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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 17  |  Issue : 1  |  Page : 103-108

Serum zinc levels in iron deficiency anemia, non-iron deficiency anemia, and normal pregnant women and its correlation with iron status and hematological parameters


1 Department of Clinical Pharmacy, College of Pharmacy, University of Duhok, Kurdistan Region, Duhok, Iraqi Kurdistan
2 Department of Pharmacology, College of Pharmacy, University of Duhok, Kurdistan Region, Duhok, Iraqi Kurdistan
3 Department of Adult Nursing, College of Nursing, University of Duhok, Duhok, Iraqi Kurdistan

Date of Submission24-Nov-2019
Date of Acceptance16-Jan-2020
Date of Web Publication17-Mar-2020

Correspondence Address:
Mr. Deldar Morad Abdulah
Department of Adult Nursing, College of Nursing, University of Duhok, Duhok
Iraqi Kurdistan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/MJBL.MJBL_91_19

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  Abstract 


Background: There is limited information on zinc deficiency in pregnant women. The present study aimed to assess the serum zinc (S. zinc) levels and its relation to iron deficiency anemia (IDA) in pregnant women. Patients and Methods: In this case–control study, S. zinc concentrations of 34 individuals diagnosed with IDA, 20 non-iron deficiency anemic pregnant women, and 32 non-anemic apparently healthy individuals were measured. Results: S. zinc was significantly lower in the IDA group (49.59 ng/dL) compared to the healthy controls (55.78; P = 0.018). The individuals in three groups were comparable in the number of persons with zinc deficiency. The study showed that S. zinc has a positive correlation with Hb (r = 0.281, P = 0.011). In addition, S. zinc had a positive correlation with hematocrit (HCT, r = 0.305, P = 0.005) and a negative correlation with serum iron (S. iron, r = 0.242, P = 0.029). Conclusions: This investigation showed that the patients with IDA have a significantly lower concentration of S. zinc and it was substantially positively correlated with Hb, red blood cell, and HCT and negatively with S. iron. Further studies are still needed to evaluate the benefits of zinc and iron supplementation in IDA patients.

Keywords: Iron deficiency anemia, pregnant women, serum zinc


How to cite this article:
Rasool SO, Zaman BA, Abdulah DM. Serum zinc levels in iron deficiency anemia, non-iron deficiency anemia, and normal pregnant women and its correlation with iron status and hematological parameters. Med J Babylon 2020;17:103-8

How to cite this URL:
Rasool SO, Zaman BA, Abdulah DM. Serum zinc levels in iron deficiency anemia, non-iron deficiency anemia, and normal pregnant women and its correlation with iron status and hematological parameters. Med J Babylon [serial online] 2020 [cited 2020 Jul 4];17:103-8. Available from: http://www.medjbabylon.org/text.asp?2020/17/1/103/280737




  Introduction Top


Zinc is an essential mineral for human health. It is relatively abundant in nature, yet at the same time, overwhelming data suggest that zinc deficiency is one of the most prevalent micronutrient deficiencies worldwide.[1]

It is recognized that zinc is important for many basic metabolic processes and hence essential for optimal growth and immunocompetence.[2] It plays an important role in many biological functions, including protein synthesis, cellular division, and nucleic acid metabolism.[3] It also plays a critical role in hemoglobin synthesis and erythropoiesis and may, therefore, play a vital role in the etiology of anemia.[4]

Scientific attention to the role of specific nutrients, especially micronutrients, in healthy pregnancy has grown steadily in recent years, beginning with numerous fields of studies of pregnancy in developing countries. Zinc and iron are micronutrients whose requirements increase with pregnancy.[5] Pregnant women worldwide are frequently iron and zinc deficient.[6] Low birth weight is associated with maternal anemia and, in some circumstances, with low iron and zinc status.[7] Therefore, cosupplementation of iron and zinc during pregnancy is common. Although iron supplementation programs are successful, studies suggest that zinc supplementation negatively affects maternal iron metabolism.[6]

Although severe zinc deficiency is relatively rare in human populations, mild-to-moderate depletion appears to be quite prevalent.[3] Information on zinc deficiency is limited; 1.2 billion people worldwide are at risk of inadequate zinc intake, and presumably, many are zinc deficient.[8] However, very little is known regarding the impact of zinc deficiency on iron status indicators in pregnant women.[6] The present study aimed to assess the serum zinc (S. zinc) levels and its relation to iron deficiency anemia (IDA) in pregnant women.


