|Year : 2018 | Volume
| Issue : 1 | Page : 7-11
Maternal anemia with pregnancy and its adverse effects
Medhat E Helmy1, Nabih I Elkhouly1, Rania A Ghalab2
1 Department of Obstetrics and Gynecology, Faculty of Medicine, Menoufia University, Menoufia, Egypt
2 Elbehera Health Sector, Elbehera, Egypt
|Date of Submission||17-Feb-2015|
|Date of Acceptance||01-Apr-2015|
|Date of Web Publication||14-Jun-2018|
Rania A Ghalab
Elbehera Health Sector, Damnhour, Elbehera
Source of Support: None, Conflict of Interest: None
This article reviews the different types of anemia with pregnancy and its adverse outcome for mother and fetus.
Data sources: Data were obtained from Medline databases (PubMed, Medscape,) and literatures from 2008 until 2014. Study selection: Studies that enabled the investigation of the advancement of early diagnosis and management of different types of anemia were selected. Data extraction: In this review, data from published studies were manually extracted and summarized. Data synthesis: In this review, the data revealed that different types of anemia affect the mother, causing headache, fatigue, weakness, and depression. Outcomes of pregnancy included intrauterine growth restriction, low Apgar scores with a high risk of birth asphyxia, and low birth weight.
Anemia during pregnancy and its management remains an important issue in perinatal medication. Correct diagnosis and treatment lead to effective management of fetal and maternal risks and improved perinatal outcome.
Keywords: anemia, birth asphyxia, low birth weight, pregnancy
|How to cite this article:|
Helmy ME, Elkhouly NI, Ghalab RA. Maternal anemia with pregnancy and its adverse effects. Menoufia Med J 2018;31:7-11
| Introduction|| |
In developing countries, pregnancy outcomes show variation based on the type of anemia. The primary cause of anemia during pregnancy is likely to be due to plasma volume expansion, and this type of anemia is not associated with negative birth outcomes. Maternal hemoglobin values during pregnancy are associated with low birth weight and preterm birth in a U-shaped relationship, with high rates of low birth weight at low and high concentrations of maternal hemoglobin .
The prevalence of anemia during pregnancy varies considerably because of differences in, for example, socioeconomic conditions, lifestyles, and health-seeking behaviors across different cultures .
Iron deficiency anemia is one of the most prevalent nutritional deficiencies according to the WHO affecting four to five billion people .
The major concern about the adverse effects of anemia on pregnant women is the belief that this population is at a greater risk of perinatal mortality and morbidity.
| Materials and Methods|| |
The study was approved by the ethical committee of the Faculty of Medicine Menoufia University. We reviewed papers on the effect of anemia on mother and its outcomes from Medline databases (PubMed, Medscape, Science Direct) and also materials available in the internet. We used the terms iron deficiency, vitamin B12, aplastic anemia, hemoglobinopathies, and the effect on the outcome of pregnancy to search the databases.
Studies that enabled the investigation of advancement of early diagnosis and management of different types of anemia were selected.
In this review, the data revealed that different types of anemia affect the mother, causing headache, fatigue, weakness, and depression. Outcomes of pregnancy included intrauterine growth restriction (IUGR), low Apgar scores with a high risk of birth asphyxia, and low birth weight.
| Results|| |
Iron deficiency in pregnancy
Iron deficiency anemia is one of the most prevalent nutritional deficiencies according to the WHO affecting four to five billion people. The prevalence rate in Egypt was reported to be around 45%, with a prevalence rate of 37% in the urban region and 63% in the rural region.
Diagnosis was made in two ways: first, by evaluating the clinical profile of the patients (weakness, headache, irritability, and varying degrees of fatigue and exercise intolerance), incidence of bleeding, and a positive family history of blood diseases; and second, by assessing the complete blood picture [Hb <11, low levels of serum ferritin is, increased levels of transferrin (Tf), and total iron binding capacity].
IDA leads to reduced work capacity, intellectual capacity, and productivity, and increased susceptibility to infection. It also results in increased maternal mortality, especially in nonindustrialized countries .
Effect of anemia on maternal mortality and morbidity
Each year more than 500 000 women die from pregnancy-related causes, 99% of these being in developing countries. The incidence of maternal mortality resulting from anemia is 34/100 000 live births.
Anemia is probably a chronic rather than an acute condition in many cases. There is a resulting compensatory shift of the oxygen dissociation curve to the right. Thus, women with very low hemoglobin concentrations may be seen during the antenatal period without the expected overt symptoms of cardiac failure. They will, however, easily become tired with any form of physical activity and may decompensate (e.g. as a result of labor). Should any adverse event such as bleeding occur, their risk for death is high .
