BACKGROUND. Screening for iron deficiency anemia is a well-established practice in pediatrics, but numerous challenges surrounding current recommendations raise questions about the effectiveness of this strategy.
OBJECTIVE. To evaluate iron deficiency anemia screening approaches, by assessing rates of follow-up testing and resolution among patients meeting screening criteria in a primary care setting.
METHODS. A retrospective cohort study was performed. We extracted electronic medical record data on complete blood counts for infants who received primary care in our clinics in the past 10 years. We calculated rates of positive screening results with 9 different measurement criteria and determined rates of follow-up testing and of documented correction of iron deficiency among those who screened positive.
RESULTS. Our cohort consisted of 4984 children who were screened at 9 to 15 months of age, between 1994 and 2004. There was a wide distribution of positive detection rates (range: 1.5–14.5%) among the 9 screening criteria. Follow-up testing rates were low. No more than 25% of infants who screened positive by any criterion underwent a repeat complete blood count within 6 months. Moreover, no more than 11.6% (range: 4.4–11.6%) had documented correction of their laboratory abnormalities.
CONCLUSIONS. Significant shortcomings exist in current iron deficiency anemia screening practices. A widely agreed-on, specific, and inexpensive screening criterion, with increased emphasis on systems-based approaches to iron deficiency screening, is needed.
iron deficiency is the most common nutritional deficiency among children in the United States.1 Infants are at particular risk for this disease because rapid growth, insufficient dietary intake, and limited absorption of dietary iron combine to deplete iron stores.2 There is a significant body of research that continues to detail the long-term sequelae of iron deficiency among infants. In numerous studies, iron deficiency has been associated with multiple defects in neurologic function,3–6 impaired renal function,7 increased absorption of lead,8 and impaired white blood cell function and immunity.9
Fortunately, iron deficiency is treatable. Health care providers have long subscribed to a program of screening for and treating infant iron deficiency anemia, in an attempt to avoid the consequences of this disorder.10–14 The American Academy of Pediatrics, for example, recommends screening for iron deficiency anemia at ∼1 year of age.14 In the most common approach, a screening test is performed and, if the result falls below a threshold level, then iron is administered in a therapeutic trial. The laboratory measurement is then repeated after sufficient time to demonstrate a response.
However, effective use of this approach presents 2 substantial challenges. One challenge is the lack of consensus regarding an optimal screening test. Hemoglobin and hematocrit measurements have long been used to detect anemia, but research has shown their poor specificity for iron deficiency.15 Therefore, alternative blood indices have been proposed. Because iron deficiency anemia is a microcytic anemia, newer approaches advocate the evaluation of mean corpuscular volumes (MCVs) and/or red blood cell distribution widths (RDWs) to elucidate more effectively true iron deficiency. In addition, there are multiple calculated indices, such as the Mentzer index, designed to differentiate types of microcytic anemia.16 These methods have varying sensitivities and specificities, which may result in significantly different rates of case finding and treatment. Another challenge is related to diagnostic follow-up monitoring. The effectiveness of iron deficiency anemia screening depends both on the clinician's timely response to screening test results that suggest iron deficiency initially and on subsequent testing to document the patient's response to therapy. Failure at the first step renders screening pointless. Failure at the second step represents a possible opportunity to detect ongoing abnormalities.
We describe a retrospective cohort study of children between 9 and 15 months of age who underwent complete blood counts (CBCs) in an inner city, primary care, pediatric network. We compared the rates at which different iron deficiency anemia screening criteria yielded positive results and the rates at which infants with these positive screening results had follow-up study results documenting resolution of their laboratory abnormalities.
We obtained approval for the study from the Indiana University institutional review board. We identified a cohort of infants who received regular well-child care within the Indiana University Medical Group Primary Care Network and who had a CBC performed as part of a well-child care visit. To assemble this cohort, we queried an electronic medical record system (Regenstrief Medical Record System, Indianapolis, IN)17 to identify all infants who had been examined (1994–2004) in one of the primary care clinics ≥3 times in their first 2 years of life. We then identified a subset of these infants who had undergone a CBC between the ages of 9 and 15 months. Only infants who had undergone CBCs within 3 days after a well-child care visit were included in this study, because the tests were more likely to be screening tests. We excluded infants who had documentation of sickle cell disease (either through diagnosis or through positive newborn screening results) in the electronic medical records.
