; , .d . 1 . . . .. . 1 1 xflwxm? .. .. ... L . H . . 1. . .... . .. . 1.. .1 1.. , 1. .. .. . . . 11 . . 1 1 . .4 ..... . p A . 11.1... u. . . ... . I. I: . .E? 1 1 olnfl.tdfll A . 1 . a. ... a 1 ¢. .. Eifimfifi .c1 n. h at). . J1. 1 1 . . . . . . . Th y:k~mfi;k .. .. ... . x q h..k.unE. . . . . . ......wlttkfik 1 1 I .u. fi..$.§u ... an. . .. ... bk; ”.mmfimnflwwd .uJubfivA 14. H 1 1”. a 1\ __ .....1]..1 1 y. . ..J 5%} .55». \filflix. a. . . 1L1 5h . . . 5.1.41 ... wait? 1 . . 1 . WT” .sHJ a. : . . . . ‘A . .... I11 . . .. u 1 . 1 aw ... 1. ... .. . r .. . . .H. .. 1:. 1...: . Hm .. ... .. 1 .. . ... . . ..1 . ... .. . .1” ,1. M11. W..J.1.X.m1.u.1m..1. : .n . .1 n 1 . . . 1. . . . .. .. . H; . . . . .Ekn1uLuL. I . a .. . . 4". . :Nv n-P 5: . .. .... . , 1 . 1 J ?n1rh$-.»3 'C“l‘ 1‘3: '2‘ H' 101 3111'!" I a .. T. H1. ht»... . A 3.... ...—41H; . ... “fluvfi . . .1 , I. Lgo. ‘V "r- I £7.11; - . .2 . . l. . ""31. H 1 ‘.'H—. '.‘\ .11).:«3323 m 1.51. "d: b. . _ Fl- . 1 '1v.( A I ll . . 11 .411 .L H .111I1.n..1u~.,3.vrr.__1 .. «pu.n..‘n.«.. . . ., . . o . '. ‘wa ‘."1v|.[54 J] 51.1.. 21.! ‘1‘... . 1. 1.111.... t r. r . 1 1 .1 1. 1 . 11 . , . .. . ...1 v.1 1 . A .... 1. . 1 .. A .IRJVJJnBS. . . 1 1 .. .... .1 . . . . . . 1. . . . ..1 1. . 1 . . . ‘ ... 7'13" . . . .v. .1 , . . .. . .1 . 1 . 1 . A 1 1 . . . 1 . . X. 1 . , ...... r , . 1 . 1 . . . h. . Jun .56., 1 i . .193. 1:19 [21... «vlmaum'mlmu. . fifiwflw 94.1.. THESIS (-1. (ZOOM Date 0-7639 llllllllllHlllllllllllllllllllllllllllllllllHlHlHHllllll 31293018345 LIBRARY 4 Michigan State University This is to certify that the thesis entitled MATERNAL IRON-DEFICIENCY ANEMIA AT ROCKY MOUNTAIN ALTITUDES presented by Cynthia Dickinson Anderson has been accepted towards fulfillment of the requirements for Master of Science degfimin Nursing? @0414? Major professor 4/26/99 MS U is an Affirmative Action/Equal Opportunity Institution PLACE IN RETURN BOX to remove this checkout from your record. TO AVOID FINE return on or before date due. MAY BE RECALLED with earlier due date if requested. DATE DUE DATE DUE DATE DUE 1M animus-ma MATERNAL IRON-DEFICIENCY ANEMIA AT ROCKY MOUNTAIN ALTITUDES BY Cynthia Dickinson Anderson A THESIS Submitted to Michigan State University in partial fulfillment of the requirements for the degree of MASTER OF SCIENCE IN NURSING College of Nursing 1999 ABSTRACT MATERNAL IRON DEFICIENCY ANEMIA AT ROCKY MOUNTAIN ALTITUDES BY Cynthia Dickinson Anderson Retrospective survey format was utilized to retrieve existing demographic and longitudinal clinical data from 132 medical records of pregnant women living at 6,000 to 7,000 feet elevation. Normal maternal values for hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration were found for the landmark anemia screening intervals throughout pregnancy. Maternal iron deficiency anemia (MIDA) was operationally defined as an MCV less than 80 fL and either an MCH less than 27 pg or an MCHC less than 32 g/dL. Only 2 cases of MIDA were found due to sampling criteria that selected for normal pregnancies. The 1989 Centers for Disease Control Guidelines were found unreliable in identifying MIDA at 6,000 to 7,000 feet elevation. Recommendations included the abandonment of MIDA screening based solely on measures of hemoglobin and/or hemotocrit, and revision of MIDA screening and diagnostic panels for populations at 6,000 to 7,000 feet elevation. Copyright by Cynthia Dickinson Anderson 1999 ACKNOWLEDGMENTS The author thanks Rachel Schiffman, PhD, thesis chair, for her guidance, persistence and patience for the duration of this project. Her input regarding organization, format, selection of theoretical model, and methods was invaluable. The author is appreciative of her assistance with administrative details and many long distance communications that were “above and beyond the call of duty.” Thesis committee members, Brigid Warren, MSN and Jacqueline Wright, MSN are appreciated for the attention to concepts, implications and specific details throughout the manuscript. Special thanks to Jackie Wright for her many words of encouragement and late night phone calls. The entire committee is thanked for the flexibility and understanding during personal crises the author endured concurrently. For technical support, the author thanks Brother Brian Dybowski, FSC, PhD, College of Sante Fe, and Jill Ryan, who provided free use of their PC's when the author's old PC 'died?, and expertise pertaining to SPSS and Excel programs. Thanks also to Gail Bryant, RN, MSN, who reviewed the manuscript several times and provided editorial input. Kaye Arnett at the College of Nursing, Michigan State University is thanked for her expertise and hard work in editing for details of format, and preparation of the final manuscript. iv Thanks also go to Elizabeth Gilmore and the Northern New Mexico Midwifery Center at Taos, Drs. Laura Wolfswinkel and Maria Rodriguez at Galisteo OB/GYN in Santa Fe, and David Land, D0, OB/GYN in Las Vegas for agreeing to participate in the study and serving as data collection sites. Special thanks go to Kathy at the Midwifery Center, Susan Dettlebach at Galisteo OB/GYN, and David Land for assisting with arrangements for data collection. Finally, the author wishes to thank the following friends, relatives and colleagues for their support and encouragement: Maggie Anderson, Graydon Anderson, Starr Cross, Paul and Juan Dickinson, Debbie Trimmer, Ric Loyd, Gail Bryant, Judy Oldknow, Lydia Sneesby, Mary Soppe, Jean Glidewell, Connie Martin, Kristi and David Rymph, Elsie Anderson, Linda Wolf, John Ford, Susan Ford Wiltshire, Penny Gonzalez, Jim LaBerge, David Land, Mary Masuk, Barbara Villa Senor, Judith Fleishman, Jan woods, and Lynn zinser-Kask. Thanks also to Elizabeth Matuk, RN for her inspirational enactment of the advanced practice role and her faith in the profession. TABLE OF CONTENTS LIST OF TABLES . . . . LIST OF FIGURES . . . . LIST OF ABBREVIATIONS . INTRODUCTION . . . . . CONCEPTUAL FRAMEWORK . Conceptual Definitions Maternal Iron-Deficiency Anemi 1a Anem1a . Iron Deficiency Iron-Deficiency Anemia . Normal Hematologic Changes During Pregnancy . . Normal Changes in Iron Demand During Pregnancy . . Evaluation of Iron Status During Pregnancy . . Maternal Iron-Deficiency Anemia Rocky Mountain Altitudes Physical Environment . Socioeconomic Environment Conceptual Definition of Altitudes . . Theoretical Framework Starfield's Model Structure Process Outcome 0 O O O MIDA at Rocky Mountain Altitudes Applied to Starfield's Model REVIEW OF THE LITERATURE Prior MIDA Studies Above 3,000 Gerritson and Walker Lamparelli et al. . Watson and Murray . Ross . . . . Hofvander . . Synthesis of Pertinent Empiri Critique of the Literature . METHODS O O O O O O O 0 Study Design . . . C Fi Feet Elevation Rocky Mountain Page viii OQOOGG H K O O O O C . ...: O H u 16 17 22 23 23 32 32 34 37 38 41 41 44 45 48 50 51 52 55 57 TABLE or CONTENTS (cont.) Sample . . . . . . . . Field Procedures . . . Sample Criteria . Data Collection . . . Recording of Data and Scoring Data Analysis . . . . Confidentiality of Human Subjects Operational Definitions . . . . MIDA . . . . . . . . . . Rocky Mount in Altitudes Assumptions and Limitations' . Assumptions . . . . . . . Limitations . . . . . . . Design Factors . . . Contamination of Result RESULTS 0 O O O O O O O O O O O O O O 0 sample C O O O O O O O O O O O O O 0 Research Questions . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . Implications for Advanced Practice Nursing Primary Care . . . . . . . . . . . Recommendations for Further Research SWARY O O O O O O O O O O O O O O O O 0 LIST OF REFERENCES 0 O O O O O O O O O O APPENDICES O O O O O O O O O O O O O O 0 Appendix A . . . . . . . . . . . . . vii 57 58 58 59 59 61 63 63 63 63 64 64 64 64 64 65 66 7O 81 88 9O 94 97 107 107 Table Table Table Table Table Table Table Table Table LIST OF TABLES Stages of Iron Deficiency with Cut-Off Values for Common Laboratory Indicators CDC Criteria - Cut-Off Values for IDA in Adult Women at Middle Altitudes . RBC Indices at Sea Level and at Altitudes Above 3,000 Feet . . . . . Prior MIDA Studies at Altitude . Sample Demographic Characteristics by Site Maternal RBC Indices at Rocky Mountain AltitUdes O O O O O O O O O Hematology Profiles for Healthy Pregnant Women at 6,000-7,000 Feet Altitude Rates Of MIDA O O O O O O 0 Rates of Maternal Anemia per 1989 CDC Guidelines . . . . . . . . Table 10: Case Comparison of Anemic Subjects: Demographic Characteristics viii Page LIST OF FIGURES Page Figure 1: The Starfield Model of the Health Services system C O O O O O O O O O O O O O I O O O O O 3 5 Figure 2: MIDA at Rocky Mountain Altitudes Utilizing Starfield . s Madel O O O O O O O O O O O O O O 4 0 ix 5 CBC CC = CDC = FEP fL g/dL = IDA = HCT = HGB IDA = IUGR LBW = MIDA MCH = MCHC MCV = ml ugldL= uglL = NHANES= PCP LIST OF ABBREVIATIONS advaced practice nurse complete blood count cubic centimeter Centers for Disease Control free erythrocyte protoporphyrin femtoliter grams per deciliter iron-deficiency anemia hematocrit hemoglobin health maintenance organization iron-deficiency anemia intrauterine growth retardation low birthweight first day of last menstrual period maternal iron-deficiency period mean copuscular hemoglobin mean corpuscular hemaglobin concentration mean corpuscular volume milligram milliliter micrograms per deciliter micrograms per liter National Health and Nutrition Examination Survey primary care practitioner X p9 = PIH = RBC 8 RBC ZP= RDW = SGA = TIBC = T8 = WHO = picograms pregnancy induced hypertension red blood cell red blood cell zinc protoporphyrin red blood cell volume distributioni width small for gestational age total iron binding capacity transferrin saturation World Health Organization xi INTRODUCTION This study describes the appearance of maternal iron- deficiency anemia (MIDA) in a sample of pregnant women living at 6,000 to 7,000 feet above sea level. The purpose of this study was to: a) call attention to the primary care practitioner's dilemma of recognizing MIDA with coexisting compensatory relative polycythemia; b) enhance the recognition of MIDA at Rocky Mountain Altitudes by presenting empiric maternal normal values for red blood cell (RBC) indices collected at the usual landmark screening intervals; c) determine MIDA incidence rates at 6,000 to 7,000 feet elevation; d) test the reliability of the 1989 Centers for Disease Control (CDC) guidelines in identifying MIDA; and e) examine the data for significant relationships between demographic variables and incidence of MIDA. MIDA is an acquired organic disease occurring during pregnancy, well known as the most common hematologic complication of pregnancy (Bently, 1985 [classic]; Cunningham, MacDonald, Gant, Leveno, & Gilstrap, 1993). Worldwide incidence of MIDA has been estimated at 50 to 60%, ranging to 80% in tropical and developing nations (DeMaeyer & Adiels-Tegman, 1985 [classic]). The Third National Health and Nutrition Examination Survey 1988-1994 (NHANES III) was the first large scale study to include pregnant women and determine MIDA incidence for the general population in the United States. Results for pregnant women are still pending 1 analysis and publication. Since the introduction of iron fortified foods, baby formulas, and supplemental food programs, there has been a significant decrease in iron- deficiency anemia (IDA) among infants and children. IDA rates in pregnant women and women of child-bearing age remain unchanged (Kim et al., 1992). Over the past 25 years, MIDA has been increasingly associated with serious complications of pregnancy, poor outcomes, and increased maternal and fetal mortality (Garn, Ridella, Petzold & Falkner, 1981; Murphy, Newcombe, O'Riordan, Colles & Pearson, 1986). Concern for maternal and child health has been escalating in Rocky Mountain states as studies reveal increased rates of maternal mortality, late prenatal care, pregnancy-induced hypertension (PIH), premature labor, increased amniotic fluid indices, intrauterine growth retardation (IUGR), low birthweight (LBW) and small for gestational age (SGA) infants (Maternal and Child Health Bureau, Health Services Division, Health and Environment Department 8 New Mexico Health Systems Agency, 1986; New Mexico Department of Health [NMDH], Public Health Division, Bureau of Vital Records 8 Health Statistics, 1996; New Mexico Prenatal Care Network a University of New Mexico, School of Medicine, Maternity and Infant Care Project, 1992; Olmas, Figueroa, Rodriguez, Halac, & Irrazabal, 1988; Unger, Weiser, McCullough, Keefer & Moore, 1988; Yancey, Moore, Brady, Milligan & Strampel, 1992; Yancey & Richards, 1994; Yip, 1987; Zamudio et al., 2 1993). Over the past 20 years, several studies have noted a direct relationship between increasing altitude and incidence rates for these complications, particularly above 6,000 feet (McCullough, Reeves & Liljegren, 1977; Moore, Hershey, Jahnigen & Bowes, 1982; Unger et al., 1988; Yancey et al., 1992; Yancey & Richards, 1994; Yip, 1987; Zamudio et al., 1993). Most of these complications are known for strong association with MIDA, hypoxia, or errors in blood volume expansion. Premature labor and LBW have been directly linked to MIDA (Cook & Lynch, 1986; Cook, Skikne & Haynes, 1994; Godfrey, Redman, Barker & Osmond, 1991; Scholl, Hediger, Fischer & Shearer, 1992). Direct relationships between MIDA and other complications remain unknown. At sea level, MIDA is easily recognized, diagnosed and treated with over-the-counter oral iron supplements. At altitudes above 3,000 feet, recognition of MIDA is complicated by the confounding variable of compensatory relative polycythemia. Since there has been so little maternal research at these altitudes, primary care practitioners (PCPs) lack empirically derived altitude- adjusted reference tables for maternal norms of the traditional screening tests, hemoglobin (HGB) and hematocrit (HCT), which are elevated in high altitude dwellers. Considering the high cost of the associated morbidity, there is pressing need for: a) an altitude-appropriate consensus definition for MIDA; b) altitude-adjusted reference tables of maternal norms for screening and differential diagnostic laboratory tests; and c) the refinement of MIDA screening guidelines for populations at altitudes above 3,000 feet. Nurses in advanced practice, such as certified nurse midwives, nurse practitioners, and clinical nurse specialists, are strategically positioned in primary care settings to play a significant role in reducing the incidence of MIDA and its associated morbidity. Advanced practice nurses (APNs) are ideally prepared to provide early identification, appropriate intervention, and individualized patient education, which is the most important feature of successful treatment (DeMaeyer, 1989; Food and Nutrition Board [FNB]; Institute of Medicine [IOM], 1993). Until a substantial database can be amassed to support the formulation of altitude-appropriate norms and standards of care, the ability of APNs and other PCPs to recognize MIDA in populations at middle altitudes remains compromised. The study questions were: 1. What are the mean empiric maternal values for red cell indices (i.e., HGB, HCT, mean corpuscular volume [MCV], mean corpuscular hemoglobin [MCH] and mean corpuscular hemoglobin concentration [MCHC]) measured at the usual screening intervals during the course of pregnancy (i.e., at less than 20 weeks from the first day of the last menstrual period [LMP), 28 weeks LMP, and 36 weeks LMP), at altitudes of 6,040, 6,400 and 7,000 feet? 2. What is the rate of MIDA when MIDA is defined as observed microcytosis (MCV < 80 fL) and hypochromia (MCH < 27 pg or MCHC < 32 g/dL)? 