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APPENDIX Background Papers for C Workshop on Nutrition and Health Status Indicators

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Can Nutritional Status Be Determined from Food Consumption or Other Measures? A. E. SCHAEFER I vividly recall the frustrations we had in developing and editing the Manual for Nutrition Surveys by the ICNND in 1957 followed by a second edition in 1963. In the early days of the ICNND'S country nutrition surveys, there was immediate recognition of the need for a procedural manual that would: 1. Establish uniformity in methods, techniques, procedures, and guidelines for conducting surveys in population groups in order to make meaningful comparisons of results within and between countries. It was recognized that in some instances more refined and precise methods were known; however, for fieldwork as in population surveys, methods were selected that had the advantage of practicability, simplicity, and reproduc- ibility. The interpretative guidelines for the biochemical data were de- veloped for use of the methods cited. 2. Outline and define responsibilities of each segment of investigation (clinical examination, anthropometric, dietary, food production and proces- sing). 3. Provide a guide for interpretation of the dietary, biochemical and clinical data. 4. Serve as a working reference of major facts essential for appraisal of nutritional status and to aid in interpretation of findings in order to draft practical recommendations to alleviate those nutritional problems discov- ered. 5. Assist in training personnel in nutrition appraisal techniques. 207

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208 APPRAISAL METHODS A. E. SCHAEFER The general objectives of a nutrition survey are to define dietary intake at the time of the study; describe dietary patterns of consumption and food prep- aration practices; assess evidence concerning the prevalence of clinical, physical, biochemical, and anthropometric measurements indicative of nu- tritional status; and identify programs for improvement. This combined ap- praisal (dietary, biochemical, physical, anthropometric) gives more mean- ingful information than any single type of study. Biochemical studies pro- vide means for estimating the proportion of the population in various broad zones of nutriture and provide an estimate of tissue reserves of the various nutrients. Dietary studies constitute an essential part of nutritional appraisal providing essential information for solution of problems uncovered. In a population survey, additional information should be collected, such as in- fant and child-feeding practices, school and institutional feeding, economy of food use, and the unique nutrient contribution of special foods. Of the various methods of appraisal, biochemical and anthropometric measurements provide the key hard-core data, applicable to an individual or population group, for diagnosis of nutritional status and provide basic data to follow improvement or further deterioration. Dietary data is restricted in use; it does not define nutritional status. It is not a diagnostic measure. All of us appreciate the limitations of a 1-day, or 3-day, 7-day, or 30-day, etc., dietary assessment be it determined by recall or food weighings. Of concern is the perpetual argument reference the validity and value of a 24-hour dietary recall versus the 1- to 3- to 7-day home record + food weighings. Should we even waste time in doing it? COMPARISON OF DIETARY INTAKE METHODS Central America, INCAP-ICNND Survey Dietary surveys in the six Central American countries included a compari- son of the following methodology: In the case of families, food consumption was estimated by a 3-day daily record, a 24-hour recall with two different approaches (interviews in the home and interviews at the clinic), and a 1-day direct food weighing. For preschool children, a 1-day direct weighing and a 3-day daily record were used. The population sample for Nicaragua included a total of 125 families randomly divided in two groups. The 24-hour recall at home and the daily 3-day record were applied to the first group of families, while the 24-hour recall at the clinic and a 1-day direct weighing were applied to the second group of families (Table 1~. A comparison of the data obtained on the family studies revealed small differences that were not statistically significant. On the other hand, com-

