serum trace elements were manifested in pre-

eclampsia and eclampsia. A higher trend of Cu/Fe ratio was

obtained in eclampsia. Serum Ca and Mg presented a pos-

itive 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 manage-

ment of preeclampsia and eclampsia, and this would support

the health care facilities.

Limitation

There have been some limitations in this study. It investi-

gated only four serum trace elements. Analysis of more trace

elements would enrich the finding. In addition to analysed

trace element profile, investigation into more aetiological

factors like oxidative stress, antioxidant level and immuno-

logical 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, Informa-

tion and Communication Technology, Government of Bangladesh, fortheir 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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