|Year : 2017 | Volume
| Issue : 2 | Page : 180-184
Evaluation of soluble transferrin receptor, soluble transferrin receptor/ferritin ratio, and other iron-related parameters of pregnant women in Cross River State, Nigeria
Ifeyinwa Maryann Okafor1, Atim B Antai2, Esien A Usanga1
1 Department of Medical Laboratory Science, Haematology Unit, College of Medical Sciences, University of Calabar, Calabar, Nigeria
2 Department of Physiology, College of Medical Sciences, University of Calabar, Calabar, Nigeria
|Date of Web Publication||14-Nov-2017|
Ifeyinwa Maryann Okafor
Department of Medical Laboratory Science, Haematology Unit, College of Medical Sciences, University of Calabar, Calabar
Introduction: Iron is one of the essential trace elements required for hemoglobin synthesis and also for many metabolic processes. Inadequate iron intake can lead to varying degrees of deficiency, from low iron stores to early iron deficiency and iron deficiency anemia and this is dangerous to both fetus and mother. Aim: This study was carried out to assess the levels of soluble transferrin receptor (sTfR), sTfR/serum ferritin (sTfR/SF) ratio, and other iron-related parameters of pregnant women in Cross River State, Nigeria, with the aim to establish reference ranges of these parameters for the population under reference. Materials and Methods: One hundred and seventy apparently healthy pregnant women within the age range of 15 and 45 years attending the antenatal clinics of health-care facilities in Cross River State, Nigeria, were enrolled in this study. The controls consisted of 100 age-matched apparently healthy nonpregnant women from the same environment. Red cell indices were determined using automated blood cell counter. Serum iron and total iron binding capacity (TIBC) were determined using colorimetric method. SF and sTfR were measured using enzyme-linked immunosorbent assay technique. Results: The mean ± standard deviation of the parameters in pregnant woman and in nonpregnant women were serum iron (82.19 ± 3.44), SF (32.15 ± 3.11), transferrin saturation with iron (22.43 ± 11.62), hemoglobin concentration (11.00 ± 0.11), and hematocrit (0.33 ± 0.30). Decreased significantly during pregnancy while TIBC (422.43 ± 19.60), sTfR (3.38 ± 0.41), and sTfR/SF ratio (176.98 ± 396.87) increased significantly in the pregnant women than in nonpregnant women (P < 0.05). The values of serum iron, SF, TIBC, and transferrin saturation were found to show significant variations in the various trimesters of pregnancy. The values of sTfR and sTfR/SF ratio increased significantly (P = 0.01 and P = 001) as trimester increases in our patients. Conclusion: This study reports, for the first time, values for sTfR and sTfR/SF ratio in apparently healthy pregnant women in Cross River State, South-South Nigeria. The study also gives an indication that the use of sTfR and sTfR/SF as a marker in assessing iron status of pregnant women needs to be explored.
Keywords: Ferritin, iron, pregnancy, soluble transferrin receptor, transferrin
|How to cite this article:|
Okafor IM, Antai AB, Usanga EA. Evaluation of soluble transferrin receptor, soluble transferrin receptor/ferritin ratio, and other iron-related parameters of pregnant women in Cross River State, Nigeria. Trop J Med Res 2017;20:180-4
|How to cite this URL:|
Okafor IM, Antai AB, Usanga EA. Evaluation of soluble transferrin receptor, soluble transferrin receptor/ferritin ratio, and other iron-related parameters of pregnant women in Cross River State, Nigeria. Trop J Med Res [serial online] 2017 [cited 2018 Dec 14];20:180-4. Available from: http://www.tjmrjournal.org/text.asp?2017/20/2/180/218211
| Introduction|| |
There have been many attempts by scholars to document normal values of various hematological parameters among pregnant Nigerian women. Some of these studies include those done in Owerri, Jos,, Ibadan, and Port Harcourt., These studies have helped establish reference ranges for hematological parameters of pregnant Nigerian woman. However, most of these studies have focused mainly on routine hematological parameters.
