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 International Journal of Medical Sciences and Pharma Research 

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Copyright  © 2025 The   Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

 

Anemia in Pregnancy: The Role of Iron Transport and Regulation

Emmanuel Ifeanyi Obeagu ¹*, S K Prajapati ², Sheo Datta Maurya ³

¹ Department of Biomedical and Laboratory Science, Africa University, Zimbabwe

² Professor & Head, Institute of Pharmacy, Bundelkhand University, Jhansi (U.P.), India

³ Pharmacist, Health Unit, Sitarampur, Eastern Railway, Asansol, West Bengal, India-713359

 

 

Introduction

Anemia during pregnancy is a global health concern, affecting millions of women each year, with significant consequences for both maternal and fetal well-being. One of the primary causes of anemia in pregnancy is iron deficiency anemia (IDA), which occurs when the body lacks sufficient iron to produce hemoglobin, the oxygen-carrying component of red blood cells. The increased iron demands during pregnancy, due to expanded blood volume and fetal growth, make women more vulnerable to iron deficiency. However, while iron deficiency is the leading cause of anemia in pregnancy, there are other contributing factors that can impair iron metabolism and exacerbate the condition, including inflammation, malabsorption, and underlying chronic diseases.¹ Iron plays a vital role in oxygen transport, immune function, and cellular energy metabolism. During pregnancy, the body undergoes numerous physiological changes that increase the need for iron, especially to support fetal development and placental growth. The increased blood volume, which can rise by up to 50% during pregnancy, significantly elevates the maternal need for iron to sustain hemoglobin production. As a result, pregnant women are at heightened risk of developing anemia if their iron intake or absorption is insufficient to meet these growing demands. Without adequate iron, the body cannot produce enough hemoglobin, leading to reduced oxygen supply to vital tissues, including the placenta, which can adversely affect fetal development and lead to complications such as preterm birth, low birth weight, and developmental delays.^2-3 Iron homeostasis is maintained by a complex system of regulation that governs iron absorption, storage, and transport. This system involves key proteins such as transferrin, which carries iron through the bloodstream, and ferritin, which stores iron in tissues like the liver and bone marrow. Hepcidin, a hormone produced by the liver, plays a central role in regulating iron levels by controlling the absorption of iron from the gastrointestinal tract and its release from storage sites. During pregnancy, hepcidin levels are typically lower to facilitate the increased absorption and mobilization of iron. However, this balance can be disrupted by factors such as inflammation, infections, or other underlying conditions, leading to either iron deficiency or iron overload, both of which have negative health consequences.^4-5

The pathophysiology of anemia in pregnancy is not limited to iron deficiency alone. While iron deficiency anemia is the most prevalent form, other forms of anemia, such as vitamin B12 deficiency anemia, folate deficiency anemia, and anemia caused by chronic diseases, can also contribute to the overall burden of anemia in pregnant women. For example, chronic inflammatory conditions, such as infections or autoimmune diseases, can lead to anemia of chronic disease, characterized by impaired iron utilization and poor iron absorption despite adequate stores. In these cases, anemia is not caused by a lack of iron but by a disruption in iron metabolism, highlighting the importance of understanding the role of iron transport and regulation in maintaining optimal iron status during pregnancy.^6-7 The consequences of anemia during pregnancy can be profound, affecting not only the mother’s health but also the fetus’s development. Maternal anemia is associated with fatigue, decreased immune function, and an increased risk of postpartum hemorrhage. For the fetus, the lack of adequate iron can lead to poor fetal growth, low birth weight, and impaired brain development. The severity of these complications depends on the degree of anemia and the timing of its onset during pregnancy. Anemia in the first and second trimesters, for instance, is associated with more significant risks to fetal development compared to anemia that develops later in pregnancy. Therefore, early identification and management of anemia are essential to mitigate these risks.^8-9

Iron Transport and Absorption in Pregnancy

Iron transport and absorption during pregnancy are critical processes that ensure adequate iron supply for both maternal and fetal needs. Due to the increased iron demands associated with pregnancy, the body undergoes several adaptive changes to enhance iron absorption from the gastrointestinal tract, mobilize stored iron, and regulate iron levels efficiently. 

