Using Ferritin Levels To Determine Iron-Deficiency Anemia in Pregnancy

Standard obstetrical practice has included screening for anemia and the provision of iron supplements to anemic patients. This approach has been based on assumptions about anemia and iron deficiency that are not supported by the literature.

Anemia in pregnancy has been reported to be associated with preterm delivery.^1,2 However, this may not take into consideration the lower hemoglobin values normally present during the second trimester. The potentially spurious association between anemia and preterm delivery could be explained by the lower hemoglobin values that are expected during the second trimester. When measured at the time of preterm delivery, these lower hemoglobin values, which are normal in the second trimester (but not in the third trimester or in a nonpregnant woman), are often believed to have led to the preterm delivery.

Normal hemogloblin values from nonpregnant women cannot be assumed to apply to those who are pregnant. Average hemoglobin levels decrease to 11.6 g per dL at 20 to 24 weeks’ gestation, with the fifth percentile at 10.5 g per dL (hematocrit=32%). Anemia in pregnancy has been defined by criteria from the Centers for Disease Control and Prevention (CDC) as a hemoglobin level of less than 11 g per dL during the first and third trimesters and less than 10.5 g per dL during the second trimester.³

When anemia is present in pregnancy it cannot be assumed to be the result of iron deficiency, even though this type of anemia has been previously reported as the most common cause.⁴ The Camden study⁵ of 826 pregnant women showed preterm delivery and low birth weight associated with iron-deficiency anemia. Only 27.9% of the pregnant women had anemia, however, and only 12.5% of the patients with anemia had an iron deficiency. Thus, only 3.5% of the entire cohort had iron-deficiency anemia.⁶

Iron deficiency in pregnancy has been defined by the National Academy of Sciences panel on nutrition and pregnancy⁷ as ferritin levels lower than 12 ng per mL. A systematic overview⁸ of 55 studies relevant to laboratory tests for diagnosis of iron-deficiency anemia in variable patient populations found serum ferritin radioimmunoassay to be the most powerful test. Ferritin levels are considered the gold standard for the diagnosis of iron-deficiency anemia in pregnancy.⁹

We report a descriptive study of the use of ferritin levels to determine the need for iron supplementation among pregnant women with anemia.

Methods

Lebanon Family Health Services is a nonprofit federally subsidized community agency providing prenatal care and women’s health services to a diverse population without restriction on the basis of financial status. The prenatal patients cared for in this practice included women aged 15 to 40 years (23.6% were younger than 19 years; 70.8%, 19 to 30 years; and 5.6%, older than 30 years) of whom 65.3% were white, 29.2% Hispanic, 4.2% African American, and 1.4% Asian.

We evaluated all patients entering into prenatal care at Lebanon Family Health Services from April 1, 1997, through December 31, 1998, using prospective data collection and retrospective record review. Prenatal vitamins (including elemental iron 30 to 60 mg/day) were prescribed to all patients. Complete blood count was tested at the initial evaluation as part of a comprehensive screening. For patients who entered prenatal care at earlier than 28 weeks’ gestation complete blood count was checked again when they had reached that point.

The CDC criteria for defining anemia are hemoglobin levels less than 11 g per dL during the first and third trimesters, and less than 10.5 g per dL during the second trimester. A hemoglobin level of less than 11 g per dL at any time during the pregnancy was used as the cutoff point for anemia in this clinical practice, in consideration of patients with uncertain or inaccurate pregnancy dating.

Patients with anemia underwent blood testing for serum ferritin level, generally 1 week after a complete blood cell count. At the time, ferritin levels were determined using different test tubes than those used for other prenatal testing, thus resulting in a delay in obtaining blood for ferritin testing. If serum ferritin was 12 ng per dL or lower, iron-deficiency anemia was diagnosed and ferrous sulfate was prescribed for the remainder of the pregnancy and the postpartum period. If serum ferritin was greater than 12 ng per dL iron deficiency was excluded, anemia was generally considered to be pregnancy related, and further evaluation and treatment was at the discretion of the treating clinician.

