Anemia in pregnancy is a major public health concern, and the World Health Organization estimates that 37% of pregnancies are affected by anemia (1). Worldwide, rates of anemia in pregnancy are higher in low income or lower-middle income countries. In the United States, a study of almost 4 million births found that prenatal anemia was more common in women who are Black (22%) or Pacific Islander (18%) and less common in those who are Asian (11%) or White (10%) (2).
Anemia in pregnant patients is associated with adverse maternal outcomes (eg, preterm delivery, placental abruption, intensive care unit admission) and adverse neonatal outcomes (eg, stillbirth, growth restriction, neurodevelopmental effects) (3, 4, 5).
During pregnancy, erythroid hyperplasia of the marrow occurs, and red blood cell (RBC) mass increases by 15 to 25% in a singleton pregnancy (6). However, a disproportionate increase in plasma volume (by 40 to 50%) results in hemodilution (hydremia of pregnancy), and thus an increased iron requirement. A physiologic anemia occurs with an average hematocrit (Hct) decrease from 38 to 45% in healthy nonpregnant women to about 34% late in a singleton pregnancy and to 30% late in a multifetal gestation. Despite hemodilution, oxygen-carrying capacity remains normal throughout pregnancy. Hct normally increases immediately after delivery due to an autotransfusion of maternal blood in the placental vessels returning to the maternal circulation.
Anemia occurs in up to one third of women during the third trimester, most commonly caused by:
Acute blood loss, usually peripartum, is a common cause of iron deficiency anemia.
References
1. World Health Information: Fact Sheet, Anaemia. May 1, 2023 (accessed May 19, 2024).
2. Igbinosa II, Leonard SA, Noelette F, et al: Racial and Ethnic Disparities in Anemia and Severe Maternal Morbidity. Obstet Gynecol. 2023;142(4):845-854. doi:10.1097/AOG.0000000000005325
3. Beckert RH, Baer RJ, Anderson JG, Jelliffe-Pawlowski LL, Rogers EE: Maternal anemia and pregnancy outcomes: a population-based study. J Perinatol. 2019;39(7):911-919. doi:10.1038/s41372-019-0375-0
4. Shi H, Chen L, Wang Y, et al. Severity of Anemia During Pregnancy and Adverse Maternal and Fetal Outcomes. JAMA Netw Open. 2022;5(2):e2147046. Published 2022 Feb 1. doi:10.1001/jamanetworkopen.2021.47046
5. Wiegersma AM, Dalman C, Lee BK, Karlsson H, Gardner RM. Association of Prenatal Maternal Anemia With Neurodevelopmental Disorders. JAMA Psychiatry. 2019 Dec 1;76(12):1294-1304. doi: 10.1001/jamapsychiatry.2019.2309. PMID: 31532497; PMCID: PMC6751782
6. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins: Practice Bulletin, Number 233, Anemia in Pregnancy. Obstet Gynecol. 2021;138(2):e55-e64. doi:10.1097/AOG.0000000000004477
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.
Fetal growth restriction should prompt and evaluation for maternal anemia.
Diagnosis of Anemia in Pregnancy
Complete blood count (CBC) and differential, followed by testing based on mean corpuscular value (MCV) value
Diagnosis of anemia begins with CBC. The following hemoglobin (Hb) and Hct levels are classified as anemic in pregnant patients (1):
First trimester: Hb < 11 g/dL; Hct < 33%
Second trimester: Hb < 10.5 g/dL; Hct < 32%
Third trimester: Hb < 11 g/dL; Hct < 33%
Usually, if women have anemia, subsequent testing is based on whether the MCV is low (< 79 fL) or high (> 100 fL) (see table Characteristics of Common Anemias):
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 vitamin B12 levels.
For anemia with mixed causes: Evaluation for both types is required.
