ASSESSING THE UTILITY OF HEPCIDIN AND TOTAL IRON-BINDING CAPACITY IN DIAGNOSING IRON DEFICIENCY DURING MID-GESTATION

Main Article Content

Saif Ahmed
Muhammad Masood Ahmed
Suman Khan
Sana Fatima
Maryam Zain
Usman Wajid
Farhat Ameer Chughtai
Muhammad Omer Iqbal
Tayyeba Idrees Butt
Maida Aslam
Aqsa Noreen

Keywords

hepcidin, total iron-binding capacity, iron deficiency, anemia, pregnancy, serum iron

Abstract

Objective: This study aimed to investigate the influence of hepcidin, a key regulator of iron homeostasis, on total iron-binding capacity (TIBC) during the second trimester of pregnancy. Understanding the relationship between hepcidin and diagnostic markers, particularly acute phase markers, is crucial for the timely diagnosis and treatment of iron deficiency during gestation. Methods: A cross-sectional study was conducted with 387 one-time blood samples collected from pregnant women during their second trimester at a teaching hospital in Lahore, Pakistan. Participants were aged 19-45 years, following the WHO age criteria, and had no comorbid conditions. Complete blood count, serum iron, ferritin, transferrin saturation, and TIBC were measured. Samples were categorized into three groups: non-iron deficiency (N-ID), iron deficiency (ID), and iron deficiency anemia (IDA). Hepcidin levels were determined using an enzyme-linked immunosorbent assay (ELISA) with antibody-coated 96-well plates based on the principle of antibody-antigen-enzyme-antibody complex formation. Correlations between hepcidin and other biochemical parameters were assessed.


Results: Hepcidin levels showed significant positive correlations with ferritin (p<0.001), transferrin saturation (p<0.001), and TIBC (p<0.001). Conclusion: Hepcidin and TIBC can serve as valuable markers for assessing serum iron bioavailability and diagnosing iron deficiency during the second trimester of pregnancy. Monitoring these parameters may help mitigate adverse pregnancy outcomes associated with iron deficiency.

