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Am Fam Physician. 2006;74(3):461-464

This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on screening for iron deficiency anemia and the supporting scientific evidence. Explanations of the ratings and of the strength of overall evidence are given in Table 1 and Table 2, respectively. The complete information on which this statement is based, including evidence tables and references, is included in the evidence synthesis1 on this topic, available on the USPSTF Web site athttp://www.uspreventiveservicestaskforce.org. The recommendation also is posted on the Web site of the National Guideline Clearinghouse athttp://www.guideline.gov.

The USPSTF grades its recommendations according to one of five classifications (A, B, C, D, or I) reflecting the strength of evidence and magnitude of net benefit (benefits minus harms).
A.The USPSTF strongly recommends that clinicians provide [the service] to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms.
B.The USPSTF recommends that clinicians provide [the service] to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.
C.The USPSTF makes no recommendation for or against routine provision of [the service]. The USPSTF found at least fair evidence that [the service] can improve health outcomes but concludes that the balance of benefits and harms is too close to justify a general recommendation.
D.The USPSTF recommends against routinely providing [the service] to asymptomatic patients. The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.
I.The USPSTF concludes that the evidence is insufficient to recommend for or against routinely providing [the service]. Evidence that [the service] is effective is lacking, of poor quality, or conflicting, and the balance of benefits and harms cannot be determined.
The USPSTF grades the quality of the overall evidence for a service on a three-point scale (good, fair, or poor).
Good:Evidence includes consistent results from well-designed, well-conducted studies in representative populations that directly assess effects on health outcomes.
Fair:Evidence is sufficient to determine effects on health outcomes, but the strength of the evidence is limited by the number, quality, or consistency of the individual studies; generalizability to routine practice; or indirect nature of the evidence on health outcomes.
Poor:Evidence is insufficient to assess the effects on health outcomes because of limited number or power of studies, important flaws in their design or conduct, gaps in the chain of evidence, or lack of information on important health outcomes.

The USPSTF is redesigning its recommendation statement in response to feedback from primary care physicians. Later in 2006 the USPSTF plans to release a new, updated recommendation statement that is easier to read and incorporates advances in USPSTF methodology. The recommendation statement below is an interim version that combines existing language and elements with a new format. Although the definitions of grades remain the same, other elements have been revised.

Summary of Screening Recommendations

The USPSTF concludes that evidence is insufficient to recommend for or against routine screening for iron deficiency anemia in asymptomatic children six to 12 months of age. I recommendation.

The USPSTF recommends routine screening for iron deficiency anemia in asymptomatic pregnant women. B recommendation.

RATIONALE

Importance. Iron deficiency anemia is associated with psychomotor and cognitive abnormalities in children. Iron deficiency anemia during pregnancy has been associated with increased risk of low birth weight, preterm delivery, and perinatal mortality. The prevalence of iron deficiency anemia has remained stable over the last decade in the general U.S. population and continues to be highest among minority and poor children. Recent studies suggest that maternal iron deficiency anemia may be associated with postpartum depression and poor performance on mental and psychomotor tests in offspring.

Detection. There is good evidence that hemoglobin is a sensitive test for iron deficiency anemia, but it has low specificity because the majority of anemias in childhood are not caused by iron deficiency. The USPSTF found insufficient evidence (i.e., no studies) that specifically addressed the accuracy of screening tests in asymptomatic pregnant women.

Benefits of Detection and Early Intervention. The USPSTF found no evidence that universal or selective screening for iron deficiency anemia in asymptomatic children results in improved health outcomes. The USPSTF found poor evidence (i.e., conflicting studies) of the effectiveness of interventions that demonstrate improved health outcomes, such as developmental status, in asymptomatic children. The USPSTF found fair evidence that treating asymptomatic pregnant women who have iron deficiency anemia results in moderate benefits in health outcomes.

Harms of Detection and Early Treatment. The USPSTF found no evidence addressing the harms of screening either children or pregnant women for iron deficiency anemia. Potential harms include false-positive results, anxiety, and cost; the small potential harms of treatment with oral iron include gastrointestinal symptoms and unintentional overdose.

USPSTF Assessment. The USPSTF was unable to determine the balance between the benefits and harms of routine screening for iron deficiency anemia in asymptomatic children six to 12 months of age. The USPSTF concludes that the benefits of routine screening for iron deficiency anemia in asymptomatic pregnant women outweigh the potential harms.

Summary of Supplementation Recommendations

The USPSTF recommends routine iron supplementation for asymptomatic children six to 12 months of age who are at increased risk for iron deficiency anemia (see Clinical Considerations for a discussion of increased risk). B recommendation.

The USPSTF concludes that evidence is insufficient to recommend for or against routine iron supplementation for asymptomatic children six to 12 months of age who are at average risk for iron deficiency anemia. I recommendation.

The USPSTF concludes that evidence is insufficient to recommend for or against routine iron supplementation for nonanemic pregnant women. I recommendation.

RATIONALE

Importance. Iron deficiency anemia is associated with psychomotor and cognitive abnormalities in children. Iron deficiency anemia in pregnancy has been associated with increased risk of low birth weight, preterm delivery, and perinatal mortality. Recent studies suggest that maternal iron deficiency anemia may be associated with postpartum depression and poor performance on mental and psychomotor tests in offspring. The prevalence of iron deficiency anemia has remained stable over the past decade in the general U.S. population and continues to be greatest among minority and poor children.