Data on other parameters such as soluble transferrin receptor (sTfR), serum iron, total iron binding capacity (TIBC), transferrin saturation with iron, soluble transferrin/ferritin ratio, and some other specific red cell indices have not been studied, especially in Calabar, Cross River State, South-South Nigeria. These parameters are of diagnostic, therapeutic, prognostic, and physiologic importance, especially in pregnant women who are prone to developing iron deficiency anemia due to increased demand of the developing fetus., sTfR can aid the diagnosis of iron deficiency and iron deficiency anemia in pregnancy., In a study from India, decreases in hemoglobin concentration, percentage transferrin saturation, and increases in TIBC were reported to suggest an increase in iron demand, turnover, and deficiency, especially among pregnant women of increasing age and gravidity.,
Reports have suggested significant differences in the values of serum iron, TIBC, serum ferritin (SF), and sTfR in pregnant Caucasian during the different trimesters of pregnancy.,,,, Reports from Nigeria have shown such variations in serum iron, TIBC, transferrin saturation with iron, and SF,, but there are no reports on sTfR values. This study was, therefore, carried out to determine the levels of sTfR, sTfR/SF ratio, and other iron status indicators of pregnant women in Cross River State, South-South Nigeria, to establish reference ranges for the parameters studied.
| Materials and Methods|| |
This was a cross-sectional multicenter study conducted in Calabar town, Cross River State, Nigeria. Apparently healthy pregnant women were recruited from three different hospitals in Calabar. One hundred and seventy pregnant women within the age range of 15–45 years were enrolled; seventy from the antenatal clinic of University of Calabar Teaching Hospital (UCTH), fifty from St. Joseph's Hospital, Ikot Ene Akpabuyo, and another fifty from UCTH extension clinic in Okoyong, Odukpani all in Cross River State. One hundred age-matched apparently healthy nonpregnant women from among staff of the same hospitals were enrolled as controls. Ethical clearance was obtained from the Cross River State Ministry of Health, and all participants signed an informed written consent to participate in the study.
Five milliliters of venous blood was collected from each participant into two sample containers, 1 ml of blood was put into sample bottles containing 2 mg of ethylenediaminetetraacetic acid, as an anticoagulant to prevent clot formation, whereas the remaining 4 ml was put into a plain sterile iron-free screw-capped bottles and allowed to clot at room temperature for 1 h. The anticoagulated blood was used for full blood count. The clotted blood sample was centrifuged at 3000 rpm for 15 min using a bench centrifuge; thereafter, the serum was carefully transferred into iron-free containers using a sterile pasture pipette and then used for estimation of iron parameters. Full blood count was carried out using automated hematology analyzer (PCE-210 version 5.10 by ERMA INC, Tokyo). Serum iron and TIBC were determined using serum iron kit (colorimetric method) by TECO Diagnostics, USA, and transferrin saturation was calculated using this formula - serum Iron concentration divided by TIBC multiplied by 100.
Ferritin was determined using human ferritin enzyme-linked immunosorbent assay (ELISA) test kit by Diagnostic Automation, Inc., USA. sTfR was measured using human sTfR ELISA Kit by BioVendor Diagnostics, USA. The manufacturer instructions were strictly followed.
Data obtained were analyzed using Statistical Package for the Social Sciences (SPSS version 16.0, SPSS Inc., Chicago, USA). Independent sample t-test and one-way analysis of variance were used.