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Can Nutritional Status Be Determined from Food Consumption? 209 TABLE 1 Comparison of Nutrient Intake by Different Methods in Families in Rural Nicaragua 24-Hour Recall In Home In Clinic 3-Day Daily 1-Day Direct Record Weighing Calories x 1,928 1,857 1,916 1,950 SD 702 639 683 674 Protein, g x 66.1 61.1 60.6 62.8 SD 26.1 23.2 22.4 24.2 Calcium, mg x 725 790 773 755 SD 455 572 457 438 Iron, mg x 17.8 16.6 18.7 17.9 SD 8.1 7.7 7.9 10.5 Retinol, mcg x 150 98 169 247 SD 569 86 570 1,270 Beta carotene, mcg x 522 481 578 527 SD 591 525 630 642 Thiamin, mg x p.87 0.82 0.92 0.91 SD 0.38 0.30 0.40 0.42 Riboflavin, mg x 0.95 0.93 0.97 0.93 SD 0.55 0.52 0.58 0.52 Niacin, mg x 10.90 9.89 10.26 9.97 SD 5.28 3.47 4.01 3.74 Vitamin C, mg x 75 59 71 57 SD 80 57 133 70 parison of the data of the preschool children revealed significant differences when comparing the 1-day direct weighing with the 3-day daily record for calcium, retinal, and riboflavin. For retinal and riboflavin, the differences were highly significant with the lower estimates found by the 1-day direct weighing (Table 2~. Examples of Use of Data Central America Nutrition Surveys, 1965-67. In a study of over 3,800 families (approximately 20,000 people) in the six Central American countries, dietary intake studies were made on a sam- ple of families on which detailed biochemical and hematological investiga- tions were carried out. Two methods of obtaining quantitative data on fam- ily food consumption were used: one by means of a 24-hour recall, using the

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210 A. E. SCHAEFER TABLE 2 Comparison of Nutrient Intake by Various Methods in Preschool Children in Rural Nicaragua 1-Day Direct 3-Day Daily Weighing Record 1,089 < 142 Calories x SD 1,100 433 Protein,g x 31.9 34.0 SD 13.7 15.8 Calcium, mg x 413 693 SD 294a 606a Iron, mg x 9.0 8.1 SD 6.0 4.0 Retinal, mcg x 47 130 SD 496 1686 Beta carotene x 167 300 SD 171a 287a Thiamin, mg x 0.44 0.50 SD 0.24 0.21 Riboflavin, mg x 0.47 0.94 SD 0.33b 0.80b Vitamin C, mg x 28 32 SD 36 33 a Significant at 5 percent probability. Significant at 1 percent probability. NOTE: X = mean; SD = standard deviation. housewife's own account of the previous day's meals; the other a 3-day record consisting of the actual recording in the home of the foods prepared and consumed. The 3-day record method was applied to a random portion of the families surveyed by the 24-hour recall. At the end of the survey in each location, typical family diets were calculated and food composites were locally prepared for subsequent chemi- cal analysis. Individual food intakes of preschool children were recorded by the 24-hour recall in most of the countries. The value and kinds of use of dietary data are illustrated in Tables 3-7. The intake of vitamin A revealed a dramatic deficit when compared to the recommended levels of vitamin A. This finding was supported by the

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Can Nutritional Status Be Determined from Food Consumption? 211 TABLE 3 Consumption of Selected Foods per Person per Day in Rural Areas (g, Edible Portion) Guate- El Sal- Hon- Nica- Costa Pana- Foods malaa vador auras ragua Rica ma Milk productsb 84 190 194 243 193 73 Eggs 13 10 13 12 15 11 Meat, poultry, and fish 44 37 41 58 40 90 Beans end oily seeds 54 59 56 72 57 20 Vegetables 66 53 51 27 66 25 Fruits 14 17 40 41 7 50 Bananas and plantains 20 16 43 72 47 99 Starchy roots and tubers 14 13 22 33 46 82 Cereal products Rice 16 27 29 54 100 186 Corn tortillas, etch 359 352 224 139 41 32 Wheat bread 36 26 12 28 54 37 Wheat flour and pastes 4 0 8 7 12 10 Others 2 6 5 16 0 0 Sugar 52 41 39 58 89 51 Fats and oil 4 15 16 19 19 26 Number of families 203 293 331 355 456 361 aIn the report on Guatemala (INCAP v-25), the figures for food consumption were those ob- tained by the 3-day-record method. In order to conform to the data in the reports for the other five countries, the dietary data for Guatemala used throughout this report are based on the 24-hour-recall method. bIn terms of liquid milk. CIn terms of grain. TABLE 4 Percent Contribution of Selected Foods to Calorie Intake of Rural Families Guate- El Sal- Hon- Nica- Costa Pana- Foods male vador auras ragua Rica ma Milk products 2.8 5.6 6.9 7.3 7.3 2.7 Eggs 1.0 0.7 1.1 0.9 1.3 0.8 Meat, poultry, and fish 3.9 3.3 5.0 5.4 3.8 7.2 Beans and oily seeds 9.5 9.7 10.7 13.0 10.7 3.9 Vegetables 1.4 0.9 1.4 0.6 2.2 1.1 Fruits 0.6 0.6 1.8 1.5 0.4 4.1 Bananas and plantains 1.1 1.0 2.9 4.8 3.2 5.9 Starchy roots and tubers 0.6 0.7 1.8 2.2 2.6 4.9 Cereal products 65.1 61.8 49.5 41.5 39.3 47.4 Sugar 9.4 7.4 8.2 11.5 17.9 8.8 Fats and oil 2.6 6.9 8.8 9.3 9.8 11.7