3. What are the mean and range values for HGB and HCT associated with MIDA at each screening interval at altitudes ranging between 6,000 and 7,000 feet elevation? 4. Do the 1989 CDC Guidelines accurately identify MIDA in this population? 5. Is there a significant relationship between demographic variables (i.e., age, race, socioeconomic status, interconceptual time interval, parity, altitude) and MIDA? Prior MIDA studies rarely utilized longitudinal data. Longitudinal changes revealed by this study may assist in understanding MIDA at altitudes between 6,000 and 7,000 feet. This altitude level marks the onset of significant increases in complications and poor outcomes of pregnancy observed in prior studies (Jackson, Mayhew & Hass, 1988a; Jackson, Mayhew & Hass, 1988b; McCullough, Reeves & Liljegren, 1977; Moore, Hershey, Jahnigen, & Bowes, 1982; Reshetnikova, Burton, Milovanov & Folkin, 1996; Unger et al., 1988; Yancey et al., 1992; Yancey & Richards, 1994; Zamudio et al., 1993). It is hoped that this study will stimulate support for a large-scale prospective MIDA study encompassing the Rocky Mountain region. A carefully conducted longitudinal study 5 with multiple data collection sites at altitudes above 3,000 feet would provide an invaluable database. The database would facilitate the development of a consensus definition, standardized tables of norms, and altitude-appropriate standards of care needed worldwide in primary care facilities serving pregnant populations at middle altitudes. CONCEPTUAL FRAMEWORK Conceptual Definitions The concepts under study are maternal iron-deficiency anemia, and Rocky Mountain Altitudes. Each concept is described and defined below. WW Maternal iron-deficiency anemia is a treatable disease that appears in many women during pregnancy. MIDA is notoriously asymptomatic and poses serious threats to the health of the pregnant woman and her fetus. To fully understand the concept of MIDA, it is useful to break the term into its parts. One must be familiar with the normal hematology profile for non-pregnant adult women and the normal changes brought about by pregnancy. For this study, one must also be aware of normal hematologic adaptations to altitude in order to distinguish normal from pathologic changes. Discussion of adaptations to altitude is contained in the section entitled “Rocky Mountain Altitudes”. Anemia Anemia is most simply described as an organic disease characterized by alterations in red blood cell morphology 6 and diminished oxygen-carrying capacity of red blood cells. These alterations result in decreased tissue oxygenation, impaired metabolism, cell death, impaired function of major organs, and possibly death. Anemias are categorized into three major groups reflecting the size of RBCs (microcytic, normocytic or macrocytic), and then further classified by the density of hemoglobin pigment (hypochromic, normochromic or hyperchromic) contained in the red cells. Structural classifications narrow the range of possible causes for observed anemias (Brown, 1991; Bushnell, 1992). I E E' . Iron deficiency is a progressive deterioration in iron status characterized by three distinct stages; first, exhaustion of iron stores, then iron-deficient erythropoiesis, and finally anemia. Exhaustion of iron stores is objectively identified by: a) drops in HGB, HCT, transferrin saturation (TS), and serum ferritin; b) a rise in total iron-binding capacity (TIBC); and c) the absence of stainable iron in bone marrow macrophages. Iron-deficient erythropoiesis is identified by: a) elevated free erythrocyte protoporphyrin (FEP) or red blood cell zinc protoporphyrin (RBC ZP); b) a drop in T8; and c) possibly a drop in MCV. Anemia is marked by all of the indicators above, plus further drops in HGB, HCT, MCV, and MCH or MCHC. Table 1 integrates tables presented in Herbert (1991), Lee (1993b), and Ulmer and Gospel (1988) for reference and cut- off values for each stage, using sea_1gyg1 norms for non: 7 cm A on A sum us.qo\mav mu 0mm oooauooa cos on omumfl usaomm ac\oav mus 6H4 can can on a can .Au\ma. omHs «H v «Hues am as n cos .Aa\mav snowshoe saumm m.w A «.6 m.muw.~ Aq\ma. uouemomu :«uuoumsoua 8 as v 6H v on as H mm n.wv cofiumusuum CfiHHOHmn—MHB sous «e A eons wenm serum ..a .»v so: o.» w o.¢~no.m dons »H A c.6Huo.~H . a Aqs\mv no: «Human mequmdmmHNmu wNMGHWIZGMH madam maHdUHGZH azmaonmonzomH omamqmmo mozmmmmmm u s . o. o . a... .szzs s 1 . OI . . .1 1. .0 o 11.. . H OHQUH. .osficomdom coma spa: >un> nosan>o ..usououe nu ounouac huouoaaoausw son: >uo> nosao>n Amsaxofim ouuouovao can cook .uovsou .ovn .wosnsvoum no ovoum .ocsuHuHm suds auo> umsan>a .HuonuaansmH .osH .uouasuooo nouans .OGHOHcoz Havocauom no scauoaooumd cauoz 0:» >3 awed unmauheoo .mow name .dd .AT myudliuqauauuaranuuqquumluqiauquqqu mama Headed .m a amass .m an .suonna auouuoue can sauauuou .mdaosd flu .Hmuonmwansqg Homanom a seq an mama unmauxeou .hom name. as mama ... meme madman .z. n can mcmnu< .3. n .uoumumos .n Haoanuom .o. a .moq .m. u an A. no 53 3:3 5 83 63 .m. u an ..mammfigm 5339.8: confines“ saw: couoaoowun mnaaosm on» can nauouaoouoa: cu .msouo HMOfimoHocnooB Hafiz tenuous an Hams usofiussoo .T e. d .Aafluda .n .sesameauriuuduuuuMIauuflsuqm .Hmma .uumnuom.s .> an ..mcowumuocamsoo anomaooflcoa can 20wuosoouusH ”muocuomwc soufi uo usoaunouu can nanososma. an "Eouu moHnmu osfluoumousw .Ho>oa com um soaoa ucosooumiso: you mosao> .muoz as v as v mas on H owa .qoxmac can“ ssumm mm v moaned 0: manage on enumn Iuo\m. one: hm v ovcono o: mvcnzo o: Hmlbm Away mo: on v on v mazes moaned 0: mmiom Imac >o= dHnHZd wHudeudmuHNmu mundeIZQMH Human MdeuHQZH szmHonmouzomH anemones mozummmmm ..ucoov H manna deficiency often co-exists with other nutritional deficiencies (i.e., folic acid, vitamin Bu, and protein) which alter the expected values for some laboratory indicators. ImnzneficiencLAnemia Dorland's Illustrated Medical Dictionary defines iron- deficiency anemia (IDA) as an ”anemia characterized by low or absent iron stores, low serum iron concentration, elevated free erythrocyte porphyrin, low transferrin saturation, elevated transferrin, low serum ferritin, low hemoglobin concentration or hematocrit, and hypochromic microcytic red blood cells” (WW1 Dictionary, 1994, p. 73). IDA is the most common nutritional deficiency worldwide, affecting 1.2 billion people (Viteri, 1994). The NHANES III data suggests that 3.3 million women of child-bearing age in the U.S. have IDA (Looker, Dallman, Carroll, Gunter & Johnson, 1997). In the past, many studies used World Health Organization (WHO) cut-off values for HGB as the only determinant to define IDA. Hemoglobin by itself is a poor indicator of iron status because it does not isolate iron- deficiency from acute inflammatory processes, chronic disease, thalassemias, or hemoglobinopathies. Normal ranges for HGB vary by gender, age (Yip, Johnson & Dallman, 1984), race (Isaacs, Altman & Yalman, 1986; Lazebnik, Kuhnert & Kuhnert, 1989; Meyers, Habicht, Johnson & Brownie, 1983; Perry, Byers, Yip & Margen, 1992), cigarette smoking, 10 duration of pregnancy (Scott & Pritchard, 1967) and altitude (Buys de Jorge et al., 1988; Dainiak, Spielvogel, Sorba & Cudkowicz, 1989; Hurtado, Merino & Delgado, 1945 [classic]; Piedras, Loria & Galvan, 1995). Recent nutritional surveys and IDA studies have used various combinations of laboratory indicators to define "true IDA". As laboratory technology advances, definitional criteria vary considerably, and it becomes difficult to compare studies. In the United States, the majority of IDA is due to acute blood loss, or dietary patterns of: a) inadequate intake of bio-available heme-iron containing foods; b) excessive intake of substances that block iron absorption in the duodenum and gastrointestinal tract; c) inadequate intake of substances that enhance iron absorption; or d) the combined effects of all three patterns (Dimperio, 1988; Farley & Poland, 1990; Finch & Cook, 1984). Other common causes of IDA include chronic blood loss, or malabsorption syndromes as encountered in chronic disease, sprue, substance abuse, eating disorders (i.e., anorexia, bulimia, and pica), or following surgical excision of portions of the stomach, duodenum, or small intestine. Less common causes of microcytic hypochromic anemias include: a) accelerated hemolysis; and b) genetic or chemically induced errors of metabolism that affect the synthesis of either the heme or globin portion of the HGB molecule (i.e., thalassemias, hemoglobinopathies, sideroblastic anemias, gallium treatment, lead or aluminum toxicity). 11 High rates of IDA are consistently reported for infants, children, adolescents, women who are menstruating, pregnant or lactating, and hemodialysis patients. Populations commonly identified as high risk include the poor, minorities, and the geographically isolated. Although 11 to 25% of American women of child bearing age have no iron stores, only three to five percent have frank anemia (Cook, Skikne, Lynch & Reuser, 1986; Dallman, Yip & Johnson, 1984; IBNMRR, 1993; Looker, Dallman, Carroll, Gunter 8 Johnson, 1997; Pilch & Senti, 1984). In U.S. studies prior to 1990, rates of IDA in Hispanic Americans were just slightly above those for non-Hispanic Whites, and rates in Native Americans were higher than those for Hispanics but less than rates in Blacks (Fanelli-Kuczmarski & Woteki, 1990; Looker, Johnson, McDowell & Yetley, 1989; National Center for Health Statistics & Department of Health and Human Services, 1985). The NHANES III data reveals a significant increase in IDA for Hispanics which is now higher than rates reported for Blacks (Looker, Dallman, Carroll, Gunter & Johnson, 1997). One out of four American prenatal clients has impaired iron status prior to conception. At highest risk are pregnant adolescents with pre-existing high iron demand to accommodate maternal growth, and impoverished, multiparous women with closely spaced pregnancies who fail to recover iron stores prior to conception (Dimperio, 1988; Lanzkowsky, 1985; Leshan, Gottlieb & Mark, 1995). 12 Although IDA is often asymptomatic, some clients present with complaints of paresthesias, reduced endurance for activity, chronic fatigue, difficulty in concentration, burning or soreness of the tongue, ulcers or fissures at the corners of the mouth, or chronic gastritis. IDA has been associated with a long list of impairments including: reduced attention span, learning disabilities, impaired cognitive, psychomotor and physical development in children and adolescents, impaired cell-mediated immunity, reduced numbers of circulating T cells, reduced killing capacity of polymorphonuclear leukocytes, reduced physical work capacity, impaired oxidative metabolism, and impaired athletic performance (as cited in Cook & Lynch, 1986, and in Cook & Skikne, 1989). Chronic IDA may manifest as koilonychia (“spoon nails’), glossitis, stomatitis, esophageal webs, chronic or atrophic gastritis, and malabsorption (as cited in Cook & Lynch, 1986). H J H l J . :1 E . E Over the past forty years, research has yielded significant insight into the physiologic coping mechanisms of human pregnancy. Scott and Pritchard's classic 1967 study revealed significant differences in HGB concentration between pregnant and non-pregnant women, and fluctuations in maternal HGB throughout the course of pregnancy. In this study of healthy young women with proven iron stores and normal folate levels, Scott and Pritchard (1967) found mean hemoglobins of 11.5 g/dL in women 16 to 22 weeks LMP, and 13 12.3 g/dL in pregnant women at term, compared to a mean HGB of 13.7 g/dL in the non-pregnant control group. During pregnancy, the white blood cell count normally rises to between 10,000 and 14,000 cells per ml of whole blood. Total blood volume gradually increases until the twentieth week LMP, and rapidly expands between 20 and 32 weeks LMP. At 32 weeks LMP, blood volume expansion stabilizes at a level ranging between 20 and 150% above baseline (an increase of at least 1000 cc) until delivery. Plasma volume rises minimally in the first 12 weeks, more dramatically between 12 and 32 weeks LMP, and remains at a level about 50% above baseline between 32 weeks LMP and delivery. The maternal red cell mass increases by 35 to 45% (250-500 cc) throughout pregnancy, with the greatest rise occurring between 28 and 36 weeks LMP. Throughout pregnancy, maternal stroke volume and cardiac output increase, reaching a maximum at term of about 30% above baseline (Bently, 1985; Hytten, 1985; Scott & Pritchard, 1967; Viteri, 1994). H J :1 . I E i E . E In the first trimester, iron demand increases only slightly, and iron stores, if present, supply the additional iron required. In the second trimester, there is a normal period of hemodilution, commonly referred to as the "physiologic anemia of pregnancy", as plasma volume increases faster than RBCs can be synthesized. The uterus, placenta and fetus are undergoing rapid growth. In an attempt to keep pace with the demand for red cells, the 14 spleen releases immature red cells, remaining maternal storage iron is "dumped" into the maternal circulation, and increased erythropoietin is released from the glomeruli of the kidneys. At 26 to 28 weeks LMP, significant drops in HGB can be detected. A drop of 2.2 g/dL below baseline is considered normal (Scott & Pritchard, 1967). Peak iron demand occurs at about 32 weeks LMP. At 36 weeks LMP, iron demand drops until delivery, and a HGB value 1.4 g/dL below baseline is normal (Scott & Pritchard, 1967). At delivery, average maternal blood loss is about 400-500 cc. The maternal red cell mass contracts to pre-pregnancy levels in the initial post-partum period. Total "iron cost" of a normal singleton pregnancy ranges between 500 and 700 mg iron (Bently, 1985; Dimperio, 1988; Lamparelli et al., 1988b; Lee, 1993b). Breast-feeding women continue to have slightly increased iron demand for the synthesis of breast milk, even when they are not menstruating. There is general agreement that it is nearly impossible for pregnant women to meet their increased needs for iron in the latter half of pregnancy through dietary sources alone (Bently, 1985; DeCherney & Pernoll, 1994; DeMaeyer, 1989; FNB & IOM, 1993; Kitay, 1994; Letsky, 1991; Viteri, 1994; Williams & Wheby, 1992). Universal iron supplementation during the latter half of pregnancy, a common practice in developed countries, is still debated in the