Prevalence of Iron Deficiency and Iron Deficiency Anemia among ...

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Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, Massachusetts. Key words: military personnel, iron, iron ...
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Prevalence of Iron Deficiency and Iron Deficiency Anemia among Three Populations of Female Military Personnel in the US Army James P. McClung, PhD, Louis J. Marchitelli, MS, Karl E. Friedl, PhD, Andrew J. Young, PhD Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, Massachusetts Key words: military personnel, iron, iron deficiency, anemia Background: Iron deficiency is the most prevalent micronutrient deficiency disease in the world and occurs in young women in the United States. Female military personnel represent a unique population faced with intense physical and cognitive demands. Objective: The objective of this study was to determine the prevalence of iron deficiency and iron deficiency anemia among three populations of female military personnel in the US Army. Methods: Iron status was assessed in 1216 volunteers. Volunteers were recruited from three groups: immediately following initial entry to the Army (IET), immediately following basic combat training (AIT), or following at least six months of permanent assignment (PP). Iron deficiency was determined using a three variable model, including cut-off values for serum ferritin, transferrin saturation, and red cell distribution width (RDW). Iron deficiency anemia was categorized by iron deficiency and a hemoglobin (Hgb) value of ⬍12 g/dL. Results: The prevalence of iron deficiency was greater in women in the AIT group (32.8%) than in the IET and PP groups (13.4 and 9.6%, respectively). The prevalence of iron deficiency anemia was greater in the AIT group (20.9%) than in the IET and PP groups (5.8 and 4.8%, respectively). Furthermore, the prevalence of iron deficiency anemia was greater in Hispanic (21.9%) and African-American military personnel (22.9%) than in Caucasian military personnel (10.5%). Conclusions: These data indicate that female military personnel experience diminished iron status following training, and that iron nutriture is an important issue facing females in the military.

INTRODUCTION

problem, affecting up to 16% of females between the ages of 12– 49 [3]. The prevalence of iron deficiency is greater in non-Hispanic black and Mexican-American females (19 –22%) than in non-Hispanic white females (10%). Furthermore, data from the NHANES 1999 –2000 study indicates that the overall prevalence of iron deficiency anemia is highest in females between the ages of 20 – 49. Female military personnel represent a unique population exposed to intense metabolic and cognitive demands as well as immune challenges, particularly during field training or when operationally deployed. Maintaining optimal iron nutriture in these women is essential, as iron deficiency and its anemia have

Iron deficiency is the most prevalent micronutrient deficiency disease in the world, affecting up to 2 billion people [1–2]. Although iron deficiency occurs at greater rates in developing countries, a significant prevalence continues to be observed in the United States (US), especially among young women. Most recently, the prevalence of iron deficiency and iron deficiency anemia in the US was determined using data from the 1999 –2000 National Health and Nutrition Examination Survey (NHANES 1999 –2000). Data from this study indicate that iron deficiency is a serious US public health

Address reprint requests to: James P. McClung, PhD, Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM), Natick, MA 01760. E-mail: [email protected] This research was performed while Dr. McClung held a National Research Council Research Associateship Award at USARIEM. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Any citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement or approval of the products or services of these organizations.

Journal of the American College of Nutrition, Vol. 25, No. 1, 64–69 (2006) Published by the American College of Nutrition 64

Iron Status in Female Military Personnel important health implications. Changes in immune function, cognitive development and behavior, energy metabolism, and work capacity have been described in animals and humans with suboptimal iron status [4 – 6]. Although studies examining iron status in female military personnel are limited, suboptimal iron intakes have been reported in female military personnel in both garrison and field training studies [7]. In male military personnel, suboptimal iron intakes have been reported during field studies [8], and perturbations in iron status occurred during intense training periods [9 –10]. The objective of the present study was to determine and compare the prevalence of iron deficiency and iron deficiency anemia among three populations of female military personnel in the US Army. The three groups included military personnel immediately following initial entry to the Army (IET), immediately following basic combat training (AIT), and during permanent party assignments (PP).

