The Effects of Prenatal Vitamin Supplementation on Operationally Significant Health Outcomes in Female Air Force Trainees

Transcription

1 MILITARY MEDICINE, 180, 5:554, 2015 The Effects of Prenatal Vitamin Supplementation on Operationally Significant Health Outcomes in Female Air Force Trainees LCdr Kirsten R. Barnes, Canadian Armed Forces*; Juste N. Tchandja, PhD, MPH ; Capt Bryant J. Webber, USAF MC ; Lt Col Susan P. Federinko, USAF MC ; Col Thomas L. Cropper, USAF (Ret.) ABSTRACT Objectives: A prenatal vitamin supplementation program for female basic military trainees at Joint Base San Antonio Lackland was initiated in June 2012 with the goals of decreasing attrition and improving performance. This project examined whether supplementation influences attrition rates, incidence of stress fractures and iron deficiency anemia, and physical performance. Methods: This was a cohort-based pilot study with an historical control group. Primary outcome measures included all-cause attrition, medical attrition, stress fractures, and iron deficiency anemia. Results: Incidence rates of all-cause attrition, medical attrition, stress fractures, and anemia were similar in both groups, although the lower medical attrition in the supplementation group approached statistical significance (risk ratio, 0.74; 95% confidence interval, ). Conclusion: Although this study found no statistical benefit, the operationally significant reduction in medical attrition of 26% suggests that providing prenatal vitamin supplementation to female basic trainees in the Air Force may be worthwhile. INTRODUCTION Female military recruits or trainees, as they are known in the U.S. Air Force face several physical, cognitive, and environmental stressors during basic military training (BMT). Given these known stressors and the subsequent risks for iron deficiency and stress fractures, the Institute of Medicine (IOM) published a report in 2006 outlining the increased mineral requirements of female trainees. Among other things, the IOM established a recommended dietary allowance of 22 mg iron/d for female service members and suggested supplementation or fortification programs for those who are unlikely to meet this requirement through diet alone, such as for female trainees. In addition to iron, calcium and vitamin D requirements may be higher among military trainees, 1 and deficiencies thereof have been associated with increased stress fractures. Specifically, in a double-blind, placebocontrolled study of female U.S. Navy recruits, daily supplementation with 2000 mg of calcium and 800 IU of vitamin D resulted in a 20% reduced incidence of stress fractures. 2 In light of this evidence, the Trainee Health Surveillance team at Joint Base San Antonio (JBSA) Lackland initiated a program in June 2012 to provide nutritional education to all incoming female trainees and offer them daily supplementation with a prenatal vitamin (containing, among other things, 27 mg of iron, 200 mg of calcium, and 400 IU of vitamin D). *Directorate Force Health Protection, Canadian Forces Health Services Group Headquarters, 1745 Alta Vista Road, Ottawa, ON, Canada K1A 0K6. Trainee Health Surveillance, 1515 Truemper Street, Bldg 6612 Rm 930, Joint Base San Antonio Lackland, TX This work is the sole responsibility of the authors and does not represent the official views of the Uniformed Services University of the Health Sciences, the Department of Defense, the U.S. Air Force, or the Canadian Armed Forces. doi: /MILMED-D The prenatal vitamin was chosen for the following reasons: (1) prenatal vitamins have an iron content that approximates the IOM s estimated 22 mg daily iron requirement for females in military training; (2) prenatal vitamins are on the organization s formulary whereas multivitamins are not and are available at a very low cost of approximately $0.03 per day; and (3) they contain other important minerals and vitamins, including calcium, vitamin D, and folic acid (the U.S. Preventive Services Task Force currently recommends that all women planning or capable of pregnancy consume a daily supplement containing 0.4 to 0.8 mg of folic acid 3 ). The program s ultimate goal was to improve performance and decrease rates of attrition (i.e., noncompletion of training), which had historically been higher among females. At the time of program initiation, female attrition was approximately 10%, compared to about 5% for males. In particular, health outcomes such as iron deficiency anemia, stress fractures, and mental health issues were known to be significant contributors to attrition from BMT for females. Iron deficiency defined as an abnormal value for at least two of the following three indicators: serum ferritin, transferrin saturation, or free erythrocyte protoporphyrin is more prevalent among females and is particularly common among female athletes and service members. 4 For females, a diagnosis of iron deficiency anemia requires both iron deficiency and a hemoglobin level below 12 g/dl. 4 Females in the U.S. Armed Forces have 7.8 times the incidence rate of iron deficiency anemia as compared to males. 5 During BMT, iron stores naturally deplete, resulting in reduced aerobic performance. 6 A study of U.S. Army females found a 20.9% prevalence of iron deficiency anemia immediately following basic training, 7 and a similar study of Israeli female recruits found a prevalence of 12.8%. 8 A stress fracture (also known as a fatigue or march fracture) is defined as a partial or complete fracture of bone that results 554

