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Anemia in Pregnancy with Normal Iron Studies

Author: Michael T. Mennuti, MD

Editor: Christopher M. Zahn, MD & Regan Theiler, MD

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Pregnancy results in a physiologic anemia due to expanded plasma volume. The red cell mass also expands, but to a lesser degree. Lack of iron supplementation results in a smaller expansion of the red cell mass and a greater degree of anemia, which may be associated with abnormal iron indices.

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. Macrocytic anemia may be due to folate or Vitamin B12 deficiency, liver disease, or alcohol abuse. Vitamin-linked anemias may be associated with malabsorption due to pernicious anemia, gastric-bypass procedures or Crohn’s disease. Vitamin-deficiency anemias may be confirmed by serum measurement. When treating B12 or folate deficiency, it is important to ensure adequate iron supplementation in addition to vitamin supplementation.

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. Alpha-thalassemia is due to gene deletion on two or more of the four α-globin genes. Beta-thalassemia is due to a mutation in one or both copies or the β-globin gene resulting in deficient (β-thalassemia minor) or absent (β-thalassemia major) β -chain production. 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.

Patients with sickle cell disorders and thalassemias carry risk of an affected fetus and may benefit from genetic counseling and testing, with possible fetal testing (CVS or amniocentesis) depending on the results of parental testing.


Further Readings:

American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: anemia in pregnancy. Obstet Gynecol. 2008 Jul;112(1):201-7. doi: 10.1097/AOG.0b013e3181809c0d.

American College of Obstetricians and Gynecologists, ACOG Committee on Obstetrics;  ACOG Practice Bulletin No. 78: hemoglobinopathies in pregnancy. Obstet Gynecol. 2007 Jan;109(1):229-37.

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


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