Variables recorded for all patients with anemia were: estimated date of delivery, last menstrual period, date of any testing for complete blood count or ferritin levels, hemoglobin value, hematocrit value, red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), any notation regarding microcytosis, and serum ferritin levels.

Results

A total of 182 patients were consecutively entered into prenatal care during the study period. Hemoglobin data were not obtained from 9 patients—4 transferred to another practice for care before initial blood testing, 2 did not carry the pregnancy until initial blood testing, and 3 were lost to follow-up before initial blood testing. Thus, hemoglobin data were available for 173 patients (95%).

Thirty-eight women (22%) had anemia defined as a hemoglobin level lower than 11 mg per dL at any time during the pregnancy. One patient was excluded from further evaluation because she entered prenatal care late, had an initial hemoglobin level of 9.6 mg per dL at 39 weeks’ gestation, and was given iron without serum ferritin determination.

Of the 37 patients with anemia who had serum ferritin level measurements, the values ranged from 3 to 91 ng per dL. Twenty of these 37 patients (54%) had iron-deficiency anemia (ferritin levels ranging from 3-10 mg/dL), and 17 patients (46%) had anemia not related to iron deficiency (range=13-91 mg/dL).

Of the 38 patients with anemia by our definition, 20 had hemoglobin levels between 10.5 and 10.9 mg per dL, of whom 10 were between 14 and 28 weeks’ gestation (second trimester). Thus only 28 patients (16%) had anemia according to the CDC criteria. Of the 27 patients with anemia according to the CDC criteria (one patient was excluded), 17 (63%) had iron-deficiency anemia, and 10 (37%) had anemia not related to iron deficiency.

Discussion

Screening for anemia in pregnancy has been based on an association with an increased risk for preterm delivery.^1,2 This association is likely due to the comparison of the natural nadir in hemoglobin values in the second trimester, measured at the time of preterm delivery, with the higher hemoglobin values, measured at the time of term deliveries; this concept, however, has not been fully evaluated.¹ Despite the lack of evidence that screening for anemia improves clinical maternal, fetal, or neonatal outcomes¹⁰ standard obstetrical practice has been to screen all pregnant women for anemia and empirically treat anemic patients with iron therapy.

Although there is no convincing data demonstrating clear harm from iron therapy during pregnancy, limiting such therapy to patients with strictly defined anemia and demonstrated iron deficiency may be prudent to minimize potential harms from a practice not shown to clearly provide benefits.

In actual practice, with the common misdating of pregnancies and the potential inefficiency of complex management rules, it is possible that cutoff hemoglobin levels of 11 mg per dL for defining anemia in pregnancy without respect to gestational age are being used instead of the CDC criteria. By doing so, more patients without iron-deficiency anemia will be labeled as anemic.

The use of hematologic indices provided with complete blood count determination would be more efficient and less costly than serum ferritin determination, if they are shown to differentiate iron deficiency from other causes of anemia in pregnant women. Scatterplots have been used to estimate the discriminatory ability of continuous variables for discerning between patient populations.¹¹ We made scatterplots for RBC, MCV, MCH, MCHC, and RDW. None of these scatterplots suggested discriminatory ability for any of these variables. The results were unchanged when limited to patients with CDC-defined anemia.

Costs

Ferritin determination may be cost-effective depending on its cost, the cost of iron therapy, the prevalence of iron-deficiency anemia (which is dependent on the criteria for defining anemia), and the nonfinancial burden of unnecessary iron therapy. The costs of sparing women unnecessary iron therapy on the basis of these variables are detailed in the [Table]. Serum ferritin level determination cost $30 at the laboratory we used for our study. Other methods of determining iron deficiency (such as iron and total iron-binding capacity levels, which cost $35) were not evaluated, since the evidence did not suggest that these values were accurate or well known in pregnant women. Using numbers derived from our study, checking the ferritin levels of 100 pregnant women with anemia would cost $3000 and spare 37 to 46 women from taking iron, at a cost of $37.24 to $73.56 to prevent 1 woman from taking an unnecessary course of iron therapy.