  Patients and Methods Top


Study design and sampling

The present study was a case–control study that included 86 pregnant women who attended the Bahdinan, Duban, and private clinics and living in different areas of Duhok governorate. The study included 140 pregnant women, from whom 86 individuals from different gestational ages: 19 from the first trimester, 34 from the second trimester, and 33 from the third trimester, were selected based on the eligibility criteria.

The patients were assigned to the following three groups based on the eligibility criteria: the first group, case/patient group: including 34 individuals diagnosed with IDA; the second group, positive control group: comprised 20 non-iron deficiency anemic pregnant women; and finally, the third group, negative control group, included 32 non-anemic, apparently healthy individuals. The data collection was carried out from August 2018 to March 2019.

Inclusion and exclusion criteria

The patients met eligibility criteria if they were aged 16 years and older and regardless of the sociodemographic perspectives. Patients with jaundice, liver diseases, hemoglobinopathies, and hemolytic diseases were excluded owing to interferences with zinc analysis.

Diagnostic and measurement criteria

A pretested questionnaire was designed to obtain information on age, gestational age, parity, and type of delivery. The diagnoses of the study groups were established according to the following criteria: case/patient group: Pregnant women diagnosed with IDA if Hb <11.5 g/dL, serum ferritin <10 ng/mL, and transferrin saturation percentage (TS%) <15%; positive control group: Pregnant women with non-IDA if Hb <11.5 g/dL, serum ferritin >10 ng/mL, and TS% >15%; and negative control group, included nonanemic, apparently healthy pregnant women if Hb >11.5 g/dL, serum ferritin >10 ng/mL, and TS% >15%.

Laboratory measurement

The blood samples were obtained from a suitable forearm vein; 7 mL of venous blood was drawn from each participant; 2 mL was placed into an EDTA containing tube and sent for the assessment of complete blood count using hematology auto-analyzer (Medonic Coulter Counter – Sweden). The remaining 5 mL was placed into a plain gel-tube and let stand for 30 min at room temperature to clot and then centrifuged at 3000 rpm for 10 min at 4°C. The obtained serum was stored in capped Eppendorf tubes and stored frozen at −28°C for future analysis. For this purpose, we divided the obtained serum from each participant into two separate capped tubes, one for iron studies (serum ferritin, serum iron [S. iron], total iron binding capacity [TIBC], and TS%) and the other for the analysis of the S. zinc.

Both S. iron and unsaturated iron binding capacity (UIBC) were identified by an enzymatic colorimetric method, called FerroZine method, using the Cobas Integra Iron Gen. 2 (Iron2) Kit and UIBC Kit, respectively, for the quantitative detection of human S. iron and UIBC, respectively, on COBAS INTEGRA 400/800 system (Roche Diagnostics GmbH, Germany).

TIBC was calculated as S. iron + UIBC = TIBC. In addition, TS% was calculated by TS% =100 × S. iron/TIBC.[9]

Serum ferritin was identified by the sandwich principle of electrochemiluminescence immunoassay “ECLIA” using the Cobas Integra Ferritin Kit for the quantitative detection of human serum ferritin on COBAS INTEGRA 400/800 system (Roche Diagnostics GmbH, Germany).

S. zinc was identified by colorimetric determination by a specific kit (presents by LTA s.r.l. via Milano, Italy) composed of two reagents (Reagent A: Borate buffer 0.37 M and pH 8.2, salicylaldoxime 12.5 mM, dimethylglyoxime 1.25 mM; Reagent B: NITRO-PAPS 0.4 mM) and a standard (zinc ion 200 μg/dl).

S. zinc reacted with the chromogen present in the reagent forming a colored compound which the color intensity is proportional to the zinc concentration present in the sample.