literature following reports of excessive perinatal mortality, fetal growth retardation, LBW, PIH, and pre-term delivery 15 associated with maternal W and smite-muse maternal HGB concentrations (Garn, Ridella, Petzold 8 Faulkner, 1981; Goodlin, Holdt 8 Woods, 1982; Koller, 1982; Koller, Sagan, Ulstein 8 Vaula, 1979; Koller, Sandevei 8 Sagen, 1980; Murphy, Newcombe, O'Riordan, Coles 8 Pearson, 1986). For this reason, it is important to identify those who truly require additional iron prior to initiating iron therapy. WW There is a long tradition of reliance on HGB and HOT as inexpensive screening tests for MIDA. For the past 15 years, serum ferritin (the new "gold standard"), TS, FEP, and serum transferrin receptor have been promoted as more sensitive indicators of maternal iron status (Guyatt et al., 1992; Ho, Yuan 8 Yeh, 1987; Lazebnik, Kuhnert 8 Kuhnert, 1989; Lee, 1993b; Lewis 8 Rowe, 1986; Marsh, Nelson 8 Koenig, 1983; Schifman, Thomasson 8 Evers, 1987; Skikne, Flowers 8 Cook, 1990; Ulmer 8 Goepel, 1988; Yepez et al., 1994). None of the newer indicators are mentioned in the American College of Obstetricians and Gynecologists (ACOG) "Standards for Obstetric-Gynecologic Services” (ACOG, 1989), nor in the "Guidelines for Perinatal Care" co-authored with the American Academy of Pediatrics (AAP)(AAP 8 ACOG, 1992). Serum iron measures are of questionable merit for differential diagnosis of MIDA since a) levels often fall during pregnancy even when iron stores are present, b) there is wide diurnal variation in individuals, and c) there is 16 significant variation from laboratory to laboratory (Lee, 1993b). In 1985, Bull and Hay (1985) concluded that norms for MCV, MCH and MCHC are universal and reliable as laboratory quality assurance standards. Although red cell distribution width (RDW) is 90-100% sensitive for iron deficiency, it is only 50-70% specific (Lee, 1993a). Ulmer and Goepel (1988) make a strong case for eliminating HGB and MCH determinations altogether, since serum ferritin levels less than 20 ug/L are diagnostic of IDA (depleted stores) at any time during pregnancy, and highly predictive of pre-term labor (p < 0.001). They observed pre-term (before 37 weeks LMP) labor rates of 52% when third trimester ferritin was less than 10 ug/L, 43% with values between 10 and 20 ug/L, and nine percent when ferritin was above 20 ug/L. They also found that HGB and MCH were poorly correlated with both serum ferritin and pre-term labor. WW Maternal IDA is a pathologic deterioration in maternal iron status, beyond the lower limits of normal changes attributable to pregnancy alone. MIDA is objectively identified by: a) the presence of microcytic [MCV < 80 fL], hypochromic [MCH < 27 pg or MCHC < 32 g/dL] RBCs, b) drops in HGB greater than 2.2 g/100 ml from baseline, c) drops in HCT greater than 4% from baseline, d) TS less than 16%, e) serum ferritin less than 10 ug/L, f) serum transferrin receptor greater than 8.5 mg/L, g) TIBC greater than 410 17 ug/L, h) FEP greater than 100 ug/dL RBC, or RBC ZP greater than 60 ug/dL, 1) serum iron less than 40 ug/dL, and j) the absence of stainable iron in bone marrow macrophages. Further confirmation of MIDA is achieved with a two week trial of oral iron supplements, resulting in a rise in HGB of 2 g/dL or more. Approximately 95% of maternal anemias in the U.S. are due to iron-deficiency (Bently, 1985; Cook, Skikne, Lynch 8 Reuser, 1986; Dallman, Yip 8 Johnson, 1984). Pilot samples from NHANES II 1976-1980 revealed U.S. MIDA rates of 10.7 to 25.5% (Expert Scientific Working Group, 1985). Prior U.S. studies of low-income women reported a third trimester MIDA incidence of 18 to 24% in Whites, and 38 to 45% in Blacks (CDC, 1990; Kim et al., 1992). Incidence of MIDA in low- income women varied significantly by race: non-Hispanic Whites were lowest (9.5% in the second trimester, 24% in third trimester), followed by Hispanics (11% and 32% respectively), then Asians and Pacific Islanders (12% and 27%), then Native Americans (13% and 33%), and highest rates were in non-Hispanic Blacks (22% and 45%). Among all races, rates of MIDA in the third trimester were at least double the rates observed in the second trimester (CDC, 1990; and as cited in IBNMRR, 1993, p. 17). Maternal_risks_of_HIDA. The increased risk of maternal death during pregnancy is 4.6% with mild MIDA and 11.25% with severe MIDA (as cited in Viteri, 1994). MIDA has been associated with the following maternal complications and 18 poor outcomes of pregnancy: pre-eclampsia, PIH, feto- maternal hemorrhage (Frikiche, Cusumano, Senterre 8 Lambotte, 1990), post-partum hemorrhage, cardiac failure during labor, and poor tolerance of minimal blood loss during delivery. Suppression of the immune system in anemic pregnant women increases their vulnerability to urinary, vaginal and cervical infections, pyelonephritis, tuberculosis and malaria (as cited in Viteri, 1994). £etal_risks_with_MIDA. Infants of women who had mild MIDA during pregnancy are at low risk for hematologic deficits at birth. However, infants of women who had severe MIDA are often premature, LBW, and at high risk for IDA, low iron stores, and smaller circulating hemoglobin mass, which manifests at two months of age (as cited in Viteri, 1994). Poor fetal outcomes associated with MIDA include: dysmaturity, SGA, LBW (Unger et al., 1988; Fleming et al., 1989), pre-term birth (Klebanoff, Shiono, Selby, Trachtenberg 8 Graubard, 1991), abortion, stillbirth, and fetal hypoxia during labor (Bhargava et al., 1989; Colmer, 1990). Definitions_gf_M1DA. In 1989, the CDC published guidelines and definitional criteria for IDA in infants, children, pregnant women (see Table 2), and women of child bearing age for use in the public health sector (CDC, 1989). The criteria listed cut-off values for HGB and HCT only. Reference tables were based on data from NHANES II and four European iron supplement studies conducted between 1975 and 19 .8 .82. do? no ..oooa .o «can. eoouooo .Ammv gang ...soaoz cousinswuooncgsu can soucafiso s.“ .3805 you 6,209.25 000.. :H nuannu Eouu counasoaso an enema mv on ma cows coaos cm 49H you mosao> «Monaco coumomosm .ouoz .umou as oosum>mau. c.0v ¢.nd o.wn h.NH o.wn @.NH O.Nv o.¢H +ooo.OH o.ov «.nH o.hm n.NH o.bn «.md o.H¢ w.nH mmmmtooom c.0n h.NH o.mm o.NH o.mn m.Hd o.ov n.nH mmmwlooom o.hn ¢.NH o.mn hind o.mn 0.HH o.mn o.n.n mmmmtooomfl o.wn H.NH o.¢n v.HH o.¢n n.HH o.wn h.NH mmmwlooow m.mn m.HH m.nn N.HH m.nm H.HH m.hn m.NH mmmmlooom o.¢n v.HH o.Nn h.OH o.Nm @.OH o.wn o.NH H0>OH 00m 80: QUE 80m m0: 803 mum 050m emu: meDBHfind mid OX3 on ASH mx3 mm ASA mx3 omw HZGZUNMNHZGZ g .N manna 1982. Additional calculations were suggested for smoking and altitude adjustments. Altitude adjustments were based on data from children in mountain states, and a classic Peruvian study on men (Hurtado, Merino 8 Delgado, 1945). Examples of operational definitions used in prior MIDA studies are: 1. HGB < 11.0 g/dL at anytime during pregnancy (WHO, 1972), 2. HGB < 11.0 g% and serum ferritin < 12 ng/ml in pregnant women at term (Ho, Yuan 8 Yeh, 1987), 3. HGB < 11.0 g/dL, TS < 16.0% and serum ferritin < 12 ug/L in Black pregnant women at term [at 5,000 feet elevation] (Lamparelli et al., 1988a), 4. "Low HGB" and 2 abnormal values out of 3 for serum ferritin (< 12 ug/L), FEP (> 28 ug/dL), or TS (< 16.0%) in post—partum Nigerian women (Daouda et al., 1991), 5. "a hemoglobin concentration (or hematocrit) that is below the 95% confidence interval (i.e., below the 2.5th percentile) for healthy, well—nourished individuals of the same age, sex, and stage of pregnancy", with cut-off values for first, second and third trimester HGB and HCT as follows: HGB < 11.0, 10.5, and 11.5 g/dL respectively, and HCT < 33, 32, and 34% respectively (Life Sciences Research Office, 1984, as cited in FNB 8 IOM, 1993), 6. serum ferritin < 12.0 ug/dL [at 5,200 feet elevation] (Lamparelli et al., 1988b), and 21 7. HGB < 10.0 or 11.0 g/dL [at 5,400 feet elevation] (Watson 8 Murray, 1969). Qgnggptnal_definitign_gf_MIDA. MIDA is a treatable, frequently asymptomatic disease acquired during pregnancy, due to a failure to meet the increased physiologic requirements for iron. This failure of adaptation may be rooted in physiologic, psychologic, social, economic, political or environmental circumstances. These circumstances may include, but are not limited to: a) pre- conceptual nutritional status, b) dietary patterns, c) eating disorders, d) substance abuse, e) religious practices, f) cultural practices related to pregnancy, 9) socioeconomic status, h) closely spaced pregnancies, i) extremes of age at conception, j) geographic isolation, k) political environment, or 1) possible genetic factors related to race. MIDA is a serious threat to maternal and infant health. It is known to cause premature labor and LBW infants, and is associated with numerous complications of pregnancy and poor pregnancy outcomes. BQQKY_Mantain_Altitndes The term "Rocky Mountain Altitudes" was selected to connote the environment within which this study was conducted, and to highlight the impact of environment upon the definitional criteria for MIDA. In conceptualizing "environment" as a variable one must consider both the physical and social circumstances affecting a population. The interaction between physical and social environment 22 variables may be so intertwined that it is impossible to isolate the variables to observe effects due strictly to one variable. Environmental, socioeconomic and demographic factors exert substantial physiologic influences on the sample population for this study. The effects of these variables are described following a brief discussion of terms encountered in the literature. It is helpful to be reminded of the mathematical conversion factor of 3.281 (1,000 meters=3,281 feet) when reviewing and comparing altitude literature, as both measures frequently appear. When reviewing physiologic studies conducted at high elevations, the following terms are common. In discussions of observed variations, the term "at altitude" is often used as a convenient contraction for "at altitudes above 3,000 feet or 1,000 meters”. 1Although no formal criteria were encountered, the term "high altitude" generally referred to elevations above 3,000 meters or 10,000 feet (i.e., Pamir, Tien Shan and Rocky Mountains), and "very high" or "extremely high altitude" referred to elevations above 5,000 meters or 15,000 feet (i.e., Andes and Himalayas). In Colorado studies, Denver (elevation 5,000 feet) was considered "at middle altitude", whereas Leadville (elevation 10,000 feet) was "at high altitude". maimljnximnment The Rocky Mountain region hosts a population of about 12.5 million, and includes the states of Arizona, Colorado, 23 Idaho, Montana, New Mexico, Utah and Wyoming. Each state contains mountains higher than 12,500 feet, with the highest peak at 14,400 feet. Altitudes of populated areas range from plateaus at 3,000 feet to mountain villages at 10,000 feet or more. The sites included in this study, Taos, Las Vegas, and Santa Fe, New Mexico, are located at altitudes of 6,040, 6,400 and 7,000 feet respectively. The town sites are located on the measured plateaus, but their outskirts merge with foothills of the Sangre de Cristo and Santa Fe mountains, whose nearby peaks range between 11,000 and 13,000 feet. The Sangre de Cristo range is considered the southeastern fork of the Rocky Mountains. The climate is arid high desert with diurnal air temperature variations of 20 to 40 degrees Fahrenheit and significant winter snowfall at elevations above 5,000 feet. Although New Mexico's population density is 13.94 people per square mile, one third of the population lives within 30 miles of Albuquerque city limits. Only three out of 33 counties have populations above 100,000. The remainder of the state is quite rural and there are large land areas of wilderness scattered throughout the state. For the cities included in this study, city limits range from about five to twelve miles in diameter. In all three cases, rural environments begin within 2 miles of city limits. All three cities lie between 60 and 140 miles northeast of Albuquerque. 24 W. A8 an adaptation to the physiologic stress of lower atmospheric pressure and lower oxygen tension, acclimated populations at altitudes above 3,000 feet demonstrate compensatory relative polycythemia due to chronic hyperactive erythropoiesis (Athens 8 Lee, 1993; Buys de Jorge et al., 1988 [classic]; Reynafarje, Lozano 8 Valdivieso, 1958 [classic]; Ross, 1988; Winslow et al., 1989). The resulting larger red cell mass is revealed as elevated RBC count, HGB and HCT, potentially masking signs of anemia. Total blood volume is increased, but total plasma volume is decreased, resulting in increased blood viscosity (Athens 8 Lee, 1993; Dainiak, Spielvogel, Sorba 8 Cudkowicz, 1989; Sanchez, Merino 8 Figallo, 1970). Rgd_gell_indigg§_at_a1titnde. Table 3 summarizes reference values for RBC indices in adult non-pregnant women at sea level, and presents empiric values obtained in studies of non-pregnant women at sea level and at altitudes above 3,000 feet. Note the altitude-dependent variations in RBC count, HGB and HCT, whereas other indices remain stable within sea level normal limits. There are minor discrepancies in the literature regarding changes in MCV at altitude. Most investigators report a slight increase (upper limits of normal range) or no change from sea level norms. In Mexico, Ruiz-Arguelles et al. (1980) observed a significant drop of more than five percent in mean MCV between sea level and 6,000 feet, 25 .aama A coauuaounm cauuuuucuuu omuaoomug Ioooav .vmaq oosouomom on» so consonoue one moosououou cousom ouoaeaoo .Hmmioa moon nocsHost Amvmav :wuoanmoawusou a Hauimoanomo .Hn no uoHHosmudinasma .Hcoaoom moonu .aa muzomz scan muses .oooa. :eaaano a oomcsoo .nau. .ononuxmus .aooav second 8 «among. .:0303 usosmoueisos no“ can mosao> Had .ouoz ao ooa as oaa am mama no snun.ou onunn onuan cocoa o.~n pn.nn e.~n o.~n n.~n o.nn I». one: mnnmu onusu anusa oozed mn.on o.on Ion. no: m.moa1as ooauao mouom cocoa p.4o ~.am s.oo ~.ao o.oo o.oo .au. >0: ao.ousu.o a.m1o.n o.m:u.o cocoa mo.o ao.m oo.¢ am.o oo.o No.4 I.se\ooaaaae. one o.om1m.av moumm serum «menu o.oo «.mo o.oo o.mo o.~o o.oo A». sum s.sauo.na m.ma1s.aa oauua «menu n.ma «.ma o.oa m.oa o.na m.na .ao\o. mom .aums oopo seems snob .amus owns .amus ooao .ammm ooan sam>ua «no .aw>ua cum Doom coo.n d>on¢ mocsufiuad us can Ho>ma com um woodccH 0mm .m magma 6 2 indicating larger numbers of small red cells. Between 6,000 and 7,000 feet, MCV was stable but below lower limits of sea level norms. At 8,700 feet, mean MCV returned to sea level norms. The bulk of data supports the concept of universal normal limits of human RBC size, independent of race, gender, age or altitude. MCV may increase by 3 million/mm3 in smokers at any altitude, due to increased levels of carboxyhemaglobin. In Equador, Yepez et al. (1994) conducted a one month trial of iron and folic acid supplementation, comparing responses at sea level and at 9,200 feet elevation. They utilized an altitude correction factor suggested by Hurtado et al. (i.e., 4% for every 1000 meters above sea level). They found WHO cut-off values for HGB to have high specificity, but low sensitivity (58%) at sea level, and no sensitivity at 9,200 feet elevation. They concluded that HGB alone was a poor criteria for anemia at both sea level and 9,200 feet. Athens and Lee (1993) suggested that there may be adaptive mechanisms which result in specific local hematologic variations. They listed geographic, geologic, occupational, cultural, dietary pattern, lifestyle and racial factors which may explain the red cell indicator differences observed by Winslow et al. (1989), who compared Himalayan Sherpas to Andean Quechas living at the same altitude level. 