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Diagnostic Challenges in Maternal Anemia: Mentzer Index in Clinical Practice

Emmanuel Ifeanyi Obeagu *

Department of Biomedical and Laboratory Science, Africa University, Zimbabwe

 

 

Introduction

Anemia during pregnancy is a global health issue that affects millions of women, with significant consequences for both maternal and fetal health. It is a condition characterized by a reduction in hemoglobin levels, leading to inadequate oxygen supply to the body's tissues. In pregnancy, anemia is particularly concerning due to the increased metabolic demands placed on the body, which can result in complications such as preterm birth, low birth weight, and even maternal mortality. Anemia during pregnancy can be caused by a variety of factors, including nutritional deficiencies, chronic diseases, and inherited blood disorders, with iron deficiency anemia (IDA) and thalassemia trait (TT) being two of the most common causes of microcytic anemia.^1-2 Iron deficiency anemia is the most prevalent form of anemia in pregnant women worldwide, primarily due to increased iron demands during pregnancy, combined with insufficient dietary intake or poor absorption of iron. In contrast, thalassemia trait, which is an inherited blood disorder, is commonly found in populations with a high prevalence of consanguinity or certain genetic backgrounds, particularly in Mediterranean, Middle Eastern, and Asian populations. Both IDA and TT share similar hematological features, such as low mean corpuscular volume (MCV) and low hemoglobin levels, which makes differentiating between these two conditions challenging. Proper diagnosis is crucial, as the treatment for IDA typically involves iron supplementation, while TT requires a different approach that may include avoiding iron supplementation and offering genetic counseling.^3-4

The Mentzer Index (MI) is a diagnostic tool developed to help differentiate between IDA and TT. This index is calculated by dividing the MCV by the red blood cell (RBC) count, yielding a value that can guide clinicians in distinguishing between the two conditions. A Mentzer Index greater than 13 typically suggests IDA, while values less than 13 are more likely to indicate thalassemia trait. The simplicity and accessibility of this tool make it an attractive first-line diagnostic method, particularly in settings with limited resources. However, while the MI offers a quick and cost-effective approach, it is not without its limitations and challenges, which can affect its diagnostic accuracy and clinical utility.^5-6 One of the main challenges in using the Mentzer Index is that it does not account for other causes of microcytic anemia, such as anemia of chronic disease or sideroblastic anemia, which can present similarly to IDA or TT. Furthermore, in pregnant women, anemia can often be multifactorial, with the presence of both iron deficiency and thalassemia trait, making the Mentzer Index less reliable in such cases. Additionally, laboratory variability, such as differences in how MCV or RBC count is measured, can lead to discrepancies in the calculation of the MI, potentially leading to misdiagnosis. As such, the MI should be seen as part of a broader diagnostic toolkit, rather than a definitive diagnostic measure.^7-8 In addition to the Mentzer Index, other diagnostic methods are often required to accurately differentiate between IDA and TT, especially in complex cases. Tests such as serum ferritin, transferrin saturation, and total iron-binding capacity (TIBC) can provide valuable information about iron status, helping to confirm or rule out iron deficiency. Hemoglobin electrophoresis is the gold standard for diagnosing thalassemia and other hemoglobinopathies, providing specific information about the types of hemoglobin present in the patient. Genetic testing may also be necessary to definitively diagnose thalassemia and to assess the need for genetic counseling.⁹ This review aims to explore the diagnostic challenges of maternal anemia, focusing on the role of the Mentzer Index in clinical practice. 