S. zinc reference values, according to the WHO guidelines, are severe deficiency: <50 μg/dL, mild-to-moderate deficiency: 50–70 μg/dL, and normal level: more than 70 μg/dL.

Statistical analysis

The descriptive purposes of the study were presented in mean and standard deviation or frequency and percentage. The comparison of general information between IDA group and positive and negative groups was examined in independent t-test or Pearson's Chi-square tests. The comparison of hematological parameters between IDA and other groups was examined in independent t-test. Correlation of S. zinc with hematological factors was examined by Pearson's correlation. In this analysis, the adjustment was made for age, gestational age, and delivery mode, and study groups. ANOVA one-way was performed to assess the S. zinc level in patients with different gestational age and delivery mode. A P < 0.05 was considered a statistically significant difference. The statistical calculations were performed by Statistical Package for the Social Sciences 24:00 (SPSS 24:00; BM, USA).

Ethical considerations

The local health ethics committee of Duhok Directorate General of Health approved the study. The study was registered as the reference number of 26062018-5 on June 26, 2018. The confidentiality of the personal information of the subjects was protected throughout the study steps.


  Results Top


Thirty-four pregnant women with IDA were compared to 20 pregnant women with non-IDA as positive control and 32 healthy pregnant women as a negative control, in this case–control study. The mean age was 29.76 years in the IDA group, 27.60 years in the positive control group, and 27.25 years in the negative control group. There was no statistical difference between the age groups (P = 0.217 and 0.122). The study groups were comparable in most of the general characteristics (P ≥ 0.05) except gravida between IDA and negative control (P = 0.041) and abortion between IDA and positive control (P = 0.034), as shown in [Table 1].
Table 1: Comparison of general information between the patients in the iron deficiency anemia group with positive and negative controls

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The patients in the IDA groups had significantly lower levels of Hb, MCV, MCHC, red blood cell (RBC), hematocrit (HCT), ferritin, S. iron, and TS compared to those in positive and negative controls. S. zinc was significantly lower in the IDA group (49.59 ng/dL) compared to the negative control (55.78 ng/dL; P = 0.018), while its concentration was comparable with the positive control (45.90 ng/dL; P = 0.303). The individuals in three groups were comparable in the number of persons with zinc deficiency (severe zinc deficiency: 58.8%, 55.0%, and 31.3% in IDA, positive, and negative control groups, respectively) [Table 2].
Table 2: Comparison of hematological parameters between the subjects in the iron deficiency anemia group with the positive and negative controls

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The correlation of S. zinc with hematological parameters with adjustment for age, gestational age, delivery, and study groups showed that S. zinc has a positive correlation with Hb (r = 0.281, P = 0.011). The analysis did not show any correlation with ferritin (P = 0.682) and TS (P = 0.051) [Table 3].
Table 3: Correlation of serum zinc with hematological parameters with adjustment of age, gestational age, and delivery mode, and study groups

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The correlation of S. zinc with hematological and biochemical parameters with adjustment for age, gestational age, delivery mode, and study groups showed that S. zinc has a positive correlation with Hb (r = 0.281; P = 0.011), RBC (r = 0.233; P = 0.035), and HCT (r = 0.305; P = 0.005) and a significant negative with S. iron (r = −0.242; P = 0.029), as shown in [Table 3].

The concentration of the S. zinc in patients with different gestational age (P = 0.372) and delivery modes (P = 0.591) was not different substantially [Table 4].
Table 4: Comparison of serum zinc concentration in iron deficiency anemia patients with different gestational age and delivery modes

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The correlation of S. zinc with gravida, para, and abortion and stillbirth was not significant. In this correlation, the analysis was adjusted for age, gestational age, delivery, and study groups [Table 5].
Table 5: Correlation of serum zinc with GPA with adjustment of age, gestational age, and delivery mode, and study groups

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  Discussion Top


Although trace elements are found in minimal quantities, they have essential roles in homeostasis. Two of the most important trace elements are iron and zinc.[10] Iron and zinc are essential micronutrients for human health. Deficiencies in these two nutrients remain a global problem, especially among women and children in developing countries.[11]