Caretakers prescribing iron therapy are familiar with its adverse effects and relatively low tolerability. In a dose-finding study¹² of 110 pregnant women randomized to 1 of 3 doses of ferrous sulfate daily, 32.4% of those taking 60 mg of elemental iron (equivalent to 325 mg of ferrous sulfate) and 40.5% of those taking 120 mg of elemental iron (equivalent to common twice a day dosing) had side effects. Dropout rates matched the side effect rates (32.4% and 38.8%, respectively). Thus, for every 5 women treated with iron, 2 will develop side effects and stop taking it.

The cost-effectiveness of ferritin determination is highly dependent on and inversely related to the prevalence of iron-deficiency anemia in the patient population. As seen in the Table, if the prevalence of iron-deficiency anemia is sufficiently low, ferritin determination may be very cost-effective.

Clinicians should consider the local costs of ferrous sulfate, ferritin determination, and the prevalence of iron-deficiency anemia in their patient population in the evaluation of the use of ferritin determination instead of empiric iron therapy. Alternately, clinicians may present some of the issues and uncertainties to their patients for combined decision making.

Conclusions

In our population of prenatal patients with anemia, only 54% had an iron deficiency. Diagnostic and therapeutic approaches to screening for anemia in pregnancy should be reconsidered and further evaluated to avoid unnecessary iron therapy.

Acknowledgments

We would like to acknowledge Siobhan Ulrich, Jan Balmer, Sue Gibson, and Tracy Chappel for their efforts in implementing the practice protocol and keeping track of patient records.

Standard obstetrical practice has included screening for anemia and the provision of iron supplements to anemic patients. This approach has been based on assumptions about anemia and iron deficiency that are not supported by the literature.

Anemia in pregnancy has been reported to be associated with preterm delivery.^1,2 However, this may not take into consideration the lower hemoglobin values normally present during the second trimester. The potentially spurious association between anemia and preterm delivery could be explained by the lower hemoglobin values that are expected during the second trimester. When measured at the time of preterm delivery, these lower hemoglobin values, which are normal in the second trimester (but not in the third trimester or in a nonpregnant woman), are often believed to have led to the preterm delivery.

Normal hemogloblin values from nonpregnant women cannot be assumed to apply to those who are pregnant. Average hemoglobin levels decrease to 11.6 g per dL at 20 to 24 weeks’ gestation, with the fifth percentile at 10.5 g per dL (hematocrit=32%). Anemia in pregnancy has been defined by criteria from the Centers for Disease Control and Prevention (CDC) as a hemoglobin level of less than 11 g per dL during the first and third trimesters and less than 10.5 g per dL during the second trimester.³

When anemia is present in pregnancy it cannot be assumed to be the result of iron deficiency, even though this type of anemia has been previously reported as the most common cause.⁴ The Camden study⁵ of 826 pregnant women showed preterm delivery and low birth weight associated with iron-deficiency anemia. Only 27.9% of the pregnant women had anemia, however, and only 12.5% of the patients with anemia had an iron deficiency. Thus, only 3.5% of the entire cohort had iron-deficiency anemia.⁶

Iron deficiency in pregnancy has been defined by the National Academy of Sciences panel on nutrition and pregnancy⁷ as ferritin levels lower than 12 ng per mL. A systematic overview⁸ of 55 studies relevant to laboratory tests for diagnosis of iron-deficiency anemia in variable patient populations found serum ferritin radioimmunoassay to be the most powerful test. Ferritin levels are considered the gold standard for the diagnosis of iron-deficiency anemia in pregnancy.⁹

We report a descriptive study of the use of ferritin levels to determine the need for iron supplementation among pregnant women with anemia.

Methods

Lebanon Family Health Services is a nonprofit federally subsidized community agency providing prenatal care and women’s health services to a diverse population without restriction on the basis of financial status. The prenatal patients cared for in this practice included women aged 15 to 40 years (23.6% were younger than 19 years; 70.8%, 19 to 30 years; and 5.6%, older than 30 years) of whom 65.3% were white, 29.2% Hispanic, 4.2% African American, and 1.4% Asian.