MATERIALS AND METHODS Subjects and Experimental Design This study was approved by the Human Use Review Committee at the US Army Research Institute of Environmental Medicine. Human subjects participated in these studies after giving their free and informed voluntary consent. Investigators adhered to Army Regulation 70-25 and US Army Medical Research and Materiel Command Regulation 70-25 on the use of volunteers in research. A total of 1216 female volunteers completed the study. All volunteers were under 45 years old, were not pregnant, and had not exercised in the four hours prior to blood collection. Volunteers were recruited at four separate geographic locations over a nine month period. The testing locations included Fort Sam Houston (TX), Fort Leonard Wood (MO), Fort Gordon (GA), and Aberdeen Proving Ground (MD). Volunteers were recruited for three specific study groups. Military personnel in the IET group included new recruits that had participated in basic combat training (BCT) for one week or less; personnel in the AIT group included trainees that were within the final two weeks of BCT and not past four weeks of the completion of the training; and the PP group included only personnel that had been at permanent duty assignments for at least six months. The BCT period consisted of eight weeks of training, including military training operations and both aerobic and muscle strength training. Military training operations included prolonged standing in formation, tactical road marches, rappelling, bayonet training, live fire exercises, and obstacle courses. Organized exercise activity was conducted 4 – 6 times per week for a period of one hour, beginning with a 10 –15 minute stretching period. Aerobic exercises included distance running and sprints. Muscle strength training included a variety of callisthenic exercises, push-ups, sit-ups, crawls, high jumps, and supine bicycles [11].

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Although the PP military personnel were heavier (p ⬍ 0.05) than the personnel in the IET and AIT groups, weight was not significantly related to either iron deficiency or iron deficiency anemia among the three groups. The PP military personnel were older (p ⬍ 0.05) than the personnel in the IET and AIT groups. Age was related to iron deficiency, but the relationship was weak and could have been due to chance, given the large number of analyses conducted. Age was not related to iron deficiency anemia. Although there was no difference in the percentage of Caucasians between the three groups, there were more (p ⬍ 0.05) African-American military personnel in the PP group than in the IET and AIT groups. Characteristics of each of the three populations appear in Table 1.

Sample Collection and Analysis Blood was collected by antecubital venipuncture into tubes (Vacutainer; Becton-Dickenson, Franklin Lakes, NJ) containing the appropriate anticoagulant. Samples were processed on site, aliquoted, frozen, and shipped to the Pennington Biomedical Research Center (Baton Rouge, LA) for iron status indicator assays. Briefly, total iron binding capacity and serum iron were determined using a Beckman Coulter Synchron CX7 (Beckman Coulter, Fullerton, CA). Serum ferritin was determined by microparticle enzyme immunoassay (IMx; Abbott Laboratories, Abbott Park, IL, USA). Transferrin saturation was determined by dividing serum iron by total iron binding capacity [12]. Red cell distribution width (RDW), hemoglobin (Hgb), and hematocrit (Hct) were determined on site with fresh blood using a hematology analyzer (ONYX, Beckman Coulter).

Classification of Iron Deficiency Perturbations in iron nutriture can be classified into two stages: iron deficiency and iron deficiency anemia. Iron deficiency occurs as iron stores decline and a decrease in transport iron occurs [4]. Iron deficiency anemia occurs as the synthesis of iron-containing proteins, such as Hgb, become compromised to the point at which values fall below a specified cut-off [6]. Table 1. Subject Characteristics (Mean ⫾ SD) Group: Characteristic Age Height (cm) Weight (kg) Ethnic Group (%) Caucasian Hispanic African-American Other

IET (n ⫽ 164) 19.8 (⫾3) 164.0 (⫾6.9) 63.5 (⫾9.6) 56.7 9.1 31.1 3.0

AIT (n ⫽ 308)

PP (n ⫽ 744)

21.8 (⫾4)* 30.0 (⫾7)† 163.1 (⫾6.5) 163.4 (⫾6.3) 64.5 (⫾7.8) 66.1 (⫾9.8)† 52.6 10.4 28.2 8.7

47.6 6.1# 40.0† 6.3

Asterisks (*) indicate differences (p ⬍ 0.05) as compared to IET and PP. Crosses (†) indicate differences (p ⬍ 0.05) as compared to IET and AIT. Number signs (#) indicate differences (p ⬍ 0.05) as compared to AIT.