27 WWW Serum ferritin, TS and TIBC appear to be unaffected by altitude, and are useful as diagnostic determinants of anemia (Hofvander, 1968; Ross, 1972). Although serum iron is unaffected by altitude, it is a poor measure of iron status during pregnancy (Lee, 1993b). 5 . i E . I Population figures from the 1994 census for Taos, Las Vegas, and Santa Fe were as follows: town site populations were 4,400, 15,600, and 62,500 respectively, and county populations were 25,000, 27,350, and 112,200 respectively. The major racial groups populating the state were non- Hispanic Whites (50%), Hispanics of both Spanish and Mexican descent (40%), and Native Americans (9%) including Pueblo, Apache, Kiowa and Navajo groups. In 1994, New Mexico was ranked the eighth fastest growing state in the nation and the Rocky Mountain region hosted five of the ten fastest growing states (NMDH, 1996). The following statistics reflect 1994 New Mexico data unless otherwise noted. Per capita personal income statewide was $17,106, ranking New Mexico 47th in income, with 20% of the population living below federal poverty level. Per capita personal income in Taos county was $13,569, in San Miguel county $12,294 and in Santa Fe $22,538. The 1994 national rate for families living below poverty level was 10%. In Taos, San Miguel and Santa Fe counties, rates were 23.8, 26.3 and 10.4% respectively. The 28 Medicaid eligible population statistics for March 1997 were as follows: for the entire state, 14.53% (245,802 out of 1,691,645), for Taos, San Miguel (Las Vegas) and Santa Fe counties, 8.6%, 23.32% and 7.12% respectively (personal communication, Anthony Garcia, New Mexico Medical Assistance Office, May 1997 [see Appendix A]). The median age was 32.4 years, reflecting the unusually high fertility rate and large population of children. There were on average 33 marriages, 27 divorces, 76 births and 33 deaths per day statewide (NMDH, 1996; NMDH, 1997). In 1994, the New Mexico birthrate, which has been significantly higher than the national birthrate for the past 20 years, was at an all time low of 16.7 live births per 1,000 population compared to the national rate of 15.2. Birthrates in Taos, San Miguel and Santa Fe counties were 14.6, 14.4 and 13.3 respectively. In 1993, the statewide birthrate among mothers aged 15 to 19 years was 37% higher .than national averages. Forty percent of births and 80% of legal induced abortions were to unmarried women. Ninety- eight percent of births occurred in hospitals. Eighty percent of births were physician assisted and about 17.5% were certified nurse midwife assisted. In 1994, there were five maternal deaths in New Mexico, yielding a maternal death rate of 18 per 100,000 live births compared to 7.0 nationally. In 1995, the New Mexico maternal death rate was 11.1 compared to 6.3 nationally. The statistic for maternal death rate varies widely each 29 year, and is skewed due to the small population. The New Mexico maternal death rate is generally above national rates. Causes of maternal deaths between 1992 and 1995 were PIH, pregnancy-related infection, pulmonary embolism and hemorrhage due to placenta previa. Fetal and infant mortality rates are consistently lower than national rates (NMDH, 1996; NMDH, 1997). The 1994 statewide incidence of LBW was one out of every 14 births, 7.3%, or 73 per 1,000 live births. LBW was above national averages in mothers aged 25 to 39 years. Five New Mexico counties reported LBW rates between 20 and 43% in mothers under 15 years old. Four counties reported LBW rates between 25 and 40% in mothers over 40 years old. The three year aggregate incidence of LBW for 1993 to 1995 in Taos, San Miguel and Santa Fe counties was 10.1%, 10.5% and 6.7% respectively, compared to the national rate of 7.3% (NMDH, 1996; NMDH, 1997). In summary, Taos and San Miguel counties had high rates of poverty and LBW whereas Santa Fe had rates closer to national rates. Birthrates in all three counties were 1-2% lower than the national rate. Fetal and infant death rates were lower than national rates. Maternal deaths were not analyzed by county, so no conclusion can be drawn. Two of the four causes of maternal death listed were complications associated with MIDA in the literature. 30 In conceptualizing the term "Rocky Mountain Altitudes", one concludes that a) Rocky Mountain inhabitants live at altitudes ranging from 3,000 to 10,000 feet elevation, b) these elevations are considered "middle altitude" by informal standards, and c) middle altitude is an environmental factor that exerts a physiologic stress, resulting in hematologic adaptations. Hematologic adaptations to altitude are expressed objectively as elevations in some RBC indices (RBC count, HGB and HCT), increased blood volume and viscosity, and decreased plasma volume, all of which vary directly with increasing altitude. There is insufficient published data to determine altitude specific corrected norms for these adaptations, or whether the hyperactive erythropoietic adaptation to middle altitude is sufficient to withstand the additional stress of pregnancy. The literature suggests that socioeconomic status and certain demographic variables are strongly associated with IDA. Also, there may be unidentified local or genetic factors influencing hematologic adaptation to altitude. These factors may be impossible to isolate individually from the effects of altitude alone. Of particular concern in this study are the factors of race, socioeconomic status, high fertility and possible frequent travel to altitudes more than 1,000 feet lower or higher than the domicile. 31 For this study, Rocky Mountain Altitudes is conceptually defined as: a) an arid, mountainous physical environment of such high vertical elevation above sea level that atmospheric pressure and oxygen tension are reduced, forcing human inhabitants to physiologically adapt in the form of hyperactive erythropoiesis, elevated RBC count, and elevated HGB and HCT values; and b) a socioeconomic environment of low population density, high fertility, high divorce rate, low per capita income, and an unusual racial mix. Theoretical Framework This study could have been applied to several theoretical frameworks including: a) Roy's Adaptation Model — the physiologic mode; b) a physiologic version of Bertalanffy's Systems Theory; and c) a modified, physiologic version of Stress Theory, integrating concepts from Selye, Hill, and McCubbin. However, the Starfield model of "The Health Services System" (Starfield, 1996), popularly known as "The Starfield Model of Primary Care", was selected as the most appropriate framework. Although all of these models can be used to explain the physiologic phenomenon under study, Starfield's model also clarifies a constellation of issues encountered in the primary care context. Starfieldls_nodel Starfield's model first appeared in the literature in 1973 (Starfield, 1973). In 1992, Starfield elaborated upon 32 the concepts in the model, demonstrated the application of the model to primary care, and described potential applications to evaluation of services and policy development (Starfield, 1992). In 1996, Starfield discussed the use of the model for guiding primary care research (Starfield, 1996). Starfield's model presents an effective framework for a) identifying particular features of the health care system, and b) understanding how these features impact the function of the system, and the health status of the population. A creative integration of systems and interactionist theories, the model a) classifies health- services variables into categories of structure, process and outcome, b) illustrates the relationship between the categories, and c) identifies intervening factors in the primary care context. Ultimately, the model reveals the relationship between the primary care system and the health status of the population it serves as the result of an interactinpmcessbetueenthenmidersefcareandthe reggiygrs of care; By simply shifting focal points, the same model can be utilized by several disciplines for multiple purposes (i.e., developing standards for clinical practice, focusing and directing research, evaluating health service delivery). The model utilizes familiar, straightforward concepts that readily address a) the practitioner's dilemma of problem recognition [MIDA], b) the influence of the peculiar environment [Rocky Mountain 33 Altitudes], and c) the relationship between problem recognition and health outcome. The goal of any health services system is to promote the well being of the population it serves. The population ("persons") defines "well being" and identifies specific health care needs within the context of its cultural beliefs and values, religious beliefs, prevailing political structure, socioeconomic structure, and physical environment. The function of the primary care system is to serve as the individual's first point of contact with the health services system. The primary care system (out- patient services) must effectively address a wide variety of health concerns, whether of an acute, chronic or maintenance nature. Where it is available, secondary care (out-patient specialist services) is activated when individuals present health problems requiring more sophisticated assessment, monitoring or intervention related to a particular body system. Tertiary care (hospitalization) is activated when intense specialized care is required to preserve and restore the health of the individual. SIIHQLHZB Using Figure 1 as a reference point, it is clear that structural features must effectively interface with the social and physical environment, in order to be relevant to the population ("persons”) served. The structure must include personnel that are educated to address issues identified by “persons” as health care needs. The range of 34 .aeeo. Eases. 2 _8_eo> 59. uses a soot .92 6.2.56 938 3 22 2938 .98 .mmee 26.63:: 22.6 uto> 262 News .2335 .m 3 3.3.. new cozeigm ..eoocoo "memo Bap—...... E9. uoaaum .202 Sofia .8228 5.8: 2: .o .802 2255 9: a 2:9". 85:82 EoEo>oEuo Swami @5315; 323.3 «.258 25.8 96ch EoEcQSco 1llll" cozaggtaa 95:29.85 cozoflmzmm oocmaooom Sense: mcofloo 92005.30 wm<0 no .5509; EoEmmommmoe EmEmmmcmE mfiocmmi coEcmooE Emfioa wmmOOEQ mm<0 ....O ZO.m_>Omm 5223 cam :38 b j k 2996 5:338 @5053: £53308 25558 moonEm new .coEommcmE coszEmmeo 3223 .o omen. EoEaSao 85:8. 5:898 wmahoamhw 35 services must address a variety of health concerns. The system must be accessible (physically and financially) and culturally acceptable to a significant portion of the population, and provide some assurance of continuity. The means of financing the system must be appropriate, adequate and acceptable within the context of the socio-cultural, political and physical environment to permit continuation of the system. Facilities and equipment must be adequate to allow provision of care, and appropriate for the social and physical environment. Management and amenities within the system must promote the function and continuation of the system. All structural features must be in place and functional to permit the process of care to occur (Starfield, 1992). The bi-directional arrow connecting structure and environment implies that environmental features (i.e., physical environment, socioeconomic factors, cultural beliefs related to health, social structure) exert strong influence over structural features (i.e., location, size and type of facilities, transport, type and use of supplies and equipment, range of services, types of personnel, financing, eligible population). It also implies that structure affects both the social and physical environment. Examples of structure affecting the social environment include: a) the employment of members of the population; b) the provision of services to the target population; c) the potential introduction of different beliefs or values; and 36 d) the attraction of visitors (staff or clients) from other locations. Examples of structure affecting the physical environment include: a) changes related to transportation of people, supplies and equipment; b) building or alteration of physical structures related to the provision of services (i.e., roads, facilities, support services, housing, food services, waste management); and c) increased utilization of natural resources and utilities. The bi-directional arrow connecting persons and structure implies that "persons" exert strong influence on structure and vice versa. "Persons" identify specific health concerns. Unless structure addresses these concerns, "persons" will not utilize the system. Structure must define the limits on the range of services and the population eligible in order to a) establish realistic expectations and maintain credibility with ”persons”, and b) promote the effective function and continuation of the system (Starfield, 1996). 