Normal pregnancy is characterized by an increase in maternal plasma volume of about 50% and an increase in red cell volume of about 25%. Because of these changes, the mean hemoglobin and hematocrit values are lower than in the nonpregnant state. Anemia in pregnancy is considered when the hemoglobin measurement is below 11 g/dL. By far, the most common causes are iron deficiency and acute blood loss anemia, the latter usually occurring in the peripartum period. Symptoms such as fatigue and dyspnea that would otherwise suggest the presence of anemia in nonpregnant women are common in pregnant women; therefore, periodic measurement of hematocrits in pregnancy is essential so that anemia can be identified and treated. In addition to its impact on maternal health, untoward pregnancy outcomes such as low birthweight and preterm delivery have been associated with second- and third-trimester anemia.
A. Iron Deficiency Anemia
The increased requirement for iron over the course of pregnancy is appreciable in order to support fetal growth and expansion of maternal blood volume. Dietary intake of iron is generally insufficient to meet this demand, and it is recommended that all pregnant women receive about 30 mg of elemental iron per day in the second and third trimesters. Oral iron therapy is commonly associated with gastrointestinal side effects, such as nausea and constipation, and these symptoms often contribute to noncompliance. If supplementation is inadequate, however, anemia often becomes evident by the third trimester of pregnancy. Because iron deficiency is by far the most common cause of anemia in pregnancy, treatment is usually empiric and consists of 60–100 mg of elemental iron per day and a diet containing iron-rich foods. Iron studies can confirm the diagnosis if necessary (see Chapter 13), and further evaluation should be considered in patients who do not respond to oral iron. Intermittent iron supplementation (eg, every other day) has been associated with fewer side effects and may be reasonable for women who cannot tolerate daily therapy.
B. Folic Acid Deficiency Anemia
Megaloblastic anemia in pregnancy is almost always caused by folic acid deficiency, since vitamin B12 deficiency is extremely uncommon in the childbearing years. Folate deficiency is usually caused by inadequate dietary intake of fresh leafy vegetables, legumes, and animal proteins. The daily requirement of folic acid increases in pregnancy, and supplementation with 0.4 mg of folate is recommended. Importantly, this dose taken during the periconceptional period has also been shown to reduce the risk of neural tube defects in the offspring. Multiple gestation, infections, malabsorption, and use of anticonvulsant drugs such as phenytoin can precipitate folic acid deficiency, and additional folate supplementation should be considered in these settings. Lactating women continue to have an increased demand for folate, and the diagnosis is sometimes made in the puerperium.
The diagnosis is made by finding macrocytic red cells and hypersegmented neutrophils on a blood smear (see Chapter 13). However, blood smears in pregnancy may be difficult to interpret, since they frequently show iron deficiency changes as well. With established folate deficiency, a supplemental dose of 1 mg/day and a diet with increased folic acid is generally sufficient to correct the anemia.
Women with sickle cell anemia are subject to serious complications in pregnancy. The anemia becomes more severe, and acute pain crises often occur more frequently. When compared with women who do not have hemoglobinopathies, women with hemoglobin SS are at increased risk for infections (especially pulmonary and urinary tract), thromboembolic events, pregnancy-related hypertension, transfusion, cesarean delivery, preterm birth, and fetal growth restriction. There also continues to be an increased rate of maternal mortality, despite an increased recognition of the high-risk nature of these pregnancies. Intensive medical treatment may improve the outcomes for both mother and fetus. Prophylactically transfusing packed red cells to lower the level of hemoglobin S and elevate the level of hemoglobin A is a controversial practice without clear benefit. Most women with sickle cell disease will not require iron supplementation, but folate requirements can be appreciable due to red cell turnover from hemolysis.
Contraceptive counseling postpartum is important, although the safest and most effective method in women with sickle cell disease is unclear. Progestin-only compounds may be ideal because progesterone has long been recognized to help prevent pain crises in some women. Intrauterine devices carry a risk of infection and combination oral contraceptives are a concern because of the thrombogenic potential; these forms of contraception have not been adequately studied in these patients.
Women with hemoglobin SC disease are also at increased risk for complications, but the morbidity does not appear to be as great as in women with SS disease. Women with either SC or SS disease are managed similarly. Women with sickle cell trait alone usually have an uncomplicated pregnancy course except for an increased risk of urinary tract infection.
Although many of the inherited or acquired causes of anemia are relatively rare in women of childbearing age, they can be encountered in pregnancy. The implications for the mother and her offspring vary widely depending on the etiology of anemia. For example, mild microcytic anemia may be caused by iron deficiency, but it could also represent anemia of chronic disease as a result of previously undiagnosed malignancy. As such, women who have anemia caused by a disorder besides a nutritional deficiency are best managed in conjunction with a maternal fetal medicine specialist and a hematologist. Additionally, women who have an inherited form of anemia (hemoglobinopathies and thalassemia syndromes, for example) should be offered genetic counseling; prenatal diagnosis, if available, should be discussed if the parents wish to know whether the fetus is affected.
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 95: Anemia in pregnancy. Obstet Gynecol. 2008 Jul;112(1):201–7. [Reaffirmed 2019]
American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 78: Hemoglobinopathies in pregnancy. Obstet Gynecol 2007 Jan;109(1):229–37. [Reaffirmed 2019]
AR. Sickle cell disease in pregnancy. South Med J. 2016 Sep;109(9):554–6.