Anemia in pregnancy

Anemia is described as a reduction in the proportion of the red blood cells. Anemia is when you don’t have enough healthy red blood cells to carry oxygen to the rest of your body. Without enough oxygen, your body cannot work as well as it should, and you feel tired and run down. Anemia is not a diagnosis, but a presentation of an underlying condition. Anemia occurs in up to one third of women during the 3rd trimester ¹⁾. The most common causes of anemia in pregnancy are:

• Iron deficiency
• Folate deficiency

Anemia can affect anyone, but women are at greater risk for this condition. In women, iron and red blood cells are lost when bleeding occurs from very heavy or long periods (menstruation).

Anemia is common in pregnancy because a woman needs to have enough red blood cells to carry oxygen around her body and to her baby. So it’s important to prevent anemia before, during and after pregnancy. Your doctor tests you for anemia at a prenatal care visit.

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. Thus during pregnancy, anemia is defined as hemoglobin (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 hemoglobin to < 10 g/dL. Despite hemodilution, oxygen-carrying capacity remains normal throughout pregnancy. Hematocrit normally increases immediately after birth.

Insufficient iron intakes during pregnancy increase a woman’s risk of iron deficiency anemia ²⁾. Low intakes also increase her infant’s risk of low birthweight, premature birth, low iron stores, and impaired cognitive and behavioral development.

An analysis of 1999–2006 data from the National Health and Nutrition Examination Survey (NHANES) found that 18% of pregnant women in the United States had iron deficiency ³⁾. Rates of deficiency were 6.9% among women in the first trimester,14.3% in the second trimester, and 29.7% in the third trimester.

Randomized controlled trials have shown that iron supplementation can prevent iron deficiency anemia in pregnant women and related adverse consequences in their infants v A Cochrane review showed that daily supplementation with 9–90 mg iron reduced the risk of anemia in pregnant women at term by 70% and of iron deficiency at term by 57% ⁴⁾. In the same review, use of daily iron supplements was associated with an 8.4% risk of having a low-birthweight newborn compared to 10.2% with no supplementation. In addition, mean birthweight was 31 g higher for infants whose mothers took daily iron supplements during pregnancy compared with the infants of mothers who did not take iron.

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.

Anemia in pregnancy causes

Usually, a woman becomes anemic (has anemia) because her body isn’t getting enough iron. Iron is a mineral that helps to create red blood cells. In pregnancy, iron deficiency has been linked to an increased risk of premature birth and low birthweight Premature birth is birth before 37 weeks of pregnancy. Low birthweight is when a baby weighs less than 5 pounds, 8 ounces at birth.

Some women may have an illness that causes anemia. Diseases such as sickle cell anemia or thalassemia affect the quality and number of red blood cells the body produces. If you have a disease that causes anemia, talk with your health provider about how to treat anemia.

If women have a hereditary anemia (such as sickle cell disease, hemoglobin S-C disease, or some thalassemias), the risk of problems is increased during pregnancy. If women are at increased risk of having any of these disorders because of race, ethnic background, or family history, blood tests to check for the disorders are routinely done before delivery. Chorionic villus sampling or amniocentesis may be done to check for these disorders in the fetus.

Low iron in pregnancy

Iron deficiency is the cause of anemia during pregnancy in about 95% of cases ⁵⁾. Iron is a mineral that the body needs for growth and development. Your body uses iron to make hemoglobin, a protein in red blood cells that carries oxygen from the lungs to all parts of the body, and myoglobin, a protein that provides oxygen to muscles. Your body also needs iron to make some hormones.

Iron deficiency anemia is usually caused by:

• Not consuming enough iron in the diet (especially in adolescent girls)
• Menstruating
• Having had a previous pregnancy

Women normally and regularly lose iron every month during menstruation. The amount of iron lost during menstruation is about the same as the amount women normally consume each month. Thus, women cannot store much iron.

To make red blood cells in the fetus, pregnant women need twice as much iron as usual. As a result, iron deficiency commonly develops, and anemia often results.

How much iron do I need?

Before getting pregnant, women should get about 18 milligrams (mg) of iron per day. During pregnancy, the amount of iron you need jumps to 27 mg per day. Most pregnant women get this amount from eating foods that contain iron and taking prenatal vitamins that contain iron. Some women need to take iron supplements to prevent iron deficiency.