229523.55 The process of care is dependent upon structure, but features both the individual and interactive activities of the providers of care and the recipients of care. The provider must be able to recognize health problems, diagnose problems accurately, manage problems with the use of appropriate and acceptable interventions, and reassess the effectiveness of the management plan. The provider must be educated and skilled, communicate effectively, be aware of 37 the social and physical environmental factors affecting "persons", provide health education related to specific diagnoses, and perform these functions in a manner acceptable to "persons". The receiver must access the system (utilization) and participate in the process of care by: a) presenting health concerns; b) participating in the assessment phase; c) understanding the health problem; d) providing input in the selection of a management plan that is acceptable to both parties; and e) participating in the plan of care. The effectiveness of the interactive process determines outcome. Outcome According to Starfield's model, the health outcome for the receiver, and ultimately, the health status of the population are the result of the interactive process of care, as indicated by the uni-directional arrow linking process and outcome. If there has been good interaction, outcomes will be favorable (i.e., prevention or management of disease, increased comfort, longevity, activity and well being of persons utilizing the system). If there has been poor interaction, outcomes will be unfavorable (i.e., no change, spread or increase in disease, or worsening of health status). Unfavorable outcomes can be traced back to ineffective process or structure. Outcome is also partially dependent on social and physical environment, as indicated by the uni-directional arrow linking these portions of the model. For instance, 38 geographic isolation or catastrophic environmental events such as drought, flood, or earthquake certainly impact the health status of a population, but these events are not necessarily a poor reflection on the primary care system. Likewise, the social environment may preclude favorable outcomes. An example might be the mother who obtains high quality baby formula intended for her malnourished infant but defeats the purpose by diluting it to low nutrient value to feed all four of her children. MIDA_aI_RQQkY_HQnnInin_AltiInd£fi_Annlifld_tn Starfieldls_nodel In applying this study to Starfield's model (Figure 2), the areas of direct fit include "physical environment” and "problem recognition". Figure 2 includes additional structure, process and outcome features of primary care for prenatal clients to complete the picture. The ”physical environment" (Rocky Mountain Altitudes) alters the hematologic norms of ”persons" (pregnant women), obscuring "problem recognition" (MIDA) using conventional standards of care (screening practices). Failure to recognize the problem leads to delayed or mis-diagnosis and inadequate management, potentially resulting in maternal or fetal complications and poor pregnancy outcome. In addition to the relationships between variables noted by Starfield, Figure 2 notes the additional relationship between environment and the provider features of problem recognition and diagnosis with a unidirectional 39 ..ooos. esteem 9.3.5 88:? 52:32 .28: 3 <9: .... some. 352.328 383 s 635859: .3303 Earlene .25 AT >56. .95 :8. 82.689 32:? 0.3.... 8 east :88 so... as 3:05:23... .83).... 52.25 0232 are .353: $8 .22: so... I 5.59586 392 .335 .28 8.9% :9: $93.52.. 3.38. x ounces. 38 “We” sameness... ...—woken.“ 33.2.6 c2333.. 5.! :9: .058: . u .. Bo. 62:2 6232.3 . k 3.65.0 cream 83. .22 5.3 :9; 23 .2328 3:255:20 .38. 3.225 32.3388 85838 0.32. .02: .22 3 3629: + 6823:. 23.... .858 to. on. 28 £28 .22 e f "2.83.... 23852.. e A 8. 9.2.3 <09 26.. 1 r... . ..eoesooo 850 see .862: sees. .08 .88. . . .5358 822... 2: 85o 333.. 22 Ease 3522: e oo 9.83 m 5 9.26.3. 688:8. $8.932 .mEoo. "COCA. so... :38 mean. 2:25:30! 598 .35... >5 5 :3 3.30 85.28:: cmEo>> _ .3: 2050.83 so: .20 09:0 .369: ..= .3 a“: to.» a. 33 a .059: >532. cos—252:. 83.62 Escaped _ .66 {0.1.38.8 . . . 28 .3265 2a. s 335593 96.3 _ 2:083.an 835.com s e s . . Essence. .eses .222 ...m. assesses 9m. stews... 1 2.285 3.82 a nests. <9: 3.38.... s {so 8...... .320 o... .852qu (Ow 26.. IE 858383 2.09. _ POIBOI .8032: 3:3 £02 an. 635: as 5.8 3522. 1 8.855 as _ 9 one Hcease 3.2 28258... 85: 928.. "080 0.00 3.955 8.33:- _ ”COECUOOOC 50303 C "23w 40 l ‘ mmZmme awn—50mm I \ wZOOhDO mePODme meOOmm arrow. This arrow demonstrates that physical environment (Rocky Mountain Altitudes) may so alter the appearance (usual diagnostic signs) of health problems that providers fail to recognize them using conventional assessment tools and standards of practice. When evidence of poor outcomes (i.e., maternal mortality, PIH, premature labor, and LBW) clusters in peculiar patterns (i.e., above 6,000 feet elevation), it becomes necessary to re-examine the system for flaws. In the case of MIDA at Rocky Mountain Altitudes, orobiom roooonition and diagnosis are impaired by: a) the lack of prior research; b) an incomplete body of knowledge [altitude-adjusted reference tables to assist in differentiating normal from pathologic changes]; and c) the lack of altitude-appropriate guidelines and standards for clinical practice. REVIEW OF THE LITERATURE Prior MIDA Studies Above 3,000 Feet Elevation Six prior MIDA studies at altitudes above 3,000 feet are located in the literature. Regrettably, all six are conducted in Africa more than nine years ago. Table 4 summarizes the numeric data in order of increasing altitude. Data contained on the table are not included in the presentation of each study. Discussion of findings is included in the critical remarks. A synthesis of empiric findings and general critique of the literature follows the presentation of individual studies. 41 co>uo uo: suou.o.~.o.on mzqzon.m.~.v.om m:qt~n.~.~.>.on mz43o~.o.~.o..m o .o.~.a.on co>«o uoc co>ao uoc suou.m.~.a.mv ngzom.v.m.~.vv mzqzwm.m.n.n.~v m:qzow.n.v.m.0v o .v.m.o.wv Euvu.m.d.m.mH m2;30m.m.o.v.na mZJINn.H.H.H.MH mZAImN.w.H.w.Na co>do uoc mzq30n~.m.a.n.vn mzqkon.h.u.v.nn m2;3-.a.a.o.vm U .m.d.v.vn c0>ao uoc c0>ao uoc m2J3mm~.v.m.o.Nv mzq3om.n.n.a.0v mZAINH.N.n.H.Hv U .m.N.N.vv mZJ3+mm.m.H.m.va mzqzom.w.a.v.mH mZASNH.m.H.o.va o.~H v m0: o.oH v mu: co>fio uo: cu>fio uoc co>ao uoc cm>ao uo: +o some v.m m-m mama m.e wQHEHuQ >.m "uuddmuluanuza o>mmummo.u.ze.~...m.~. o>vmuono.u.se.~...o.w. o>m~-mmo.u.:s.~...m... osvmnoma.u.as.....m.e. a.s.ua.m...m... HNM HN N N NH v hm co>ao uoc «nu.m.n.v.wN «uu.w.w.m.mw wuu.a.m.o.hw «uu.a.a.a.oo Huu.m.w.w.vo «uu.m.h.m.mo «nu.w.m.m.mm «uu.m.m.n.mm «nu.v.m.a.hm duu.N.H.H.HH .uu.N.H.m.N~ wuu.m.a.m.NH HNM HNM HNM M NH v hm own v MB o.HH v m0: co>ao uoc «uu.o.n.n.mw «uu.m.N.m.mN «uu.m.n.o.mm auu.m.h.v.wm auu.m.h.w.om «nu.m.o.m.wm auu.m.m.m.wm «nu.m.m.m.wm fiuu.m.m.m.mm Huu.m.a.h.aa fiuu.N.H.H.NH Huu.m.H.H.mH o.HH v mo: co>fio uoc cv>.v uoc co>ao uoc mzAZwN~.v.m.m.Hv quzwww.m.n.m.av U .m.~.m.Nv mzowaA.....p.m. mzqzmmv.m.o.m.m. "m4 omthmo (DH: . .aw. ozoz on .qw. :02 Au .qw. Hun . .aw. so: o.o.s.m.v. o.m.o.~.m. on... no... u .m.o.m.m. .Eoo.\o .qw. mun anus .002. an: .ooms emu... nooem 9mm... uoomm Hum... Abow... 9mm... .OOmcnoomm meadoHazH . .v NHQMH. uuvcn>uo:. ..upm.. «mom. ..mmaH. sauna: . comumz. ..nmmm.. .UWHH UUCUuOHGH OZU C0 UOUfi>OHQ OHM WCOHHMUHU OUOAQEOU ..mwmflv .Hm um “Hawququo ..mmmma. .UHO mumo>no> ..a co ...mumosms. ..vmm.. noxsmz . cwmu.uuwo. .mzq mxowzanAI .QDOHO HOuucounU .uouwweauuuauu .muoz VN-zmme .Nnom «mama emsumnN mumu .m.uom mvnom ~ mmsum. nanmm m ax; mxmmz sm mmum o.um moan neum emum m..nm on. man. Ova. mmemmzome sm av co. mm ev ev m. mDOmo somezou we we. so. oo. vNN om. qHo eoz zm>Ho eoz mmmame xuHo soc co>ao .0: o. v mu: .m.m . .uu .mm . so» s. mzoz 4a.: .0 mmewud .4m.»~.wfl .mm.»~.on Am vuo.m .o e Ase .o.:.: .nm.»~.oe «mavas.¢~ Ammvam.~o Ach»6.~m Ase osmoeomz .Hflcun.m An V»H.v An .«o.m A» c»6.an .av «no: mmoH>omm mozamomzH AN vwm.~ .a can.~ Ac v Ac c any cmfim< AH .«o.o AH .»4.H Ao v .6 V .o. consumam m>Humz .nmeam.~o .oe.»m.«m Acevaocfl .n www.mfl any annexe: no cascadm .uivm4n 33134.4 3 v $3»~.vm :5 swan: Owcmamwmlco: mo was moms oHamHmmaoamamo .m manna .6 V66.6 .6 V64.6 .6 V66.6 .6 V .oV «nos no noon .6 V .6 V .6 V .6 V .sV owns» .66Vu6.66 .6 V66.66 .4 V66.66 .4 V66.66 .6V 63» .46Vu6.66 .66V64.66 .6 V66.66 .6 V66.66 .qV 6:6 .66V66.66 .44V66.66 .66V66.66 .66V66.66 .qV 66>66 no: no 6:6: 96.6 6.6 6.6 66.6 2 66666664666: 626 626696666 .4 V66.6 .6 V66.4 .6 V66.6 .6 V .6V onos no noon .4 V66.6 .6 V66.4 .6 V66.6 .6 V .6V owns» .66Vu6.66 .6 V66.66 .6 V66.66 .4 V66.66 .6V 63» .66Vu4.64 .66V66.64 .66V66.94 .4 V66.66 .6V 6:6 .64Va4.66 .66V66.66 .66V66.96 .66V66.66 .6V 6:6: 66.6 66.6 6.6 66.6 a 66666>H666 6oon>mmm .66V66.66 .66V64.66 .6 V66.66 .6 V .6V wnos no cannon .66V66.66 .96V66.66 .66V66.66 .66V66.66 .oV 6n6nn .64V66.66 .66V66.66 .66V66.66 .4 V66.66 .6V 666666 .66V66.66 .66V69.46 .6 V66.66 .6 V66.66 .oV umn66 64.6 64.6 66.6 66.6 6 66662626666 66966 66¢ 66 69246 6666> 666 6669 66966669666666 ..ncooV 6 66669 68 69 «H.NN MH.mH no.0N wo.HN WQUGOE onlwm #h.b wm.m $0.0H nm.oa mEUCOE wmldn am.m wo.m wo.oa «m.OH mSHCOB onlmN «b.Hm «m.mN «m.Nn «n.6N mSHEOE cm W an.HH wm.m wo.mH «n.wm m£#:OE vmlmH ”H.o ww.w «m.h o mBHCOE mHlnH an.nm ww.nH wo.oa o mSHCOB NH w vh.v ww.m wm.~ o mQHGOE NAIF ”n.nd #w.m wm.h o mSHCOE mic no.HN H.5H w.HN 0.9N a A<>mmBZH WZHB A m<fl m0<8 UHBmHmmfiodmdmo ..noooV 6 66669 exceptional in that women were spacing pregnancies by at least 18 months. Research Questions For research question one, mean empiric values for red cell indices are summarized by screening interval and altitude level on Table 6. Table 7 summarizes “normal values”; the calculated mean for all remaining data after anemic cases were eliminated from the sample. Findings for each indicator follows. HGB Mean HGB values at all sites ranged between 12.5 and 13.9 g/dL, in agreement with prior findings (Ruiz-Arguelles et al., 1980; Robles-Gil and Gonzales-Teran, 1948; Ross, 1972; Hofvander, 1968) of mean HGB levels ranging from 12.5 to 14.6 g/dL. There was a predictable drop from baseline of about 1.0 g/dL in mean HGB at 28 weeks LMP, and a small rise in mean HGB of 0.1-0.5 g/dL between 28 and 36 weeks LMP. This pattern is consistent with variations reported by Scott & Pritchard (1967), and well within the normal limits (drop of 2.2 g/dL at 28 weeks, then a rise of about 0.7 g/dL at 36 weeks) they described. An interesting pattern is revealed when looking at HGB range values on Table 6. Lower limits of the range decline and ranges widen both as altitude increases and as pregnancy progresses. Perhaps this pattern suggests that physiologic adaptation to altitude (hyperactive erythropoiesis) is beginning to be taxed by pregnancy. 70 666 66 64 6 «6 6.66-6.6 6.46-6.66 6.66:6.6 6\2 6666n .66.6V66.66 .66.6V66.66 .66.6V66.66 6\2 .awV: 626 66663 66 666 66 66 6 u: 6.46:6.66 6.46:6.66 6.46:6.66 6.2 66:6n .66.6V66.66 .66.6V46.66 .66.6V66.66 6.2 .aqu 626 66663 66 666 66 66 66 «6 6.66-6.66 6.66:6.66 4.66-6.66 6.66:6.66 6666n .66.6V46.66 .66.6V66.66 .66.6V66.66 .66.6V66.66 .awV: ma mxwm.’ ON w .66\6V 2666666266 6666 6666-6 6666 6666 6666 6646 6666 6466 66626 666 66966 666 66 69266 66om> 666 6669 66696966 wuddufluddlnfluuandzlflMudmIHMIMHUHGQHIUQMIHMQHMMMS .6 66669 666 66 66 66 u: 6.64-6.66 6.64-4.66 6.64-6.66 6.64-6.46 6666n .66.6V46.66 .64.6V66.66 .66.4V66.66 .64.6V66.66 .auVa 666 66663 66 466 66 66 66 no 6.64-6.66 6.64-6.66 4.64-6.66 6.64-6.66 66:6n .64.6V66.66 .66.6V66.66 .66.6V66.66 .66.6V66.66 .amVa 626 66663 66 666 66 66 66 «6 6.64-4.66 6.64-4.66 6.64-6.46 6.64-6.66 66:6n .66.6V66.66 .66.6V46.66 .66.6V66.64 .66.6V46.64 .una ma mxwflsa ON w .6V 9666696266 6666 6666-6 6666 6666 6666 6646 6666 6466 66626 666 66966 666 66 69266 66663 666 6669 66696966 ..6cooV 6 66669 66 66 66 6 n 6 6.66-6.66 6.66-6.66 4.46-6.66 6.2 6666n .66.6V66.66 .46.6V66.66 .66.6V46.66 6.2 .awVa 626 66663 66 66 66 66 6 ac 6.66-4.66 6.66-4.66 6.66-6.66 6.2 6666n .66.6V46.66 .46.6V66.66 .66.6V64.66 6.2 .aqu 666 66663 66 466 66 66 6 u: 6.46-6.66 6.46-6.66 6.46-6.66 6.2 6666n .66.6V66.66 .46.6V46.66 .66.6V66.66 6.2 .amVa a @3003 ON w .66V :62 666 66 66 6 u: 6.666-6.66 6.666-6.66 6.666-6.66 6.2 66:6n .66.6V46.66 .64.4V6.66 .66.6V64.66 6.2 .aan 666 66663 66 466 66 66 6 u: 6.666-6.66 6.666-6.66 6.666-4.46 6.2 66:6n .66.4V66.66 .66.4V66.66 .66.4V66.66 6.2 .aan 626 66663 66 666 66 66 66 u: 6.66-6.66 6.66-6.66 4.66-6.66 6.46-6.66 6666n .66.4V64.66 .66.4V66.66 .66.4V66.66 .66.6V66.66 .awVa m5 m¥0w3 ON w .66V 362 6666 6666-6 6666 6666 6666 6646 6666 6466 66626 666 66966 666 66 69266 66663 666 6669 66696966 ..6666V 6 66669 3 7 .mouaou young as» an 0660666 660660666666 0:6 666606660666 cmmsumn 66666069 :6 6:0666666> 6006666 6660 0:66663 .66666069 >00~oumamn co 66:66> =0: 60:60:6 60: 660 6068 :6 >uouuuonoa 0:8 .666n6666> 66626 606 manwamm>6 6666 o: 6663 666:6 666606cC6 6.2 .6602 666 66 . 66 6 «6 6.66-6.66 6.66-6.66 6.66-6.66 6.2 66:66 .66.6V66.66 .46.6.46.46 .66.6.66.66 6.2 .66.: 666 66663 66 466 66 66 6 «6 4.66-6.66 4.66-6.66 6.66-6.66 6.2 66:66 646.6666.46 .66.6.66.46 .66.6V66.66 6.2 .666: 626 66663 66 666 66 66 66 «6 6.66-4.66 6.66-4.66 6.66-6.66 6.66-6.66 66:66 .66.6.64.46 666.6666.46 666.6666.46 664.6666.46 6666: 666 66663 66 m .66 666: 6666 6666-6 6666 6666 6666 6646 6666 6466 66626 666 66666 666 66 66266 66663 666 6666 NQDBHfifld A.u:oov m manna 74 ..6 66669 666. 66666666 666 666 .6. 666 .66.6 66 v 666: 66 66 66 v 666 666 .66 66 v >66. 6666666666 66666666666 666 .6. 66 665360 66 6064. 60 66660 96.666.666.666 an 666666.60 663 669666656 .66.—6.60.6. b.6666: 6.66.9. .0632 .66.6.66.46 64 .64.6.66.66 66 6 .66.6. 666: .66.6.46.66 66 .66.6.66.66 66 6 .66. so: .66.6.66.66 64 .66.6.66.66 66 6 .66. >6: .66.6.66.66 64 .66.6.66.66 66 .66.6.66.66 66 .6. 966 .66.6.64.66 64 .66.6.66.66 66 6 .66.6. 666 angled .66.6.66.46 44 .66.6.66.66 66 6 .66.6. 666: .66.6.66.66 66 .66.6.66.66 66 6 .66. 66:64 .66.6.66.66 44 .66.6.66.66 66 6 .66. 36:.- .66.6.66.66 64 .46.6.66.66 66 .66.6.64.66 66 .6. 966 .66.6.66.66 64 .46.6.66.66 66 6 .66.6. 666 gm .66.6.64.46 44 .66.6.66.46 66 .66.6.66.46 66 .66.6. 666: .66.6.66.66 44 .46.6.66.66 66 6 .66. 66: .64.6.64.66 64 .66.6.66.66 66 .66.6.66.66 66 .66. >6: .66.6.66.64 64 .64.6.66.64 46 .46.6.66.64 66 .6. 966 .46.6.66.66 64 .46.6.66.66 46 .66.6.66.66 46 .66.6. 666 3 .66. z 6 .66. z 6 .66. z 6 6666 6666 6666 6646 6666 6666 -6 a - ... II... o - .-:o. ...,o- a o -6 o u- o o 4640 o ...-o . 6. 0HQME Prior studies (Ruiz-Arguelles et al., 1980; Robles-Gil & Gonzales-Teran, 1948; Ross, 1972; Hofvander, 1968) found mean HCT values ranging between 40 and 45%. The empiric data were 2.5-4% lower than expected, in slight disagreement with prior studies. For the sub-set of “normal” healthy subjects (Table 7), mean HCT ranged from 37.4 to 40.9% in this study. The observed drop between the initial and 28 week screens ranged between 2 and 3.3%. The observed rise between 28 and 36 weeks ranged between 0.8 and 2.4%. M91 Ruiz-Arguelles et al. (1980) found mean MCV ranging between 89.7 and 91.2 fL. Mean MCV for this study ranged between 89.4 and 92.7 fL in close agreement, and lying well within the reference range of 80—95 fL. Of note, the range of values widened and variation increased directly as altitude increased. Outliers were just as likely to represent macrocytosis as microcytosis. MCH The reference range for MCH is 27-31 pg (Pagana & Pagana, 1992). At 7,450 feet altitude, Robles-Gil and Gonzales-Teran (1948) observed a mean MCH value of 30.33 pg and a range of 25-35 pg. Mean MCH values for the current study ranged from 30.71 to 31.41 pg. There was a very slight trend towards upper limits of normal or hyperchromia. The observed range of MCH values was 25.1 to 35.3 pg, identical to the Robles-Gil and Gonzales-Teran (1948) study. 