We evaluated all patients entering into prenatal care at Lebanon Family Health Services from April 1, 1997, through December 31, 1998, using prospective data collection and retrospective record review. Prenatal vitamins (including elemental iron 30 to 60 mg/day) were prescribed to all patients. Complete blood count was tested at the initial evaluation as part of a comprehensive screening. For patients who entered prenatal care at earlier than 28 weeks’ gestation complete blood count was checked again when they had reached that point.

The CDC criteria for defining anemia are hemoglobin levels less than 11 g per dL during the first and third trimesters, and less than 10.5 g per dL during the second trimester. A hemoglobin level of less than 11 g per dL at any time during the pregnancy was used as the cutoff point for anemia in this clinical practice, in consideration of patients with uncertain or inaccurate pregnancy dating.

Patients with anemia underwent blood testing for serum ferritin level, generally 1 week after a complete blood cell count. At the time, ferritin levels were determined using different test tubes than those used for other prenatal testing, thus resulting in a delay in obtaining blood for ferritin testing. If serum ferritin was 12 ng per dL or lower, iron-deficiency anemia was diagnosed and ferrous sulfate was prescribed for the remainder of the pregnancy and the postpartum period. If serum ferritin was greater than 12 ng per dL iron deficiency was excluded, anemia was generally considered to be pregnancy related, and further evaluation and treatment was at the discretion of the treating clinician.

Variables recorded for all patients with anemia were: estimated date of delivery, last menstrual period, date of any testing for complete blood count or ferritin levels, hemoglobin value, hematocrit value, red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), any notation regarding microcytosis, and serum ferritin levels.

Results

A total of 182 patients were consecutively entered into prenatal care during the study period. Hemoglobin data were not obtained from 9 patients—4 transferred to another practice for care before initial blood testing, 2 did not carry the pregnancy until initial blood testing, and 3 were lost to follow-up before initial blood testing. Thus, hemoglobin data were available for 173 patients (95%).

Thirty-eight women (22%) had anemia defined as a hemoglobin level lower than 11 mg per dL at any time during the pregnancy. One patient was excluded from further evaluation because she entered prenatal care late, had an initial hemoglobin level of 9.6 mg per dL at 39 weeks’ gestation, and was given iron without serum ferritin determination.

Of the 37 patients with anemia who had serum ferritin level measurements, the values ranged from 3 to 91 ng per dL. Twenty of these 37 patients (54%) had iron-deficiency anemia (ferritin levels ranging from 3-10 mg/dL), and 17 patients (46%) had anemia not related to iron deficiency (range=13-91 mg/dL).

Of the 38 patients with anemia by our definition, 20 had hemoglobin levels between 10.5 and 10.9 mg per dL, of whom 10 were between 14 and 28 weeks’ gestation (second trimester). Thus only 28 patients (16%) had anemia according to the CDC criteria. Of the 27 patients with anemia according to the CDC criteria (one patient was excluded), 17 (63%) had iron-deficiency anemia, and 10 (37%) had anemia not related to iron deficiency.

Discussion

Screening for anemia in pregnancy has been based on an association with an increased risk for preterm delivery.^1,2 This association is likely due to the comparison of the natural nadir in hemoglobin values in the second trimester, measured at the time of preterm delivery, with the higher hemoglobin values, measured at the time of term deliveries; this concept, however, has not been fully evaluated.¹ Despite the lack of evidence that screening for anemia improves clinical maternal, fetal, or neonatal outcomes¹⁰ standard obstetrical practice has been to screen all pregnant women for anemia and empirically treat anemic patients with iron therapy.

Although there is no convincing data demonstrating clear harm from iron therapy during pregnancy, limiting such therapy to patients with strictly defined anemia and demonstrated iron deficiency may be prudent to minimize potential harms from a practice not shown to clearly provide benefits.

In actual practice, with the common misdating of pregnancies and the potential inefficiency of complex management rules, it is possible that cutoff hemoglobin levels of 11 mg per dL for defining anemia in pregnancy without respect to gestational age are being used instead of the CDC criteria. By doing so, more patients without iron-deficiency anemia will be labeled as anemic.