What foods provide iron?

Iron is found naturally in many foods and is added to some fortified food products. You can get recommended amounts of iron by eating a variety of foods. Foods high in iron include:

• Lean meat, seafood, and poultry.
• Iron-fortified breakfast cereals, breads and pastas
• White beans, lentils, spinach, kidney beans, and peas.
• Nuts and some dried fruits, such as raisins.
• Eggs
• Organ meats (liver, giblets)
• Red meat
• Seafood (clams, oysters, sardines)
• Spinach and other dark leafy greens

Iron in food comes in two forms: heme iron and nonheme iron. Nonheme iron is found in plant foods and iron-fortified food products. Meat, seafood, and poultry have both heme and nonheme iron.

Your body absorbs iron from plant sources better when you eat it with meat, poultry, seafood, and foods that contain vitamin C, such as citrus fruits, strawberries, sweet peppers, grapefruit, tomatoes, and broccoli. Foods containing vitamin C can increase the amount of iron your body absorbs.

Calcium (in dairy products like milk) and coffee, tea, egg yolks, fiber and soybeans can block your body from absorbing iron. Try to avoid these when eating iron-rich foods.

Table 1. Selected Food Sources of Iron

Food	Milligrams per serving	Percent DV*
Breakfast cereals, fortified with 100% of the DV for iron, 1 serving	18	100
Oysters, eastern, cooked with moist heat, 3 ounces	8	44
White beans, canned, 1 cup	8	44
Chocolate, dark, 45%–69% cacao solids, 3 ounces	7	39
Beef liver, pan fried, 3 ounces	5	28
Lentils, boiled and drained, ½ cup	3	17
Spinach, boiled and drained, ½ cup	3	17
Tofu, firm, ½ cup	3	17
Kidney beans, canned, ½ cup	2	11
Sardines, Atlantic, canned in oil, drained solids with bone, 3 ounces	2	11
Chickpeas, boiled and drained, ½ cup	2	11
Tomatoes, canned, stewed, ½ cup	2	11
Beef, braised bottom round, trimmed to 1/8” fat, 3 ounces	2	11
Potato, baked, flesh and skin, 1 medium potato	2	11
Cashew nuts, oil roasted, 1 ounce (18 nuts)	2	11
Green peas, boiled, ½ cup	1	6
Chicken, roasted, meat and skin, 3 ounces	1	6
Rice, white, long grain, enriched, parboiled, drained, ½ cup	1	6
Bread, whole wheat, 1 slice	1	6
Bread, white, 1 slice	1	6
Raisins, seedless, ¼ cup	1	6
Spaghetti, whole wheat, cooked, 1 cup	1	6
Tuna, light, canned in water, 3 ounces	1	6
Turkey, roasted, breast meat and skin, 3 ounces	1	6
Nuts, pistachio, dry roasted, 1 ounce (49 nuts)	1	6
Broccoli, boiled and drained, ½ cup	1	6
Egg, hard boiled, 1 large	1	6
Rice, brown, long or medium grain, cooked, 1 cup	1	6
Cheese, cheddar, 1.5 ounces	0	0
Cantaloupe, diced, ½ cup	0	0
Mushrooms, white, sliced and stir-fried, ½ cup	0	0
Cheese, cottage, 2% milk fat, ½ cup	0	0
Milk, 1 cup	0	0

Footnotes: * DV = Daily Value. The U.S. Food and Drug Administration (FDA) developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for iron on Nutrition Facts and Supplement Facts labels and used for the values in Table 1 is 18 mg for adults and children age 4 years and older ⁶⁾. FDA requires food labels to list iron content. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

What kinds of iron dietary supplements are available?

Iron is available in many multivitamin-mineral supplements and in supplements that contain only iron. Iron in supplements is often in the form of ferrous sulfate, ferrous gluconate, ferric citrate, or ferric sulfate. Dietary supplements that contain iron have a statement on the label warning that they should be kept out of the reach of children. Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6.