76 Standard deviations were less than 2.2, indicating tight clustering around the mean or small variation. MCHC The reference range for MCHC is 32-36% (Pagana & Pagana, 1992). All mean MCHC values fell between 33.6 and 34.6%, and standard deviations were less than 1.3%. There were very few outliers at 36 weeks LMP, again indicating tight clustering around the mean. Prior studies (Ruiz- Arguelles et al., 1980; Robles-Gil & Gonzales-Teran, 1948) of non-pregnant women noted mean MCHC values ranging between 30 and 34.5%. Values obtained in this study were well within the reference range and, although slightly higher, in agreement with prior studies. In answering the second research question, “What is the rate of MIDA when MIDA is defined as MCV < 80 fL and HCH < 27 pg or MCHC < 32 g/le , the data revealed only two cases of MIDA. Both cases occurred in Las Vegas, one upon initial screen and one at the 36 week LMP screen. The observed rates for MIDA were none at Taos, none at Santa Fe, and at Las Vegas, 0.4% at s 20 weeks LMP, 0% at 28 weeks LMP, and 0.4% at 36 weeks LMP. The overall rate of MIDA for the entire sample was 0.75% at initial and 36 week LMP screens. These values were summarized on Table 8. The third research question, “What are the mean and range values for HGB and HCT associated with MIDA2', could not be answered because of the extremely low rate of MIDA observed. The single case of MIDA at s 20 weeks LMP had the 77 .aocmcwmua 0:6656 mafia 666 66 66.6 66 v 666: 66 66 66 v 66: 666666 666 .66 66 v 36: 66 6666666 663 666: .6662 666.6 6 .6u6.64.6 6 626 66663 66 6 6 6 6 666 66663 66 666.6 6 .6u6.64.6 6 626 66663 66 w 6666 6666:6666 6666 6666 6666 6646 6666 6466 266666 66666 664 66 66z<6 66663 666 6666 adHfilHdlwuHum . m manna. 78 following CBC values: HGB=11.5 g/dL, HCT=34.3 %, MCV-77.9 fL, MCH=26.1 pg, and MCHC=33.6 g/dL. The single case at 36 weeks LMP had the following CBC values: HGB=10.3 g/dL, HCT=31.1 %, ncv=75.7 fL, uca=25.1 pg, and acne-33.1 g/dL. Demographic characteristics for these cases were summarized in Table 10. For the fourth research question, 'Do the 1989 CDC Guidelines (see Table 2) accurately identify MIDA in this population?”, the data indicate that CDC Guidelines are more accurate in detecting iron-deficiency than identifying actual anemia. For the single case of MIDA at s 20 weeks LMP, the KGB and HCT values were borderline, just above the CDC cut-off values, although the MCV and MCH were abnormally low and indicative of anemia. The CDC criteria missed this case. For the single case of MIDA at 36 weeks LMP, the CDC criteria identified this individual as anemic both at the 28 and 36 week LMP screens, indicating accuracy in detecting some stage of iron-deficiency was present, although not specific as to severity. In general, the CDC criteria identified more cases of MIDA than were actually present by this study's operational definition, and missed one case of actual MIDA. Number of cases and rates of MIDA identified by CDC Criteria were summarized on Table 9. For research question five, “Is there a significant ~relationship between demographic variables and HIDAR’, the rate of MIDA was too low to conduct any meaningful analyses. 79 .66.66 6:6 .6.66 .6.66 6663 666663 666-666 606 .66\6 6.66 6:6 .6.66 .6.66 6663 666663 666-666 666 .66 66:66 666 .666366666666 66.66 6:6 6.66 .o.vn 0663 6069666 60503 and 0:6 6069 606 609H6> 6601650 90: .aao>wuooammu mammuom as: #003 on can ASH 6x663 66 .mzn 63603 omv 606 noxm 6.66 can 6.66 .6.66 6663 mmanaom 66503 and 0:6 6069 6:6 606 609663 660:6:0 mom .6 66269 5066 66666660 coo 6:6 566666669 66026V _8 on NN NH N u: #hN.hN w¢H.on woo.on «mm.OH mzfi mx003 wn ON NH @ N n: «mH.mH ne¢.wfl woo.mH wnm.oa QZH m¥0m3 mN H H o o "c wmb.o “on.d o 0 mid mx003 ON 6 HM cochlooow UM cock um oovw HM 0669 zmmflom mNBHm Q44 mm <82 mdfl m0<8 auaHAuuHauIudulNdNdIHuaI«HHMQQIHMQHuHMZIHaIWuHMM .6 66666 Table 10. WW :1 I 'I’ Demographic Case 1 Case 2 Variable G s 20 weeks LMP e 36 weeks LMP Age 25 21 Marital status married married Race Hispanic Hispanic Insurance provider Medicaid Private Pregnancy # 4 2 Parity 1 0 Prior abortions/miscarriages 2 1 Interconceptual time interval 24 months > 36 months DISCUSSION 0f greatest importance, this study discovered normal values for red cell indices of healthy, pregnant women living at 6,000 to 7,000 feet elevation. Table 6 summarizes the raw data, and Table 7 summarizes data from the “normal“ sub-set. Table 7 is the first empirically derived table of normal maternal red cell indices at 6,000 to 7,000 feet elevation to appear in the U.S. literature. Cases identified as anemic by the CDC Criteria were often borderline or had only one abnormal value for MCV, MCH 0r MCHC. These cases were probably representative of impaired 81 iron status, although not fully anemic by the operational definition. The sub-set of “normals" was created to ascertain the most reliable mean and standard deviation values for the healthiest women in the sample. In this healthy population, there was no indication of a sudden change in values between altitudes that might account for poor outcomes of pregnancy or other phenomena. Rates of MIDA were not determined for the altitude interval of 6,000 to 7,000 feet due to the small number of cases found (two) and sampling criteria that selected for normal pregnancies. Approximately 80 percent of records reviewed did not meet the sampling criteria. Late prenatal care, age at conception (under 18 years old), smoking, premature labor, multiple fetus pregnancy (i.e., twins), change in domicile or inability to confirm the altitude of the subject's domicile from available information excluded many potential cases from the sample. The 1989 CDC Criteria were not accurate in identifying MIDA in this sample. The criteria detected iron deficiency, but were inaccurate as to severity. One concludes that these criteria are unreliable for the detection of MIDA in populations at elevations between 6,000 and 7,000 feet. Primary care practices utilizing CDC tables may be over- or under-diagnosing MIDA, although the prudent practitioner would be alerted to borderline or suspicious values warranting further diagnostic investigation. 82 The Starfield Model was effective in describing the relationship between environment and the process of care, and the relationship between environment and outcome. It was also effective in giving direction to future research efforts in the primary care context. For this study, the model required a small refinement highlighting the relationship between environment and process of care (i.e., the provider features of problem recognition and diagnosis). Retrospective survey for retrieval of existing longitudinal data was effective as a means of determining normal RBC indices for normal pregnancies with good outcomes at altitudes above 3,000 feet. Longitudinal data were important in appreciating changes in laboratory values as pregnancy progressed. Retrospective survey imposed limitations on items of data available for study (i.e., demographic variables, clinical data), sampling criteria, and upon the interpretation of findings. Racial distribution patterns among the three sites were radically different than reported state racial distribution statistics (i.e., 50% non-Hispanic White, 40% Hispanic, 9% Native American). The Taos sample was 84% non-Hispanic White and only 16% Hispanic. There were no Native Americans in the Taos sample although a major pueblo is located less than 20 miles from the Midwifery Center. The Las Vegas sample was 100% Hispanic. The Santa Fe sample was more evenly mixed, but still reflected a higher concentration of Hispanics than expected. For the pooled sample, non- 83 Hispanic Whites (35%) and Native Americans (0.8%) were under-represented, and Hispanics were over-represented (63%). Surprisingly, there were more Asians (1.5%) than Native Americans in the sample. The under-representation of Native Americans in the sample is unclear, but might be explained by the provision of free prenatal services to registered Native Americans through the U.S. Public Health Service (PHS). Primary care services were available at individual pueblo PHS clinics, local public health clinics and at the PHS hospital in Santa Fe. The unusual ethnic distribution patterns in Taos and Las Vegas can be traced to historic settlement patterns. Legal and socioeconomic factors may explain the wide differences noted in insurance provider categories from site to site. Low numbers of cases with private insurance in the Taos sample reflected the political and economic environment. Few Taos businesses provided health insurance benefits to employees. Although state Medicaid regulations permitted direct reimbursement to Certified Nurse Midwives in 1996, some third party payors did not. The absence of health maintenance organizations reflected the small size and relative isolation of the community. In 1996, the Midwifery Center was one of four prenatal care provider sites in Taos and the fee for prenatal care and delivery was 55% lower than fees charged by other providers. Certainly, economic factors influenced the selection of prenatal care provider in the Taos sample. Perhaps this finding reveals a 84 "”‘—""I social phenomenon that women who opt for midwifery services or home birth are less likely to have health insurance, or that there is strong financial motivation to select midwifery services. The Medicaid eligible statistics did not accurately reflect the high reliance on Medicaid for prenatal care in the Taos and Las Vegas samples. The State of New Mexico provided special temporary medical assistance (through Medicaid) and supplemental food programs (through W.I.C.) for infants and pregnant women. The income criteria for the temporary programs were more liberal than for the standard programs. The “Medicaid eligible statistics" were inaccurate in reflecting levels of poverty by county (especially in Taos) and did not reflect the distribution of funds for special programs targeting pregnant women. Although the Medicaid eligible statistic indicated similar levels of poverty in Taos and Santa Fe, per capita personal income and poverty level statistics did not. The discrepancies in insurance status at these two sites were dramatic. These differences are explained by: a) the dissimilar availability of health insurance benefits through employers at each location; b) a difference in the number of prenatal care options available at each location; and 0) practice policies which restrict the number of new clients who rely on Medicaid. One must be mindful of differences in services provided and type of practice. The Santa Fe OB/GYN group practice routinely managed high-risk obstetric cases 85 and required a doctor assisted hospital delivery. The Taos midwifery practice routinely screened out (or referred out) high-risk cases and provided midwife assisted home birth or delivery in the home-like birth center. Planned hospital delivery was not offered as a service to Midwifery Center clients at that time. These features limited the clientele at each site. In Taos, the lack of RBC indices for the 28 and 36 week LMP MIDA screens was attributed to a practice policy of utilizing HCT only, due to the financial status of the clientele. The Taos data for “insurance provider” imply that 82% were at or below poverty level. This explains why more thorough lab screening was not performed routinely. In regards to interconceptual time interval, the literature suggests that pregnancies be spaced by 18 to 24 months to allow for full recovery of maternal iron stores. Subjects with interconceptual time intervals of more than 36 months were scored as zero (NY) for statistical analyses, as these subjects were well beyond the danger period for incomplete recovery of iron stores. The Taos sample was exemplary in spacing pregnancies at least 18 months apart. Without further research it is impossible to ascertain if these women were financially motivated, health-consciously motivated, or if this was merely a chance finding. One recalls that in Taos 32% had no health insurance and 50% relied on Medicaid. This group also had the highest percentage of non-Hispanic Whites, and displayed the highest 86 rate of abortion or miscarriage (47%). One might speculate that a) these women more readily utilized legal abortion for contraceptive failure or as a means of spacing pregnancies, or b) the midwives had made an impact on decisions regarding spacing of pregnancy through patient education. There are three reasons why such low rates of MIDA were found in this study. One is that subjects were in a state of chronic hyperactive erythropoiesis pre-conceptually due to altitude adaptation. The other reasons are selective sampling, and retrospective design. Sampling criteria very effectively selected for apparently healthy women who demonstrated healthy behaviors and had normal singleton pregnancies with term deliveries. About eighty percent of records reviewed failed to meet the sampling criteria. Complicated pregnancies, unhealthy behaviors (e.g., smoking, extreme age at conception, late prenatal care) and preterm deliveries were intentionally screened out of the sample. Retrospective design assisted in ascertaining normal laboratory values utilizing pre-existing data for traditional screening measures. Determination of normal values is essential for recognition of pathologic deviation (MIDA). Unfortunately, the sampling criteria suppressed desirable information about abnormal laboratory values at middle altitude. Prospective study design and liberal sampling criteria would remedy this problem. Although this study was unable to correlate demographic variables with incidence of MIDA due to inadequate sample 87 size, several prior studies have addressed this issue and identified high risk groups. High risk groups have been more aggressively studied than have normal populations in differing environments, to the detriment of the knowledge base. This study begins to address this gap in the literature. Additionally, nutrition surveillance systems are operational and one anticipates publication of the NHANES III data for pregnant women. Implications for Advanced Practice Nursing and Primary Care APNs are encouraged to play an active role in changing current protocols and practice policies related to MIDA screening, diagnosis and management. Table 7 will provide empiric evidence to assist APNs in justifying the need for further diagnostic testing for pregnant women that live at 6,000 to 7,000 feet elevation and have borderline or clearly abnormal values upon screening for MIDA. It is clear that several conventional screening and diagnostic tests for anemia are not valid during pregnancy or in populations living at altitudes above 3,000 feet. Until a nationally recognized authority revises standards of care and MIDA screening guidelines for populations at altitude, health maintenance organizations, Medicaid and managed care groups will continue to refuse payment for “non-standard” laboratory tests. If PCPs are limited to HGB and/or HCT screening for low-income or managed care clients, at least they will now have some basis for suspicion of impaired iron status, MIDA, and the potential for related complications. 