Recognition of Risk Status. A validated risk assessment tool to guide primary care physicians in identifying persons who would benefit from iron supplementation has not been developed.

Benefits of Risk Assessment and Preventive Medication. The USPSTF found fair evidence that iron supplementation (e.g., iron-fortified formula, iron supplements) may improve neurodevelopmental outcomes in children at increased risk for iron deficiency anemia. The USPSTF found poor evidence (i.e., poor-quality and conflicting studies) that iron-fortified formula or supplementation improves neurodevelopmental outcomes in children six to 12 months of age if they are not at increased risk for iron deficiency anemia. The USPSTF found poor evidence (i.e., poor-quality studies) that iron supplementation may improve health outcomes in nonanemic pregnant women.

Harms of Risk Assessment and Preventive Medication. The USPSTF found fair evidence that oral iron supplementation increases the risk for unintentional overdose and gastrointestinal symptoms. Given appropriate protection against overdose, these harms are small. There is poor evidence (i.e., poor-quality studies) that iron supplementation for nonanemic pregnant women results in an increased risk for harms.

USPSTF Assessment. The USPSTF concludes that the moderate benefits of iron supplementation in asymptomatic children six to 12 months of age who are at increased risk for iron deficiency anemia outweigh the potential harms. The USPSTF was unable to determine the balance between the benefits and harms of iron supplementation in children six to 12 months of age who are at average risk for iron deficiency anemia, and of iron supplementation in nonanemic pregnant women.

Clinical Considerations

  • These USPSTF recommendations address screening for iron deficiency anemia and iron supplementation in children six to 12 months of age who are at increased risk and average risk, in asymptomatic pregnant women, and in nonanemic pregnant women. Infants younger than six months, older children, nonpregnant women, and men are not addressed.

  • Iron deficiency anemia can be defined as iron deficiency (i.e., abnormal values for serum ferritin, transferrin saturation, and free erythrocyte protoporphyrin) with a low hemoglobin or hematocrit value. Iron deficiency is much more common than iron deficiency anemia and is part of a continuum that ranges from iron depletion to iron deficiency anemia. Many of the negative health outcomes of iron deficiency are associated with its extreme manifestation, iron deficiency anemia. Iron deficiency also has been associated with negative neurodevelopmental outcomes in children.

  • Other causes of anemia vary by population and include other nutritional deficiencies, abnormal hemoglobin (e.g., thalassemia), enzyme defects, and anemia associated with acute and chronic infections.

  • In the United States, race, income, education, and other socioeconomic factors are associated with iron deficiency and iron deficiency anemia. Persons considered to be at high risk for iron deficiency include adult females, recent immigrants, and adolescent females who are fad dieters or obese. Premature and low–birth-weight infants also are at increased risk for iron deficiency.

  • Venous hemoglobin is more accurate than capillary hemoglobin for identifying anemia. Ferritin has the highest sensitivity and specificity for diagnosing iron deficiency in anemic patients.

  • Iron deficiency anemia usually is treated with oral iron preparations. The likelihood that iron deficiency anemia identified by screening will respond to treatment is unclear because many families do not adhere to treatment and because the rate of spontaneous resolution is high. Ninety-seven percent of infant formula sold in the United States is iron fortified. Substantial reductions in the incidence of iron deficiency and iron deficiency anemia have been demonstrated in healthy infants fed iron-fortified formula or iron-fortified cereal, compared with infants fed cow's milk or unfortified formula.

  • Iron supplements accounted for 30 percent of fatal pharmaceutical overdoses in children between 1983 and 1990, and iron poisoning has been observed even in the context of controlled trials in which parents were instructed in the safe storage and use of iron products. A reduction in deaths of children caused by iron overdose was observed when unit-dose packaging was required between 1998 and 2002; this requirement was overturned by the courts in 2003.

The Discussion section that is usually included in USPSTF recommendation statements is available in the complete recommendation statement athttp://www.ahcpr.gov/clinic/uspstf06/ironsc/ironrs.htm.

Recommendations from Other Groups

The Centers for Disease Control and Prevention (CDC) recommends screening for iron deficiency anemia in high-risk infants, high-risk preschool age children, pregnant women, and nonpregnant women of child-bearing age. The CDC also recommends universal iron supplementation to meet the iron requirements of pregnancy.2

The American Academy of Pediatrics (AAP) recommends screening all infants nine to 12 months of age and then six months later; for children at high risk, screening should be performed once a year from two to five years of age. The 2005 AAP breastfeeding guidelines recommend continuing breastfeeding for at least the first year of life and beyond, while introducing complementary foods rich in iron beginning at about six months of age; breastfed infants weaned before 12 months of age should receive iron-fortified infant formula. The AAP recommends that preterm and low–birth-weight infants receive iron supplementation before six months of age.3,4

The American Academy of Family Physicians recommends screening for iron deficiency anemia in high-risk infants six to 12 months of age and in infants whose principal dietary intake is unfortified cow's milk.

The American College of Obstetricians and Gynecologists recommends prenatal screening for all women at the earliest pre-natal visit and early in the third trimester.

This series is coordinated by Joanna Drowos, DO, contributing editor.

A collection of USPSTF recommendation statements published in AFP is available at https://www.aafp.org/afp/uspstf.

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