Iron Absorption: The primary site of iron absorption in the body is the duodenum and upper jejunum of the small intestine. Iron from food sources is typically present in two forms: heme iron, which is found in animal-based foods such as meat, and non-heme iron, which is found in plant-based foods. Heme iron is more easily absorbed than non-heme iron. The absorption of non-heme iron, however, is influenced by several dietary factors. Vitamin C, for instance, enhances non-heme iron absorption by reducing ferric iron (Fe3+) to the more absorbable ferrous form (Fe2+), while certain substances such as tannins, calcium, and phytates can inhibit iron absorption. During pregnancy, there is an increased need for both heme and non-heme iron, prompting the body to adapt by enhancing absorption.^10-11

Regulation of Iron Absorption: The absorption of iron is tightly regulated by the body's needs, with the key regulatory mechanism involving the hormone hepcidin. Hepcidin is produced by the liver in response to iron levels and inflammation. It controls the absorption of iron from the intestine and its release from storage sites (e.g., the liver and macrophages) by binding to and degrading the iron-exporting protein ferroportin. During pregnancy, hepcidin levels tend to decrease to facilitate the increased absorption of iron, which is needed for the expanding blood volume and the developing fetus. However, elevated hepcidin levels due to inflammation or infections can reduce iron availability, leading to functional iron deficiency even when iron stores are sufficient. This process highlights the complexity of iron regulation during pregnancy and its impact on anemia.^12-13

Iron Transport: Once absorbed, iron is transported in the bloodstream by transferrin, a glycoprotein that binds to iron and delivers it to various tissues, including the bone marrow, where it is used for hemoglobin production in red blood cells. The iron-transferrin complex is recognized by transferrin receptors on target cells, facilitating the uptake of iron. In pregnancy, the increased iron demands for both maternal blood volume expansion and fetal development lead to an increase in transferrin levels. Additionally, iron is stored in the liver, spleen, and bone marrow as ferritin, a protein that acts as a reserve, which can be mobilized when iron intake or absorption is inadequate. The body maintains a delicate balance between iron absorption, storage, and transport to ensure sufficient iron availability, especially during the higher demands of pregnancy.¹⁴

Pregnancy-Specific Adaptations: During pregnancy, the body adapts to meet the heightened iron demands through several physiological changes. There is an increased absorption of dietary iron, and the iron transport system is upregulated to ensure sufficient delivery to the placenta and fetus. In addition to these changes, pregnant women experience an increase in blood volume, which dilutes the concentration of red blood cells, further elevating the need for iron to support the synthesis of hemoglobin. These adaptations, however, can be inadequate if the intake or absorption of iron is insufficient, leading to iron deficiency and, subsequently, anemia. Moreover, the placenta itself plays a role in transferring iron to the fetus, which is crucial for fetal development, particularly for brain development and overall growth. A disruption in maternal iron status can therefore negatively impact both maternal and fetal health.¹⁵

Iron Regulation and Homeostasis

Iron regulation and homeostasis are vital processes that maintain the balance of iron in the body, ensuring its availability for critical functions like oxygen transport, cellular metabolism, and immune function, while preventing toxicity associated with excess iron. The body’s ability to tightly regulate iron levels is especially important during pregnancy, where iron demands increase significantly to support the expanded maternal blood volume, fetal growth, and placental development. Disruptions in iron regulation can lead to either iron deficiency or overload, both of which can have detrimental effects on maternal and fetal health. The key players in iron regulation include hepcidin, transferrin, ferritin, and ferroportin, each of which plays a specific role in iron absorption, storage, and distribution.¹⁶