Impaired iron absorption is caused by a decrease in zinc levels, which is found in the structure of enzymes that coordinate or catalyst iron metabolism.[12] Coexistence of zinc and iron deficiency has attracted the interest of many researchers, and there have been many studies about this subject.[10]

Micronutrient interactions are particularly important during pregnancy because the developing fetus is very vulnerable to inappropriate micronutrient status.[13] Micronutrient deficiency, whether clinical or subclinical, may affect growth, cognition, and reproductive performance. In pregnant women, moderate-to-severe deficiencies of iron and zinc has been shown to increase the risk of low birth weight, pregnancy complications, and birth defects.[14]

Several reports demonstrate that maternal zinc deficiency during pregnancy is linked with adverse pregnancy outcomes, including abortion, preterm delivery, stillbirth, and fetal neural tube defects.[15]

In this study, S. zinc was significantly lower in IDA group (49.59 ng/dL) compared to the negative control (55.78; P = 0.018), while its concentration was comparable with the positive control (45.90; P = 0.303). In a study conducted by Ece et al., the S. zinc levels were lower in the IDA group than the control group (P = 0.017). There was a statistically significant difference between the two groups, as in our study. As a result, it has been suggested that S. zinc levels should be checked in pregnant women with iron deficiency.[16]

Another study conducted by Kelkitli et al. also recorded lower S. zinc levels in anemic patients than in the control groups (P < 0.001).[17] These results were all compatible with our results.

Saaka [4] included pregnant women who attended antenatal care in a region in Ghana. The patients were randomly and double-blind assigned into an interventional group who received a combined supplement of 40 mg zinc as zinc gluconate and 40 mg iron as ferrous sulfate. However, the control group received 40 mg elemental iron only. They found that women who had low plasma zinc levels were three-fold increased odds of developing deficiency (odds ratio 3.41, 95% confidence interval: 1.19–9.76). They concluded that iron–zinc supplementation is effective in increasing Hb levels and serum ferritin values in women with IDA in early pregnancy but not in women with sufficient iron level.

One of the reasons for iron deficiency occurring with zinc deficiency, other than diet, is the increase in production of zinc protoporphyrin and usage of zinc, instead of iron in the protoporphyrin structure.[18]

In the present study, there was a positive correlation between zinc with Hb and HCT; however, a weak negative correlation was found between zinc with S. iron and ferritin. This finding is in consistence to the finding of Arijanty et al.;[19] they also found a weak negative correlation between plasma zinc level and ferritin level, which could be due to competitive inhibition of zinc by ferritin.

Nonsignificant statistical difference was found regarding the concentration of S. zinc between IDA group with the positive and negative control groups, with P = 0.059 and 0.79, respectively. The concentration of S. zinc between different gestational age groups (P = 0.372) and delivery mode (P = 0.591) did not show substantial difference too. The correlation of S. zinc with gravida, para, and abortion and stillbirth was also not significant.

Due to lack of studies regarding zinc status in pregnant women and the high prevalence of IDA in pregnancy, this study was conducted in pregnant women with IDA. We tried to find out whether zinc deficiency coexists with iron deficiency or not.

With the help of this study, iron and zinc supplementation instead of only iron replacement may be considered in cases of iron deficiency. Further studies are still needed to evaluate the benefit of zinc and iron supplementation in IDA patients.

Strengths and limitations

To our knowledge, this the first study in this field using two control (+ve and −ve) groups to demonstrate the relation of zinc to non-IDA. The most obvious limitation of the present study was the small sample size. We recommend a larger sample size and an interventional type of study by supplying zinc to the patients with IDA and follow-up changes in hematological parameters after correction of zinc status.


  Conclusions Top


This investigation showed that the patients with IDA have a significantly lower concentration of S. zinc and it was substantially positively correlated with Hb, RBC, and HCT and negatively with S. iron. Further studies are still needed to evaluate the benefit of zinc and iron supplementation in IDA patients.

