NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
McDonagh M, Cantor A, Bougatsos C, et al. Routine Iron Supplementation and Screening for Iron Deficiency Anemia in Pregnant Women: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2015 Mar. (Evidence Syntheses, No. 123.)
This publication is provided for historical reference only and the information may be out of date.
Routine Iron Supplementation and Screening for Iron Deficiency Anemia in Pregnant Women: A Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet].
Show detailsPurpose and Previous U.S. Preventive Services Task Force Recommendation
This report was commissioned by the U.S. Preventive Services Task Force (USPSTF) in order to update its 2006 recommendation on screening and supplementation for iron deficiency anemia in pregnancy.1
The USPSTF previously recommended routine screening for iron deficiency anemia in asymptomatic, pregnant women (B recommendation). This recommendation was based on fair evidence that the benefits of routine screening for iron deficiency anemia in asymptomatic, pregnant women outweigh the potential harms. The USPSTF found insufficient evidence (no studies) that specifically addressed the accuracy of screening tests in asymptomatic, pregnant women but found fair evidence that treating asymptomatic, pregnant women for iron deficiency anemia results in moderate benefits in health outcomes.1
The USPSTF also previously concluded that the evidence was insufficient to recommend for or against routine iron supplementation for nonanemic pregnant women (I statement). This recommendation was based on poor evidence that iron supplementation may improve health outcomes in nonanemic pregnant women. In addition, the USPSTF found no validated risk-assessment tools to use as guidance for identifying individuals who would benefit from iron supplementation. Therefore, the USPSTF concluded that there was insufficient evidence to determine the balance between the benefits and harms of routine iron supplementation for nonanemic pregnant women.1
Condition Definition
Iron is required in the production of hemoglobin, an essential protein found in red blood cells that transports oxygen throughout the body from the respiratory organs and returns carbon dioxide. Over time, iron is stored in the body for use in hemoglobin production. Iron deficiency occurs when the level of stored iron becomes depleted. Iron deficiency anemia occurs when iron levels are sufficiently depleted to produce anemia, characterized by hypochromic and microcytic red blood cells.2,3
Defining iron deficiency anemia in pregnant women is imprecise given pregnancy-associated changes in plasma volume and red cell mass, normal differences in hemoglobin concentrations, and ethnic variation. Physiological anemia of pregnancy is observed in healthy pregnant women and occurs as the result of greater expansion of plasma volume relative to the increase in hemoglobin mass and erythrocyte volume associated with pregnancy. This normal physiological change is responsible for a modest decrease in hemoglobin levels and is often referred to as dilutional anemia of pregnancy. The Centers for Disease Control and Prevention (CDC)4 and the World Health Organization5 define iron deficiency anemia in pregnancy as iron deficiency (serum ferritin <12 μg/L) with a hemoglobin level of less than 11g/dL (or <110 g/L) and a hematocrit level of less than 33 percent. However, since hemoglobin and hematocrit levels are typically lower in black adults, the Institute of Medicine (IOM) recommends lowering the hemoglobin cutoff level by 0.8 g/dL in this population.6
Iron deficiency is the most common pathological cause of anemia in pregnancy. Total iron loss associated with pregnancy and lactation is about 1,000 mg. Iron is necessary for both fetal and placental development and to expand the maternal red cell mass. Iron is commonly prescribed as part of a prenatal multivitamin or as a separate supplement because it is assumed most women do not have adequate iron stores to handle the demands of pregnancy.
Evidence of test sensitivity and specificity for iron deficiency anemia in pregnant women is not available. Therefore, anemia alone (hemoglobin level <11 g/dL) is not an ideal screening parameter for iron deficiency anemia. In most clinical settings, the simplest and most cost-effective measurement is a complete blood count (CBC), which includes measurements of hemoglobin, hematocrit, mean corpuscular volume, and red blood cell distribution width (a measure of variability in red cell size).
Serum ferritin may be useful in diagnosing iron deficiency in pregnant women, who often have elevated serum transferrin in the absence of iron deficiency. In one study of pregnant women,7 serum ferritin was found to be a good indicator of reduced iron stores, with a sensitivity of 90 percent and specificity of 85 percent when used as a screening tool for iron deficiency. Ferritin is an acute phase reactant and can be elevated because of inflammatory states, including liver disease, infection, and malignancy. A patient with iron deficiency and inflammation may have a falsely normal ferritin concentration. Serum ferritin may be of limited usefulness when concentrations decrease during late pregnancy, despite the presence of bone marrow iron.5
Prevalence and Risk Factors
All pregnant women are at higher risk for iron deficiency than nonpregnant women because of increased iron needs during pregnancy as a result of the growth of the fetus and placenta, increased red cell mass, and the expansion of maternal blood volume, especially as the pregnancy progresses into the third trimester.3,6,8-10 Analysis of National Health and Nutrition Examination Survey (NHANES) epidemiological data from 1999 to 2006 found an overall prevalence of iron deficiency in pregnancy near 18 percent, with 5 percent of pregnant women found to be anemic; prevalence of iron deficiency increased from 6.9 to 14.3 to 28.4 percent across the three trimesters.10 Older NHANES data from 1999 to 2000 found a prevalence of iron deficiency anemia in pregnancy of 2 to 3 percent.11 From 2000 to 2004, one report found rates of iron deficiency anemia of 1.8 percent in a low-income minority U.S. population in the first trimester, 8.2 percent in the second trimester, and 27.4 percent in the third trimester.9 Additional estimates of iron deficiency anemia in pregnant women are not readily available.