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Iron Status in Female Military Personnel In the present study we utilized a three variable model to categorize iron deficiency. We chose to use a multiple variable model based upon studies that showed that the prevalence of anemia among persons with only one abnormal indicator of iron status was only slightly higher than the entire population, and that the prevalence of anemia is much greater in persons with two or three abnormal indicators [13]. Multiple variable models are useful methods for determining the prevalence of iron deficiency in populations because they overcome misclassifications that may occur due to errors in single indicators, and have been used to determine the prevalence of iron deficiency in the NHANES studies [3,12,14]. In the present study, female military personnel were categorized as iron deficient if they presented with two of the following three indicators of abnormal iron status: serum ferritin ⬍12 ng/mL, transferrin saturation ⬍16%, or RDW ⬎15%. Military personnel were classified as having iron deficiency anemia if they were iron deficient and had Hgb levels below 12 g/dL.

Statistical Analysis Statistical analysis was performed using commercially available statistical software (SPSS 13.0; SPSS Inc., Chicago, IL). Descriptive statistics are presented as means ⫾ standard deviation (SD). Differences were assessed using a one-way analysis of variance (ANOVA). When a significant overall effect was detected, data was subjected to post-hoc analysis using Tukey’s HSD. For comparison of the ethnic characteristics of the groups (Table 1), a Pearson Chi-square was utilized followed by a Fisher’s Exact Test (2-sided) to determine pvalues. A minimum p-value of 0.05 was the necessary condition for statistical significance.

RESULTS Diminished Markers of Iron Status Following BCT Iron status was diminished in female military personnel immediately following BCT, as all of the status indicators measured in this study were significantly decreased in the AIT group as compared to the IET group. Markers of iron storage and transport were affected, as serum ferritin and transferrin saturation were reduced (p ⬍ 0.001) and RDW was increased (p ⬍ 0.05) in the AIT group as compared to the IET group (Table 2). Furthermore, levels of Hgb and Hct were reduced (p ⬍ 0.001) in the AIT group as compared to both the IET and PP groups (Table 2). There was no difference in these markers of iron status in the PP group as compared to the IET group, indicating that iron status is improved upon completion of at least six months at a permanent duty station.

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Table 2. Indicators of Iron Status in Female Military Personnel during Three Phases of Training (Mean ⫾ SD) Group: Indicator Serum Ferritin (ng/mL) Transferrin Saturation (%) RDW (%) Hgb (g/dL) Hct (%)

IET

AIT

PP

33.9 (⫾28.1) 20.5 (⫾17.8)* 36.4 (⫾31.2) 21.8 (⫾10.4) 15.6 (⫾8.5)*

23.1 (⫾11.0)

13.2 (⫾1.1) 13.2 (⫾1.0) 39.1 (⫾2.7)

13.2 (⫾1.0) 13.0 (⫾0.9) 38.5 (⫾2.6)

13.6 (⫾1.3)* 12.6 (⫾1.0)* 37.5 (⫾3.0)*

Asterisks (*) indicated significant (p ⬍ 0.05) differences as compared to IET and PP.

Prevalence of Iron Deficiency and Iron Deficiency Anemia in Female Military Personnel Using the three variable model, the overall prevalence of iron deficiency was 13.4% in female military personnel upon initial entry into the Army (Fig. 1A). The prevalence of iron deficiency increased dramatically following BCT, to 32.8% in the AIT group, and was lower (9.6%) in the PP group. Likewise, the prevalence of iron deficiency anemia in the IET group was 5.8%, increased dramatically to 20.9% in the AIT group, and fell to 4.8% among women in the PP group (Fig. 1B).