Maternal anemia and infant health
Maternal IDA is associated with adverse health outcomes, including low infant birth weight, inferior health of the newborn, and maternal mortality. In one study, over 20% of maternal mortalities were attributed to anemia. An analysis of several studies showed that there was a higher incidence of iron deficiency among infants born to mothers with IDA during pregnancy compared with infants born to mothers with adequate iron status. Iron deficiency at birth has been associated with developmental delays in children.
Pregnant women should be advised to have a realistic, easily digestible, and affordable balanced diet rich in iron and protein, along with an enhancer for iron absorption, such as a vitamin C-rich food (e.g. orange juice).
Pregnant women should begin taking low-dose (30 mg/day) oral iron at the first prenatal visit as primary prevention of iron deficiency .
Steps for controlling iron-deficiency anemia during pregnancy
- Identification of the underlying cause and its appropriate treatment.
- Dietary advice: Pregnant women should be advised to have a realistic, easily digestible, and affordable balanced diet rich in iron and protein, along with an enhancer such as a vitamin C-rich food source (e.g. orange juice).
- Response to therapy with parenteral iron is similar to that with oral iron. Iron sucrose has excellent efficacy, minimum side-effects, and leads to rapid rise in hemoglobin concentration .
Vitamin B12 deficiency
During pregnancy, there is a gradual decline in serum vitamin B12 levels; however, this does not represent body stores or deficiency and may be independent of dietary intake due to increased metabolic needs. The FAO/WHO recommends a 40% increase in dietary vitamin B12 intake. During pregnancy, deficiency of vitamin B12 is rare. However, megaloblastic anemia due to vitamin B12 deficiency was reported in pregnant women in Zimbabwe and India .
During pregnancy, vitamin B12 deficiency presents with the symptoms and signs of anemia, as well as that of spinal and peripheral nerve involvement. These include mental slowness, memory defects, hallucinations, and numbness or tingling in the extremities.
Adverse effects on pregnancy
Low levels of vitamin B12 increase the risk of birth defects such as neural tube defects.
Prevention and treatment
A diet rich in vitamin B12 is essentially the best prevention. In case of proven deficiency, 1 mg intramuscularly once per week is recommended.
Folate deficiency results in a type of anemia in which the low levels of folic acid result in macrocytosis and the development of megaloblastic bone marrow .
Clinical features of folate deficiency include symptoms of anemia, hyperpigmentation, and a low-grade fever, which begins to fall within 24–48 h of vitamin therapy and returns to normal within a few days.
Adverse effects on pregnancy
Possible pregnancy complications secondary to maternal folate status may include spontaneous abortion, abruptio placentae, congenital malformations (e.g. neural tube defect), and severe language development delay in the offspring.
Prevention and treatment
A prophylactic daily dose of 400 μg is recommended for all women, during the preconception period and throughout the pregnancy. Food fortification with folic acid is possible.
During pregnancy, folate deficiency is treated with folic acid, usually 5 mg daily orally for 4 months.
Hemoglobinopathies and pregnancy
Thalassemia is a group of genetic conditions leading to impaired production of the globin chains and resulting in red cells with inadequate hemoglobin content. Fetal hemoglobin consists of 2a and 2r chain and so the fetus cannot be affected by β-thalassemia .
The α-globin chain synthesis is determined by two genetic loci of each chromosome 16, thus four alleles in total. α-Thalassemia commonly results from deletion of the genes or, less commonly, mutation. The pattern of abnormalities is ethnically specific .
Two genetic loci for b-globin chain synthesis exist, one on each chromosome. The disease can be classified clinically into minor (carrier), intermedia, and major subtypes on the basis of the degree of reduced b-globin chain synthesis .
Maternal health and obstetric outcome
Women with homozygous β-thalassemia are as likely as their healthy peers to be in a relationship, sexually active, and intend to have children. Because the understanding of genetics and reproduction is suboptimal, a higher rate of unplanned pregnancies tend to occur. Most of the available studies on the effect of thalassemia syndromes on pregnancy outcome is confined to β-thalassemia major and intermedia, whereas studies are few on pregnancy in women with the thalassemia traits. Despite increasing recognition of women with hemoglobin E syndromes, information on pregnancy outcome in affected women is minimal, except for the suggestion of high risk of perinatal loss and IUGR .
Treatment for thalassemia
Blood transfusions, iron chelation therapy, and bone marrow transplants are among the treatment methods for thalassemia. Regular transfusions can help keep hemoglobin and red blood cell numbers at normal levels. Iron chelation therapy removes excess iron from the blood and thus prevents organ damage .