Acknowledgments

We would like to present our profound thanks to Bahdinan and Duban Clinic's Lab staff, Dr. Alaa Hani Laboratory, and Dr. Amer A. Mehe Laboratory, for their generous support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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International Zinc Nutrition Consultative Group (IZiNCG), Brown KH, Rivera JA, Bhutta Z, Gibson RS, King JC, et al. International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 2004;25:S99-203.  Back to cited text no. 1
    
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Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, et al. Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 2013;382:427-51.  Back to cited text no. 2
    
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Chaffee BW, King JC. Effect of zinc supplementation on pregnancy and infant outcomes: A systematic review. Paediatr Perinat Epidemiol 2012;26 Suppl 1:118-37.  Back to cited text no. 3
    
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Saaka M. Combined iron and zinc supplementation improves haematologic status of pregnant women in upper West region of Ghana. Ghana Med J 2012;46:225-33.  Back to cited text no. 4
    
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Raimi O, Falade O, Folorunso O, Lawal A. Zinc and iron levels in pregnancy: A review. Pak J Food Sci 2012;22:53-60.  Back to cited text no. 5
    
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de Jong N, Romano AB, Gibson RS. Zinc and iron status during pregnancy of Filipino women. Asia Pac J Clin Nutr 2002;11:186-93.  Back to cited text no. 7
    
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Nguyen P, Grajeda R, Melgar P, Marcinkevage J, Flores R, Ramakrishnan U, et al. Effect of zinc on efficacy of iron supplementation in improving iron and zinc status in women. J Nutr Metab 2012;2012:216179.  Back to cited text no. 8
    
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Burtis CA, Ashwood ER, Bruns DE. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics-e-Book. United States of America: Elsevier Health Sciences; 2012.  Back to cited text no. 9
    
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Özhan O, Erdem N, Aydoǧdu İ, Erkurt A, Kuku İ. Serum zinc levels in iron deficient women: A case-control study. Turk J Haematol 2016;33:156-8.  Back to cited text no. 10
    
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Fischer Walker C, Kordas K, Stoltzfus RJ, Black RE. Interactive effects of iron and zinc on biochemical and functional outcomes in supplementation trials. Am J Clin Nutr 2005;82:5-12.  Back to cited text no. 11
    
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Abdelhaleim AF, Abdo Soliman JS, Amer AY, Abdo Soliman JS. Association of zinc deficiency with iron deficiency anemia and its symptoms: Results from a case-control study. Cureus 2019;11:e3811.  Back to cited text no. 12
    
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Upadhyaya C, Mishra S, Ajmera P, Sharma P. Serum iron, copper and zinc status in maternal and cord blood. Indian J Clin Biochem 2004;19:48-52.  Back to cited text no. 13
    
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Seshadri S. Prevalence of micronutrient deficiency particularly of iron, zinc and folic acid in pregnant women in South East Asia. Br J Nutr 2001;85 Suppl 2:S87-92.  Back to cited text no. 14
    
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Wang H, Hu YF, Hao JH, Chen YH, Su PY, Wang Y, et al. Maternal zinc deficiency during pregnancy elevates the risks of fetal growth restriction: A population-based birth cohort study. Sci Rep 2015;5:11262.  Back to cited text no. 15
    
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Ece A, Uyanik BS, Işcan A, Ertan P, Yiǧitoǧlu MR. Increased serum copper and decreased serum zinc levels in children with iron deficiency anemia. Biol Trace Elem Res 1997;59:31-9.  Back to cited text no. 16
    
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Kelkitli E, Ozturk N, Aslan NA, Kilic-Baygutalp N, Bayraktutan Z, Kurt N, et al. Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia. Ann Hematol 2016;95:751-6.  Back to cited text no. 17
    
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Hastka J, Lasserre JJ, Schwarzbeck A, Hehlmann R. Central role of zinc protoporphyrin in staging iron deficiency. Clin Chem 1994;40:768-73.  Back to cited text no. 18
    
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Arijanty L, Nasar SS, Madiyono B, Gatot D. Relationships between plasma zinc and ferritin with nutritional status in thalassemic children. Paediatr Indones 2006;46:220-4.  Back to cited text no. 19
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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