The Mentzer Index: A Diagnostic Tool in Maternal Anemia

The Mentzer Index (MI) is a simple and widely used diagnostic tool that helps differentiate between two of the most common causes of microcytic anemia in pregnancy: iron deficiency anemia (IDA) and thalassemia trait (TT). It is calculated by dividing the mean corpuscular volume (MCV) by the red blood cell (RBC) count, resulting in an index value that can offer insight into the underlying cause of anemia. The MI is based on the premise that IDA and TT present with different patterns of red blood cell morphology. While IDA typically leads to a high RBC count with low MCV due to iron deficiency, TT usually results in a relatively normal RBC count with lower MCV because of defective hemoglobin synthesis.^10-11 A MI value greater than 13 generally suggests that the anemia is due to iron deficiency, while a value less than 13 is typically indicative of thalassemia trait. The simplicity of this calculation makes the Mentzer Index an attractive option, particularly in settings where access to advanced diagnostic tools or resources is limited. It provides a quick, inexpensive, and relatively reliable method to screen for IDA and TT, facilitating early detection and guiding appropriate management strategies for pregnant women.¹² Despite its advantages, the Mentzer Index has several limitations that can affect its diagnostic accuracy. For instance, the MI does not account for other causes of microcytic anemia, such as anemia of chronic disease or sideroblastic anemia, which can share similar hematological features with IDA and TT. Additionally, in pregnant women, anemia can often be multifactorial, involving both iron deficiency and thalassemia trait, which may lead to overlapping clinical features. As a result, the MI may be less accurate in these complex cases and may require confirmation through additional diagnostic tests. Furthermore, laboratory errors and variations in MCV and RBC count measurements can influence the MI calculation, potentially leading to misinterpretation and inappropriate treatment decisions.¹³

In clinical practice, the Mentzer Index is most effective when used as an initial screening tool, with follow-up confirmatory tests employed as needed to verify the diagnosis. In cases where the MI suggests IDA, serum ferritin levels, transferrin saturation, and total iron-binding capacity (TIBC) can help confirm iron deficiency. If thalassemia trait is suspected based on a low MI, hemoglobin electrophoresis can be used to identify abnormal hemoglobin patterns, providing a definitive diagnosis. Genetic testing may also be useful for further confirmation, especially in populations at high risk for thalassemia.¹⁴ While the Mentzer Index is a valuable diagnostic tool in identifying the cause of microcytic anemia, it should not be used in isolation. Clinicians should consider the patient's clinical history, other hematological indices, and additional laboratory tests to ensure an accurate diagnosis. By combining the MI with other diagnostic methods, healthcare providers can improve their ability to differentiate between iron deficiency anemia and thalassemia trait, allowing for more tailored and effective treatment approaches for pregnant women. Ultimately, accurate diagnosis and management of maternal anemia are critical for reducing maternal and fetal morbidity and mortality, highlighting the importance of utilizing the Mentzer Index as part of a comprehensive diagnostic approach.^15-16

Diagnostic Challenges in Maternal Anemia

Maternal anemia is a common and significant health concern during pregnancy, affecting millions of women worldwide. The condition is often linked to adverse maternal and fetal outcomes, including preterm birth, low birth weight, and maternal fatigue. Identifying the precise cause of anemia is essential for appropriate treatment and prevention of complications. However, diagnosing anemia in pregnancy presents unique challenges, as it can result from various underlying conditions, including nutritional deficiencies, chronic diseases, and inherited blood disorders. The two most common causes of microcytic anemia during pregnancy are iron deficiency anemia (IDA) and thalassemia trait (TT), both of which share overlapping hematological features, making accurate diagnosis challenging.^17-18 One of the primary diagnostic challenges in maternal anemia is distinguishing between IDA and thalassemia trait. Both conditions present with low mean corpuscular volume (MCV) and low hemoglobin levels, making it difficult to differentiate them based on basic laboratory findings alone. While IDA is typically characterized by low iron stores and a reduced ability to produce hemoglobin, thalassemia trait involves a genetic defect that impairs hemoglobin production without necessarily affecting iron status. Given the shared clinical features, misdiagnosis can occur if the underlying cause is not properly identified. In some cases, women may have both conditions simultaneously, further complicating diagnosis and treatment.¹⁹