88 Until standardized tables for populations above 3,000 feet are available, practitioners are encouraged to revise MIDA screens and diagnostic panels locally. Red cell indices (CBC or hematology profile) may be considered the minimum acceptable screen for populations above 3,000 feet elevation. The addition of serum ferritin is prudent. For borderline screen values (at or below the first standard deviation below the mean) differential diagnostic testing should include serum ferritin (if not included with the screen), TS, TIBC and either FEP or RBC ZP in addition to the usual folate and cyanobalamin (vitamin Bu). For pregnant women, serum iron can be dropped from the standard anemia profile as these values are ambiguous at best. While awaiting results from diagnostic testing, APNs can initiate a trial of oral iron supplements, confident that there is no risk for iron toxicity and its related complications. APNs can play a significant role in reducing MIDA incidence and preventing complications related to MIDA. As primary care providers, APNs can: a) select altitude- appropriate screening and diagnostic tools; b) educate prenatal clients about MIDA; c) promote the use of effective post—partum contraception; d) promote change in local protocols for MIDA screening, diagnosis and management; and e) conduct small-scale MIDA and outcome studies for their own practice. APN entrepreneurs can specialize in preventative community education, case management, lecture presentations for the academic and professional communities, 89 and publication of articles in professional journals. APNs in academic settings can enhance the education of future nurses, APNs and PCPs by including MIDA education in the obstetric portion of the curriculum. APN researchers can approach local universities, state health departments, existing prenatal nutrition surveillance groups, or existing maternal and infant care projects for support of statewide prospective MIDA studies. By networking, a regional network and database could be formed in conjunction with prospective studies. Recommendations for Further Research Although MIDA is not currently a “hot topic” for research, the impact of managed care and outcome studies may soon spur renewed interest. MIDA research provides an excellent opportunity for multi-disciplinary cooperation in expanding the knowledge base for Primary Care. APNs are faced with a unique opportunity to take the lead in MIDA research and make important scientific contributions. The next step for research is to determine maternal norms for red cell indices at altitudes ranging from 3,000 to 10,000 feet above sea level. Standardized tables defining normal values for the traditional screening intervals in 1,000 foot elevation intervals are greatly needed. Simultaneous measures of MCV, MCHC, serum ferritin, TS, TIBC and FEP are highly desirable. Longitudinal data for these measures would assist in fully assessing iron status and defining acceptable changes in individuals 90 throughout pregnancy. Prospective longitudinal studies are essential for clarifying acceptable laboratory values and defining acceptable limits of net change in laboratory values in individuals at landmark intervals throughout pregnancy. Correlations of pregnancy outcome with these laboratory measures may provide insight into causal relationships or identify early indicators for poor pregnancy outcomes. Funding for such projects may exist within state public health departments or existing national surveillance projects. The second step is to assess the scope of the problem. It is important to determine MIDA incidence rates nationwide, by region, by state, and at various altitudes. The NHANES III data may provide some answers. Prospective longitudinal studies are still needed to assess the severity of the problem at middle altitudes. To assure significant gains in knowledge about MIDA, sampling criteria should not exclude subjects under 18 or over 45 years old, smokers, those who sought prenatal care after 20 weeks LMP, or those with multiple fetus pregnancy. These subjects need to be studied simultaneously, but separately as sub-groups. Sampling criteria should assure that subjects a) have achieved full physiologic adaptation to the specified altitude level under study, b) do not spend significant amounts of time at altitudes more than 500 feet higher or lower than their domicile, and c) can verify the location (altitude) of their domicile. 91 The most difficult step is to determine the underlying cause of MIDA. Is MIDA merely a phenomenon of poor nutritional status in conjunction with the physiologic stress of adaptation to pregnancy? One wonders if there is a genetic hematopoietic factor related to ethnicity or race that makes certain groups high risk for IDA, or if high incidence in particular groups really due to socioeconomic status or other underlying factors. Data from Blacks indicates a genetic difference in hemoglobin production. Why has IDA incidence in Hispanics jumped so dramatically? Is this a phenomenon of sampling, an increase in the Hispanic population, or is there a genetic reason for this finding? The isolation of demographic variables will require sophisticated research methods and complex data analysis techniques. It would be helpful to know the weighted value of particular demographic variables (i.e., socioeconomic status, interconceptual time interval, race, age). The revision of guidelines for routine MIDA screening is long over-due. Throughout the literature, experts in the field (Bothwell, Bull & Hay, Charlton, Cook, DeMaeyer, Johnson, Yepez, Yip) agree that HGB and HCT are poor measures of maternal iron status. Considering the advances in laboratory technology in the past 25 years, it is time to abandon these crude measures. For 15 years, numerous investigators have promoted the use of serum ferritin, TS and serum transferrin receptor as more sensitive indicators 92 of maternal iron status, yet these measures are not addressed by nationally recognized authorities responsible for setting standards for prenatal care. There are so many variables affecting HGB values that results are ambiguous at best. In the primary care context, it is extremely cumbersome to calculate multiple "correction factors" for each patient to obtain meaningful results. The technology exists to support the formulation of new straightforward standards for evaluating iron status in pregnant women. Serum ferritin shows promise. The development of simple, inexpensive tests for serum ferritin, TS and transferrin receptor designed for use at primary care sites would be beneficial. The challenges of revising standards of care and developing new guidelines for MIDA screening and diagnosis remains. An addendum to current standards and guidelines that addresses known variations at altitudes above 3,000 feet would be valuable. The empiric evidence in this study suggests that there is minimal variation in mean values for red cell indices within the altitude interval of 6,000 to 7,000 feet. Therefore, a single standard could be applied to the entire thousand foot interval. In these days of managed care, it will be important to substantiate the cost- effectiveness of the new screening profile. In order to encourage changes in third party payor policies, a nationally respected authority (i.e., ACOG, the American Academy of Pediatrics or perhaps the World Association of 93 Perinatologists) must endorse revisions for a) a consensus definition of MIDA, b) standards of practice for prenatal care, and c) guidelines for MIDA screening and diagnostic profiles MIDA that apply to populations residing between sea level and 10,000 feet elevation. SUMMARY Although maternal iron deficiency anemia is the most common complication of pregnancy, little research has been done at altitudes above 3,000 feet. Recognition of MIDA at elevations above 3,000 feet is complicated by compensatory relative polycythemia, presenting a dilemma for APNs in primary care. Normal elevations in RBC count, H68 and HCT in altitude acclimated individuals can potentially mask anemia when relying upon traditional screening measures to evaluate iron status, especially in pregnant women. Empirically derived altitude-adjusted reference tables for maternal norms of RBC indices and specific recommendations for MIDA screening in altitude-induced polycythemic populations could not be found in the existing literature. The Starfield Model of the Health Services System served as a conceptual framework. Starfield's Model adequately addressed the primary care provider issues of problem recognition and diagnosis. The model required refinement regarding the impact of environmental factors which may alter conventional diagnostic indicators to the point of obscuring the suspected disease. 94 Existing data were extracted from 132 medical records of pregnant women that lived at altitudes ranging from 6,000 to 7,000 feet elevation. Only two cases of MIDA were found because sampling criteria selected for normal pregnancies. The 1989 CDC Criteria were unreliable in detecting MIDA. Mean, standard deviation and range values for RBC indices at the traditional prenatal screening intervals were found for healthy pregnant women upon eliminating cases of MIDA and cases of borderline or impaired iron status identified by CDC Criteria. Rates of MIDA incidence and correlations of MIDA with demographic factors could not be calculated due to the low rate of MIDA found. APNs in communities located above 3,000 feet were challenged to revise their individual practice protocols and promote local revisions of MIDA screening and diagnostic panels to reflect altitude-appropriate measures. CBC (or hematology profile) and serum ferritin were recommended as the minimal MIDA screening tools for populations at middle altitude. Nationally recognized authorities were challenged to revise the definition of MIDA, screening guidelines and standards for prenatal care to include populations residing at altitudes from sea level to 10,000 feet elevation. Research leading to the development of standardized tables for maternal norms of iron status indicators for altitudes ranging up to 10,000 feet was encouraged. Other suggestions for further research included: a) determination of efficacy and cost-effectiveness for specific maternal iron 95 indicators; b) determination of weighted values for demographic risk factors; and c) the development of assessment tools for serum ferritin and transferrin saturation for use in Primary Care facilities. 96 LIST OF REFERENCES LIST OF REFERENCES American Academy of Pediatrics (AAP), 8 American College of Obstetricians and Gynecologists (ACOG). (1992). (3rd ed.). Elk Grove Village, IL: American Academy of Pediatrics. American College of Obstetricians and Gynecologists (1000). (1989). standards_for_ohstetrisznxnscolosic_serxioes (7th Ed. ). Washington, DC: Author. Athens, J.W., & Lee, G.R. (1993). Polycythemia: erythrocytosis. In G.R. Lee, T.C. Bithell, J. Foerster, J.W. Athens, & J.N. Lukens (Eds.), flintzeheLe_Cliniee1 Hematology (9th Ed.) (pp. 1245-1261). Philadelphia: Lea 8 Febiger. Bently, D. (1985). Iron metabolism and anaemia in Pregnancy- Clinics_in_naematolog¥1_11. 613-628- Bhargava, M., Kumar, R., Iyer, P., Ramji, S., Kapani, V., & Bhargava, s. (1989). Effect of maternal anaemia and iron depletion on fetal iron stores, birthweight and gestation. Acta_2ediatrica.$oandinaxicai_1§. 321-322- Brown, R. (1991). Determining the cause of anemia: General approach with emphasis on microcytic hypochromic anemias. Posturednate_Medicine1_&2(6). 161- 170- Bull, B., & Hay, K. (1985). Are red blood cell indexes international? Medicine1_1021 604- 606- Bushnell, F. (1992). A guide to primary care of iron- deficiency anemia. Nurse_Eraotitioner1_11(11). 68- 74- Buys de Jorge, M., Contrini, M., Miranda, C., Carrera, C., Torrejon, 1., Martin, B., 8 Scaro, J. (1988). Maternal and fetal hematologic values at high altitude. Sengre (Barcelona), 11(2), 97-101. (In Spanish with English abstract.) Centers for Disease Control. (1989). CDC criteria for anemia in children and child-bearing aged women. Meztelity and_norbid11¥_fleekl¥_Benort1_3&(22). 400-404- Centers for Disease Control. (1990). Anemia during pregnancy among low income women in the US. Mertelity_end Mo:bidit¥_fleekl¥_8enort1_32(5). 73-76 81- 97 Colmer, J. (1990). Anemia in pregnancy as a risk factor for infant iron deficiency-Valencia infant aenemia cohort etudY- Jonrnal_of_2aediatrio_Berinatal_Enidemiolon¥1 4(2), 196-204. Cook, J.D., 8 Lynch, S.R. (1986). The liabilities of iron deficiency. Bleed+_68, 803-809. Cook, J., Skikne, J., Lynch, 8., 8 Reuser, M. (1986). Estimates of iron sufficiency in the U.S. population. Blood1_68. 726-731- Cook, J. 8 Skikne, B. (1989). Iron deficiency: Definition and diagnosis. 225(5), 349-55. Cook, J., Skikne, B., 8 Baynes, R. (1994). Iron deficiency: The global perspective. Adyeneee_in Exner1mental_Medisine_and_Biolon¥1_1§6,219-223. Cunningham, F., MacDonald, P., Gant, N., Leveno, N., 8 Gilstrap, L. III (Eds.) (1993). Hilliams_thtetriss (19th Ed.) (pp. 1171-1176). Norwalk, CT: Appleton 8 Lange. Dainiak, N., Spielvogel, H., Sorba, S., 8 Cudkowicz, L. (1989L Erythropoietin and the polycythemia of high altitude dwellers. W 17" 21-0 Dallman, P., Yip, R., 8 Johnson, C. (1984). Prevalence and causes of anemia in the United States, 1976-1980. American_J0urnal_of_Clinisal_Nntrition1_12. 437-445. Daouda, H., Galan, P., Prual, A., Sekou, H., 8 Hercberg, S. (1991). Iron status in Nigerian mothers and their newborns. International_lournal_of_Yitamin_and Nutrition_Researeh1_61, 46-50- DeCherney, A.H., 8 Pernoll, M.L. (Eds.) (1994). (pp- 448-450). Norwalk, CT: Appleton 8 Lange. DeMaeyer, E., 8 Adiels-Tegman, M. (1985). The prevalence of anaemia in the world. Quarterl¥1_38. 302-316- DeMaeYer. E- (1989). Erexenting_and_sontrollinn_iron o:— 'g ..-‘n'. g 00. o u. 0". Q . ° ; 0| 0; Geneva: World Health Organization. Dimperio, D. (1988). Erenatal_nutr1tion1_Clinical guidelinee_fer_nnzeee. White Plains, NY: March of Dimes. 98 ' (28th ed.) . (1994). Philadelphia: W. B. Saunders Co. Expert Scientific Working Group (1985). Summary of a report on assessment of the iron nutritional status of the 0.8. Pepulation. American_1onrnal_of_£linisal_Nntr1tion1 AZ, 1318-1330. Fanelli-Kuczmarski, M., 8 Woteki, C. (1990). Monitoring the nutritional status of the Hispanic population: Selected findings for Mexican Americans, Cubans and Puerto Ricans. Nutrition_Todax1_25(3). 6-11. Farley, P., 8 Foland, J. (1990). Iron deficiency anemia: How to diagnose and correct. Pee;gzedne§e_nedieine‘ 81(2), 89-93, 96, 101. Finch, C., 8 Cook, J. (1984). Iron deficiency. ' ' , 471-477. Fleming, A.F., Harrison, K.A., Briggs, N.D., Attai, E.D.E., Ghatoura, G.B.S., Akintunde, E.A., 8 Shah, N. (1989). Anaemia in young primigravidae in the guinea savanna of Nigeria: Sickle-cell trait gives partial protection against malaria. Parasitoloax1_lfi(4). 395-404. Food and Nutrition Board (FNB), 8 Institute of Medicine (IOM). Earl, R., 8 Woteki, C. (Eds.) (1993). Izen nemen_ef_enildheezing_egeL Washington, DC: National Academy Press. Frikiche, A., Cusumano, G., Senterre, J., 8 Lambotte, R. (1990). Fetomaternal hemorrhage: A cause of fetal morbidity and mortality. Reyne_Medieele_de_Liege (Liege), &§(10), 498-503. Garcia, Anthony (May 13, 1997). Personal communication - citing HMGR152X (March 1997) and Population projections for the State of New Mexico by age and sex 1990-2020, Bureau of Business and Economic Research, University of New Mexico. Office of Medical Assistance, State of New Mexico. [Appendix AJ Garn, S., Ridella, S., Petzold, A., 8 Falkner, F. (1981). Maternal hematological levels and pregnancy outcomes. Seminars_in_2erinatoloax1_5. 