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References

1. Abioye, Ajibola I., Said Aboud, Zulfiqar Premji, Analee J. Etheredge, Nilupa S. Gunaratna, Christopher R. Sudfeld, Robert Mongi, et al. 2016. “Iron Supplementation Affects Hematologic Biomarker Concentrations and Pregnancy Outcomes among Iron-Deficient Tanzanian Women1-3.” Journal of Nutrition 146 (6): 1162–71. https://doi.org/10.3945/jn.115.225482.
2. Abioye, Ajibola I., Said Aboud, Zulfiqarali Premji, Analee J. Etheredge, Nilupa S. Gunaratna, Christopher R. Sudfeld, Ramadhani A. Noor, et al. 2020. “Hemoglobin and Hepcidin Have Good Validity and Utility for Diagnosing Iron Deficiency Anemia among Pregnant Women.” European Journal of Clinical Nutrition 74 (5): 708–19. https://doi.org/10.1038/s41430-019-0512-z.
3. Abu-Ouf, Noran M., and Mohammed M. Jan. 2015. “The Impact of Maternal Iron Deficiency and Iron Deficiency Anemia on Child’s Health.” Saudi Medical Journal 36 (2): 146–49. https://doi.org/10.15537/smj.2015.2.10289.
4. Amer, Atef, Yousri Aboelmagd, and Mohamed Elshahat. 2020. “Study of Hepcidin Level in Egyptian Hcv Infected Patients and Its Correlation to Iron and Total Iron Binding Capacity.” Plant Archives 20: 2110–16.
5. Article, Original. 2016. “Nasif” 26 (January 2013): 958–61.
6. Bencaiova, Gabriela Amstad, Deborah Ruth Vogt, and Irene Hoesli. 2019. “Serum Hepcidin and Iron Status Parameters in Pregnant Women and the Association with Adverse Maternal and Fetal Outcomes : A Study Protocol for a Prospective Cohort Study,” 1–8. https://doi.org/10.1136/bmjopen-2019-032280.
7. Brannon, Patsy M., Patrick J. Stover, and Christine L. Taylor. 2017. “Integrating Themes, Evidence Gaps, and Research Needs Identified by Workshop on Iron Screening and Supplementation in Iron-Replete Pregnant Women and Young Children.” American Journal of Clinical Nutrition 106: 1703S-1712S. https://doi.org/10.3945/ajcn.117.156083.
8. Cacoub, Patrice, Gael Nicolas, Katell Peoc’h, Pierre Asfar, Thomas Kerforne, Karim Asehnoune, Philippe Seguin, et al. 2020. “Anemia and Its Associated Factors among Women of Reproductive Age in Eastern Africa: A Multilevel Mixed-Effects Generalized Linear Model.” PLoS ONE 0 (September): 1–8. https://doi.org/10.12996/gmj.2020.161.
9. Camaschella, Clara. 2015. “Iron-Deficiency Anemia.” New England Journal of Medicine 372 (19): 1832–43. https://doi.org/10.1056/NEJMra1401038.
10. Choi, Jong Weon, Moon Whan Im, and Hwan Pai. 2000. “Serum Transferrin Receptor Concentrations during Nor- Mal Pregnancy,” 1 (5): 725–27.
11. Clénin, German E. 2017. “The Treatment of Iron Deficiency without Anaemia (in Otherwise Healthy Persons).” Swiss Medical Weekly 147 (2324): 1–17. https://doi.org/10.4414/smw.2017.14434.
12. Concentration, Serum Ferritin, Early Third Trimester, Preterm Birth, Low Birth, Weight Based, and Gestational Age. 2021. “임신 제3삼분기 혈청 페리틴과 조산 및 저체중아와의 연관성” 25 (1): 55–62.
13. Daru, J., J. Allotey, J. P. Peña-Rosas, and K. S. Khan. 2017. “Serum Ferritin Thresholds for the Diagnosis of Iron Deficiency in Pregnancy: A Systematic Review.” Transfusion Medicine 27 (3): 167–74. https://doi.org/10.1111/tme.12408.
14. Dewey, Kathryn G., Brietta M. Oaks, Patsy M. Brannon, Patrick J. Stover, and Christine L. Taylor. 2017. “U-Shaped Curve for Risk Associated with Maternal Hemoglobin, Iron Status, or Iron Supplementation.” American Journal of Clinical Nutrition 106 (Id): 1703S-1712S. https://doi.org/10.3945/ajcn.117.156075.
15. Galesloot, Tessel E., Sita H. Vermeulen, Anneke J. Geurts-Moespot, Siem M. Klaver, Joyce J. Kroot, Dorlene Van Tienoven, Jack F.M. Wetzels, et al. 2011. “Serum Hepcidin: Reference Ranges and Biochemical Correlates in the General Population.” Blood 117 (25): 218–25. https://doi.org/10.1182/blood-2011-02-337907.
16. Gambia, The, Amat Bah, Sant-rayn Pasricha, Momodou W Jallow, Ebrima A Sise, Rita Wegmuller, Andrew E Armitage, Hal Drakesmith, Sophie E Moore, and Andrew M Prentice. 2017. “Serum Hepcidin Concentrations Decline during Pregnancy and May Identify Iron Deficiency : Analysis of a Longitudinal Pregnancy Cohort In.” Journal of Nutrition, 1131–37. https://doi.org/10.3945/jn.116.245373.1131.
17. Gilbert, Richard, Aneta Tawfik, and Thomas Kampfrath. 2015. “Pregnant Woman with Markedly Increased Iron Binding Capacity” 787: 2014–15. https://doi.org/10.1373/clinchem.2014.234229.
18. Hassan, Iman S. 2018. “To Study of Hepcidin Levels and Certain Hematological Parameters in Pregnant Women.” Al-Mustansiriyah Journal of Science 28 (3): 44. https://doi.org/10.23851/mjs.v28i3.545.
19. Kałuzna-Czyz, Monika, Urszula Grzybowska-Chlebowczyk, Halina Woś, and Sabina Wiȩcek. 2018. “Serum Hepcidin Level as a Marker of Iron Status in Children with Cystic Fibrosis.” Mediators of Inflammation 2018. https://doi.org/10.1155/2018/3040346.