2 from the repeated application of a stress lower than that required to fracture the bone in a single loading situation. 9 Stress fractures are commonly diagnosed in the military population, especially among recruits, whose incidence exceeds that of nonrecruits by 18 times. 10 The risk of stress fracture in female recruits ranges from 1.2 to 12 times that of male recruits, with reported rates ranging from 1.6% to 21.0%. 2,9,11 13 Sixty percent of U.S. Army female recruits who sustain a stress fracture during BMT do not complete training. 2 As a result, stress fractures incur considerable expense for the military and negatively affect military readiness. 2 We conducted a cohort-based pilot study to analyze the relationship between prenatal vitamin supplementation in females during U.S. Air Force BMT and subsequent attrition rates, iron deficiency and stress fracture rates, and physical fitness performance. Since the Air Force is the only U.S. service branch conducting such a program, the results could influence health promotion programs at other military training sites and, potentially, in other high-stress environments worldwide. METHODS JBSA Lackland is located in San Antonio, Texas, and is the sole site for U.S. Air Force enlisted BMT. At any given time, there are approximately females undergoing such training, with each course lasting 8.5 weeks. As of August 29, 2012, all incoming female trainees were offered prescriptions for prenatal vitamins during their first week of training and counseled about the potential benefits and risks of taking such supplementation. This study examined data on all female trainees who began BMT between August 29, 2012 and March 27, 2013, a group consisting of 4,303 females. An historical comparison group was selected, which included all 4,051 female trainees who began BMT at Lackland between August 31, 2011 and March 28, The use of a seasonmatched comparison group was intended to control for any environmental differences that may affect training during different months of the year (e.g., endogenous vitamin D production from sun exposure). The study size was based on data availability and not on an a priori power calculation. Given the 4,303 female trainees who were offered prenatal vitamins during the study period and a 7.3% risk of all-cause attrition in the comparison group, a relative risk of 0.79 would have been required to obtain 80% power. The primary outcome of interest was the rate of attrition because of all causes. Secondary outcomes included rates of medical attrition, iron deficiency anemia diagnoses, stress fracture diagnoses, and performance on the Air Force physical fitness assessment. Attrition from BMT has a number of causes, with medical attrition accounting for about 30 to 40% of cases (unpublished data from Lackland Trainee Health Surveillance). Other causes of attrition include fraudulent enlistment (e.g., lying on official documents), mental health issues, and positive urine toxicology screening on arrival. The Air Force physical fitness assessment consists of four components: waist circumference (scored out of 20 points), 1 minute of push-ups (10 points), 1 minute of sit-ups (10 points), and a 1.5 mile timed run (60 points). Pull-ups are also performed as part of the assessment during BMT, although they do not factor into the final score. A body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) is also obtained for basic trainees. During the 8.5 weeks of BMT, trainees complete the assessment at multiple times, with the initial assessment performed within a week of arrival and the final assessment performed within a week of graduation. For this study, initial BMI and component scores were used to compare the two groups at baseline, and final BMI and component scores were used to compare intervention effectiveness. Fitness data were only available for those who completed BMT. As part of their routine operations, the Trainee Health Surveillance team at JBSA Lackland collects data on demographics, trainee attrition, and medical encounter information. Medical encounter information is based on International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9) codes logged in the Armed Forces Health Longitudinal Technology Application, whereas demographic and attrition information is derived from the Basic Military Training System database. This study was reviewed and approved by the Office of Research at the Uniformed Services University, Bethesda, Maryland. Incidence rates were compared for all-cause attrition, medical attrition, stress fracture diagnoses, and anemia diagnoses in female trainees who either were or were not offered prenatal vitamin supplementation. Using the chi-square test, these rates were compared to determine relative risks (RR) and 95% confidence intervals (CI). The number needed to treat (NNT; defined as the inverse of the absolute risk reduction) for each of these outcomes was also