Hepcidin: Hepcidin is the central regulator of iron homeostasis. It is a hormone produced mainly in the liver, which controls the absorption of iron from the intestine and the release of stored iron from macrophages and hepatocytes. Hepcidin binds to ferroportin, the protein responsible for exporting iron from cells into the bloodstream, and induces its internalization and degradation. When hepcidin levels are high, iron absorption from the gut is reduced, and iron release from stores is inhibited, resulting in a decrease in circulating iron. During pregnancy, hepcidin levels tend to decrease to allow for greater iron absorption and mobilization to meet the increased demand. However, this regulation can be altered by factors such as inflammation, infection, or chronic disease, leading to functional iron deficiency, where iron is unavailable despite sufficient stores.¹⁷

Iron Absorption and Transport: Iron absorption occurs primarily in the duodenum and upper jejunum of the small intestine. Once absorbed, iron is transported in the bloodstream by transferrin, a glycoprotein that binds to iron and delivers it to tissues and organs where it is required. The transferrin receptors on the surface of cells facilitate the uptake of transferrin-bound iron. Once inside the cell, iron is either incorporated into hemoglobin (in erythroid precursors) or stored as ferritin in tissues like the liver and spleen. Iron storage as ferritin helps prevent iron toxicity, as excess free iron can catalyze the formation of harmful free radicals through Fenton’s reaction. During pregnancy, the increased iron needs for both maternal blood volume expansion and fetal development result in higher levels of transferrin, enhancing iron transport to tissues, especially to the placenta.¹⁸

Iron Stores and Ferritin: The body stores iron primarily in the form of ferritin, which is found in the liver, spleen, bone marrow, and other tissues. Ferritin serves as a buffer to prevent iron deficiency and toxicity, releasing iron when needed for processes like hemoglobin synthesis. The body maintains a balance between iron absorption, transport, and storage, with ferritin serving as an indicator of the body's iron reserves. In pregnancy, ferritin levels are monitored to assess iron status and determine whether iron supplementation is necessary. Low ferritin levels are indicative of depleted iron stores, often preceding a decrease in circulating hemoglobin and the onset of anemia. Conversely, elevated ferritin levels may indicate iron overload or inflammation, as ferritin is also an acute-phase reactant in inflammatory conditions.¹⁹

Iron Homeostasis in Pregnancy: During pregnancy, the body adapts to increased iron requirements due to the growing fetus, placenta, and increased maternal blood volume. To meet these needs, there is an increase in iron absorption from the diet, facilitated by the reduced levels of hepcidin, which allows for greater intestinal iron uptake. However, this adaptation is often not enough to meet the heightened demands, particularly in the presence of poor iron intake, malabsorption, or chronic blood loss. Iron regulation in pregnancy also becomes influenced by factors such as gestational age, maternal health, and the presence of underlying conditions like infections, which can elevate hepcidin levels and impair iron availability. Effective regulation is essential for maintaining maternal health and promoting proper fetal development, especially for brain development, which is highly dependent on iron.²⁰

Disruptions in Iron Homeostasis: Disruptions in iron regulation can lead to two main disorders: iron deficiency anemia and iron overload. Iron deficiency anemia is the most common form of anemia during pregnancy and is typically caused by insufficient dietary intake, impaired absorption, or excessive blood loss. On the other hand, iron overload, which is less common but equally concerning, can occur if there is excessive iron supplementation or a genetic predisposition, such as in hereditary hemochromatosis. Both conditions have significant health implications; iron deficiency anemia can impair oxygen delivery to tissues, leading to fatigue, impaired immune function, and poor fetal outcomes, while iron overload can lead to oxidative stress and damage to organs such as the liver and heart.²¹