Sickle cell anemia with pregnancy
Sickle hemoglobinopathies are more common among individuals whose ancestors are from sub-Saharan Africa, India, Saudi Arabia, and Mediterranean countries. Pregnancy in women with sickle cell disease (SCD) has become more common as a direct result of improved survival due to the advances in medical care and generalized interventions that begin at birth. These interventions include early detection with newborn screening, institution of antibiotic prophylaxis with penicillin, immunization against encapsulated bacteria, and most recently the National Institutes of Health (NIH) consensus recommendation of administering hydroxyurea for its proven role in disease modification. As survival improves, more women affected with SCD reach childbearing age and subsequently face the challenges associated with their fertility and desire for reproduction .
Pregnancy-associated complications in sickle cell disease
Maternal complications due to SCD include pulmonary embolism, acute chest syndrome, pneumonia, and severe pain crises. Prophylaxis of these complications is paramount because they may precipitate delivery. Cerebral vein thrombosis, stroke, venous thromboembolism, pulmonary hypertension, infection, postpartum hemorrhage, cardiomyopathy, and increased maternal mortality are additional maternal risks. Maternal risks include pre-eclampsia, eclampsia, abruptio placentae (from placental necrosis following vascular thrombosis), preterm labor, and premature or preterm premature rupture of membranes The women with SCD also had fewer live born infants and a greater proportion of prematurity, lower mean gestational age at delivery, and lower birth weights .
Pregnancy management in sickle cell disorders
For all women with SCD who are pregnant or contemplating pregnancy, a multidisciplinary team approach is essential, drawing on the expertise of obstetricians, nutritionists, primary care physicians, and hematologists. Once a diagnosis of SCD is confirmed and characterized, ideally a preconception consultation should occur .
Aplastic anemia is caused by failure of bone marrow to carry erythropoiesis. It is diagnosed by means of complete blood picture showing pancytopenia and bone marrow biopsy showing an empty bone marrow .
Aplastic anemia occurs due to an abnormality in the bone marrow cells called the stem cells. Stem cells are the basic 'mother cells' that develop into the three types of blood cells. In aplastic anemia, something either destroys the stem cells or drastically changes the environment of the bone marrow such that the stem cells are unable to develop properly.
The disease affects one of every 25 000–40 000 of those who are treated with the medication chloramphenicol (now rarely used in the USA), but it is much rarer in people treated with other drugs.
Treatment of aplastic anemia should include a combination of withdrawal of potentially offending agents supportive care (e.g. transfusion, antibiotics) and some form of definitive therapy (e.g. hematopoietic cell transplantation, immunosuppressive regimens) for patients with severe aplastic anemia or very severe aplastic anemia. Blood and platelet transfusions should be used selectively in patients who are candidates for hematopoietic cell transplantation to avoid sensitization. At present, the combination of antithymocyte globulin and appears to be most effective cyclosporine immunosuppressive regimen .
| Discussion|| |
Pregnant women with early diagnosis of anemia but without iron treatment had a significantly shorter gestational age at delivery and somewhat higher rate of preterm births. However, this higher rate of preterm birth was not found in anemic pregnant women with iron supplementation during the first trimester of pregnancy. The incidence of pregnancy complications was higher in anemic pregnant women. This study uncovered an increased risk of complications among pregnant Saudi women with SCD, as well as an increased risk for mortality and morbidity among infants born to anemic mothers in this group. Complications of pregnancy examined in the present study included SCC, anemia, infections, toxemia, IUGR, preterm labor, and repeated hospital admissions, all of which were significantly higher in the SCD group than in the control group ,,,,,. Nonetheless, the present result suggests that the pregnancy-related complications of SCD encountered in Saudi Arabia are not as serious as those reported in Nigeria and the USA. This difference might reflect a possible improvement in the management of SCD in Saudi Arabia ,,,,.
| Conclusion|| |
Iron deficiency is the most common deficiency state in the world, affecting more than two billion people globally. Although it is particularly prevalent in less-developed countries, it remains a significant problem in the developed world, even where other forms of malnutrition have already been almost eliminated. Effective management is needed to prevent adverse maternal and pregnancy outcomes, including the need for red cell transfusion.
For pregnant and nonpregnant patients with a-thalassemia or β-thalassemia, hemolytic anemia caused by ineffective erythropoiesis is the major complication. Imbalanced nonstoichiometric production of α-globin and b-globin chains leads to disruptions in red cell physiology, causing intramedullary destruction of erythroid precursors and hemolysis of circulating red blood cells. Extramedullary hematopoiesis occurs when anemia is severe. In an attempt to maintain erythropoietic needs, iron use is increased through reduction in hepcidin levels, leading to hemochromatosis independent of transfusion therapy. Splenectomy can be helpful in improving anemia but confers an increased risk of thrombosis, particularly in patients with HbE thalassemia.