calculated. Mean fitness measures were compared using independent-samples t-tests, with a 2-sided p-value established at All analyses were performed with SPSS version 20. RESULTS At baseline, mean BMI (23.44 vs ; p = 0.546) and run time (15.81 minutes vs minutes; p = 0.719) were similar in the supplementation and comparison groups, respectively (Table I). The supplementation group had a smaller mean waist circumference (29.10 vs ; p < 0.001) and completed more push-ups (28.70 vs ; p < 0.001) and sit-ups (15.36 vs ; p = 0.001) at baseline. The risk of all-cause attrition in the prenatal vitamin supplementation group was nonsignificantly reduced by 8% (RR 0.92; 95% CI, ), with an NNT of 163 to prevent one trainee attrition. Likewise, the risk of medical attrition in the supplementation group was nonsignificantly reduced by 26% (RR 0.74; 95% CI, ), with an NNT of 176. For stress fractures there was a nonsignificant reduction of 3% (RR 0.97; 95% CI, ), and for iron 555

3 TABLE I. Comparison of Initial Fitness-Related Characteristics Between Study Groups a N Mean SD N Mean SD Mean Difference p-value BMI 3, , Waist Circumference (Inches) 3, , <0.001 Initial Run Time (Minutes) 3, , Initial Push-Ups 3, , <0.001 Initial Sit-Ups 3, , a Fitness data were only available for those females who completed basic training. SD, standard deviation. TABLE II. deficiency anemia there was a nonsignificant increase of 8% (RR 1.08; 95% CI, ) (Table II). The mean final run time was minutes (4.8 seconds) longer in the prenatal vitamin supplementation group than in the comparison group (p = 0.014). The mean number of push-ups was 0.38 greater in the supplementation group ( p = 0.045). There were no differences found between the mean number of sit-ups and pull-ups completed between the two groups (Table III). DISCUSSION This analysis of an existing health promotion program found a statistically nonsignificant effect of prenatal vitamin supplementation on attrition from training and on development of stress fractures and iron deficiency anemia among females undergoing U.S. Air Force BMT. The null findings may be explained by a number of reasons. First, the low baseline rates of these outcomes among female trainees at JBSA Lackland, rates which are lower than those reported in other military training populations, 2,9,11 13 suggest that preexisting preventive measures had been optimized in this population. Second, it is possible that 8.5 weeks of supplementation did not allow adequate Comparison of Attrition and Health-Related Outcomes Between Study Groups Total n % n % N RR 95% CI NNT All-cause Attrition % % Medical Attrition % % Stress Fractures % % ,576 Iron Deficiency Anemia % % CI, confidence interval; NNT, number needed to treat; RR, relative risk. time to demonstrate a statistically significant impact and that the prenatal vitamin may be more efficacious if it were initiated before starting BMT. Third, given the daily doses of calcium and vitamin D that were protective against stress fractures in a U.S. Navy recruit population 2000 mg and 800 IU, respectively 2 it may be reasonable to conclude that the 200 mg calcium and 400 IU vitamin D in the prenatal vitamin are insufficient to prevent stress fractures in female military recruits. Fourth, increased clinical suspicion for iron deficiency anemia during the intervention period, leading to increased screening and diagnoses, may have resulted in a cointervention bias, whereby the supplementation group falsely appeared to have an increased risk of anemia (RR 1.08). This was a limitation of both the observational nature of the study design and the fact that medical outcomes were based only on diagnoses entered into the electronic medical record, rather than on complete capture of all outcomes in the study population. The 26% reduction in medical attrition in the prenatal supplementation group, though not statistically significant at a = 0.05 (95% CI, ), is operationally adequate to justify continuation of a program that is inexpensive and has few if any associated harms. Clearly, further research is justified to delineate the potential impact of prenatal vitamin TABLE III. Comparison of Final Fitness Measures Between Study Groups N Mean SD N Mean SD Mean Difference p-value Final Run Time (Minutes) Final Push-Ups Final Sit-Ups Final Pull-Ups < SD, standard deviation. 556

4 supplementation on the health and performance of female military trainees. A randomized control trial that could account for the confounders and biases described below would provide a more robust evidence base for this intervention. With respect to overall fitness as a measure of performance in female recruits, although some differences were found between the two groups on their final fitness tests, prenatal vitamin supplementation did not appear to produce any significant effects. The strengths of this study included its relatively large sample size with enough power to detect an operationally significant reduction of 21% in all-cause attrition, control for seasonal variation by using a time-matched historical comparison group, complete capture of female trainees undergoing U.S. Air Force BMT during the surveillance period, and its potential generalizability