Regulation of Iron Homeostasis and Implications for Treatment: Understanding the mechanisms of iron regulation and homeostasis is critical for the effective treatment of anemia in pregnancy. The first-line treatment for iron deficiency anemia is iron supplementation, but this must be done carefully to avoid over-supplementation, which can lead to side effects and, in severe cases, iron overload. Monitoring of iron status through ferritin, hemoglobin, and transferrin levels is essential to guide treatment. For women at risk of iron overload, such as those with a genetic predisposition to hemochromatosis, caution must be exercised to avoid excessive iron intake. In addition to iron supplementation, dietary modifications and addressing underlying conditions that affect iron absorption or utilization are also important components of managing iron deficiency and ensuring proper iron homeostasis during pregnancy.²²

Clinical Implications and Complications

The clinical implications of iron regulation during pregnancy are substantial, given that adequate iron levels are essential for the well-being of both the mother and the developing fetus. Disruptions in iron regulation, whether due to deficiency or overload, can lead to significant health complications that may affect pregnancy outcomes. Understanding the impact of these disruptions is critical for optimizing maternal care, preventing adverse outcomes, and ensuring the healthy development of the fetus.²³

Iron Deficiency and Anemia during Pregnancy: Iron deficiency anemia (IDA) is one of the most common complications of pregnancy, affecting a large percentage of pregnant women globally. As the body’s iron stores become depleted, the ability to produce hemoglobin—an iron-containing protein necessary for oxygen transport—diminishes. This leads to reduced oxygen delivery to both maternal and fetal tissues. Clinically, IDA manifests as fatigue, weakness, pallor, and dizziness, and in severe cases, it can impair cognitive function and immune response. Iron deficiency can also increase the risk of preterm birth, low birth weight, and intrauterine growth restriction (IUGR), which can have long-term effects on the child's health. Additionally, pregnant women with IDA are at higher risk of developing postpartum hemorrhage and may experience longer recovery times following delivery.²⁴

Iron Overload and Its Complications: While iron deficiency is more commonly observed, iron overload is also a serious concern, particularly in women who receive excessive iron supplementation or have conditions that predispose them to increased iron absorption, such as hereditary hemochromatosis. Excess iron in the body can lead to oxidative stress, which can damage tissues and organs. In pregnancy, iron overload can result in complications such as gestational diabetes, hypertension, and liver dysfunction. The placenta, which serves as the primary interface for nutrient and gas exchange between the mother and fetus, may be impaired by excessive iron, leading to disruptions in fetal development. Iron overload is also associated with increased risk of fetal abnormalities and may impair fetal brain development, which is heavily reliant on iron for neural development. Thus, maintaining a balance in iron levels is critical to avoid the risks associated with both iron deficiency and overload.²⁵

Disruption of Iron Homeostasis in Inflammatory Conditions: Inflammation and infection are common during pregnancy, and they significantly affect iron homeostasis. Inflammatory cytokines, such as interleukin-6 (IL-6), stimulate the production of hepcidin, which regulates iron absorption and release. During inflammation, elevated hepcidin levels reduce the amount of iron available for the body to use, leading to functional iron deficiency even in the presence of sufficient iron stores. This can contribute to anemia of chronic disease (ACD), a condition characterized by low iron availability despite normal or elevated iron stores. In pregnant women, ACD can exacerbate the effects of iron deficiency anemia and make it more challenging to manage anemia effectively. Infections such as malaria and helminthiasis, which are prevalent in some parts of the world, can also interfere with iron metabolism and exacerbate anemia.²⁶

Impact on Maternal Health and Pregnancy Outcomes: The clinical implications of inadequate iron levels during pregnancy extend beyond anemia. Iron deficiency can impair the immune system, making pregnant women more susceptible to infections. This not only increases the risk of complications but can also prolong the recovery time from infections. Additionally, iron deficiency can lead to compromised cardiac function, as the heart must work harder to compensate for reduced oxygen transport, which may increase the risk of heart failure in severe cases. Iron deficiency has also been linked to an increased risk of preeclampsia, a condition characterized by high blood pressure and organ damage, particularly affecting the kidneys and liver. The maternal cardiovascular system is already under strain due to pregnancy, and iron deficiency can exacerbate this, leading to serious complications for both the mother and fetus.²⁷