Weekly supplementation of iron folate for all menstruating women, including school girls, is recommended. Globally, more than 460 million nonpregnant women (15–49 years) are estimated to be anemic and two-third of them are reported to be from Asia. WIFS programs for WRA have been effective in reducing the prevalence of anemia in certain districts in Vietnam, the Philippines, and Cambodia. Selecting a fixed day in the week as 'WIFS Day' or 'Iron Day' could be effective in addressing the problem of forgetfulness and improving compliance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
McLean E, Cogswell M, Egli I, Wojdyla D, de Benoist B. Worldwide prevalence of anaemia, WHO Vitamin and Mineral Nutrition Information System, 1993-2005. Public Health Nutr 2009;12
(4):444-54. doi: 10.1017/S1368980008002401. Epub 2008 May 23.
Breymann C, Honegger C, Holzgreve W. Diagnosis and treatment of iron deficiency anemia during pregnancy and postpartum. Arch Gynecol Obstet 2011; 282
Killip S, Bennett JM, Chambers MD. Iron deficiency anemia. Am Fam Physician 2007; 75
Yajnik CS, Deshpande SS, Jackson AA, Refsum H, Rao S, Fisher DJ, et al.
and folate concentrations during pregnancy and insulin resistance in the offspring: the Pune Maternal Nutrition Study. Diabetologia 2008; 51
Cohen AR, Galanello R, Pennell DJ, Cunningham MJ, Vichinsky E. Hematology Am Soc Hematol Educ Program. 2004:14-34.
Lucke T, Pfister S, Durken M. Neurodevelopmental outcome and haematological course of a long-time survivor with homozygous alpha-thalassaemia: case report and review of the literature. Acta Paediatr 2005; 94
Hasley C, Roberts I. The role of hydroxyurea in sickle cell disease. Br J Haematol 2003; 120
Ngo C, Kayem G, Habibi A, Benachi A, Goffinet F, Galactéros F, Haddad B. Pregnancy in sickle cell disease: maternal and fetal outcomes in a population receiving prophylactic partial exchange transfusions. Eur J Obstet Gynecol Reprod Biol 2010; 152
Deka D, Banerjee N, Roy KK, Choudhary VP, Kashyap R, Takkar D. Aplastic anaemia during pregnancy: variable clinical course and outcome. Eur J Obstet Gynecol Reprod Biol 2001; 94
Marijke A.K.A. Braeken, Alexander Jones, Renée A. Otte, Ivan Nyklíček andBea R.H. Van den Bergh, Potential benefits of mindfulness during pregnancy on maternal autonomic nervous system function and infant development, Psychophysiology 2016;54
Al RA, Unlubilgin E, Kandemir O, Yalvac S, Cakir L, Haberal A. Intravenous versus oral iron for treatment of anemia in pregnancy: a randomized trial. Obstet Gynecol 2005; 106
Khalafallah A, Dennis A, Bates J, Bates G, Robertson IK, Smith L, et al
. A prospective randomized, controlled trial of intravenous versus oral iron for moderate iron deficiency anaemia of pregnancy. J Intern Med 2010; 268
Rappaport VJ, Velazquez M, Williams K. Hemoglobinopathies in pregnancy. Obstet Gynecol Clin North Am 2004; 31
Centers for Disease Control (CDC). CDC criteria for anemia in children and childbearing-aged women. Morb Mortal Wkly Rep 1989; 38
Christian P, Murray-Kolb LE, Khatry SK, Katz J, Schaefer BA, Cole PM, et al
. Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal. JAMA 2010; 304
Bonds DR. Three decades of innovation in the management of sickle cell disease: the road to understanding the sickle cell disease clinical phenotype. Blood Rev 2005; 19
Kettaneh A, Eclache V, Fain O, Sontag C, Uzan M, Carbillon L, et al
. Pica and food craving in patients with iron-deficiency anemia: a case - control study in France. Am J Med 2005; 118
Kochhar PK, Kaundal A, Ghosh P. Intravenous iron sucrose versus oral iron in treatment of iron deficiency anemia in pregnancy: a randomized clinical trial. J Obstet Gynaecol Res 2013; 39
Rohilla M, Raveenran A, Dhaliwal KL. Severe anemia in pregnancy: a tertiary hospital experience from northern India. J Obstet Gynaecol 2010; 30
Antony AC. Megaloblastic anemias. Chapter 167. In: Goldman L, Schafer AI, editors Goldman's Cecil Medicine
. 24th ed. Philadelphia, PA: Saunders Elsevier; 2011: 1066-75.