to other female military recruits, especially in the Air Force. The study should be interpreted cautiously, however, given its limitations. Because of the use of an historical comparison group and the absence of randomization, this study is best viewed as an investigational pilot study based on cohort study principles. Its findings may be influenced by potential confounders that were not measured such as macro- and micronutrient intake during meals and menstrual abnormalities and by various biases, such as contamination bias (e.g., if trainees in the comparison group had been taking prenatal vitamins in the months leading up to training or had been prescribed prenatal vitamins during their time in BMT). Cointervention bias is also possible, but the authors are unaware of any other significant interventions, such as programmatic changes in nutritional education or meal plans that occurred during the surveillance period. Since it is unknown which trainees actually received and took the prenatal vitamin, the findings should also be interpreted as reflecting the effectiveness, rather than the efficacy, of the prenatal vitamin. It is reasonable to assume that many trainees in the intervention arm, though offered the supplement, did not consume the supplements. Among those who did consume them, moreover, it is unknown how many doses were missed during the 8.5 weeks of training. In a survey of 161 females conducted in early 2014, 99% reported accepting the prescription, 65% taking the supplement on most days, and 47% taking the supplement daily throughout the entirety of training (Lt Col Stacey Van Orden, Performance Nutrition, personal communication). These data are consistent with pharmacy review, which found a supplement prescription distribution rate approaching 99%. In light of this high rate of acceptance, it was deemed unnecessary to exclude trainees who were not prescribed the supplement from the analysis. This study was further limited by lack of standardized case definitions of outcome measures and lack of other pertinent data. For the purposes of this study, ICD-9 codes were used to determine incident diagnoses of stress fractures and iron deficiency anemia. Given interprovider variability in diagnosing and coding these conditions, however, there may have been some variability in outcome data. Furthermore, it was impossible to exclude prevalent (i.e., preexisting) cases of iron deficiency anemia. Demographic data such as age, date of birth, and race/ethnicity were unavailable in the database, and fitness assessment data (i.e., height, weight, initial run time, initial push-ups, and initial sit-ups) were not obtainable for individuals who failed to complete training. Adjustment for potential confounders for the outcomes of interest was therefore limited. Finally, since the dates of training initiation and attrition were unknown, medical outcomes were assigned as binary variables and not based on person-time. CONCLUSIONS Beginning in June 2012, a daily prenatal vitamin supplement was offered to all females entering U.S. Air Force BMT. Among the 4,303 females who enlisted between August 29, 2012 and March 27, 2013 and who were thus offered the supplement rates of all-cause attrition, medical attrition, stress fracture, and iron deficiency anemia were statistically equivalent to the 4,051 females who entered training during the same period of time the previous year. Nonetheless, given (1) the operationally significant reduction in medical attrition of 26%, (2) the low rates of stress fracture and anemia in this population at the outset of the study, (3) the IOM recommendations for iron requirements during military training, (4) the low cost and absence of associated harms, and (5) the potential for other benefits not analyzed in the present study, the findings of this report do not justify discontinuation of the prenatal vitamin supplementation program. Further research should be considered to delineate the impact of prenatal vitamin supplementation on other medical outcomes in U.S. Air Force BMT, as well as the impact of other vitamin and mineral formulations on health and performance in warrior and athlete populations. ACKNOWLEDGMENTS The authors acknowledge Robert DeFraites, MD, MPH; Tomoko Hooper, MD, MPH; and Roger Gibson, DVM, MPH, PhD, of the Uniformed Services University of the Health Sciences (USUHS) for their assistance in the design and development of this project and also Cara Olsen, MS, DrPH, of USUHS for statistical consultation. REFERENCES 1. National Research Council: Mineral Requirements for Military Personnel: Levels Needed for Cognitive and Physical Performance During Garrison Training. Washington, DC, The National Academies Press, Lappe J, Cullen D, Haynatzki G, Recker R, Ahlf R, Thompson K: Calcium and vitamin D supplementation decreases incidence of stress fractures in female navy recruits. J Bone Miner Res 2008; 23(5): U.S. Preventive Services Task Force: Folic Acid to Prevent Neural Tube Defects. Available at uspstf/uspsnrfol.htm; accessed June 11, Wilson C, Brothers M: Iron deficiency in women and its potential impact on military effectiveness. Nurs Clin North Am 2010; 45(2):

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