Another challenge is the multifactorial nature of anemia in pregnancy. Pregnant women are at risk for several types of anemia, and a single diagnostic test may not always provide sufficient information to determine the exact cause. For example, some women may experience anemia due to iron deficiency, while others may have anemia due to folate deficiency, vitamin B12 deficiency, or anemia of chronic disease. Additionally, pregnancy-induced changes, such as increased blood volume and altered iron metabolism, can further complicate the interpretation of standard laboratory tests. The complexity of these overlapping factors requires a thorough clinical evaluation, including a detailed patient history, physical examination, and a variety of diagnostic tests.²⁰ Diagnostic tools such as the Mentzer Index have been proposed to help differentiate between IDA and TT, but they are not foolproof. The Mentzer Index, which is calculated by dividing the mean corpuscular volume (MCV) by the red blood cell count, can suggest whether the anemia is likely due to IDA or thalassemia. However, this index has its limitations and may not always provide a definitive diagnosis. Factors such as laboratory errors, coexisting conditions, or the presence of mixed anemia can lead to inaccurate results. Additionally, other hematological disorders, such as anemia of chronic disease, can present similarly to IDA and TT, further complicating the diagnostic process.²¹ In addition to the Mentzer Index, clinicians may rely on other diagnostic tests, including serum ferritin, transferrin saturation, total iron-binding capacity (TIBC), and hemoglobin electrophoresis, to confirm the diagnosis. While serum ferritin and transferrin saturation are useful for identifying iron deficiency, hemoglobin electrophoresis is necessary for confirming the presence of thalassemia trait or other hemoglobinopathies. In some cases, genetic testing may be required to definitively diagnose thalassemia and assess the need for genetic counseling, particularly in populations with a high prevalence of inherited blood disorders.²²

The Role of Complementary Diagnostic Methods

The diagnosis of maternal anemia, particularly distinguishing between iron deficiency anemia (IDA) and thalassemia trait (TT), can be complex due to the overlap in clinical presentation and laboratory findings. While tools like the Mentzer Index provide a useful starting point, they are not always sufficient in isolation, especially when anemia is multifactorial or when coexisting conditions complicate the picture. To achieve an accurate diagnosis and guide appropriate treatment, it is essential to use a combination of diagnostic methods that complement each other. These methods not only help refine the initial clinical suspicion but also assist in confirming the underlying cause of anemia, thereby optimizing maternal and fetal health outcomes.²³ One of the most commonly used complementary diagnostic tests is the serum ferritin level, which reflects the body’s iron stores. In cases of IDA, serum ferritin levels are typically low, while in thalassemia trait, ferritin levels are generally normal or only mildly reduced. Another important test is the transferrin saturation (TS), which can help assess the iron status more directly. Low transferrin saturation levels are indicative of iron deficiency, while normal or elevated levels are more consistent with thalassemia trait. Total iron-binding capacity (TIBC) is also useful for evaluating iron deficiency, as elevated TIBC is a hallmark of IDA, while it tends to remain normal in thalassemia trait. These tests, when used in conjunction, provide a clearer picture of the patient’s iron status and help differentiate between IDA and thalassemia trait.²⁴

Hemoglobin electrophoresis plays a crucial role in diagnosing thalassemia and other hemoglobinopathies. This test allows for the separation of different types of hemoglobin, enabling the detection of abnormal hemoglobin patterns that are characteristic of thalassemia, sickle cell disease, and other inherited blood disorders. In women suspected of having thalassemia trait, hemoglobin electrophoresis can confirm the presence of abnormal hemoglobin types, such as HbA2, which is elevated in thalassemia. This method is particularly important in populations where thalassemia is prevalent, as it provides definitive confirmation of the diagnosis and guides further management, including genetic counseling.²⁵ In addition to these tests, genetic testing is becoming increasingly important, particularly in high-risk populations or cases where the diagnosis remains unclear. Genetic testing can identify mutations associated with thalassemia and other hemoglobinopathies, providing a definitive diagnosis. It is particularly useful in identifying carriers of the disease and assessing the risk of passing on genetic conditions to offspring. Moreover, genetic testing can be helpful when there is a possibility of coexisting conditions, such as thalassemia trait combined with other inherited disorders, which might complicate the clinical picture.²⁶ Furthermore, in cases where anemia is multifactorial, as is often the case in pregnancy, it is important to consider other potential causes. For example, anemia of chronic disease (ACD), which often occurs in the context of infection, inflammation, or chronic illness, can present similarly to IDA and thalassemia. In these cases, complementary tests such as C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) may help identify underlying inflammatory or infectious conditions. Additionally, vitamin B12 and folate levels should be measured if there is suspicion of deficiencies in these nutrients, which can also contribute to anemia during pregnancy.²⁷

Conclusion

The diagnosis of maternal anemia remains a critical aspect of prenatal care, as it significantly impacts both maternal and fetal health outcomes. Given the complexities and overlapping features of different types of anemia, such as iron deficiency anemia (IDA) and thalassemia trait (TT), relying solely on a single diagnostic method can lead to misdiagnosis and inappropriate treatment. The Mentzer Index serves as a useful initial screening tool, but its limitations highlight the importance of employing complementary diagnostic methods to achieve an accurate diagnosis. Tests such as serum ferritin, transferrin saturation, hemoglobin electrophoresis, and genetic testing all provide valuable insights into the underlying cause of anemia. 

