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 International Journal of Medical Sciences and Pharma Research 

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Maternal Anemia in the Context of Infectious Diseases during Pregnancy: A Review

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

Maternal anemia is one of the most common medical conditions during pregnancy, affecting millions of women worldwide. Defined as a reduction in the hemoglobin concentration of the blood, maternal anemia can lead to a range of complications that affect both maternal and fetal health. According to the World Health Organization (WHO), approximately 40% of pregnant women are affected by anemia, with iron deficiency being the most prevalent cause. However, maternal anemia can result from a variety of factors, including infectious diseases, nutritional deficiencies, and chronic medical conditions. Infectious diseases such as malaria and HIV are particularly significant contributors to anemia in pregnancy, complicating diagnosis and management.^1-2 Infections during pregnancy pose a unique challenge because they not only affect the mother’s health but can also influence the developing fetus. Malaria, caused by Plasmodium parasites, is a leading cause of maternal anemia in regions where malaria transmission is endemic. The parasite destroys red blood cells and triggers an immune response that leads to further anemia. Pregnant women are particularly vulnerable to severe malaria due to changes in their immune systems and the increased physiological demands of pregnancy. The combination of malaria and anemia during pregnancy is associated with higher maternal morbidity and mortality, as well as adverse pregnancy outcomes, including preterm birth, low birth weight, and fetal death.^3-4

Similarly, HIV infection complicates pregnancy by impacting the immune system, leading to chronic inflammation and bone marrow suppression, both of which contribute to anemia. HIV-infected women may also experience opportunistic infections that exacerbate anemia and other pregnancy-related complications. Additionally, iron and other nutritional deficiencies, often present in HIV-infected individuals, further contribute to the development of anemia. The management of anemia in HIV-positive pregnant women requires a multifaceted approach, including the use of antiretroviral therapy (ART) to control viral replication and prevent the worsening of anemia.⁵ The presence of infectious diseases like malaria and HIV makes the diagnosis of maternal anemia more complex. Both malaria and HIV can cause anemia through different mechanisms, including hemolysis, decreased red blood cell production, and nutritional deficiencies. Moreover, co-infection with other pathogens, such as tuberculosis or parasitic infections, can further complicate the clinical picture. Identifying the underlying cause of anemia in pregnant women is crucial for ensuring appropriate treatment and improving pregnancy outcomes. Diagnostic tests, including blood smears, rapid diagnostic tests (RDTs), and HIV testing, are essential for identifying the specific infectious cause of anemia.^6-7 Effective management of maternal anemia in the context of infectious diseases involves treating both the anemia and the underlying infection. In malaria, the primary treatment involves the use of antimalarial medications, with the choice of drug depending on the trimester of pregnancy. Artemisinin-based combination therapies (ACTs) are generally recommended for second and third-trimester malaria, while alternative treatments are used in the first trimester. In HIV-infected pregnant women, the management of anemia requires a combination of antiretroviral therapy to control viral load and nutritional support to address deficiencies. Blood transfusions may also be necessary in cases of severe anemia.^8-9This review aims to provide an overview of maternal anemia in the context of infectious diseases during pregnancy, focusing on the causes, mechanisms, clinical implications, and management strategies for anemia associated with malaria and HIV.

Causes and Mechanisms of Maternal Anemia in the Context of Infectious Diseases

Maternal anemia during pregnancy can be caused by a variety of factors, with infectious diseases playing a significant role in its development. Infections such as malaria, HIV, and other parasitic or bacterial infections can contribute to anemia through direct and indirect mechanisms, often exacerbating the condition in pregnant women. Understanding these causes and mechanisms is essential for effective diagnosis, treatment, and management of anemia in the context of infectious diseases.¹⁰ Malaria is one of the leading infectious causes of maternal anemia, particularly in regions where the disease is endemic. The malaria parasite, Plasmodium, infects red blood cells (RBCs), causing their destruction (hemolysis) and leading to a reduction in the overall RBC count. Pregnant women are particularly vulnerable to severe malaria, as pregnancy induces immunological changes that make it harder to clear the parasite from the bloodstream. The increased blood volume during pregnancy also increases the parasitic load, exacerbating the destruction of RBCs. Furthermore, malaria induces an inflammatory response, which results in the release of pro-inflammatory cytokines, leading to a reduced production of red blood cells in the bone marrow. This combination of hemolysis and bone marrow suppression results in anemia, which can be worsened by concurrent nutritional deficiencies, such as iron and folate.^11-12