The use of hematologic indices provided with complete blood count determination would be more efficient and less costly than serum ferritin determination, if they are shown to differentiate iron deficiency from other causes of anemia in pregnant women. Scatterplots have been used to estimate the discriminatory ability of continuous variables for discerning between patient populations.¹¹ We made scatterplots for RBC, MCV, MCH, MCHC, and RDW. None of these scatterplots suggested discriminatory ability for any of these variables. The results were unchanged when limited to patients with CDC-defined anemia.

Costs

Ferritin determination may be cost-effective depending on its cost, the cost of iron therapy, the prevalence of iron-deficiency anemia (which is dependent on the criteria for defining anemia), and the nonfinancial burden of unnecessary iron therapy. The costs of sparing women unnecessary iron therapy on the basis of these variables are detailed in the [Table]. Serum ferritin level determination cost $30 at the laboratory we used for our study. Other methods of determining iron deficiency (such as iron and total iron-binding capacity levels, which cost $35) were not evaluated, since the evidence did not suggest that these values were accurate or well known in pregnant women. Using numbers derived from our study, checking the ferritin levels of 100 pregnant women with anemia would cost $3000 and spare 37 to 46 women from taking iron, at a cost of $37.24 to $73.56 to prevent 1 woman from taking an unnecessary course of iron therapy.

Caretakers prescribing iron therapy are familiar with its adverse effects and relatively low tolerability. In a dose-finding study¹² of 110 pregnant women randomized to 1 of 3 doses of ferrous sulfate daily, 32.4% of those taking 60 mg of elemental iron (equivalent to 325 mg of ferrous sulfate) and 40.5% of those taking 120 mg of elemental iron (equivalent to common twice a day dosing) had side effects. Dropout rates matched the side effect rates (32.4% and 38.8%, respectively). Thus, for every 5 women treated with iron, 2 will develop side effects and stop taking it.

The cost-effectiveness of ferritin determination is highly dependent on and inversely related to the prevalence of iron-deficiency anemia in the patient population. As seen in the Table, if the prevalence of iron-deficiency anemia is sufficiently low, ferritin determination may be very cost-effective.

Clinicians should consider the local costs of ferrous sulfate, ferritin determination, and the prevalence of iron-deficiency anemia in their patient population in the evaluation of the use of ferritin determination instead of empiric iron therapy. Alternately, clinicians may present some of the issues and uncertainties to their patients for combined decision making.

Conclusions

In our population of prenatal patients with anemia, only 54% had an iron deficiency. Diagnostic and therapeutic approaches to screening for anemia in pregnancy should be reconsidered and further evaluated to avoid unnecessary iron therapy.

Acknowledgments

We would like to acknowledge Siobhan Ulrich, Jan Balmer, Sue Gibson, and Tracy Chappel for their efforts in implementing the practice protocol and keeping track of patient records.

Standard obstetrical practice has included screening for anemia and the provision of iron supplements to anemic patients. This approach has been based on assumptions about anemia and iron deficiency that are not supported by the literature.

Anemia in pregnancy has been reported to be associated with preterm delivery.^1,2 However, this may not take into consideration the lower hemoglobin values normally present during the second trimester. The potentially spurious association between anemia and preterm delivery could be explained by the lower hemoglobin values that are expected during the second trimester. When measured at the time of preterm delivery, these lower hemoglobin values, which are normal in the second trimester (but not in the third trimester or in a nonpregnant woman), are often believed to have led to the preterm delivery.

Normal hemogloblin values from nonpregnant women cannot be assumed to apply to those who are pregnant. Average hemoglobin levels decrease to 11.6 g per dL at 20 to 24 weeks’ gestation, with the fifth percentile at 10.5 g per dL (hematocrit=32%). Anemia in pregnancy has been defined by criteria from the Centers for Disease Control and Prevention (CDC) as a hemoglobin level of less than 11 g per dL during the first and third trimesters and less than 10.5 g per dL during the second trimester.³

When anemia is present in pregnancy it cannot be assumed to be the result of iron deficiency, even though this type of anemia has been previously reported as the most common cause.⁴ The Camden study⁵ of 826 pregnant women showed preterm delivery and low birth weight associated with iron-deficiency anemia. Only 27.9% of the pregnant women had anemia, however, and only 12.5% of the patients with anemia had an iron deficiency. Thus, only 3.5% of the entire cohort had iron-deficiency anemia.⁶