Characteristics of Common Anemias
Etiology or Type | Morphologic Changes | Special Features |
|---|---|---|
Blood loss, acute | Normochromic-normocytic, with polychromatophilia | If severe, possible nucleated RBCs and left shift of the WBCs Leukocytosis Thrombocytosis |
Blood loss, chronic | Same as iron deficiency | Same as iron deficiency |
Same as vitamin B12 deficiency | Serum folate < 5 ng/mL (< 11 nmol/L) RBC folate < 225 ng/mL RBCs (< 510 nmol/L) Nutritional deficiency and malabsorption (in sprue, pregnancy, infancy, or alcohol use disorder) | |
Spheroidal microcytes Normoblastic erythroid hyperplasia Reticulocytosis | Increased MCHC Increased RBC osmotic fragility Shortened survival of labeled RBCs | |
Spheroidal microcytes Normoblastic erythroid hyperplasia Reticulocytosis | Increased MCHC Increased RBC osmotic fragility Shortened survival of labeled RBCs Positive direct antiglobulin test | |
Hemolysis | Normochromic-normocytic Reticulocytosis Marrow erythroid hyperplasia | Increased serum indirect bilirubin and LDH, low haptoglobin Increased stool and urine urobilinogen Hemoglobinuria in intravascular hemolysis Hemosiderinuria |
Infection, cancer, chronic inflammation, or renal disease | Normochromic-normocytic early, then microcytic Normoblastic marrow Normal or increased iron stores | Decreased serum iron Decreased total iron-binding capacity Elevated serum ferritin Normal or increased marrow iron content |
Microcytic, with anisocytosis and poikilocytosis Reticulocytopenia Hyperplastic marrow, with delayed hemoglobination | Possible achlorhydria, smooth tongue, angular cheilosis, and spoon nails Absent stainable marrow iron Low serum iron Increased total iron-binding capacity Low serum ferritin | |
Marrow failure | Normochromic-normocytic (may be macrocytic) Reticulocytopenia Failed marrow aspiration (often) or evident hypoplasia of erythroid series or of all elements | Idiopathic (> |
Marrow replacement (myelophthisis) | Anisocytosis and poikilocytosis (eg, teardrop cells) Nucleated RBCs Early granulocyte precursors Marrow aspiration possibly failing or showing leukemia, myeloma, myelofibrosis, or metastatic cells | Marrow infiltration with infectious granulomas, tumors, fibrosis, or lipid histiocytosis Possible hepatomegaly and splenomegaly Possible bone changes (osteosclerosis) |
Macrocytosis Red cell agglutination Reticulocytosis | Follows exposure to cold Results from a cold agglutinin or hemolysin test Sometimes postinfectious (paroxysmal cold hemoglobinuria) | |
Leukopenia Thrombocytopenia Reticulocytosis | Hemoglobinuria, sometimes with frankly dark morning urine Hemosiderinuria Thrombosis Smooth muscle dystonia causing abdominal pain, esophageal spasm, erectile dysfunction Variable degree of bone marrow failure (cytopenias) | |
Anisocytosis and poikilocytosis Some sickle cells in peripheral smear Sickling of all RBCs in preparation with hypoxia or hyperosmolar exposure Reticulocytosis | Most common in people of African ancestry in the United States Urinary hyposthenuria Hb S detected during electrophoresis Bone changes on x-ray Stroke and other thrombotic events Possibly painful vaso-occlusive crises and leg ulcers, stroke | |
Usually hypochromic but dimorphic with normocytes and macrocytes Hyperplastic marrow, with delayed hemoglobination Ringed sideroblasts | Usually stainable marrow iron (plentiful), but can be reduced Some congenital forms respond to vitamin B6 administration Can be part of a myelodysplastic syndrome | |
Microcytic Target cells Basophilic stippling Anisocytosis and poikilocytosis in homozygotes Nucleated RBCs in homozygotes Reticulocytosis | Elevated Hb A2 and Hb F (in beta-thalassemia) Mediterranean ancestry (common) In homozygotes, anemia from infancy Splenomegaly Bone changes on radiographs | |
Oval macrocytes Anisocytosis Reticulocytopenia Hypersegmented WBCs Megaloblastic marrow | Serum B12 < 200 pg/mL (< 145 pmol/L) Elevated methylmalonic acid and homocysteine Increased LDH Antibodies to intrinsic factor in serum (pernicious anemia) Frequently, GI and CNS symptoms | |
CNS = central nervous system; GI = gastrointestinal; Hb = hemoglobin; LDH = lactic dehydrogenase; MCHC = mean corpuscular hemoglobin concentration; RBC = red blood cell; WBC = white blood cell. | ||
Diagnosis reference
1. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins: Practice Bulletin, Number 233, Anemia in Pregnancy. Obstet Gynecol. 2021;138(2):e55-e64. doi:10.1097/AOG.0000000000004477
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 cause of anemia.
Transfusion is indicated for maternal Hb levels < 6 g/dL (which is associated with abnormal fetal oxygenation) and 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 solely on the Hb (1).
For women with anemia in the third trimester, clinicians should make appropriate preparations to prevent blood loss or manage hemodynamic status while considering whether blood loss during delivery is likely to result in severe anemia and whether the patient is not a candidate for blood transfusion (eg, in Jehovah's Witness patients).
Pearls & Pitfalls
|
Treatment reference
1. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins: Practice Bulletin, Number 233, Anemia in Pregnancy. Obstet Gynecol. 2021;138(2):e55-e64. doi:10.1097/AOG.0000000000004477
Key Points
The increases in red blood cell mass and hemodilution during pregnancy cause a physiologic anemia, but oxygen-carrying capacity remains normal throughout pregnancy.