| Results|| |
The mean age of pregnant women and control was 29 ± 14.0 and 27 ± 12.0, respectively (P = 0.06). The mean hematocrit in pregnant women and controls was 0.33 I/I (standard deviation [SD] ±0.30; 95 confidence interval [CI] =22.9–43.5) and 0.37l/l (SD ± 0.07; 95% CI = 31.4–43.5), respectively (P = 0.02). The mean hemoglobin in pregnant women and controls was 11.02 g/dl (SD ± 0.11; 95 CI = 7.4–14.0) and 12.32 g/dl (SD ± 0.20; 95% CI = 9.8–13.8), respectively (P = 0.02). The total white blood cell count and platelet counts were 8.68 and 7.15 and 160.2 and 144.2 × 109/L, respectively (P < 0.05). The red cell indices mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), and red blood cell (RBC) were not statistically different in the two groups studied. The mean ± SD of serum iron (ug/dl) were 85.53 ± 3.44 in pregnant women and 106.46 ± 7.68 in nonpregnant women (P = 0.02). The mean SF in the pregnant women was 32.15 ng/ml (SD = 3.11; 95% CI = 5.0–262.2) and 54.64.3 ng/ml (SD = 7.76; 95% CI 7.8–98.4) in the nonpregnant controls (P = 0.01). The mean ± SD of transferrin with iron (%) and TIBC (ug/dl) was 22.43 ± 11.62 and 442.43 ± 19.60 in pregnant women and 29.66 ± 2.0 and 355.3 ± 11.14 in nonpregnant women, respectively (P < 0.02). The mean sTfR in the pregnant women was 3.38 ug/dl (SD = 0.41; 95% CI = 0.5–22.9) and 1.39 ug/dl (SD = 0.12; 95% CI 1.0–3.0) in the nonpregnant controls (P = 0.01). The mean sTfR/ferritin ratio in the pregnant women was 176.98 (SD = 396.87; 95% CI = 2.84–2884) and 46.19 (SD = 66.57; 95% CI 2.36–256) in the nonpregnant controls (P = 0.01) [Table 1]. Hemoglobin, hematocrit, MCV, MCH, MCHC, RBC, white blood cell, and platelets were not statistically significantly different in different trimesters. sTfR in the three trimesters increased progressively from 1.34 ± 0.4 μg/ml in the first trimester to 2.98 ± 0.72 μg/ml in the second trimester to 3.59 ± 0.74 μg/ml in the third trimester (P = 0.04) [Table 2]. [Table 2] also shows the values of sTfR/ferritin ratio in the three trimesters, i.e., 105.01 ± 137.85, 169.97 ± 348.40, and 217.94 ± 504.35, respectively, to increase significantly (P = 0.02) as trimester increases.
|Table 1: Hematological and biochemical parameters of pregnant and nonpregnant women|
Click here to view
|Table 2: Hematological and biochemical parameters in the three trimesters of pregnancy|
Click here to view
| Discussion|| |
Pregnant women recorded lower values in most of the parameters investigated than nonpregnant women of similar age. The mean hemoglobin, hematocrit, serum iron, SF, and transferrin saturation with iron were significantly reduced (P ≤ 0.02) in pregnant than nonpregnant women, whereas TIBC, sTfR, and sTfR/ferritin ratio significantly (P ≤ 0.01) increased in pregnant than nonpregnant women. These differences can be attributed to the hemodynamic changes that are associated with pregnancy as well as increase demand by the fetus, and it confirms the earlier reports that in pregnancy assessing iron status is difficult because of the profound hemodynamic changes associated with pregnancy which inadvertently affect several indexes of iron status.
