Serum Zinc Concentration in Iranian Pre-eclampsic and Normotensive Pregnant Women
.........................................................................................................................

I. Nourmohammadi,* A. Akbaryan, Sh.Fatemi,** A.R. Meamarzadeh+ and E. Noormohammadi++

*Department of Biochemistry, College of Medicine
**Department of Obstetrics and Gynecology, College of Medicine

+Cellular Molecular Research Center
Iran University of Medical Science
Tehran Iran

++Department of cell biology
University of Oklahoma
Norman, Oklahoma USA

Correspondence to:
Issa Nourmohammadi, PhD
Associate Professor
Department of Biochemistry, College of Medicine
Iran University of Medical Sciences
Crossroads of Chamran and Hemmat
Tehran, Iran
E.mail: cmrc_iums@yahoo.com

 

SUMMARY In this case-control study, serum zinc concentration was measured in a study group consisting of 40 pre-eclamptic Iranian women.

Zinc (Zn), is the most abundant micronutrient in the human body, and has gained much popularity for its illustrative role in enhancing reproductive health. Zn is required for optimal cellular function working with more than 300 enzymes in a variety of fashions, serving as a catalyst for numerous reactions or acting as a cofactor, or simply playing a structural role as a stabilizing component^[1].
In developing countries, where improper or inadequate nutrient intake is a special challenge, chronic Zn deficiency or nutriture imbalance may have a disturbing influence on maternal health and pregnancy outcome^[2].

Physiological alterations in Zn concentration has been associated with the prevalence of pathological conditions in pregnancy including the common hypertension disorder known as pre-eclampsia. Although the etiology of this heterogeneous syndrome remains unknown, there is a claim that minerals, including Zn, may be important and beneficial in preventing this pregnancy malady^[3].

Nominal information is available on Zn status during pregnancy-induced hypertension in our community. Therefore, the general purpose of this study is to evaluate serum Zn concentration in pregnant women with pre-eclampsia and compare these results with Zn levels in normotensive pregnant women in order to discover a possible link between Zn and pre-eclampsia and determine if this factor could be used as a potential means for early diagnosis of this dangerous medical problem.

The study group was comprised of pre-eclampsic pregnant women in their third trimester (n=40) with a mean age of 25.6±4.7 years (range 18-35). An equal number (n=40) of normotensive pregnant women with a mean age 26.3±4.5 years (range 18-37) were recruited as the control group. A detailed general physical examination was performed on all study participants before inclusion of each individual in the protocol. Excluded were patients with diabetes, kidney or liver problems, pre-existing hypertension and smokers.

Blood pressure (BP) was measured by trained nurses and pre-eclampsia was defined as BP ³ 140 Hg systolic and ³ 90 mm Hg diastolic on readings of at least 6 or more hours apart accompanied by proteinuria > 300 mg/liter in a 24 hour urine collection.

For Zn serum analysis, samples were carefully collected in metal-free tubes in order to ensure no contamination and stored at -86°C at the Cellular Molecular Research Center until they were analyzed by atomic absorption spectrophotometry [Unicam] according to established methods.
For quality control assurance, each sample was measured in triplicate and a calibration curve was established with a commercial solution with known Zn concentration (seronorm) The CV of repeated zinc analysis of pooled serum was approximately 4%.

Serum levels of Hemoglobin (Hb) and albumin were measured with routine laboratory methods and expressed as g/dl.

Statistical significance for the comparison of mean was determined using Student's t-test and Pearson correlation appropriate software (SPSS 10 for Windows). P values of <0.05 were considered significant.

The mean serum Zn concentration in pre-eclamptic patients was 64.12±10 mg /dl, ranging from 40.5-85.0 mg/dl. The lowest reading was from an 18 year old pregnant mother. The mean serum value was higher for normotensive pregnant women, with a finding of 98.72±8.7 mg /dl, ranging from 82.1-1.02mg /dl. This difference was found to be statistically significant. (P<0.001).

Pre-eclamptic patients had significantly higher mean systolic and diastolic pressure of 149.5±6.18 and 92.79±3.1, respectively than those who had normal pregnancy. About 50% of patients gave birth to babies of 2500 g or less body weight. There was significant correlation between serum zinc concentration of mother and birth weight of infant (P<0.001).

On further analysis there was no correlation statistically between patients' serum albumin and Hb when comparing to control subjects. Table 1 lists results.

Several investigators in recent years have reported that reduced levels of Zn may have a positive association to pre-eclempsia. Kumra^[4] showed serum Zn concentration to be 43% lower in pre-eclamptic women when comparing to normotensive controls (P<0.0001). Lazebnik^[5] reported the Zn levels to be 19% lower in expectant women with hypertension than in healthy control subjects (P<0.002).

In a study with 21 pre-eclampsia patients in their third trimester Ilhan et al.,^[6] found a significant decrease in serum Zn concentration (82.94±28.93 mg/dl) when comparing to normotensive women (125.19±24.23). (P<0.005). Similarly, our data provided evidence of a decrease in serum zinc concentrations in pre-eclamptic pregnant mothers.

In a double-blind study, using Zn supplementation on low-income pregnant women, Hunt et al.^[7] showed that incidence of pregnancy induced hypertension was significantly lower than in the placebo group (P<0.0003).

Conversely, others have refuted any association between hypozincemia and pre-eclamptic conditions and contradictory results have appeared in literature.

Lao^[8], working with 45 Chinese patients found no differences exist in either plasma or erythrocyte Zn levels between pre-eclamptic women and control group. A Zn supplementation study with middle-class pre-eclampsic women in Demark^[9] reported results similar to Lao's. In another study with supplemental Zn in 246 British women with pre-eclampsia, Mahomed et al.^[10] found a higher incidence of pre-eclampsia with low socioeconomic status. Tamura^[11] also reported no significant association between plasma Zn concentration and several types of hypertension during pregnancy.

Despite intense efforts and research aimed at elucidating the causative factors of pre-eclampsia during pregnancy, the incidence of which is still between 3% and 10%, diverse views on its pathogenisis remain^[12].

Progressive depletion of zinc during the course of healthy pregnancy due to physiological changes is a normal process. In developing countries, a variety of other factors also may disturb serum Zn homeostasis in child-bearing women. Further, deterioration of Zn levels in pre-eclamptic patients has been attributed to serum estrogen, cortisol levels or Zn transport proteins, as well as interaction of Zn with toxic metals like cadmium by some authors^{[13, 14]}.

Recent thinking is also turning to oxidative stress as a possible factor in the pathogenesis of pre-eclampsia and complications may arise from free-radical contribution;^[15] that is, an imbalance between maternal pro-oxidants and antioxidants may likely promote genesis for pre-eclampsia.
Zinc, an antioxidant, is a catalyst for the endogenous antioxidant enzyme superoxide dismutase (SOD) which has been demonstrated to be reduced in red blood cells in pre-eclampsia^{[16, 17]}.
Thus, this suggests the low concentration of Zn may be a link between oxidative stress and pre-eclampsia.

While our findings can be considered consistent with others who have looked into the relation between Zn and pre-eclampsia, the existence of contrary evidence only highlights the obvious need for more prospective documented studies to find the exact cause-effect relationship of Zn imbalance in women at risk for development of pregnancy induced pre-eclampsia.

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