We extracted demographic information, including age, race/ethnicity, gender, and health insurance status, for all children meeting the study criteria. Race/ethnicity was categorized as Hispanic, non-Hispanic white, non-Hispanic black, or other race. For simplicity, we refer to these groups as Hispanic, white, black, and other, respectively. Health insurance status was categorized as private, public, or no insurance. We categorized insurance in this way because it is used commonly as a marker for socioeconomic status.18
We extracted CBC results for all subjects who met the aforementioned criteria. CBCs included red blood cell count, RDW, hemoglobin level, hematocrit level, and MCV. We anticipated that infants would sometimes undergo multiple CBCs within the 6-month time window; in such cases, only the first CBC was used for analysis.
Nine different criteria for presumptively identifying iron deficiency, as described in the literature, were applied to these CBC results. The 9 criteria fit within 2 groupings, ie, simple screens typically recommended as the standard of care and other, more-specific screens for microcytosis.
Typically, simple screens are defined as either low hematocrit levels or low hemoglobin levels. Because abnormal thresholds for these 2 indices are not uniform in the literature, we chose 3 different criteria for this study, as follows: hematocrit level of <33%,11, 12, 14 hemoglobin level of <11 g/dL,11, 12 and hemoglobin level of <10.5 g/dL.19
Because clinicians had access to a series of other red blood cell indices within this cohort, we also evaluated 6 more-specific markers of iron deficiency. Microcytosis is characterized by a low MCV and an elevated RDW. The Mentzer index (MCV divided by red blood cell count) is used to differentiate between microcytic anemia caused by iron deficiency and that caused by thalassemias. Once again, given the variety of thresholds in the literature, we created 3 different criteria for microcytosis, as follows: MCV of <70 μm3 and RDW of >14%12; MCV of <70 μm3 and RDW of >14.5%20; and MCV of <70 μm3, RDW of >14.5%, and Mentzer index of >13.16, 20
We also created 3 other criteria to resemble the practice patterns within our clinical setting. Clinicians who authored this study, along with many other pediatricians who work in our outpatient clinics, define positive screening results for iron deficiency anemia as a low hemoglobin or hematocrit level with a low MCV. We therefore defined these final screening criteria as follows: hematocrit level of <33% and MCV of <70 μm3, hemoglobin level of <11 g/dL and MCV of <70 μm3, and hemoglobin level of <10.5 g/dL and MCV of <70 μm3.
We tallied the rate of positive screening results with each of these 9 screening criteria. We then reviewed the records of all children who screened positive with each of these 9 criteria, to determine whether the children underwent subsequent CBCs within 6 months after the positive screening tests. We also determined whether the follow-up CBCs documented resolution of the previous laboratory anomaly, with the same screening criteria.
Our initial cohort consisted of 4984 infants who underwent 5374 CBC evaluations within 3 days after a well-child care visit between 9 and 15 months of age. The distribution of these subjects according to race/ethnicity, gender, and insurance status at the time of screening is shown in Table 1. This distribution is typical of children treated in our clinics.
There was a wide distribution of initial positive screening rates among the 9 screening criteria (Table 2). In general, the 3 simple screens had higher positive screening rates (range: 5.5–14.5%) than did the more-specific markers that assessed microcytosis (range: 1.5–3.6%). Among the 9 criteria, an average of 18.3% of infants underwent follow-up CBCs within 6 months after positive screening tests. Follow-up rates were consistently low, for both standard screening methods (range: 14.3–22.5%) and the 6 more-specific measures of microcytosis (range: 16.0–25.0%).
Of those who received follow-up testing, no more than one half (range: 25.8–46.7%) demonstrated correction of their initial values (Table 3). Among children who screened positive with any criterion, no more that 11.6% (range: 5.3–11.6%) had documented correction of their laboratory abnormalities within 6 months after positive screening results.
Our analysis showed that very few infants between 9 and 15 months of age with anemia received proper follow-up monitoring after screening for iron deficiency. This is of concern, because infant iron deficiency screening has become a standard of care in the United States; it is recommended by the American Academy of Pediatrics and the US Preventive Services Task Force, and it is required by the Medicaid Early and Periodic Screening, Diagnosis, and Treatment standards in most states. Screening can potentially prevent neurodevelopmental and other sequelae of iron deficiency. However, any effective screening strategy must both identify and properly treat infants to achieve effective management. Our results suggest that we have achieved neither of these.