20. Kemna, Erwin H.J.M., Harold Tjalsma, Hans L. Willems, and Dorine W. Swinkels. 2008. “Hepcidin: From Discovery to Differential Diagnosis.” Haematologica 93 (1): 90–97. https://doi.org/10.3324/haematol.11705.
21. Koenig, Mary Dawn, Lisa Tussing-Humphreys, Jessica Day, Brooke Cadwell, and Elizabeta Nemeth. 2014. “Hepcidin and Iron Homeostasis during Pregnancy.” Nutrients 6 (8): 3062–83. https://doi.org/10.3390/nu6083062.
22. Konz, T., M. Montes-Bayón, and S. Vaulont. 2014. “Hepcidin Quantification: Methods and Utility in Diagnosis.” Metallomics 6 (9): 1583–90. https://doi.org/10.1039/c4mt00063c.
23. Koperdanova, Marianna, and Jonathan O. Cullis. 2015. “Interpreting Raised Serum Ferritin Levels.” BMJ (Online) 351 (August): 9–11. https://doi.org/10.1136/bmj.h3692.
24. Krafft, Alexander, Laura Murray-Kolb, Nils Milman, Christine M. Pfeiffer, and Anne C. Looker. 2017. “Laboratory Methodologies for Indicators of Iron Status: Strengths, Limitations, and Analytical Challenges.” Journal of Pregnancy 106: 1606S-1614S. https://doi.org/10.3945/ajcn.117.155887.
25. Lopez, Anthony, Patrice Cacoub, Iain C. Macdougall, and Laurent Peyrin-Biroulet. 2016. “Iron Deficiency Anaemia.” The Lancet 387 (10021): 907–16. https://doi.org/10.1016/S0140-6736(15)60865-0.
26. Manolov, V, B Marinov, M Velizarova, B Atanasova, V Vasilev, K Tzatchev, I Bogov, G Genchev, and R Emilova. 2015. “Anemia in Pregnancy and Serum Hepcidin Levels.” International Journal of Advanced Resrarch 3 (1): 758–61.
27. Pagani, Alessia, Antonella Nai, Laura Silvestri, and Clara Camaschella. 2019. “Hepcidin and Anemia: A Tight Relationship.” Frontiers in Physiology 10 (October): 1–7. https://doi.org/10.3389/fphys.2019.01294.
28. Pasricha, Sant Rayn, Zoe McQuilten, Mark Westerman, Anthony Keller, Elizabeta Nemeth, Tomas Ganz, and Erica Wood. 2011. “Serum Hepcidin as a Diagnostic Test of Iron Deficiency in Premenopausal Female Blood Donors.” Haematologica 96 (8): 1099–1105. https://doi.org/10.3324/haematol.2010.037960.
29. Pretorius, Etheresia, and Douglas B. Kell. 2014. “Diagnostic Morphology: Biophysical Indicators for Iron-Driven Inflammatory Diseases.” Integrative Biology (United Kingdom) 6 (5): 486–510. https://doi.org/10.1039/c4ib00025k.
30. Ray, Joel G., Howard Berger, and Alison L. Park. 2020. “Population-Based Study of Serum Ferritin in Early Pregnancy and Adverse Perinatal Outcomes.” Paediatric and Perinatal Epidemiology 34 (6): 706–12. https://doi.org/10.1111/ppe.12687.
31. Rukuni, Ruramayi, Marian Knight, Michael F. Murphy, David Roberts, and Simon J. Stanworth. 2015. “Screening for Iron Deficiency and Iron Deficiency Anaemia in Pregnancy: A Structured Review and Gap Analysis against UK National Screening Criteria.” BMC Pregnancy and Childbirth 15 (1): 1–11. https://doi.org/10.1186/s12884-015-0679-9.
32. Sangkhae, Veena, Allison L. Fisher, Shirley Wong, Mary Dawn Koenig, Lisa Tussing-Humphreys, Alison Chu, Melisa Lelić, Tomas Ganz, and Elizabeta Nemeth. 2020. “Effects of Maternal Iron Status on Placental and Fetal Iron Homeostasis.” Journal of Clinical Investigation 130 (2): 625–40. https://doi.org/10.1172/JCI127341.
33. Sangkhae, Veena, and Elizabeta Nemeth. 2017. “Regulation of the Iron Homeostatic Hormone.” https://doi.org/10.3945/an.116.013961.micronutrient.
34. Senga, Edward L., Gibby Koshy, and Bernard J. Brabin. 2012. “Zinc Erythrocyte Protoporphyrin as Marker of Malaria Risk in Pregnancy - A Retrospective Cross-Sectional and Longitudinal Study.” Malaria Journal 11: 1–8. https://doi.org/10.1186/1475-2875-11-249.
35. “Statistical Analysis.” n.d.
36. “Statistics Solutions.” n.d.
37. Who. 2011. “Serum Ferritin Concentrations for the Assessment of Iron Status and Iron Deficiency in Populations. Vitamin and Mineral Nutrition Information System.” Who, 1–5.
38. World Health Organization. 2014. “Serum Transferrin Receptor Levels for the Assessment of Iron Status and Iron Deficiency in Populations.” WHO : Vitamin and Mineral Nutrition Information System, 4–7.
39. Wray, Katherine, Angela Allen, Emma Evans, Chris Fisher, Anuja Premawardhena, Lakshman Perera, Rexan Rodrigo, et al. 2017. “Hepcidin Detects Iron de Fi Ciency in Sri Lankan Adolescents with a High Burden of Hemoglobinopathy : A Diagnostic Test Accuracy Study,” no. November 2016: 196–203. https://doi.org/10.1002/ajh.24617.
40. Zimmermann, Michael B. 2008. “Methods to Assess Iron and Iodine Status.” British Journal of Nutrition 99 (SUPPL. 3): 2–9. https://doi.org/10.1017/S000711450800679X.
41. Zimmermann, Michael B., and Richard F. Hurrell. 2007. “Nutritional Iron Deficiency.” Lancet 370 (9586): 511–20. https://doi.org/10.1016/S0140-6736(07)61235-5.

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