The most commonly cited risk factors for iron deficiency anemia or iron deficiency in pregnant women include eating a diet poor in iron-rich foods (e.g., vegan diet), having gastrointestinal issues that affect absorption, or having a short interval between pregnancies.12 In addition, 1999 to 2006 NHANES data found a higher prevalence of iron deficiency anemia among non-Hispanic black (30%) and Mexican American (24%) women than white women (14%).10 In one study, parity of two or more was associated with increased prevalence of iron deficiency (28%) compared with parity of zero (12%) or one (17%);10 however, no associations were found in women with lower educational levels or family income, which are mentioned as risk factors in other sources.6,9 For example, a study of women through 6 months postpartum found that 10 percent of those with an income with a poverty index ratio less than 130 percent (the level used to determine Federal aid status) had iron deficiency anemia compared with 2 percent of women whose incomes were above this threshold.13 Iron deficiency anemia in pregnancy can persist into the postpartum period, with an estimated prevalence of 4 percent.14 Finally, one study and one NHANES analysis found correlations between higher body mass index and decreased iron levels in pregnant women.15,16
Burden of Disease/Illness
Pregnant women with iron deficiency anemia or iron deficiency may experience clinical symptoms of fatigue, weakness, pallor, tachycardia, and shortness of breath.17
In pregnant women, the association between iron status and negative outcomes for both women and their infants is inconclusive. Numerous older observational studies have shown various measures of iron status, including iron deficiency anemia, to be associated with serious negative infant outcomes, including low birthweight,18-20 premature birth,18-23 and perinatal death.19 Notably, a literature review found that maternal anemia diagnosed at entry to prenatal care is associated with an increased risk for preterm delivery but anemia diagnosed during the third trimester is not associated with these negative outcomes, postulating that “this lack of association during the third trimester occurs because of third-trimester hemodilution, which makes it difficult to distinguish between gravidas with iron-deficiency anemia and those who experienced a good prognostic sign—an expanded plasma volume.”24 Alternatively, Cochrane reviews of up to 49 trials conducted in mostly developing countries that compared daily oral iron versus intermittent oral iron supplementation or assessed iron treatment during pregnancy found overall methodologically poor evidence showing no effect on infant outcomes, including low birthweight, delayed development, preterm birth, infection, and postpartum hemorrhage.25-28 In the current review, we examined trial and controlled observational study evidence from countries similar to the United States that assessed the effects of routine supplementation, screening, and screening-related treatment on maternal and infant outcomes.
Rationale for Screening/Screening Strategies
Screening for iron deficiency anemia in asymptomatic, pregnant women may lead to earlier identification and therefore earlier treatment, which has the potential to prevent serious negative health outcomes. Strategies for screening can include either routine screening or targeted screening based on established risk factors, risk-assessment instruments, or diagnostic tests. Routine screening in pregnant women may occur when they present for prenatal care.
Current Clinical Practice
Supplementation
Primary prevention of iron deficiency during pregnancy includes adequate dietary iron intake and iron supplementation. This may include starting an oral low-dose (e.g., 30 mg/day) iron supplement at the beginning of pregnancy or integrating iron-rich foods and foods that enhance iron absorption. Prophylaxis for iron deficiency anemia in high-risk populations may be accomplished with higher doses of supplementation (e.g., 60 to 100 mg elemental iron per day).
Treatment
Treatment of iron deficiency in pregnancy is the same as that in nonpregnant, postpartum, premenopausal, and postmenopausal women. Pregnant women with iron deficiency anemia are generally treated with additional iron in combination with prenatal vitamins and dietary counseling. The dosage of elemental iron required to treat iron deficiency anemia in adults is 120 mg per day for 3 months.5 Therapy should continue for 3 months after the anemia is corrected to allow iron stores to become replenished.29 There are no standard recommendations for followup after initiating therapy for iron deficiency anemia; however, one suggested course is to perform a CBC every 3 months for 1 year.30
Iron is available orally as ferrous fumarate, ferrous sulfate, or ferrous gluconate. Each iron salt provides different amounts of elemental iron (e.g., ferrous sulfate has 20% elemental iron per mg while ferrous fumarate has 33%). Dosing for adults with iron deficiency anemia is divided into two to four doses per day, depending on the elemental iron content of the dose (Table 1). While there is no evidence of a difference in efficacy between the salt forms, there are many different formulations on the market whose specific characteristics may affect the efficacy and tolerability profile of the product. For example, it has been suggested that some slow-release formulations release iron too far down the gastrointestinal tract for optimal absorption.