HIV infection also contributes significantly to maternal anemia during pregnancy, but through different mechanisms than malaria. HIV-infected women often experience anemia due to bone marrow suppression, which is exacerbated by the chronic inflammation and immune dysregulation caused by the virus. HIV can directly affect erythropoiesis, the process by which new red blood cells are produced in the bone marrow, leading to reduced RBC production. Additionally, HIV-associated chronic inflammation increases the production of hepcidin, a hormone that regulates iron homeostasis. Elevated levels of hepcidin limit iron absorption from the gut and sequester iron in storage sites, which contributes to iron-deficiency anemia. In pregnant women with HIV, anemia is often multifactorial, with nutritional deficiencies, opportunistic infections, and ART-related bone marrow suppression compounding the effects of the disease.¹³ Other infectious diseases, such as tuberculosis, helminthic infections, and bacterial infections, can also contribute to anemia during pregnancy. Tuberculosis, for instance, can cause anemia through chronic inflammation and nutrient malabsorption, while helminths such as hookworms can directly lead to blood loss, further exacerbating anemia in pregnancy. Additionally, infections often lead to a reduced appetite and poor nutritional intake, which can worsen pre-existing anemia. Bacterial infections, especially those that lead to sepsis, can trigger an acute inflammatory response that impairs the production of red blood cells and results in anemia of chronic disease (also known as anemia of inflammation).¹⁴ Co-infections further complicate the pathophysiology of anemia in pregnancy. Pregnant women living in malaria-endemic areas are often co-infected with other parasites or have underlying HIV infections. The combined effects of these infections can result in more severe anemia due to additive mechanisms of hemolysis, suppressed bone marrow function, and impaired iron metabolism. Co-infection with multiple pathogens often leads to a synergistic worsening of maternal anemia, increasing the risk of severe maternal and fetal outcomes, such as preterm labor, low birth weight, and maternal mortality.¹⁵

Clinical Implications of Maternal Anemia in the Context of Infectious Diseases

Maternal anemia in the context of infectious diseases during pregnancy presents significant clinical challenges, both for the mother and the developing fetus. The coexistence of anemia and infections such as malaria, HIV, and other parasitic or bacterial infections can lead to severe complications that affect pregnancy outcomes, increase maternal morbidity and mortality, and pose risks to fetal development.¹⁶One of the most critical clinical implications of maternal anemia is its contribution to increased maternal morbidity and mortality. Severe anemia, characterized by hemoglobin levels that are dangerously low, can lead to profound fatigue, cardiovascular strain, and diminished oxygen supply to vital organs. In pregnant women, anemia can exacerbate existing health issues, such as preeclampsia or hypertension, and lead to an increased risk of complications during labor and delivery, including postpartum hemorrhage. The presence of infectious diseases, particularly malaria and HIV, further complicates these risks, as they may alter the immune response, reduce the body’s ability to recover from blood loss, and hinder the effectiveness of treatments such as transfusions. In areas with high rates of malaria and HIV, the combination of these factors can be a significant contributor to maternal mortality.¹⁷ For the fetus, maternal anemia and the presence of infections during pregnancy increase the likelihood of adverse pregnancy outcomes, such as preterm birth, low birth weight, and intrauterine growth restriction (IUGR). Anemia impairs the ability of the blood to carry oxygen, which is crucial for fetal development. The reduction in oxygen supply can lead to fetal hypoxia, which in turn can hinder proper organ development and growth. Infections like malaria and HIV further exacerbate these risks by directly affecting fetal health. Malaria, for example, can cause placental malaria, which disrupts blood flow to the placenta and reduces nutrient and oxygen delivery to the fetus. HIV, on the other hand, increases the risk of vertical transmission, potentially leading to congenital HIV infection. Furthermore, the presence of infections can complicate maternal care, requiring additional interventions and increasing the risk of complications such as fetal distress during labor.¹⁸