sTfR and sTfR/SF ratio were observed to be significantly higher in pregnant women (P ≤ 0.01), these also increased significantly as trimester increased (P = 0.04). Transferrin receptor is a disulfide-linked transmembrane glycoprotein that plays an essential role in cellular iron uptake, especially in bone marrow Although it is a cell membrane protein, small quantities circulate in blood and are called sTfR. Previous investigators have suggested that sTfR is a sensitive indicator of tissue iron deficiency.,,, Blood concentrations are increased several folds in patients with iron deficiency, whereas they remain within the normal range in those with iron overload and anemia of chronic disease. Serum sTfR concentration is not affected by pregnancy unless the patient is also iron deficient. Unlike SF, sTfR is not affected by infection and inflammation, and it may distinguish anemia due to chronic disease from that due to iron deficiency., Apparently, increases in sTfR and sTfR/ferritin ratio values seen among our patients with increasing gestation may perhaps be a mechanism to ensure a fetal adequate iron delivery on account of the decreasing serum iron concentration with gestation in our patients. This suggests that the deviation in sTfR and other iron-related parameters is part of the mechanism aiding in the increased absorption of iron from the gastrointestinal tract., This increased absorption is known to occur late in pregnancy and is consistent with an increased rate of iron turnover from the plasmatic pool either to maternal storage or to the fetus whose need for iron is increasing. In a study by Skikne et al., the mean sTfR/ferritin ratio increased from <100 in the presence of adequate iron stores to over 2000 at the time of significant iron depletion. In our study, the sTfR/ferritin ratio in control was <100 but was significantly increased in pregnant women and also as trimester increases indicating significant functional iron depletion. According to Pettersson et al., a high sTfR/ferritin ratio indicated iron deficiency with or without inflammation. Our results appear to concur with this finding. Raised sTfR levels may be seen in conditions associated with erythroid hyperplasia such as α-thalassaemia and autoimmune hemolytic anemia but none of the pregnant women and the nonpregnant women that were involved in this study had these conditions.
The pattern of a significant increase in TIBC and decrease in transferrin saturation with iron, serum iron, and SF seen among the pregnant women is consistent with previous reports in Port Harcourt Nigerian., TIBC is known to be increased in pregnancy and during iron overload.,, The reported increases in TIBC with pregnancy in our patients are, therefore, expected considering previous reports from Calabar and Port Hacourt of possible preexisting iron deficiency anemia among pregnant women;, therefore, the values of TIBC obtained in the present study were generally higher than reported values in a study on pregnant women in Port Harcourt, Nigeria. In conclusion, this study reports, for the first time, values for sTfR and sTfR/SF ratio in apparently healthy pregnant women in Cross River State, South-South, Nigeria. The study also suggests that the use of sTfR and sTfR/SF as a marker in assessing iron status of pregnant women needs to be explored.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Okoroiwu IL, Obeagu EI, Elemchukwu Q, Ochei KC. Determination of ferritin level and total iron binding capacity in pregnancy and postpartum subjects in Owerri. IOSR J Dent Med Sci 2014;13:70-3.
Onwukeme KE, Uguru VE. Haematological values in pregnancy in Jos. West Afr J Med 1990;9:70-5.
Onwukeme KE. Puerperal haematological indices in the Nigerian. Afr J Med Med Sci 1992;21:51-5.
Akingbola TS, Adewole IF, Adesina OA, Afolabi KA, Fehintola FA, Bamgboye EA, et al.
Haematological profile of healthy pregnant women in Ibadan, South-Western Nigeria. J Obstet Gynaecol 2006;26:763-9.
Dapper DV, Ibe CJ, Nwauche CA. Haematological values in pregnant women in Port Harcourt, Nigeria. Niger J Med 2006;15:237-40.
Amah-Tariah FS, Ojeka SO, Dapper DV. Haematological values in pregnant women in Port Harcourt, Nigeria II: Serum iron and transferrin, total and unsaturated iron binding capacity and some red cell and platelet indices. Niger J Physiol Sci 2011;26:173-8.
Okafor IM, Asemota EA, Antai AB, Usanga EA. Prevalence of iron deficiency anaemia among pregnant women in Calabar, Cross River State Nigeria. IOSR J Pharm Biol Sci 2013;7:60-4.
Pavord S, Myers B, Robinson S, Allard S, Strong J, Oppenheimer C; British Committee for Standards in Haematology. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol 2012;156:588-600.
Akesson A, Bjellerup P, Berglund M, Bremme K, Vahter M. Serum transferrin receptor: A specific marker of iron deficiency in pregnancy. Am J Clin Nutr 1998;68:1241-6.