Guidelines on iron supplementation during pregnancy vary, but many recommend some form of iron supplementation to prevent iron deficiency anemia:

• The American College of Obstetricians and Gynecologists (ACOG) states that good and consistent evidence shows that iron supplementation decreases the prevalence of maternal anemia at delivery ⁷⁾. However, it acknowledges that only limited or inconsistent evidence shows that iron deficiency anemia during pregnancy is associated with a higher risk of low birthweight, preterm birth, or perinatal mortality. The American College of Obstetricians and Gynecologists recommends screening all pregnant women for anemia and treating those with iron deficiency anemia (which it defines as hematocrit levels less than 33% in the first and third trimesters and less than 32% in the second trimester) with supplemental iron in addition to prenatal vitamins ⁸⁾.
• The Centers for Disease Control and Prevention (CDC) recommends that all pregnant women, at their first prenatal visit, begin taking an oral, low dose (30 mg/day) supplement of iron and be screened for iron deficiency anemia ⁹⁾. Women with iron deficiency anemia (which it defines as a hemoglobin concentration less than 9 g/dL or a hematocrit level less than 27%) should be treated with an oral dose of 60-120 mg/day of iron.
• In contrast, the U.S. Preventive Services Task Force (USPSTF) has concluded that the current evidence is insufficient to recommend for or against both screening for iron deficiency anemia in pregnant women and routinely supplementing them with iron to prevent adverse maternal health and birth outcomes ¹⁰⁾. They note, however, that their recommendation does not apply to pregnant women who are malnourished, have symptoms of iron deficiency anemia, or those with special hematologic conditions or nutritional needs that increase iron requirements.

The Institute of Medicine notes that because the median intake of dietary iron by pregnant women is well below the Estimated Average Requirement (EAR), pregnant women need iron supplementation ¹¹⁾. The Dietary Guidelines for Americans advises that women who are pregnant take an iron supplement when recommended by an obstetrician or other health-care provider ¹²⁾. It adds that low intakes of iron are a public health concern for pregnant women.

Note: Estimated Average Requirement (EAR) is the average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.

Some iron supplements may cause heartburn, constipation or nausea. Here are some tips to avoid or reduce these problems:

• Take the supplement on an empty stomach. If it upsets your stomach, take the supplement with a small amount of food.
• Take the supplement with orange juice or a vitamin C supplement.
• Don’t take a supplement with dairy products (milk, cheese, yogurt), eggs, high-fiber foods (whole grain breads and cereals, raw vegetables), spinach, tea or coffee. Don’t take an iron supplement if you’re taking an antacid.

Am I getting enough iron?

Most people in the United States get enough iron. However, certain groups of people are more likely than others to have trouble getting enough iron:

• Teen girls and women with heavy periods.
• Pregnant women and teens.
• Infants (especially if they are premature or low-birthweight).
• Frequent blood donors.
• People with cancer, gastrointestinal (GI) disorders, or heart failure.

What happens if I don’t get enough iron?

In the short term, getting too little iron does not cause obvious symptoms. The body uses its stored iron in the muscles, liver, spleen, and bone marrow. But when levels of iron stored in the body become low, iron deficiency anemia sets in. Red blood cells become smaller and contain less hemoglobin. As a result, blood carries less oxygen from the lungs throughout the body.

Symptoms of iron deficiency anemia include gastrointestinal upset, weakness, tiredness, lack of energy, and problems with concentration and memory. In addition, people with iron deficiency anemia are less able to fight off germs and infections, to work and exercise, and to control their body temperature. Infants and children with iron deficiency anemia might develop learning difficulties.

Iron deficiency is not uncommon in the United States, especially among young children, women under 50, and pregnant women. It can also occur in people who do not eat meat, poultry, or seafood; lose blood; have gastrointestinal diseases that interfere with nutrient absorption; or eat poor diets.

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.

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. Genetic screening genetic screening for some of these disorders is available.

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

• Maternal infection (most often, pneumonia, urinary tract infections [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 urinary tract infections but is not associated with severe pregnancy-related complications.

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.

Sickle cell disease

In addition to causing symptoms of anemia, sickle cell disease increases the risk of the following during pregnancy:

• Infections: Pneumonia, urinary tract infections, and infections of the uterus are the most common.
• High blood pressure: About one third of pregnant women who have sickle cell disease develop high blood pressure during pregnancy.
• Heart failure
• Blockage of arteries in the lungs by blood clots (pulmonary embolism): This problem may be life threatening.
• Problems in the fetus: The fetus may grow slowly or not as much as expected (small for gestational age). The fetus may be born prematurely.