Prevalence of Iron Deficiency and Iron Deficiency Anemia among Ethnic Groups Upon initial entry to the Army, the prevalence of iron deficiency was similar between Caucasian and Hispanic military personnel (8.9 vs. 7.1%) and higher in African-American military personnel (16.7%) (Table 3). In the AIT group, the prevalence of iron deficiency was greater in Hispanic and African-American military personnel (43.8 and 32.5%) than in Caucasian personnel (24.8%). Rates of iron deficiency in the PP group were similar between the ethnic groups. Rates of iron deficiency anemia in the IET group were greatest (8.3%) in African-American military personnel (Table 3). In the AIT group, the prevalence of iron deficiency anemia in Hispanic and African-American military personnel (21.9 and 22.9%) was more than double that of Caucasian personnel (10.5%). The prevalence of iron deficiency anemia in the PP group was also highest (5.6%) in African-American military personnel as compared to Caucasian (2.0%) and Hispanic (0%) personnel.

DISCUSSION Iron deficiency and its anemia are known to affect physical, cognitive, and immune function [4 – 6]. Female military personnel are exposed to various physical, cognitive, and immune challenges, especially during field training or when operationally deployed, and changes in iron status could impact their

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Fig. 1. Prevalence of iron deficiency (A) and iron deficiency anemia (B) among three populations of female military personnel. The definition of iron deficiency was an abnormal value for at least two of the following three indicators: serum ferritin, transferrin saturation, and RDW. The definition of iron deficiency anemia was iron deficiency as well as a low Hgb value.

Table 3. Prevalence of Iron Deficiency and Iron Deficiency Anemia in Select Ethnic Groups of Female Military Personnel during Three Phases of Training Group: Prevalence (%) Iron Deficiency1 Caucasian Hispanic African-American Iron Deficiency Anemia2 Caucasian Hispanic African-American

IET

AIT

PP

8.9 7.1 16.7

24.8 43.8 32.5

7.9 6.8 8.7

2.2 0 8.3

10.5 21.9 22.9

2.0 0 5.6

1

The definition of iron deficiency was an abnormal value for at least two of the following three indicators: serum ferritin, transferrin saturation, and RDW. 2 The definition of iron deficiency anemia was iron deficiency as well as a low Hgb value.

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response to these challenges. Perturbations in iron status have been reported in male military personnel during intense training periods [9 –10], but iron status has never been investigated in female military personnel. However, suboptimal iron intakes have been reported in both male and female military personnel in garrison and field training studies [7– 8]. Therefore, the objective of the present study was to determine and compare the prevalence of iron deficiency and iron deficiency anemia among three populations of female military personnel in the US Army. The major findings of this cross-sectional study indicate that the prevalence of iron deficiency and iron deficiency anemia is elevated in military personnel immediately following BCT as compared to initial entry to the Army and after six months assignment to a permanent duty station. Furthermore, the prevalence of iron deficiency and iron deficiency anemia in military personnel in that population is greater in Hispanic and African-American personnel than in Caucasian personnel. A three variable model was used to determine the prevalence of iron deficiency in this study. Multiple variable models are useful methods for determining the prevalence of iron deficiency in populations because they overcome misclassifications that may occur due to errors arising from any single indicator [12]. The three variables we chose as indicators of iron status included serum ferritin, transferrin saturation, and RDW, each of which have been utilized as reliable markers of iron nutriture [12]. In the present study, the overall prevalence of iron deficiency in female military personnel upon initial entry to the Army (IET) was 13.4%, which is similar to the prevalence seen among lower income women from NHANES 1999 –2000. Rates of iron deficiency anemia were also similar in female military personnel in the IET group as compared to the rates for American females between the ages of 20 – 49 determined using the NHANES 1999 –2000 data (5.8% vs. 4%). Our data indicate that iron status is diminished among female military personnel immediately upon completion of BCT as compared to initial entry to the Army or during permanent assignments. One possible contributing factor for the decline in iron status seen in female military personnel following BCT is the effect of sustained physical training. Numerous studies have shown that physical training affects iron status and anemia [15]. In one study, sustained submaximal exercise caused decreased levels of Hgb, Hct, and mean corpuscular volume in male military personnel during a six day march [16]. Others have shown diminished serum iron, ferritin, and Hgb levels in both male and female athletes following a seven week training period [17]. Although the mechanism by which physical training results in diminished iron status remains unknown, possible explanations include increased iron loss in sweat and urine [18], exercise-induced increases in red blood cell fragility [16], the acute-phase response [9,19], or plasma volume expansion [20]. Another possible contributing factor for the decline in iron status in female military personnel following BCT is dietary intake. Garrison dining facilities and military field feeding

