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Anemia in Pregnancy with Normal Iron Studies

4/1/2010 - Michael T. Mennuti, MD

Editor: Christopher M. Zahn, MD

Pregnancy results in a physiologic anemia due to the 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 gastric-bypass procedures or Crohn disease. Vitamin-associated anemias may be confirmed by serum measurement. 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 the β-globin gene resulting in deficient or absent β-chain production. Diagnosis of sickle cell disorders requires hemoglobin electrophoresis. The number and degree of genes affected determines the degree of anemia, which may range from mild and essentially asymptomatic, to severe. Mean corpuscular volume (MCV) will be low (<80 fL) in patients with thalassemia trait. For patients with suspected thalassemia, hemoglobin electrophoresis is indicated. 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. More severe thalassemias in pregnancy (particularly β-thalassemia major) is uncommon. Hemoglobin H disease may have favorable outcomes. For women with β-thalassemia major, pregnancy is only recommended in those with normal cardiac function; fetal growth may be at risk.

Both sickle cell disorders and thalassemias may carry risk of an affected fetus depending on the presence of mutations in the parents and may benefit from genetic counseling and testing, with possible fetal testing (CVS or amniocentesis) depending on the results of parental testing. In vitro fertilization and preimplantation genetic diagnosis may be an alternative.

Further Readings:

ACOG Practice Bulletin Number 95: Anemia in Pregnancy. (Reaffirmed 2015)

ACOG Practice Bulletin Number 78: Hemoglobinopathies in Pregnancy. (Reaffirmed 2015)

Hematogical Disorders. In: Williams Obstetrics, 24th Edition. Eds. F. Gary Cunningham, et al. New York, NY: McGraw-Hill, 2014, pp 1101-7.

Original Approval April 2010. Last Revised September 2016.


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