155- -162. [Collaborative Perinatal Project]. 99 Gerritsen, T., 8 Walker, A. (1954). The effect of habitually high iron intake on certain blood values in Pregnant Bantu women. Jonrnal_of_Clinical_Inxestigationi 21, 23-26. Godfrey, R., Redman, C., Barker, D., 8 Osmund, C. (1991). The effect of maternal anaemia and iron deficiency on the ratio of fetal weight to placental weight. British Jonrnal_of_Qhstetrics_and_§¥naecolog¥1_28. 886-891. Goodlin, R., Holdt, D., 8 W00ds, R. (1982). Pregnancy- induced hypertension associated with hypervolemia: Case report. American_Journal_of_Qbstetrics_and_£¥necolog¥1_142. 114-115. Guyatt, G., Oxman, A., Ali, M., Willan, A., McIlroy, W., 8 Patterson, C. (1992). Laboratory diagnosis of iron- deficiency anemia: An overview. Journal_of_§eneral_1nternal Medicineifz 145- 153. Herbert, V. (1991). Diagnosis and treatment of iron disorders: Introduction and medicolegal considerations. Hofinital_2ractice1_2§(Sunpl. 3. April). 4-6. Ho, C., Yuan, C., 8 Yeh, S. (1987). Serum ferritin levels and their significance in normal full-term pregnant women. International_Ionrnal_of_Gxnecolog¥_and_0bste121231 25(4), 291-295. Hofvander, Y. (1968). Hematological investigations in Ethiopia, with special reference to a high iron intake. Aota_Medica_Scandinaxica1_SHDnlement_121 8 4-74. Hurtado, A., Merino, C. 8 Delgado, E. (1945). Influence of anoxemia on the hematopoietic activity. Archixes_of_International_uedisinei_15. 284-323. Hytten, F. (1985). Blood volume changes in normal Pregnancy. Clinics_1n_naematolog¥1_11. 601-612. Interagency Board for Nutrition Monitoring and Related Research [IBNMRR]: (1993) NnLI1t19n_anitQI1n§_in_thfi H 'l i S! l :1 ll 1 I J I i E' i' E I] O O O O O Q. 0'. q o. no. 0 .0 ... - - g 6 0‘. -u. Ervin, B., 8 Reed, D. (Eds.). Hyattsville, MD: Public Health Service. Isaacs, D., Altman, D.G., 8 Valman, H.B. (1986). Racial differences in red cell indices. Jenrnal_ef_glinieel Patholog¥+_32. 105-109. 100 Jackson, M., Mayhew, T., 8 Haas, J. (1988a). On the factors which contribute to thinning of the villous membrane in human placentae at high altitude. I: Thinning and regional variation in thickness of the trophoblast. Placentai_2. 1-8. Jackson, M., Mayhew, T., 8 Haas, J. (1988b). On the factors which contribute to thinning of the villous membrane in human placentae at high altitude. II: An increase in the degree of peripheralization of fetal capillaries. Pleeentee 2, 9-18. Johnson, M. (1990). Iron: Nutrition monitoring and nutrition status assessment. 152991.111. 1485-1491- Kim, I., Hungerford, D., Yip, R., Kuester, S., Zyrkowski, C., 8 Trowbridge, F. (1992). Pregnancy nutrition surveillance system - U. S. 1979- 1990. Mertelity_end uorb1d11¥_fleele_Benort1_11. (SS-7 November 27). 25-41. Kitay, D. (1994). Iron deficiency. In F. Zuspan, 8 E. Quilligan (Eds.). Cnrrent_theran¥_1n_obstetrics_and gyneeelegy, (pp. 421-424). Philadelphia: W. B. Saunders. Klebanoff, M., Shiono, P., Selby, J., Trachtenberg, A., 8 Graubard, B. (1991L Anemia and spontaneous preterm birth. ;n‘ 3| 0 q- e .0. - - ... 5.; e 00‘ ' 59-63. Koller, O. (1982). The clinical significance of hemodilution during pregnancy. Snrxe¥1_31(11), 649-52. Koller, O., Sagen, N., Ulstein, M., 8 Vaula, D. (1979). Fetal growth retardation associated with inadequate haemodilution in otherwise uncomplicated pregnancy. Aete Qbstetrica_et_6¥nesologica_Scandinayicai_58. 9- 13. Koller, 0., Sandevei, R., 8 Sagen, N. (1980). High hemoglobin levels during pregnancy and fetal risk. ' , 53- 56. Lamparelli, R., Bothwell, T., MacPhail, A., VanDerWesthuyzen, J., Baynes, R., 8 MacFarlaine, B. (1988a). Nutritional anaemia in pregnant coloured women in Johannesburg. sonth_Afr1can_Medical_Journali_11(8). 477-481. Lamparelli, R., VanDerWesthuyzen, J., Bothwell, T., Pienaar, L., and Baynes, R. (1988b). Anaemia in pregnant Indian women in Johannesburg. Sonth_African_Medisal_Journa11 14(4), 170-173. 101 Lanzkowsky, P. (1985). Problems in diagnosis of iron deficiency anemia. 2ed12t21e_Annale1_1A(9), 618-637. Lazebnik, N., Kuhnert, B., 8 Kuhnert, P. (1989). Th effect of race on serum ferritin during parturition. Jenrnel W“) . 591-596. Lee, G. R. (1993a). Microcytosis and the anemias associated with impaired hemoglobin synthesis. In G. R. Lee, T. C. Bithell, J. Foerster, J. W. Athens, 8 J. N. Lukens (Eds. ). HintmheLleinicaLHematolm (9th ed. ) (PP- 791- 807). Philadelphia: Lea 8 Febiger. Lee, G. R. (1993b). Iron deficiency and iron-deficiency anemia. In G. R. Lee, T. C. Bithell, J. Foerster, J. W. Athens 8 J. N. Lukens (Eds.). ' ' (9th ed.)(pp. 808-839). Philadelphia: Lea 8 Febiger. Leshan, L., Gottleib, M. 8 Mark, D. (1995L Anemia is prevalent in an urban African-American adolescent Pepulation. W4 433-437 . Letsky, E. (1991). Hematologic disorders. In W. Barron, 5 M- Lindheimer (Eds.). Wm (pp. 272-322). Chicago: Mosby Year Book. Lewis, G., 8 Rowe, D. (1986). Can a serum ferritin estimation predict which pregnant women need iron? 3:111eh , 15- 16. Looker, A. C., Dallman, P. R., Carroll, M. D., Gunter, E. W., 8 Johnson, C. L. (1997). Prevalence of iron deficiency in the United States. lenzne1_ef_;he_Amerieen WU” . 973-976. Looker, A. C., Johnson, C. L., McDowell, M., 8 Yetley, E. (1989). Iron status: Prevalence of impairment in three Hispanic groups in the United States. Amez1een_1enznel_ef Clininal_NntriLiQn+_12 553- 558. Marsh, W. Jr., Nelson, D., 8 Koenig, H. (1983). Free erythrocyte protoporphyrin [FEP] II. The FEP test is clinically useful in classifying microcytic RBC disorders in adults. MW“) . 661- 6. Maternal and Child Health Bureau, Health Services Division, Health and Environment Department, 8 The New Mexico Health Systems Agency (1986). The_hee1§h_ef_me§heze_fi W. Albuquerque. NM: Author. 102 McCullough, R., Reeves, J., 8 Liljegren, R. (1977L Fetal growth retardation and increased infant mortality at high altitude. Arsh11es_of_En¥1ronmental_nealth1_12 36- 39. Meyers, L., Habicht, J-P., Johnson, C. L. 8 Brownie, C. (1983). Prevalences of anemia and iron deficiency anemia in black and white women in the United States estimated by two methods. W436) . 1042- 1049. Moore, L., Hershey, D., Jahnigen, D., 8 Bowes, W. Jr. (1982). The incidence of pregnancy-induced hypertension is increased among Colorado residents at high altitude. Murphy, J., Newcombe, R., O'Riordan, J., Coles, E., 8 Pearson, J. (1986). Relationship of hemoglobin levels in first and second trimesters to outcome of pregnancy. Laneeti 1(8488), 992-994. [Cardiff Birth Survey, Wales, UK]. National Center for Health Statistics (NCHS), 8 Department of Health and Human Services (DHHS), (1985). Plan 1 l' E II H' . fl 1!] i H l ili Exam1nat1on_surye¥_lflHANESli_12&z:1284. Series 1 (plan). No. 191. and Series 11 (results). Hyattsville, MD: Public Health Service. New Mexico Department of Health [NMDH], Public Health Division, Bureau of Vital Records 8 Health Statistics, (June 1996). ' repent. Santa Fe, NM: Author. New Mexico Department of Health [NMDH], Public Health Division, Office of Information Management, New Mexico Vital Records 8 Health Statistics, (October 1997). 1225_Neu_uexiee seleoted_health_statist1cs_:_annual_renort. Santa Fe. NM: Author. New Mexico Prenatal Care Network, 8 University of New Mexico, School of Medicine, Maternity and Infant Care Preject (1992). A_better_startTfor_a_better_future_1988: 122Q1_Erenatal_care_1n_Nen_Mex1co___a_state_and_sonnt¥ analysis (2nd ed.). Albuquerque, NM: New Mexico Prenatal Care Network. Olmas, J., Figueroa, J., Rodriguez, L., Halac, E., 8 Irrazabal, D. (1988). Altitude and birthweight [letter]. Jonrnal_of_2ediatrissi_113 786- 787. Pagana, K. D., 8 Pagana, T. J. (1992). Mesbyis . Chicago: Mosby Year Book. 103 Perry, G., Byers, T., Yip, R., 8 Margen, S. (1992). Iron nutrition does not account for the hemoglobin differences between blacks and whites. Ian:nai_ef_flntzitien1 122, 1417-1424. Piedras, J., Loria, A., 8 Galvan, I. (1995). Red blood cell indices in a high altitude hospital population. Aroh1xes_of_Medical_Besearohi_26. 65-68. Pilch, 8., 8 Senti, F. (Eds.)(1984). Assessment_ef_tne hased_on_data_o0llected_1n_the_Second_National_Health_and ' ' ' ' - Bethesda, MD: Life Sciences Research Office of the Federation of American Societies for Experimental Biology. Reshetnikova, 0., Burton, G., Milovanov, A., 8 Fokin, E. (1996). Increased incidence of placental chorioangioma in high-altitude pregnancies: Hypobaric hypoxia as a possible etiologic factor. Amer1can_Jonrnal_of_0bstetr1cs_8 Gynecolog¥1_111. 557-561. Reynafarje, C., Lozano, R., 8 Valdivieso, J. (1958). The polycythemia of high altitude: Iron metabolism and related aspects. Bleed1_i§, 433-455. Robles-Gil, J., 8 Gonzales-Teran, D. (1948). Determination of the number of erythrocytes, volume of packed red cells, hemoglobin and other hematologic standards in Mexico City (altitude 7,457 feet). Bleed1_1, 660-681. Ross, S. (1972). Haemaglobin and haematocrit values in pregnant women on a high iron intake and living at high altitude. Commonwealth1_12. 1103-1107. Ruiz-Arguelles, G., Sanchez-Medal, L., Loria, A., 8 Cordova, M. (1980). Red cell indices in normal adults residing at altitudes from sea level to 2670 meters. Amer1oan_Journal_of_nematolog¥1_a. 265-271. Sanchez, C., Merino, C., 8 Figallo, M. (1970). Simultaneous measurement of plasma volume and cell mass in polycythemia of high altitude. Jennnai_ef_npniied RhYfiinQ§¥1_Zflo 775 773- Schifman, R., Thomasson, J., 8 Evers, J. (1987). Red blood cell zinc protoporphyrin testing for iron-deficiency anemia in pregnancy. gynecolog¥1_151, 304- 307. 104 Scholl, T., Hediger, M., Fischer, R., 8 Shearer, J. (1992). Anemia vs. iron deficiency: Increased risk of pre- term delivery in a prospective study. Ameriean_1ennna1_efi Clinical.flnizitinni_§5. 985-938- Scott, D., 8 Pritchard, J. (1967). Iron deficiency in healthy Young college women. J0nrnal_of_the_American_Hedical Associationi_122(12), 147-150. Skikne, B., Flowers, C., 8 Cook, J. (1990). Serum transferrin receptor: A quantitative measure of tissue iron deficiency. Bieed1_1§, 1870-1876. Starfield, B. (1973). Health services research: a working model. Nen_England_J0nrnal_of_uedicinsi_2891.132- 136. Starfield 8. (1992). Primar¥_sarei_oonsentl exaluat1onl_and_nolis¥ (pp. 3-21). New York: Oxford University Press. Starfield, B. (1996L A framework for primary care research. Jonrnal_0f_£amil¥_2racticsi_12(2). 181- 185. Ulmer, H., 8 Goepel, E. (1988). Anemia, ferritin and Pro-term labor. Jonrnal_of_Ber1natal_Med121ne1_16(5-6). 459- 465. Unger, C., Weiser, J., McCullough, R., Keefer, S., 8 Moore, L. (1988). Altitude, low birthweight and infant mortality in Colorado. Jonrnal_of_the_American_nedical Associat1on1_252 3427- 3432. Viteri, F. (1994L The consequences of iron deficiency and anemia in pregnancy. Adyances_1n_Exnerimental_Med121ne and_Biologyi_3fiz, 127- 139. Watson, W., 8 Murray, E. (1969). Serum iron and haemoglobin levels in pregnant East African women of mixed tribal origin. Journal_of_Qbstetrics_and_§¥naesolog¥ IBritish_commonuealthli_1§. 366-369. Williams, M. D., 8 Wheby, M. S. (1992). Anemia in pregnancy. Med1cal_Cl1nics_of_North_Amer1ca1_16. 631-647. Winslow, R., Chapman, H., Gibson, C., Samaja, M., Monge, C., Goldwasser, E., Sherpa, M., Blume, F., 8 Santolaya, R. (1989). Different hematologic responses to hypoxia in Sherpas and Quechua indians. Jen:na1_ef_npniied Physiolog¥1_§§. 1551-1569- 105 World Health Organization, (1972). Nutritional anaem1as1_BenQrt_of_a_HHQ_nroun—of_sxnerts. Technical Report Series No. 503. Geneva: Author. Yancey, M., Moore, J., Brady, R., Milligan, D., 8 Strampel, W. (1992). The effect of altitude on umbilical cord blood gases. Qhstetrics_8_§¥necolnn¥1_12 571- 574. Yancey, M., 8 Richards, D. (1994). Effect of altitude on the amniotic fluid index. Jon:nal_gf_nengductiyg Medicine1_12 101-104. Yepez, R., Estevez, E., Galan, P., Chauliac, M., Davila, M., Calle, A., Estrella, R., Masse-Raimbault, A-M., 8 Hercberg, S. (1994) . Anémie en altitude: validité. du critere de definition [Anemia at altitude: validity of definitional criteria]. Qahiers_5anté+_1, 9-13 (in French with summary in English). Yip, R. (1987). Altitude and birth weight. Journal_gfi Eed1atricsi_111 (6, Pt 1), 869-876. Yip, R., Johnson, C., 8 Dallman, P. (1984L Age-related changes in laboratory values used in the diagnosis of anemia and iron deficiency. Nutrit1on1_12 427-436. Zamudio, S., Palmer, 8., Dahms, T., Berman, J., McCullough, R. G., McCullough, R. E., 8 Moore, L. (1993). Blood volume expansion, preeclampsia, and infant birth weight at high altitude. 1ournal_of_Annlied_Bh¥siolon¥1_15. 1566-1573. 106 APPENDIX A RESEARCH AND GRADUATE STUDIES SI MISS-21” FM 517K324"! “”7““ ”SW” We“ Wham I' A. MICHIGAN STATE 0 N I v r. R s I T Y. October 27, 1997 10: Rachel r. Schiffaan A230 Life Sciences 22: 138.: 97-537 TITLE: HHTBRIIL 1R0. DCFICIIICY ANIHIA AI ROCKY MOUNTAII ALRITUDBB REVISION IIGUIQTID: "/5 CATEGORY: ' l-’ APPROVAL BASS: 10 20],? The university Committee on Research Involving egaan Subjects'(ucnrfls) review or this proJect is complete. I an pleas to adVise that the rights and welfare of the human subjects appear to be adequately rotacted and methods to obtain informed consent are a ropriate. Eggrefore, the DCRIBS approved this project and any rev sions listed “0 IIMIWAL: OCRIMS approval is valid for one calendar year. beginning with the approval date shown above. Investigators planning to continue a project bgzznd one year must use the green renewal form.(encloaed with original a royal letter or when a project is renewed) to seek te certification. There is a maximum of four such expedit renewals possible. Investigators wishi to continue a roject beyond that time need to submit it again or complete rev ew. ~ REVISIONS: UCRIHS must review an as in rocedures involving human subjects, rior to initiation of change. If this is done at the time o renewal. please use the green renewal form. To revise an approved protocol at an 0 her time during the year send your written re est to the IRS Chair, requesting revised approval and referent ng the project's IRB a and title. Include in your request a description of the change and any revised ins ruments, consent forms or advertisements that are applicable. saoatnns/ CHANGES: Should either of the following arise during the course of the work. investi ators must noti UCRIRS promptly: (l) roblems (unexpected s de effects comp aints, e c.) involving uman subjects.or ( _changes in the research environment or new information indicating greater risk to the human sub'ects than existed when the protocol was prsViously reviewed an approved. if we can be of any future help please do not hesitate to contact us at (517)355-2190 or Fax (517): i- 171. AA vid 3. Wright. Ph. 185 Chair Sincerely. DEH:de cc: Cynthia D. Anderson 1137