Anemia-related fatigue and weakness in pregnant women can also significantly impact their ability to engage in daily activities and care for themselves and their families. Chronic fatigue from anemia can hinder a woman’s physical and emotional well-being, potentially affecting her mental health and quality of life. This is especially concerning in the context of infectious diseases, where the physical toll of the infection, combined with anemia, can lead to poor maternal nutrition, limited mobility, and increased vulnerability to other illnesses. Furthermore, the psychosocial burden of living with anemia and infections during pregnancy, particularly in resource-limited settings, can contribute to maternal stress, which in turn affects both maternal and fetal health.¹⁹ Increased risk of infection transmission is another significant clinical implication of maternal anemia in the context of infectious diseases. Pregnant women with HIV are at an increased risk of opportunistic infections due to the immune suppression caused by the virus. The presence of anemia, combined with chronic inflammation, can further compromise the immune system, leaving the mother more vulnerable to infections that can affect her health and that of the fetus. Additionally, maternal anemia in the context of malaria increases the risk of parasitic load and transmission to the fetus, leading to congenital malaria or other malaria-related complications. In these cases, the maternal immune system’s ability to mount an effective response to the infection is impaired, leading to prolonged illness and a greater likelihood of complications.¹⁹ Lastly, healthcare resource burden is an important clinical implication, particularly in low-resource settings where maternal anemia and infectious diseases are prevalent. The combination of anemia and infections requires a comprehensive approach to care, including early diagnosis, proper treatment of the underlying infections, and management of anemia, which often involves blood transfusions and nutritional support. These interventions demand significant healthcare resources, both in terms of medication, monitoring, and skilled personnel. In areas where resources are limited, the burden on healthcare systems is substantial, and the inability to provide timely and appropriate care can lead to poor maternal and fetal outcomes.²⁰

Diagnostic Approaches

The diagnosis of maternal anemia in the context of infectious diseases requires a thorough and multi-faceted approach, as the causes of anemia can vary widely and may be influenced by the presence of infections such as malaria, HIV, and other parasitic or bacterial diseases. Accurate diagnosis is essential for determining the appropriate treatment strategies, as anemia due to infectious causes may require distinct management compared to anemia resulting from nutritional deficiencies or other non-infectious conditions. The diagnostic approach includes a combination of clinical assessment, laboratory tests, and infection-specific diagnostic tools.

Clinical Assessment

The initial step in diagnosing anemia in pregnant women involves a detailed clinical evaluation. A thorough medical history is essential, with particular focus on the woman’s exposure to infectious diseases, such as malaria and HIV, especially in endemic regions. It is also important to assess the patient’s nutritional status, obstetric history, and any signs or symptoms suggestive of infections, including fever, chills, weight loss, fatigue, or gastrointestinal symptoms. The physical examination may reveal pallor, tachycardia, low blood pressure, or signs of underlying infections such as malaria or HIV. Malaria, for example, may present with fever, anemia, hepatomegaly, and splenomegaly, while HIV-infected women may present with signs of opportunistic infections or chronic illness.^21-22

Laboratory Tests for Anemia

The cornerstone of diagnosing maternal anemia is measuring hemoglobin levels through a complete blood count (CBC). Anemia is typically diagnosed when hemoglobin levels fall below 11 g/dL, with varying degrees of severity. In addition to hemoglobin concentration, the CBC also provides important information such as hematocrit levels, red blood cell count, mean corpuscular volume (MCV), and red cell distribution width (RDW), which help classify the anemia (e.g., microcytic, normocytic, or macrocytic). In cases of infectious-related anemia, further examination of red blood cell morphology can reveal abnormalities such as hypochromia (pale cells) or anisocytosis (variability in cell size), which may point to specific causes of anemia.²³