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Iron Status in Female Military Personnel programs are designed to provide the nutrients and energy necessary to maintain health and performance under all conditions. Nevertheless, underconsumption of food by military personnel during field exercises has been identified as a major concern for physical performance [21], and inadequate iron intake has been observed in male and female military personnel during both garrison and field training studies [7– 8]. Although neither energy nor iron intake data were collected during this study, collection of such data will be necessary for the identification of the mechanism by which iron status is diminished following BCT in future studies. We found that the prevalence of iron deficiency and iron deficiency anemia was greatest in Hispanic and African-American female military personnel following BCT. In fact, the prevalence of iron deficiency anemia in Hispanics and AfricanAmericans was double that of Caucasians in the AIT group. Elevated prevalences of iron deficiency and iron deficiency anemia have also been identified in minorities in the American population. Data from the NHANES 1999 –2000 study indicates that the prevalence of iron deficiency in African-American and Mexican American females aged 20 – 49 is double that of Caucasian females [3]. Furthermore, in data collected from NHANES II and Hispanic HANES, the prevalence of iron deficiency anemia in Mexican American females aged 20 – 44 was more than double that of Caucasian females of the same age [22]. The difference in the prevalence of iron deficiency and iron deficiency anemia among ethnic groups following BCT is difficult to explain. Although diminished iron status in minorities has been attributed to inadequate iron intake due to poor socioeconomic status in American populations [23], it may be assumed that all individuals in the AIT group from this study were offered the same diet during BCT. It is possible that there are biological differences in iron metabolism among ethnic groups, as recent studies have demonstrated that even after adjusting for sociodemographic and dietary factors, Mexican American women remain at risk for low iron stores [24]. Our finding that the prevalence of iron deficiency and iron deficiency anemia is elevated in female military personnel immediately following BCT suggests that strategies to sustain and enhance iron nutriture might be beneficial for women engaged in sustained physical training. Recent data suggests that iron deficiency, even without anemia, impairs adaptation in endurance capacity after aerobic training in women [25]. Furthermore, changes in immune function, cognitive development and behavior, energy metabolism, and work capacity have been described in animals and humans with suboptimal iron status [4 – 6]. Iron supplementation may be of value for female military personnel during BCT, as iron supplementation has been shown to improve progressive fatigue resistance and endurance in iron-depleted, nonanemic women [26 –27]. Iron fortification of foods may be another cost-effective method for preventing iron deficiency and iron deficiency anemia in female military personnel [28 –29]. Study limitations include the cross-sectional design of the

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study, since differences in iron status between the three groups could be the result of differences in iron-related variables other than BCT. We did note differences in age and weight between the three groups of women, but since these variables were not significantly related to the iron status measures, it seems unlikely that they can account for the differences in iron status between the groups. However, not all potential confounding variables could be measured in this study, so it would be useful to confirm our results in a longitudinal study that could follow the same group of women from entry into the military through the completion of basic training. In summary, the major finding of this study was that the prevalence of iron deficiency and iron deficiency anemia is increased in female military personnel following BCT. Furthermore, the prevalence of iron deficiency anemia among Hispanic and African-American soldiers was double that of Caucasian soldiers. These results suggest that iron status is an important issue facing female military personnel during training, and that improving iron status through supplementation or fortification of the diet should be considered.

ACKNOWLEDGMENT This project was initially conceived by LTC(ret) Kathleen Westphal, with funding support obtained from the 1994 Defense Women’s Health Research Program. We also wish to acknowledge the important technical support provided by Dr. Jennifer Rood and her staff in the Clinical Chemistry laboratory at the Pennington Biomedical Research Center, Baton Rouge, LA.

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Received August 29, 2005; revision accepted December 15, 2005.

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