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Anemia in Pregnancy

By Lara A. Friel, MD, PhD, Assistant Professor, Maternal-Fetal Medicine Division, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Texas Health Medical School at Houston, McGovern Medical School

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Normally during pregnancy, erythroid hyperplasia of the marrow occurs, and RBC mass increases. However, a disproportionate increase in plasma volume results in hemodilution (hydremia of pregnancy): Hct decreases from between 38 and 45% in healthy women who are not pregnant to about 34% during late single pregnancy and to 30% during late multifetal pregnancy. Thus during pregnancy, anemia is defined as Hb < 10 g/dL (Hct < 30%). If Hb is < 11.5 g/dL at the onset of pregnancy, women may be treated prophylactically because subsequent hemodilution usually reduces Hb to < 10 g/dL. Despite hemodilution, oxygen-carrying capacity remains normal throughout pregnancy. Hct normally increases immediately after birth.

Anemia occurs in up to one third of women during the 3rd trimester. The most common causes are

Obstetricians, in consultation with a perinatologist, should evaluate anemia in pregnant Jehovah's Witness patients (who are likely to refuse blood transfusions) as soon as possible.

Symptoms and Signs

Early symptoms of anemia are usually nonexistent or nonspecific (eg, fatigue, weakness, light-headedness, mild dyspnea during exertion). Other symptoms and signs may include pallor and, if anemia is severe, tachycardia or hypotension.

Anemia increases risk of

  • Preterm delivery

  • Postpartum maternal infections

Diagnosis

  • CBC, followed by testing based on MCV value

Diagnosis of anemia begins with CBC; usually, if women have anemia, subsequent testing is based on whether the MCV is low (< 79 fL) or high (> 100 fL):

  • For microcytic anemias: Evaluation includes testing for iron deficiency (measuring serum ferritin) and hemoglobinopathies (using hemoglobin electrophoresis). If these tests are nondiagnostic and there is no response to empiric treatment, consultation with a hematologist is usually warranted.

  • For macrocytic anemias: Evaluation includes serum folate and B12 levels.

  • For anemia with mixed causes: Evaluation for both types is required.

Treatment

  • Treatment to reverse the anemia

  • Transfusion as needed for severe symptoms

Treatment of anemia during pregnancy is directed at reversing the anemia (see below).

Transfusion is usually indicated for any anemia if severe constitutional symptoms (eg, light-headedness, weakness, fatigue) or cardiopulmonary symptoms or signs (eg, dyspnea, tachycardia, tachypnea) are present; the decision is not based on the Hct.

Pearls & Pitfalls

  • Transfusion decisions are not based on the Hct but on the severity of symptoms.

Key Points

  • Hemodilution occurs during pregnancy, but oxygen-carrying capacity remains normal throughout pregnancy.

  • The most common causes of anemia during pregnancy are iron deficiency and folate acid deficiency.

  • Anemia increases risk of preterm delivery and postpartum maternal infections.

  • If Hb is < 11.5 g/dL at the onset of pregnancy, consider treating women prophylactically.

  • Treat the cause of the anemia if possible, but if patients have severe symptoms, transfusion is usually indicated.

Iron Deficiency Anemia in Pregnancy

About 95% of anemia cases during pregnancy are iron deficiency anemia. The cause is usually

  • Inadequate dietary intake (especially in adolescent girls)

  • A previous pregnancy

  • The normal recurrent loss of iron in menstrual blood (which approximates the amount normally ingested each month and thus prevents iron stores from building up)

Diagnosis

  • Measurement of serum iron, ferritin, and transferrin

Typically, Hct is 30%, and MCV is < 79 fL. Decreased serum iron and ferritin and increased serum transferrin levels confirm the diagnosis of iron deficiency anemia.

Treatment

  • Usually ferrous sulfate 325 mg po once/day

One 325-mg ferrous sulfate tablet taken midmorning is usually effective. Higher or more frequent doses increase GI adverse effects, especially constipation, and one dose blocks absorption of the next dose, thereby reducing percentage intake.

About 20% of pregnant women do not absorb enough supplemental oral iron; a few of them require parenteral therapy, usually iron dextran 100 mg IM every other day for a total of 1000 mg over 3 wk. Hct or Hb is measured weekly to determine response. If iron supplements are ineffective, concomitant folate deficiency should be suspected.

Neonates of mothers with iron deficiency anemia usually have a normal Hct but decreased total iron stores and a need for early dietary iron supplements.

Prevention

Although the practice is controversial, iron supplements (usually ferrous sulfate 325 mg po once/day) are usually given routinely to pregnant women to prevent depletion of body iron stores and prevent the anemia that may result from abnormal bleeding or a subsequent pregnancy.

Folate Deficiency Anemia in Pregnancy

Folate deficiency (see also Megaloblastic Macrocytic Anemias) increases risk of neural tube defects and possibly fetal alcohol syndrome. Deficiency occurs in 0.5 to 1.5% of pregnant women; macrocytic megaloblastic anemia is present if deficiency is moderate or severe.

Rarely, severe anemia and glossitis occur.

Diagnosis

  • Measurement of serum folate

Folate deficiency is suspected if CBC shows anemia with macrocytic indices or high RBC distribution width (RDW). Low serum folate levels confirm the diagnosis.

Treatment

  • Folic acid 1 mg po bid

Treatment is folic acid 1 mg po bid.

Severe megaloblastic anemia may warrant bone marrow examination and further treatment in a hospital.

Prevention

For prevention, all pregnant women and women who are trying to conceive are given folic acid 0.4 to 0.8 mg po once/day. Women who have had a fetus with spina bifida should take 4 mg once/day, starting before conception.

Hemoglobinopathies in Pregnancy

During pregnancy, hemoglobinopathies, particularly sickle cell disease, Hb S-C disease, and beta- and alpha-thalassemia, can worsen maternal and perinatal outcomes (for genetic screening for some of these disorders, see Table: Genetic Screening for Some Ethnic Groups).

Preexisting sickle cell disease, particularly if severe, increases risk of the following:

  • Maternal infection (most often, pneumonia, UTIs, and endometritis)

  • Pregnancy-induced hypertension

  • Heart failure

  • Pulmonary infarction

  • Fetal growth restriction

  • Preterm delivery

  • Low birth weight

Anemia almost always becomes more severe as pregnancy progresses. Sickle cell trait increases the risk of UTIs but is not associated with severe pregnancy-related complications.

Treatment of sickle cell disease during pregnancy is complex. Painful crises should be treated aggressively. Prophylactic exchange transfusions to keep Hb A at 60% reduce risk of hemolytic crises and pulmonary complications, but they are not routinely recommended because they increase risk of transfusion reactions, hepatitis, HIV transmission, and blood group isoimmunization. Prophylactic transfusion does not appear to decrease perinatal risk. Therapeutic transfusion is indicated for the following:

  • Symptomatic anemia

  • Heart failure

  • Severe bacterial infection

  • Severe complications of labor and delivery (eg, bleeding, sepsis)

Hb S-C disease may first cause symptoms during pregnancy. The disease increases risk of pulmonary infarction by occasionally causing bony spicule embolization. Effects on the fetus are uncommon but, if they occur, often include fetal growth restriction.

Sickle cell–beta-thalassemia is similar to Hb S-C disease but is less common and more benign.

Alpha-thalassemia does not cause maternal morbidity, but if the fetus is homozygous, hydrops and fetal death occur during the 2nd or early 3rd trimester.

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