A sudden, severe attack of pain, called sickle cell crisis, may occur during pregnancy as at any other time. The more severe that sickle cell disease is before pregnancy, the higher the risk of health problems for pregnant women and the fetus, and the higher the risk of death for the fetus during pregnancy. Sickle cell anemia almost always worsens as pregnancy progresses.

If given regular blood transfusions, women with sickle cell disease are less likely to have sickle cell crises, but they become more likely to reject the transfused blood. This condition, called alloimmunization, can be life threatening. Also, transfusions to pregnant women do not reduce risks for the fetus. Thus, transfusions are used only if one of the following occurs:

• The anemia causes symptoms, heart failure, or a severe bacterial infection.
• Serious problems, such as bleeding or an infection of the blood (sepsis), develop during labor and delivery.

If a sickle cell crisis occurs, women are treated as they would be if they were not pregnant. They are hospitalized and given fluids intravenously, oxygen, and drugs to relieve pain. If the anemia is severe, they are given a blood transfusion.

Signs and symptoms of anemia in pregnancy

Anemia takes some time to develop. In the beginning, you may not have any signs or they may be mild. Mild forms of anemia may not cause any symptoms. Fatigue, or feeling tired, is a common symptom. This is because the hemoglobin in red blood cells carries oxygen. A lack of oxygen reduces energy. It can cause your heart to work harder to pump oxygen.

Anemia can produce other symptoms, such as:

• Fatigue (very common)
• Dizziness
• Headache
• Cold hands and feet
• Pale skin
• Irregular heartbeat (fast, slow, or uneven heartbeat)
• Chest pain
• Shortness of breath
• Brittle nails or hair loss
• Strange food cravings (known as pica).

Because your heart has to work harder to pump more oxygen-rich blood through the body, all of these signs and symptoms can occur. Contact your doctor if you have any of these symptoms.

If anemia persists, the following may result:

• The fetus may not receive enough oxygen, which is needed for normal growth and development, especially of the brain.
• Pregnant women may become excessively tired and short of breath.
• The risk of preterm labor is increased.

The bleeding that normally occurs during labor and delivery can dangerously worsen anemia in these women. Also, women with anemia are more likely to develop infections after delivery.

Anemia in pregnancy diagnosis

Anemia is usually detected when doctors do a routine complete blood count at the first examination after pregnancy is confirmed.

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

• For microcytic anemias (low MCV): 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 (high MCV): Evaluation includes serum folate and vitamin B12 levels.
• For anemia with mixed causes: Evaluation for both types is required.

Iron deficiency anemia in pregnancy diagnosis

• Measurement of serum iron, ferritin, and transferrin

Typically, hematocrit (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.

Folate deficiency diagnosis

• Measurement of serum folate

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

Anemia in pregnancy treatment

Treatment of anemia during pregnancy is directed at reversing the anemia and depends on the underlying cause of the anemia.

Whether blood transfusions are needed depends on whether the following occur:

• Symptoms, such as light-headedness, weakness, and fatigue, are severe.
• Anemia affects breathing or the heart.

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 hematocrit.

Iron deficiency anemia in pregnancy treatment

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) before the woman became pregnant

Treatment

Usually ferrous sulfate 325 mg tablet taken midmorning once daily is usually effective. Higher or more frequent doses increase gastrointestinal 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 intramuscular (IM) every other day for a total of ≥ 1000 mg over 3 weeks. Hematocrit or hemoglobin 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 hematocrit 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 treatment

Folate deficiency increases risk of neural tube defects and possibly fetal alcohol syndrome. Folate (folic acid) deficiency may also cause anemia during pregnancy. If folate is deficient, the risk of having a baby with a birth defect of the brain or spinal cord (neural tube defect), such as spina bifida, is increased.

Folate 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.

Treatment

Treatment of folate deficiency is folic acid 1 mg orally twice a day.

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 oral once per day. Women who have had a fetus with spina bifida should take 4 mg once/day, starting before conception.

Hemoglobinopathies in pregnancy treatment

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)

If a sickle cell crisis occurs, women are treated as they would be if they were not pregnant. They are hospitalized and given fluids intravenously, oxygen, and drugs to relieve pain. If the anemia is severe, they are given a blood transfusion.