The most common causes of nonphysiologic anemia during pregnancy are iron deficiency and folate deficiency.
Anemia in pregnancy is associated with adverse maternal outcomes (eg, preterm delivery, placental abruption, and intensive care unit admission) and adverse neonatal outcomes (eg, stillbirth, growth restriction, neurodevelopmental effects).
Advise all pregnant patients to take low-dose iron supplements in the first trimester to prevent anemia at delivery.
Treat the cause of the anemia if possible, but transfusion is usually indicated in patients with an Hb < 6 g/dL or severe symptoms.
Iron Deficiency Anemia in Pregnancy
Iron deficiency anemia is the most common pathologic cause of anemia in pregnancy. The cause of iron deficiency anemia is usually:
Inadequate dietary intake in reproductive-aged women
Recurrent loss of iron in menstrual blood (which approximates the amount normally ingested each month and thus prevents iron stores from building up)
Blood loss from a previous pregnancy
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 oral iron supplements every day or every other day
Sometimes intravenous (IV) iron
Most prenatal vitamins contain the recommended daily allowance of ferrous iron during pregnancy (27 mg) (1). In patients with iron deficiency anemia, a higher dose is needed (eg, 325 mg ferrous sulfate [65 mg elemental iron]). Iron is usually taken daily but may be taken every other day if a patient has bothersome gastrointestinal effects, especially constipation.
About 20% of pregnant women treated with oral iron supplements do not absorb enough supplemental iron or cannot tolerate the adverse effects; these patients require parenteral therapy. The iron deficit may be calculated, and the iron can often be replaced over 1 to 3 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.
Treatment reference
1. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins: Practice Bulletin, Number 233, Anemia in Pregnancy. Obstet Gynecol. 2021;138(2):e55-e64. doi:10.1097/AOG.0000000000004477
Prevention of Iron Deficiency Anemia in Pregnancy
All pregnant patients should take low-dose iron supplements in the first trimester to prevent anemia at delivery (1). If Hb is < 11.5 g/dL at the onset of pregnancy, additional supplemental iron may be given prophylactically because subsequent hemodilution usually reduces Hb to < 10 g/dL.
Prevention reference
1. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins: Practice Bulletin, Number 233, Anemia in Pregnancy. Obstet Gynecol. 2021;138(2):e55-e64. doi:10.1097/AOG.0000000000004477
Folate Deficiency Anemia in Pregnancy
Folate deficiency increases risk of neural tube defects and possibly fetal alcohol syndrome. Deficiency occurs in 0.5 to 1.5% of pregnant women; megaloblastic macrocytic anemia 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 complete blood count (CBC) shows anemia with macrocytic indices or high red blood cell (RBC) distribution width (RDW). Low serum folate levels confirm the diagnosis.
Treatment of Folate Deficiency Anemia in Pregnancy
Severe megaloblastic anemia may warrant bone marrow examination and further treatment.
Prevention of Folate Deficiency Anemia in Pregnancy
1). Women who have had a fetus with spina bifida should take 4 mg once a day, starting 3 months before conception and continuing through 12 weeks of gestation (2).
Folate deficiency anemia references
1. US Preventive Services Task Force, Barry MJ, Nicholson WK, et alJAMA. 2023;330(5):454-459. doi:10.1001/jama.2023.12876
2. American College of Obstetricians and Gynecologists' Committee on Practice Bulletins: Practice Bulletin, Number 187, Neural Tube Defects. Obstet Gynecol. 2017 (reaffirmed 2021);130(6):e279-e290. doi:10.1097/AOG.0000000000002412
Hemoglobinopathies in Pregnancy
During pregnancy, hemoglobinopathies, particularly sickle cell disease, Hb S-C disease, and beta- and alpha-thalassemia, are associated with increased risks of adverse maternal and perinatal outcomes (1). Genetic screening for some of these disorders is available.
Maternal sickle cell disease, particularly if severe, is associate with the following maternal or fetal/neonatal complications (2):
Maternal infection (eg, pneumonia, urinary tract infections [UTIs], and sepsis)
Acute chest syndrome
Venous and arterial thromboembolism
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 second or early third trimester.
Hemoglobinopathies references
1. American College of Obstetricians and Gynecologists' Committee on Obstetrics: Practice Bulletin No. 78: Hemoglobinopathies in Pregnancy. Obstet Gynecol. 2007 (reaffirmed 2021);109(1):229-237. doi:10.1097/00006250-200701000-00055
2. Kuo K, Caughey AB: Contemporary outcomes of sickle cell disease in pregnancy. Am J Obstet Gynecol. 2016;215(4):505.e1-505.e5055. doi:10.1016/j.ajog.2016.05.032