Table 1
Iron Formulations Available for Supplementation or Treatment.
Adverse events are typically limited to gastrointestinal tract symptoms that limit the ability or willingness of patients to adhere to the regimen. It is estimated that 10 to 20 percent of patients may report nausea, constipation, epigastric distress, and/or vomiting while taking oral iron, and the cause is thought to be directly related to the dose of elemental iron. The absorption of iron is inhibited by food (up to a 40% decrease)5 and antacids, and is enhance by a more acidic environment. Therefore, experts usually recommend avoiding dosing with meals or within 2 hours of taking antacids and taking the dose with orange juice or ascorbic acid to maximize absorption. However, for patients who experience gastrointestinal adverse effects that affect adherence to the regimen, slowly increasing the dose over several days, reducing the amount of elemental iron taken per dose or daily, or taking the iron with food may improve symptoms. These measures will likely mean that a longer duration of therapy is required. Urine and stool may be darker in color when taking iron, and liquid formulations can cause temporary gray staining of the teeth and gums. Iron can cause important interactions with several drugs and can be fatal in overdose in children.
Indications for the use of injectable iron are the same for pregnant women as for nonpregnant women, and there are concerns about adverse effects, including allergic reactions, and cost. Intravenous iron is generally used only to replenish iron stores in selected patients who have not tolerated a trial of oral iron therapy or those with severe iron deficiency.31
Recommendations of Other Groups
Screening
The American Congress of Obstetricians and Gynecologists,12 the U.S. Department of Veterans Affairs/Department of Defense (VA/DoD),32 the CDC,3 and the American Academy of Family Physicians33 recommend that all pregnant women be screened for anemia at some point during pregnancy. The VA/DoD recommends screening during the first prenatal visit and recommends against routine repeat screening in asymptomatic, pregnant women. The IOM recommends screening for anemia in high-risk pregnant women during each trimester and at 4 to 6 weeks postpartum.6 The Canadian Task Force on Preventive Health Care does not have a current recommendation for this topic.
Routine Supplementation
While the CDC3 and the World Health Organization34 recommend universal iron supplementation in pregnant women, the VA/DoD states that there is insufficient evidence to recommend for or against universal supplementation.32 The IOM,6 American Congress of Obstetricians and Gynecologists,12 and American Academy of Family Physicians33 recommend screening and treatment as necessary in lieu of routine supplementation. The Canadian Task Force on Preventive Health Care does not have a current recommendation for this topic.
Contextual Questions
Contextual Question 1. How Well Do Risk-Assessment Tools Identify Pregnant Women at Increased Risk for Iron Deficiency Anemia?
There is limited evidence available that evaluates risk-prediction tools to identify pregnant women at increased risk for iron deficiency anemia. We identified one study conducted in the United States in a population of primarily black urban pregnant women (n=141) that developed a risk-prediction tool to identify those at increased risk for iron deficiency anemia.35 The study used a number of formulas with various hematological indexes (i.e., red blood cell counts, mean corpuscular volume, and hemoglobin) to create a scoring system to predict risk. Anemia was measured using a CBC and serum ferritin was the gold standard. Points were awarded based on specific CBC measures (hemoglobin level and red blood cell distribution width) and gestational age. The study found that a risk score of 2 or greater was the best predictor of iron deficiency anemia, correctly identifying 74 percent of women with iron deficiency anemia (sensitivity, 45%; specificity, 88%; positive likelihood ratio, 1.1). However, the area under the receiving operator characteristic curve was only 0.66 (95% confidence interval [CI], 0.6 to 0.7), indicating overall poor predictive value. The authors suggest that more data must be collected to validate this model, in addition to validating results in more diverse populations.
We did not identify any other studies that evaluated risk-assessment tools to identify pregnant women with iron deficiency anemia.
Contextual Question 2. What Is the Yield (Number of New Diagnoses) of Repeat (Periodic) Screening in Asymptomatic, Pregnant Women, and at What Timing Intervals?
We did not identify any studies that addressed repeat screening or the timing of screening.
- Introduction - Routine Iron Supplementation and Screening for Iron Deficiency An...Introduction - Routine Iron Supplementation and Screening for Iron Deficiency Anemia in Pregnant Women
Your browsing activity is empty.
Activity recording is turned off.
See more...