Iron deficiency in pregnancy has been defined by the National Academy of Sciences panel on nutrition and pregnancy⁷ as ferritin levels lower than 12 ng per mL. A systematic overview⁸ of 55 studies relevant to laboratory tests for diagnosis of iron-deficiency anemia in variable patient populations found serum ferritin radioimmunoassay to be the most powerful test. Ferritin levels are considered the gold standard for the diagnosis of iron-deficiency anemia in pregnancy.⁹

We report a descriptive study of the use of ferritin levels to determine the need for iron supplementation among pregnant women with anemia.

Methods

Lebanon Family Health Services is a nonprofit federally subsidized community agency providing prenatal care and women’s health services to a diverse population without restriction on the basis of financial status. The prenatal patients cared for in this practice included women aged 15 to 40 years (23.6% were younger than 19 years; 70.8%, 19 to 30 years; and 5.6%, older than 30 years) of whom 65.3% were white, 29.2% Hispanic, 4.2% African American, and 1.4% Asian.

We evaluated all patients entering into prenatal care at Lebanon Family Health Services from April 1, 1997, through December 31, 1998, using prospective data collection and retrospective record review. Prenatal vitamins (including elemental iron 30 to 60 mg/day) were prescribed to all patients. Complete blood count was tested at the initial evaluation as part of a comprehensive screening. For patients who entered prenatal care at earlier than 28 weeks’ gestation complete blood count was checked again when they had reached that point.

The CDC criteria for defining anemia are hemoglobin levels less than 11 g per dL during the first and third trimesters, and less than 10.5 g per dL during the second trimester. A hemoglobin level of less than 11 g per dL at any time during the pregnancy was used as the cutoff point for anemia in this clinical practice, in consideration of patients with uncertain or inaccurate pregnancy dating.

Patients with anemia underwent blood testing for serum ferritin level, generally 1 week after a complete blood cell count. At the time, ferritin levels were determined using different test tubes than those used for other prenatal testing, thus resulting in a delay in obtaining blood for ferritin testing. If serum ferritin was 12 ng per dL or lower, iron-deficiency anemia was diagnosed and ferrous sulfate was prescribed for the remainder of the pregnancy and the postpartum period. If serum ferritin was greater than 12 ng per dL iron deficiency was excluded, anemia was generally considered to be pregnancy related, and further evaluation and treatment was at the discretion of the treating clinician.

Variables recorded for all patients with anemia were: estimated date of delivery, last menstrual period, date of any testing for complete blood count or ferritin levels, hemoglobin value, hematocrit value, red blood cell count (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), red cell distribution width (RDW), any notation regarding microcytosis, and serum ferritin levels.

Results

A total of 182 patients were consecutively entered into prenatal care during the study period. Hemoglobin data were not obtained from 9 patients—4 transferred to another practice for care before initial blood testing, 2 did not carry the pregnancy until initial blood testing, and 3 were lost to follow-up before initial blood testing. Thus, hemoglobin data were available for 173 patients (95%).

Thirty-eight women (22%) had anemia defined as a hemoglobin level lower than 11 mg per dL at any time during the pregnancy. One patient was excluded from further evaluation because she entered prenatal care late, had an initial hemoglobin level of 9.6 mg per dL at 39 weeks’ gestation, and was given iron without serum ferritin determination.

Of the 37 patients with anemia who had serum ferritin level measurements, the values ranged from 3 to 91 ng per dL. Twenty of these 37 patients (54%) had iron-deficiency anemia (ferritin levels ranging from 3-10 mg/dL), and 17 patients (46%) had anemia not related to iron deficiency (range=13-91 mg/dL).

Of the 38 patients with anemia by our definition, 20 had hemoglobin levels between 10.5 and 10.9 mg per dL, of whom 10 were between 14 and 28 weeks’ gestation (second trimester). Thus only 28 patients (16%) had anemia according to the CDC criteria. Of the 27 patients with anemia according to the CDC criteria (one patient was excluded), 17 (63%) had iron-deficiency anemia, and 10 (37%) had anemia not related to iron deficiency.

