Normally during pregnancy, erythroid hyperplasia of the marrow occurs, and red blood cell (RBC) mass increases. However, a disproportionate increase in plasma volume results in hemodilution (hydremia of pregnancy): hematocrit (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. The following hemoglobin (Hb) and Hct levels are classified as anemic:
1st trimester: Hb < 11 g/dL; Hct < 33%
2nd trimester: Hb < 10.5 g/dL; Hct < 32%
3rd trimester: Hb < 11 g/dL; Hct < 33%
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 Red Blood Cell Production Red blood cell (RBC) production (erythropoiesis) takes place in the bone marrow under the control of the hormone erythropoietin (EPO). Juxtaglomerular cells in the kidney produce erythropoietin... read more 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 of Anemia in Pregnancy
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
Diagnosis of Anemia in Pregnancy
Complete blood count (CBC), followed by testing based on mean corpuscular value (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 Overview of Hemolytic Anemia At the end of their normal life span (about 120 days), red blood cells (RBCs) are removed from the circulation. Hemolysis is defined as premature destruction and hence a shortened RBC life span... read more (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 vitamin B12 levels.
For anemia with mixed causes: Evaluation for both types is required.
Treatment of Anemia in Pregnancy
Treatment to reverse the anemia
Transfusion as needed for severe symptoms or fetal indications
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
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 Iron Deficiency Anemia Iron deficiency is the most common cause of anemia and usually results from blood loss; malabsorption, such as with celiac disease, is a much less common cause. Symptoms are usually nonspecific... read more . 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) before the woman became pregnant
Diagnosis of Iron Deficiency Anemia in Pregnancy
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 of Iron Deficiency Anemia in Pregnancy
Usually ferrous sulfate 325 mg orally once a 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. The iron deficit may be calculated, and the iron can often be replaced over one or two infusions. 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 of Iron Deficiency Anemia in Pregnancy
Although the practice is controversial, iron supplements (usually ferrous sulfate 325 mg orally once a 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 Folate Deficiency Folate deficiency is common. It may result from inadequate intake, malabsorption, or use of various drugs. Deficiency causes megaloblastic anemia (indistinguishable from that due to vitamin... read more increases risk of neural tube defects Overview of Congenital Neurologic Anomalies Congenital brain anomalies usually cause severe neurologic deficits; some may be fatal. Some of the most serious neurologic anomalies (eg, anencephaly, encephalocele, spina bifida) develop in... read more and possibly fetal alcohol syndrome Fetal Alcohol Syndrome Alcohol exposure in utero increases the risk of spontaneous abortion, decreases birth weight, and can cause fetal alcohol syndrome, a constellation of variable physical and cognitive abnormalities... read more . Deficiency occurs in 0.5 to 1.5% of pregnant women; megaloblastic macrocytic anemia Megaloblastic Macrocytic Anemias Megaloblastic anemias result most often from deficiencies of vitamin B12 and folate. Ineffective hematopoiesis affects all cell lines but particularly red blood cells. Diagnosis is usually based... read more is present if deficiency is moderate or severe.
Rarely, severe anemia and glossitis occur.
Diagnosis of Folate Deficiency Anemia in Pregnancy
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 of Folate Deficiency Anemia in Pregnancy
Folic acid 1 mg orally twice a day
Treatment is folic acid 1 mg orally twice a day.
Severe megaloblastic anemia may warrant bone marrow examination and further treatment in a hospital.
Prevention of Folate Deficiency Anemia in Pregnancy
For prevention, all pregnant women and women who are trying to conceive are given folic acid 0.4 to 0.8 mg orally once a day. Women who have had a fetus with spina bifida should take 4 mg once a day, starting before conception.
Hemoglobinopathies in Pregnancy
During pregnancy, hemoglobinopathies, particularly sickle cell disease Sickle Cell Disease Sickle cell disease (a hemoglobinopathy) causes a chronic hemolytic anemia occurring almost exclusively in people with African ancestry. It is caused by homozygous inheritance of genes for hemoglobin... read more , Hb S-C disease Hemoglobin S-C Disease Hemoglobin S-C disease is a hemoglobinopathy that causes symptoms similar to those of sickle cell disease, but usually less severe. (See also Overview of Hemolytic Anemia.) The heterozygous... read more , and beta- and alpha- thalassemia Thalassemias Thalassemias are a group of inherited microcytic, hemolytic anemias characterized by defective hemoglobin synthesis. Alpha-thalassemia is particularly common among people with African, Mediterranean... read more , can worsen maternal and perinatal outcomes. Genetic screening genetic screening Genetic Screening for Some Ethnic Groups for some of these disorders is available.
Preexisting sickle cell disease, particularly if severe, increases risk of the following:
Maternal infection (most often, pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more , urinary tract infections [UTIs] Postpartum Pyelonephritis Pyelonephritis is bacterial infection of the renal parenchyma. Pyelonephritis may occur postpartum if bacteria ascend from the bladder. The infection may begin as asymptomatic bacteriuria during... read more , and endometritis Postpartum Endometritis Postpartum endometritis is uterine infection, typically caused by bacteria ascending from the lower genital or gastrointestinal tract. Symptoms are uterine tenderness, abdominal or pelvic pain... read more )
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:
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.