Fetal Consequences of Disrupted Iron Regulation: Iron plays a crucial role in fetal development, particularly in the development of the brain and nervous system. Insufficient iron during pregnancy can have long-lasting effects on the fetus, including impaired cognitive development, lower IQ, and behavioral issues later in life. Iron deficiency is particularly concerning in the early stages of pregnancy, as it is during this time that the fetal brain undergoes rapid growth and development. Additionally, iron deficiency during pregnancy is associated with increased risks of preterm birth, intrauterine growth restriction (IUGR), and stillbirth. Fetal iron deficiency may also impair the fetus's ability to produce hemoglobin and red blood cells, leading to anemia, which further exacerbates the risk of preterm delivery and developmental delays.²⁸

Management and Prevention: Clinically, the management of iron-related disorders during pregnancy focuses on both prevention and treatment. Iron supplementation is the standard approach for treating iron deficiency anemia and preventing its complications. However, careful monitoring is necessary to avoid iron overload, especially in women with a history of hereditary hemochromatosis or those at risk for excess iron intake. In cases of iron overload, phlebotomy or iron chelation therapy may be considered. Inflammatory conditions that affect iron metabolism require careful management of underlying causes to prevent the functional iron deficiency that exacerbates anemia. Additionally, managing anemia involves addressing the root causes, such as improving dietary intake of iron-rich foods, providing appropriate supplementation, and monitoring iron levels regularly. Collaboration between obstetricians, hematologists, and nutritionists is essential to ensure optimal iron status throughout pregnancy.²⁹

Management and Therapeutic Approaches

Effective management of iron-related disorders in pregnancy is crucial for promoting maternal and fetal health. Both iron deficiency and iron overload require distinct therapeutic strategies, and a tailored approach is necessary for optimal outcomes. This involves addressing the root causes of iron imbalances, implementing appropriate interventions, and regularly monitoring maternal and fetal health.

1. Iron Supplementation for Iron Deficiency Anemia: The first line of treatment for iron deficiency anemia (IDA) in pregnancy is oral iron supplementation. Typically, ferrous sulfate or other forms of ferrous iron are prescribed, as they are well-absorbed and effective in replenishing iron stores. The usual dose is 30-60 mg of elemental iron per day. It is important to note that iron absorption is enhanced in an acidic environment, so it is often recommended that iron supplements be taken on an empty stomach, although this can cause gastrointestinal discomfort in some women. To minimize side effects such as constipation and nausea, lower doses or slow-release formulations may be used. In cases where oral iron supplementation is not effective, or if the woman has severe anemia, intravenous (IV) iron therapy may be considered. IV iron preparations, such as iron sucrose or ferric carboxymaltose, allow for rapid replenishment of iron stores, especially in cases of malabsorption, poor compliance with oral iron, or significant anemia that cannot be corrected through oral supplementation alone.³⁰

2. Dietary Interventions: Alongside pharmacologic treatment, dietary modifications play a significant role in managing iron deficiency in pregnancy. Pregnant women are encouraged to consume iron-rich foods such as lean meats, poultry, fish, lentils, beans, fortified cereals, and dark leafy greens. The absorption of non-heme iron (from plant-based sources) can be enhanced by consuming foods high in vitamin C, such as citrus fruits, strawberries, and bell peppers. Conversely, certain foods and substances can inhibit iron absorption, including calcium-rich foods, coffee, tea, and high-fiber foods. Counseling on optimal eating habits and nutrient timing can help enhance the effectiveness of iron supplementation and dietary intake. Pregnant women should be educated on how to balance iron-rich foods and avoid inhibitors to maximize iron absorption.³¹