Discussion

Screening for anemia in pregnancy has been based on an association with an increased risk for preterm delivery.^1,2 This association is likely due to the comparison of the natural nadir in hemoglobin values in the second trimester, measured at the time of preterm delivery, with the higher hemoglobin values, measured at the time of term deliveries; this concept, however, has not been fully evaluated.¹ Despite the lack of evidence that screening for anemia improves clinical maternal, fetal, or neonatal outcomes¹⁰ standard obstetrical practice has been to screen all pregnant women for anemia and empirically treat anemic patients with iron therapy.

Although there is no convincing data demonstrating clear harm from iron therapy during pregnancy, limiting such therapy to patients with strictly defined anemia and demonstrated iron deficiency may be prudent to minimize potential harms from a practice not shown to clearly provide benefits.

In actual practice, with the common misdating of pregnancies and the potential inefficiency of complex management rules, it is possible that cutoff hemoglobin levels of 11 mg per dL for defining anemia in pregnancy without respect to gestational age are being used instead of the CDC criteria. By doing so, more patients without iron-deficiency anemia will be labeled as anemic.

The use of hematologic indices provided with complete blood count determination would be more efficient and less costly than serum ferritin determination, if they are shown to differentiate iron deficiency from other causes of anemia in pregnant women. Scatterplots have been used to estimate the discriminatory ability of continuous variables for discerning between patient populations.¹¹ We made scatterplots for RBC, MCV, MCH, MCHC, and RDW. None of these scatterplots suggested discriminatory ability for any of these variables. The results were unchanged when limited to patients with CDC-defined anemia.

Costs

Ferritin determination may be cost-effective depending on its cost, the cost of iron therapy, the prevalence of iron-deficiency anemia (which is dependent on the criteria for defining anemia), and the nonfinancial burden of unnecessary iron therapy. The costs of sparing women unnecessary iron therapy on the basis of these variables are detailed in the [Table]. Serum ferritin level determination cost $30 at the laboratory we used for our study. Other methods of determining iron deficiency (such as iron and total iron-binding capacity levels, which cost $35) were not evaluated, since the evidence did not suggest that these values were accurate or well known in pregnant women. Using numbers derived from our study, checking the ferritin levels of 100 pregnant women with anemia would cost $3000 and spare 37 to 46 women from taking iron, at a cost of $37.24 to $73.56 to prevent 1 woman from taking an unnecessary course of iron therapy.

Caretakers prescribing iron therapy are familiar with its adverse effects and relatively low tolerability. In a dose-finding study¹² of 110 pregnant women randomized to 1 of 3 doses of ferrous sulfate daily, 32.4% of those taking 60 mg of elemental iron (equivalent to 325 mg of ferrous sulfate) and 40.5% of those taking 120 mg of elemental iron (equivalent to common twice a day dosing) had side effects. Dropout rates matched the side effect rates (32.4% and 38.8%, respectively). Thus, for every 5 women treated with iron, 2 will develop side effects and stop taking it.

The cost-effectiveness of ferritin determination is highly dependent on and inversely related to the prevalence of iron-deficiency anemia in the patient population. As seen in the Table, if the prevalence of iron-deficiency anemia is sufficiently low, ferritin determination may be very cost-effective.

Clinicians should consider the local costs of ferrous sulfate, ferritin determination, and the prevalence of iron-deficiency anemia in their patient population in the evaluation of the use of ferritin determination instead of empiric iron therapy. Alternately, clinicians may present some of the issues and uncertainties to their patients for combined decision making.

Conclusions

In our population of prenatal patients with anemia, only 54% had an iron deficiency. Diagnostic and therapeutic approaches to screening for anemia in pregnancy should be reconsidered and further evaluated to avoid unnecessary iron therapy.

Acknowledgments

We would like to acknowledge Siobhan Ulrich, Jan Balmer, Sue Gibson, and Tracy Chappel for their efforts in implementing the practice protocol and keeping track of patient records.