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Anemia in Pregnancy with Normal Iron Studies

Author: Michael T. Mennuti, MD

Editor: William Po, MD

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The two most common causes of anemia in pregnancy and the puerperium are iron deficiency and acute blood loss. Pregnancy results in a physiologic anemia due to expanded plasma volume. The red cell mass also expands, but to a lesser degree. All pregnant women should be screened for anemia with a complete blood count in the first trimester and again at 24 0/7–28 6/7 weeks of gestation. Patients who meet criteria for anemia based on hematocrit levels less than 33% in the first and third trimesters and less than 32% in the second trimester should be evaluated to determine the cause. If iron deficiency is ruled out, other etiologies should be investigated. 

Classification derived from an iron-supplemented population lists the following levels as anemic: hemoglobin (g/dL) and hematocrit (percentage) levels below 11 g/dL and 33%, respectively, in the first trimester; 10.5 g/dL and 32%, respectively, in the second trimester; and 11 g/dL and 33%, respectively, in the third trimester 

Anemias may be categorized by whether they are inherited or acquired, underlying causative mechanism, or red blood cell morphology

Anemia in the presence of normal iron indices may be microcytic, normocytic, or macrocytic. Microcytic anemia is most commonly related to thalassemias or anemia of chronic disease. Normocytic anemia may also be due to chronic disease as well as bone marrow suppression, chronic renal or endocrine dysfunction, hypothyroidism, and hemolysis, including sickle cell disease. Acute blood loss may result in a normocytic anemia. Chronic blood loss will often lead to iron deficiency. Measurement of serum ferritin levels has the highest sensitivity and specificity for diagnosing iron deficiency in anemic patients. Levels of less than 30 micrograms/L confirm iron deficiency anemia. The CDC recommends screening for iron deficiency anemia in pregnant women and implementing universal iron supplementation to meet the iron requirements of pregnancy except in the presence of certain genetic disorders, such as hemochromatosis

Macrocytic anemia may be megaloblastic or nonmegaloblastic. Causes of megaloblastic anemia include folate and vitamin B12 deficiency and pernicious anemia. Causes of nonmegaloblastic anemia include alcoholism, liver disease, myelodysplasia, aplastic anemia, hypothyroidism, and an increased reticulocyte count. When treating B12 or folate deficiency, it is important to ensure adequate iron supplementation in addition to vitamin supplementation. Macrocytic anemia in pregnancy caused by vitamin B12 (cyanocobalamin) deficiency may be encountered in women who have had a partial or total gastric resection or in women with Crohn disease. Women who have had a total gastrectomy require 1,000 micrograms of vitamin B12, intramuscularly, at monthly intervals.

Thalassemias and sickle cell disease are more common in certain ethnic groups. Sickle cell disease is most common in woman of African origin, α-thalassemia is more common in those of Southeast Asian, African, and West Indian descent, and β-thalassemia is more common in those of Mediterranean, Asian, Middle Eastern, Hispanic, and West Indian descent. Diagnosis of sickle cell disorders or thalassemias requires hemoglobin electrophoresis. The number and degree of affected genes determines the degree of anemia, which may range from mild and essentially asymptomatic, to severe. Mean corpuscular volume (MCV) will be low (<80 fL/ red cell) in patients with thalassemia trait. Beta-thalassemia is associated with elevated Hb F (fetal hemoglobin) and elevated Hemoglobin A2. Alpha-thalassemia trait has a normal electrophoresis and can only be identified with molecular testing.

Sickle cell disease in pregnancy may be associated with significant morbidity and mortality. Increased folate supplementation (4 mg/day) is required due to red cell turnover. Pregnancies affected by α-thalassemia trait or β-thalassemia minor are generally not different from unaffected pregnancies. For the rare woman with β-thalassemia major, pregnancy is only recommended in those with normal cardiac function and fetal growth should be monitored.

Low-dose iron supplementation is recommended starting in the first trimester to decrease the prevalence of maternal anemia at delivery.

Severe anemia with maternal hemoglobin levels less than 6 g/dL has been associated with abnormal fetal oxygenation, resulting in non-reassuring fetal heart rate patterns, reduced amniotic fluid volume, fetal cerebral vasodilatation, and fetal death. Thus, maternal transfusion should be considered for fetal indications in cases of severe anemia.

Based on the available evidence regarding efficacy and side effect profile for use in pregnancy after the first trimester and postpartum, parenteral iron may be considered for those who cannot tolerate or do not respond to oral iron or for those with severe iron deficiency later in pregnanc

Further Readings:

American College of Obstetricians and Gynecologists' Committee on Practice Bulletins—Obstetrics. Anemia in Pregnancy: ACOG Practice Bulletin, Number 233. Obstet Gynecol. 2021 Aug 1;138(2):e55-e64. doi: 10.1097/AOG.0000000000004477. PMID: 34293770.

ACOG Committee on Obstetrics. ACOG Practice Bulletin No. 78: hemoglobinopathies in pregnancy. Obstet Gynecol. 2007 Jan;109(1):229-37. doi: 10.1097/00006250-200701000-00055. PMID: 17197616.


Original Approval April 2010. Revised September 2016. Reaffirmed January 2018. Minor revision July 2019; Minor Revision March 2021; Minor Revision September 2022


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