Conflict of Interest: Author declares no potential conflict of interest with respect to the contents, authorship, and/or publication of this article.

Source of Support: Nil

Funding: The authors declared that this study has received no financial support.

Informed Consent Statement: Not applicable. 

Data Availability Statement: The data supporting in this paper are available in the cited references. 

Ethics approval: Not applicable.

References

1. Rahman MM, Abe SK, Rahman MS, Kanda M, Narita S, Bilano V, Ota E, Gilmour S, Shibuya K. Maternal anemia and risk of adverse birth and health outcomes in low-and middle-income countries: systematic review and meta-analysis. The American journal of clinical nutrition. 2016; 103(2):495-504. https://doi.org/10.3945/ajcn.115.107896 PMid:26739036

2. Obeagu EI, Ezimah AC, Obeagu GU. Erythropoietin in the anaemias of pregnancy: a review. Int J Curr Res Chem Pharm Sci. 2016;3(3):10-18. https://doi.org/10.22270/ijmspr.v10i2.95

3. Okamgba OC, Nwosu DC, Nwobodo EI, Agu GC, Ozims SJ, Obeagu EI, Ibanga IE, Obioma-Elemba IE, Ihekaire DE, Obasi CC, Amah HC. Iron Status of Pregnant and Post-Partum Women with Malaria Parasitaemia in Aba Abia State, Nigeria. Annals of Clinical and Laboratory Research. 2017;5(4):206.

4. Petrakos G, Andriopoulos P, Tsironi M. Pregnancy in women with thalassemia: challenges and solutions. International journal of women's health. 2016:441-451. https://doi.org/10.2147/IJWH.S89308 PMid:27660493 PMCid:PMC5019437

5. Obeagu EI, Adepoju OJ, Okafor CJ, Obeagu GU, Ibekwe AM, Okpala PU, Agu CC. Assessment of Haematological Changes in Pregnant Women of Ido, Ondo State, Nigeria. J Res Med Dent Sci. 2021 Apr;9(4):145-148.

6. Agreen FC, Obeagu EI. Anaemia among pregnant women: A review of African pregnant teenagers. Journal of Public Health and Nutrition. 2023;6(1):138.

7. Arora S, Rana D, Kolte S, Dawson L, Dhawan I. Validation of new indices for differentiation between iron deficiency anemia and beta thalessemia trait, a study in pregnant females. International Journal of Scientific Reports. 2018; 4(2):26. https://doi.org/10.18203/issn.2454-2156.IntJSciRep20180394

8. Obeagu EI, Obeagu GU, Insights into Maternal Health: Mentzer Index for Early Anemia Detection, International Journal of Medical Sciences and Pharma Research,2024;10(4):44-49 https://doi.org/10.22270/ijmspr.v10i4.122

9. Obeagu EI, Influence of Hemoglobin Variants on Vaso-Occlusive Phenomena in Sickle Cell Anemia: A Review, International Journal of Medical Sciences and Pharma Research, 2024;10(2):54-59 https://doi.org/10.22270/ijmspr.v10i2.104

10. Iolascon A, Andolfo I, Russo R, Sanchez M, Busti F, Swinkels D, Aguilar Martinez P, Bou‐Fakhredin R, Muckenthaler MU, Unal S, Porto G. Recommendations for diagnosis, treatment, and prevention of iron deficiency and iron deficiency anemia. Hemasphere. 2024; 8(7):e108. https://doi.org/10.1002/hem3.108 PMid:39011129 PMCid:PMC11247274

11. Obeagu EI, Obeagu GU, Chukwueze CM, Ikpenwa JN, Ramos GF. Evaluation of protein C, protein S and fibrinogen of pregnant women with malaria in Owerri metropolis. Madonna University journal of Medicine and Health Sciences ISSN: 2814-3035. 2022 Apr 19;2(2):1-9.