The vast array of proposed criteria for the presumptive identification of iron deficiency anemia led to widely varying case finding rates. With the standard American Academy of Pediatrics and Centers for Disease Control and Prevention criteria (hemoglobin level of <11 g/dL and/or hematocrit level of <33%), an average of 14.4% of this cohort screened as positive. However, more-specific markers of microcytosis identified ∼2.3% on average, a number that approaches recently documented iron deficiency prevalence statistics.12 Although we cannot tell from these data which criteria provide the best combination of sensitivity and specificity, providing comprehensive follow-up services to 14% of a clinic population is both difficult and expensive. Adding the MCV to standard screening methods could potentially lead to the underdiagnosis and undertreatment of iron deficiency and therefore merits additional investigation. These data demonstrate conclusively, however, that poor follow-up care was independent of the clinicians' use of a more-stringent set of criteria, because rates were poor with all 9 criteria.
Also of concern is the low rate at which clinicians documented resolution of positive iron deficiency screening results, regardless of criteria. Even when multiple criteria were considered, at best 12% of infants had documented resolution of their presumptive iron deficiency. Moreover, <25% had any kind of follow-up testing documented. Even if there were consensus about the best screening test, testing has little value if there is not an appropriate response to positive test results.
Failure to provide follow-up care after positive screening tests for anemia almost certainly results from systems failures. To respond to the test, a clinician must first see the result of the test and must recognize that the result is abnormal. The patient must receive therapy and return for follow-up testing, and the clinician must provide the follow-up testing when the patient returns. Failure at any of these steps, alone or in combination, could lead to the poor follow-up rates seen in our system.
The central problem might be a failure of the system to support screening as a process rather than an isolated test. If screening is performed routinely at the 12-month visit but there is no system for responding to the results, then the situation observed in our study might result. A systems-based approach might include broader involvement of clinical and nonclinical staff members and prompt and reminder systems (either electronic or paper-based).21, 22
The results of our study have several limitations that should be considered. First, the study was conducted in a Midwestern urban clinic network associated with the county hospital. The practice patterns and patient population might differ from other settings throughout the nation. Nonetheless, we think the issues highlighted here deserve consideration in any pediatric practice. Second, the study was retrospective, and we needed to make several inferences. For example, we defined children who had made ≥3 primary care visits to the practice network as “belonging” to that clinic, and we would expect anemia screening and follow-up monitoring to take place there. However, this method has been used successfully elsewhere.21 We also assumed that the purpose of the initial CBC was to screen for iron deficiency. We think this is justified because of the age (9–15 months) and the temporal association with a primary care visit. However, even if the intent of the CBC was not to screen for anemia in all cases, the lack of documented follow-up care is an indictment of the system. Finally, it could be argued that some children who met the screening criteria did not actually have iron deficiency anemia and therefore would not necessarily be expected to exhibit resolution in follow-up testing. Although this might be true for children who met standard hemoglobin or hematocrit screening thresholds, results obtained with our other criteria, which included highly specific measures of microcytosis, were correlated with recent national prevalence statistics and still reflected poor rates of follow-up care.
To serve effectively the children entrusted to our care, pediatricians need to reexamine how we approach iron deficiency. If we choose to proceed with a screen-and-treat approach to secondary prevention, then we must have uniform definitions of screening criteria and we must have effective systems to respond to abnormalities. Otherwise, we are wasting time and money while compromising children's care.
Funding for the group performing this research was provided by the Riley Children's Foundation.
- Accepted April 21, 2005.
- Address correspondence to Paul G. Biondich, MD, MS, Riley Research 330, 699 West Dr, Indianapolis, IN 46074. E-mail:
The views expressed in this article are those of the authors and do not necessarily represent the views of the Indiana University School of Medicine.
The authors have indicated they have no financial relationships relevant to this article to disclose.
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- Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr.2001;131(suppl 2) :649S– 668S
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- ↵US Preventive Services Task Force. Screening for iron deficiency anemia, including iron prophylaxis. In: Guide to Clinical Preventive Services. 2nd ed. Baltimore, MD: Williams & Wilkins; 1996:231–246
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- Copyright © 2006 by the American Academy of Pediatrics