Infection-Specific Diagnostic Tools

In the context of infectious diseases, specific diagnostic tests are required to identify the underlying cause of anemia. For malaria, blood smears or rapid diagnostic tests (RDTs) are commonly used. A blood smear is examined under a microscope to detect the presence of Plasmodium parasites inside red blood cells, which can confirm malaria infection. RDTs, which detect specific antigens associated with the Plasmodium parasite, provide a faster diagnosis, especially in settings where microscopy may not be available. In areas with high malaria prevalence, a positive malaria test can help determine whether malaria-induced hemolysis is contributing to the anemia.²⁴ For HIV, the diagnosis is made through serological testing using enzyme-linked immunosorbent assays (ELISA) or rapid HIV tests, which detect antibodies or antigens in the blood. Confirmatory testing with a western blot or PCR may be needed to definitively diagnose HIV infection. In addition to HIV testing, it is essential to monitor HIV viral load and CD4+ T-cell counts, as these parameters help assess the stage of infection and immune function, which can contribute to the anemia through bone marrow suppression and chronic inflammation.²⁵ For other infectious causes, such as tuberculosis or helminthic infections, specific tests are also necessary. Tuberculosis can be diagnosed using sputum smear microscopy, chest X-rays, or molecular techniques like PCR for detecting Mycobacterium tuberculosis. Helminth infections, such as hookworm or schistosomiasis, can be identified by stool or urine examination for eggs, or serological testing to detect antibodies against specific parasites.

Additional Tests for Anemia Etiology

In cases where anemia is suspected to be multifactorial, additional laboratory investigations may be required to identify coexisting conditions. These tests might include serum ferritin and serum iron levels to assess iron status, vitamin B12 and folate levels to detect deficiencies, and reticulocyte counts to evaluate bone marrow response to anemia. In pregnant women with HIV, testing for opportunistic infections, such as cytomegalovirus or toxoplasmosis, may also be useful, as these infections can further exacerbate anemia.²⁶

Imaging and Other Diagnostic Modalities

In cases of suspected severe or chronic infections, imaging studies such as ultrasound may be used to assess organ involvement (e.g., hepatomegaly or splenomegaly in malaria). This can help evaluate the severity of infection and its impact on the development of anemia. In severe cases, a bone marrow biopsy may be considered to directly assess the impact of infections such as HIV on erythropoiesis, though this is less commonly used in routine practice.²⁷

Management of Maternal Anemia in the Context of Infectious Diseases

The management of maternal anemia in the context of infectious diseases involves addressing both the anemia and the underlying infection. Treatment strategies must be tailored to the specific infectious disease causing the anemia, while also considering the unique needs of pregnant women. This dual approach is essential to reduce maternal and fetal morbidity and mortality, as both anemia and infections can have severe consequences during pregnancy. Management strategies should include medical interventions for infection control, anemia correction, and supportive care, with careful monitoring of the pregnancy.²⁸

1. Treatment of Underlying Infectious Diseases

The first step in managing maternal anemia related to infectious diseases is to treat the underlying infection. In the case of malaria, the use of antimalarial drugs is crucial. Artemisinin-based combination therapies (ACTs) are the most effective treatments for malaria during pregnancy. However, dosing and specific drug choices must be carefully considered to avoid teratogenic effects or adverse outcomes, especially during the first trimester. In regions where malaria is endemic, pregnant women should receive preventive treatment, such as intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp), to reduce the risk of infection and its complications, including anemia.²⁹ For HIV-infected pregnant women, management involves both antiretroviral therapy (ART) to suppress viral replication and prevent mother-to-child transmission, and treatment of any opportunistic infections. ART is critical to improving immune function and reducing the inflammatory effects that contribute to anemia. Co-infections such as tuberculosis or parasitic infections may require specific treatment regimens, with antibiotics or antiparasitic drugs, respectively. When managing HIV-related anemia, healthcare providers also focus on maintaining adequate nutrition and addressing any bone marrow suppression or iron metabolism disruptions caused by chronic inflammation.³⁰ Other infections that contribute to maternal anemia, such as helminthic infections, require the use of anthelmintic medications, typically safe during pregnancy, to eliminate the parasites and prevent blood loss and iron deficiency. Tuberculosis requires a combination of anti-TB drugs, while other infections may necessitate specific antibiotic or antiviral treatments based on the identified pathogen.