12. Obeagu EI, Obeagu GU. Neonatal Outcomes in Children Born to Mothers with Severe Malaria, HIV, and Transfusion History: A Review. Elite Journal of Nursing and Health Science, 2024; 2(3): 38-58

13. Sahli CA, Bibi A, Ouali F, Fredj SH, Dakhlaoui B, Othmani R, Laouini N, Jouini L, Ouenniche F, Siala H, Touhami I. Red cell indices: differentiation between β-thalassemia trait and iron deficiency anemia and application to sickle-cell disease and sickle-cell thalassemia. Clinical Chemistry and Laboratory Medicine (CCLM). 2013; 51(11):2115-24. https://doi.org/10.1515/cclm-2013-0354 PMid:23800659

14. Hoffmann JJ, Nabbe KC, van den Broek NM. Effect of age and gender on reference intervals of red blood cell distribution width (RDW) and mean red cell volume (MCV). Clinical Chemistry and Laboratory Medicine (CCLM). 2015; 53(12):2015-9. https://doi.org/10.1515/cclm-2015-0155 PMid:26536583

15. Miftahussurur M, Husada D, Ningtyas WS. Association Association Of Shine and Lal Index Β-Thalassemia Trait Screening Results with Anaemia and Low Birth Weigh. International Journal of Nursing And Midwifery Science (IJNMS). 2023; 7(3):290-296. https://doi.org/10.29082/IJNMS/2023/Vol7/Iss3/543

16. Shahid H, Saleem M, Naseer N, Tabussam S, Aziz A, Ullah S. Evaluation of Srivastava index to distinguishing Beta-Thalassemia Trait from Iron Deficiency. Pakistan Journal of Medical & Health Sciences. 2022;16(05):1225. https://doi.org/10.53350/pjmhs221651225

17. Vehapoglu A, Ozgurhan G, Demir AD, Uzuner S, Nursoy MA, Turkmen S, Kacan A. Hematological indices for differential diagnosis of Beta thalassemia trait and iron deficiency anemia. Anemia. 2014; 2014(1):576738. https://doi.org/10.1155/2014/576738 PMid:24818016 PMCid:PMC4003757

18. Urrechaga E. Discriminant value of% microcytic/% hypochromic ratio in the differential diagnosis of microcytic anemia. Clinical chemistry and laboratory medicine. 2008;46(12):1752-1758. https://doi.org/10.1515/CCLM.2008.355 PMid:19055451

19. Obeagu EI, Obeagu GU, Anemia in Pregnancy: Mentzer Index as a Predictor for Iron Supplementation Needs, International Journal of Medical Sciences and Pharma Research, 2024;10(4):39-43 https://doi.org/10.22270/ijmspr.v10i4.121

20. Obeagu EI, Obeagu GU. Sickle cell anaemia in pregnancy: a review. International Research in Medical and Health Sciences. 2023 Jun 10;6(2):10-13. https://doi.org/10.22270/ijmspr.v10i2.103

21. Obeagu EI, Ubosi NI, Uzoma G. Antioxidant Supplementation in Pregnancy: Effects on Maternal and Infant Health. Int. J. Adv. Multidiscip. Res. 2023;10(11):60-70.

22. Obeagu EI, Obeagu GU. Mitigating Oxidative Stress in Pregnancy through Antioxidant Supplementation: A Narrative Review. Int. J. Curr. Res. Chem. Pharm. Sci. 2024;11(9):7-17.

23. Obeagu EI, Obeagu GU. Enhancing Maternal and Fetal Well-being: The Role of Antioxidants in Pregnancy. Elite Journal of Medical Sciences. 2024;2(4):76-87.

24. Obeagu EI, Obeagu GU. Antioxidant Supplementation and Prevention of Early Pregnancy Loss: A Narrative Review. Int. J. Curr. Res. Chem. Pharm. Sci. 2024;11(9):28-37. https://doi.org/10.22270/ijmspr.v10i4.120

25. Obeagu EI, Obeagu GU. Molar Pregnancy: Update of prevalence and risk factors. Int. J. Curr. Res. Med. Sci. 2023;9(7):25-28. https://doi.org/10.19080/JGWH.2023.25.556169

26. Obeagu EI, Obeagu GU. Hypoxia-induced Metabolic Changes in Pregnancy: Clinical Perspectives. Elite Journal of Medicine. 2024;2(8):50-59.

27. Obeagu EI, Obeagu GU. Hemolysis Challenges for Pregnant Women with Sickle Cell Anemia: A Review. Elite Journal of Haematology. 2024;2(3):67-80.