3. Addressing Inflammatory and Infectious Causes of Iron Deficiency: In cases where iron deficiency is compounded by underlying inflammatory or infectious conditions, managing the root cause is essential. Inflammatory cytokines, such as interleukin-6 (IL-6), increase hepcidin production, which blocks iron absorption and mobilization. Therefore, treating infections and managing chronic inflammatory conditions is critical to resolving functional iron deficiency. For example, appropriate antibiotics should be administered for bacterial infections like urinary tract infections (UTIs) or malaria, and antiparasitic treatments are necessary for helminthiasis. In women with chronic conditions like inflammatory bowel disease (IBD), rheumatoid arthritis, or autoimmune disorders, treatment of the underlying disease with immunosuppressive medications or biologics may be required. The management of these conditions not only addresses inflammation but also reduces its impact on iron metabolism.³²

4. Monitoring Iron Status and Tailoring Treatment: Regular monitoring of iron status is crucial to avoid both iron deficiency and iron overload. This involves measuring serum ferritin levels, hemoglobin concentration, transferrin saturation, and total iron-binding capacity (TIBC). Ferritin levels provide a good indication of iron stores, and hemoglobin measurements reflect the extent of anemia. In cases of iron overload, monitoring transferrin saturation and serum ferritin levels is essential to ensure that excessive iron accumulation does not occur, especially when iron supplementation is prescribed. In pregnant women at risk of iron overload, such as those with hereditary hemochromatosis or chronic liver disease, periodic phlebotomy may be considered as a therapeutic strategy to reduce excess iron. For women with suspected or diagnosed iron overload, avoiding iron supplementation and focusing on dietary management may be necessary to prevent complications associated with iron toxicity.³³

5. Management of Iron Overload: In contrast to iron deficiency, iron overload during pregnancy requires careful management to avoid complications such as oxidative damage, gestational diabetes, and fetal harm. Women with inherited conditions like hereditary hemochromatosis may experience excess iron absorption, and iron supplementation must be avoided. For women diagnosed with iron overload, therapeutic interventions such as iron chelation therapy may be considered. These treatments help remove excess iron from the body and prevent tissue damage. However, the use of iron chelators during pregnancy is not routinely recommended due to potential risks to fetal development, and such therapies should only be initiated under strict medical supervision. The use of chelating agents like deferoxamine or deferasirox is more commonly indicated post-partum in women with persistent iron overload.³⁴

6. Multidisciplinary Approach: The management of anemia and iron regulation during pregnancy requires a collaborative approach involving obstetricians, hematologists, nutritionists, and primary care providers. Regular monitoring, individualized care plans, and patient education on the importance of iron supplementation, dietary adjustments, and adherence to prescribed treatments are essential for optimizing maternal and fetal health. The healthcare team must also be attentive to the underlying causes of anemia, whether related to iron deficiency, chronic disease, or iron overload, and tailor treatments accordingly. Early detection and intervention can prevent severe complications such as preterm birth, low birth weight, and cognitive deficits in the child, thus improving overall pregnancy outcomes.^35-36

Conclusion

The regulation of iron during pregnancy is critical for the health of both the mother and the developing fetus. Anemia, particularly iron deficiency anemia, remains a prevalent and significant concern in pregnancy, impacting maternal well-being and leading to adverse pregnancy outcomes such as preterm birth, low birth weight, and impaired cognitive development in children. Effective management of iron levels involves a combination of supplementation, dietary modifications, and addressing underlying causes, such as infections or inflammatory conditions, that may impair iron metabolism. Additionally, careful monitoring of iron status is essential to avoid both iron deficiency and iron overload, which can have serious health implications.

The pathophysiology of iron transport, absorption, and regulation is complex and multifactorial. Iron supplementation, particularly oral or intravenous iron, remains the cornerstone of treatment for iron deficiency, but personalized care is needed to cater to individual patient needs. Special attention should be paid to populations at risk of non-iron deficiency anemia, such as those with chronic diseases or genetic predispositions, ensuring that they receive appropriate treatment to optimize pregnancy outcomes.

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.

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