2. Correction of Anemia

Once the underlying infection is treated or controlled, the next step in managing anemia is to correct the anemia itself. The treatment approach depends on the severity and type of anemia. Iron-deficiency anemia is the most common form of anemia during pregnancy, and supplementation with oral or intravenous iron is typically the first-line treatment. Oral iron supplementation is commonly used, though it may be associated with gastrointestinal side effects such as nausea or constipation. In cases of severe anemia or when oral iron supplementation is not tolerated or ineffective, intravenous iron or blood transfusions may be necessary.³¹ However, in the context of infectious diseases, treatment of anemia requires additional consideration. For example, in malaria, iron supplementation should be approached cautiously, as iron may facilitate the growth of Plasmodium parasites. In these cases, iron supplementation is typically deferred until the acute malaria infection has been treated and the patient’s condition has stabilized. Similarly, in HIV-infected pregnant women, while iron supplementation is important to address deficiency, careful monitoring is needed to ensure that supplementation does not lead to complications, such as oxidative stress or exacerbating anemia caused by ART-induced bone marrow suppression.³² In cases of anemia of chronic disease, which can occur due to the chronic inflammation associated with infections like HIV or tuberculosis, the focus shifts to managing the underlying infection and inflammation. In this context, erythropoiesis-stimulating agents (ESAs) may be used in select cases, particularly for women with severe anemia that does not improve with iron supplementation alone. These agents stimulate red blood cell production in the bone marrow and can be particularly beneficial when there is significant bone marrow suppression from chronic infections.

3. Supportive Care

In addition to specific treatments for infection and anemia, supportive care is critical in managing maternal anemia in the context of infectious diseases. This includes nutritional support to ensure adequate intake of essential nutrients, including iron, folate, vitamin B12, and protein. Nutritional counseling should be provided to help pregnant women improve their diet, focusing on iron-rich foods and other micronutrients necessary for erythropoiesis and overall health.³³ Hydration is another critical aspect of supportive care, particularly in cases of severe anemia or infection, as dehydration can exacerbate maternal symptoms and worsen anemia. Close monitoring of vital signs, including blood pressure, heart rate, and oxygen saturation, is important to detect signs of complications such as heart failure or preeclampsia, which can be triggered by anemia.³⁴ Additionally, pregnant women with anemia may require monitoring and early intervention for fetal well-being, as anemia can impact placental blood flow and oxygen delivery to the fetus. Regular ultrasound scans, fetal heart rate monitoring, and assessments for signs of intrauterine growth restriction or fetal distress may be necessary.³⁵

4. Prevention and Early Intervention

Preventive strategies are an essential part of managing maternal anemia, especially in areas with high rates of infectious diseases. Intermittent preventive treatment with antimalarial medications in malaria-endemic regions and routine screening for HIV and other infections during pregnancy are critical to prevent anemia from becoming severe. Prophylactic iron supplementation is also widely recommended to prevent iron deficiency, although, as mentioned, it must be balanced carefully in the presence of infections such as malaria.³⁶ In women who are already infected with diseases such as HIV or malaria, early and regular monitoring for anemia and related complications allows for timely interventions, reducing the risk of severe anemia and improving both maternal and fetal outcomes.

Conclusion

Maternal anemia in the context of infectious diseases presents a complex challenge that requires a comprehensive and individualized approach to treatment. The interplay between infections such as malaria, HIV, and other parasitic or bacterial diseases can exacerbate anemia and complicate pregnancy outcomes. Effective management involves not only treating the underlying infectious disease but also correcting the anemia through appropriate supplementation, transfusions, and supportive care. The importance of early diagnosis and targeted therapy cannot be overstated, as timely intervention significantly improves maternal and fetal health outcomes. Preventive strategies, including regular screening for infections and routine iron supplementation, are critical for reducing the risk of anemia during pregnancy, particularly in regions with a high burden of infectious diseases. Furthermore, supportive care focused on optimizing nutrition, hydration, and monitoring of fetal well-being is essential for managing the multifactorial nature of maternal anemia in this context. By combining infection control with anemia management and preventive measures, healthcare providers can reduce the risk of complications, enhance maternal health, and improve 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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