Okafor IM, Okpokam DC, Antai AB, Usanga EA. Soluble transferrin receptor as a marker in the diagnosis of iron deficiency anaemia, a study in Calabar. Int J Biomed Lab Sci 2014;3:40-6.
Kurhade GA, Khanorkar SV, Puranik BM, Kher JR, Patwardhan SA, Agrawal S. Serum level of iron and transferrin in pregnancy and postpartum period. Indian J Physiol Pharmacol 1994;38:34-8.
Lee HS, Kim MS, Kim MH, Kim YJ, Kim WY. Iron status and its association with pregnancy outcome in Korean pregnant women. Eur J Clin Nutr 2006;60:1130-5.
Berymann C. Iron deficiency and anaemia in pregnancy: Modern aspects of diagnosis and therapy. Eur J Obstet Gynecol Reprod Biol 2005;123:3-13.
Shams R. Comparison of serum ferritin levels in three trimesters of pregnancy and their correlation with increasing gravidity. Int J Pathol 2007;5:26-30.
Pasricha SR, Flecknoe-Brown SC, Allen KJ, Gibson PR, McMahon LP, Olynyk JK, et al.
Diagnosis and management of iron deficiency anaemia: A clinical update. Med J Aust 2010;193:525-32.
Lulla RR, Thompson AA, Liem RI. Elevated soluble transferrin receptor levels reflect increased erythropoietic drive rather than iron deficiency in pediatric sickle cell disease. Pediatr Blood Cancer 2010;55:141-4.
World Health Organization. Serum ferritin concentrations for the assessment of iron status and iron deficiency in populations. Bull World Health Organ 2011;101:244-66.
Baynes RD, Shih YJ, Cook JD. Production of soluble transferring receptor by K563 erythroleukemia cells. Br J Haematol 1991;78:450-5.
Jayaranee S, Sthaneshwar P. Serum soluble transferrin receptor in hypochromic microcytic anaemia. Singapore Med J 2006;47:138.
Skikne BS, Flowers CH, Cook JD. Serum transferrin receptor: A quantitative measure of tissue iron deficiency. Blood 1990;75:1870-90.
Huebers H, Beguin Y, Poortrakul P, Einspahr D, Finch CA. Intact transferrin receptors in human plasma and their relation to erythropoiesis. Blood 1990;75:102-7.
Elzahrani SS. Prevalence of iron deficiency anemia among pregnant women attending antenatal clinics at Al-Hada hospital. Can J Med 2012;3:10-4.
Lynch S. Case studies: Iron. Am J Clin Nutr 2011;94:673S-8S.
Raza N, Sarwar I, Munazza B, Ayub M, Suleman M. Assessment of iron deficiency in pregnant women by determining iron status. J Ayub Med Coll Abbottabad 2011;23:36-40.
Khalafallah AA, Dennis AE. Iron deficiency anaemia in pregnancy and postpartum: Pathophysiology and effect of oral versus intravenous iron therapy. J Pregnancy 2012;2012:630519.
Pettersson T, Kivivuori SM, Siimes MA. Is serum transferrin receptor useful for detecting iron-deficiency in anaemic patients with chronic inflammatory diseases? Br J Rheumatol 1994;33:740-4.
Dacie JV, Lewis SM. Practical Haematology. 10th
ed. Calabar: Churchill Livingstone; 2010. p. 412-4.
Gibson RS, Abebe Y, Stabler S, Allen RH, Westcott JE, Stoecker BJ, et al.
Zinc, gravida, infection, and iron, but not Vitamin B-12 or folate status, predict hemoglobin during pregnancy in Southern Ethiopia. J Nutr 2008;138:581-6.
Cook JD, Monsen ER. Food iron absorption in human subjects. III. Comparison of the effect of animal proteins on nonheme iron absorption. Am J Clin Nutr 1976;29:859-67.
[Table 1], [Table 2]