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212 A. E. SCHAEFER TABLE 5 Average Intake of Calories and Specific Nutrients per Person per Day in Rural Families Guate- E1 Sal- Hon- Nica- Costa Pana- mala vador auras ragua Rica ma Calories 2,117 2,146 1,832 1,986 1,894 2,089 Total protein, g 68.0 67.9 58.0 64.4 53.6 60.1 Animal protein, g 15.4 17.3 18.5 23.4 18.5 26.6 Vitamin A., flu 2,420 900 1,280 1,700 1,800 1,830 Riboflavin, mg 0.80 0.78 0.79 0.93 0.84 0.69 Iron, mg 17.9 11.6 15.5 18.2 15.4 14.3 TABLE 6 Percent Adequacy of Average Intake of Calories and Specific Nutrients in Rural Families Guate- E1 Sal- Hon- Nica- Costa Pana- mala vador auras ragua Rica ma Calories 109 109 89 96 91 104 Protein 133 128 108 115 98 112 Vitamin A 68 24 34 44 49 49 Riboflavin 70 66 64 75 68 58 Iron 178 114 152 175 150 141 TABLE 7 Percent Distribution of Rural Families by Adequacy of Vitamin A Intake Country No. of Families <25 Percent Adequacy 25-49 50-74 75-99 ~ 100 Guatemala 200 44 22 10 6 17 E1 Salvador 278 69 19 7 3 2 Honduras 323 57 26 9 2 6 Nicaragua 331 45 23 13 8 11 Costa Rica 414 44 26 11 7 12 Panama 352 42 32 13 5 8 biochemical evidence. Likewise when the data were analyzed by "low," "medium," and "high" socioeconomic index (Figure 1), the serum vita- min A concentration or urinary riboflavin values were lower in the poorer . . socioeconomic groups. The incidence of clinical symptoms specifically related to nutrient de- ficiencies was not as high as the occurrence of biochemical values in the "deficient" or "high risk" range. This is to be expected.

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Can Nutritional Status Be Determinedfrom Food Consumption? 213 800 700 con ~5 <., 600 - 500 400 LL o m 200 100 I Interpretation Nicaragua - :-:-:- --:-: :-:-. :-:-: .:~ .: --:-: :-:-:- :.:.:-. :-:-:- :-:-: :-:-:- :-:-: Am: --:-: -.-.:.: :::::: :::::: :-:- . ........ :.:-.:-. :-:-:- :-:-. -:-:- .:.:, :-:-:- :--.:- ::~ .~.- .~ :-:-:- :-:-: .:.:-.: :-:-: :-:-:- :-:-: ---:- . _ _ _ _ Costa R ice Panama _., ..... :-:-:- :-:-: ....... :-:- ,........ :-:-: :- -:- :-:-: .:-:.: :-:-: :: ,.. .:-.:-: :-:-: :-:-:- ..... ~. .:: :-:-:- :::..-. :-.: :-:-: :-:-:- :-:-: :-.:-: :-:-: :-:-:- .......... :-:-: :-:-:- ..... :-:-: :-:-:- *,: :-:-: :-:- .:-:-. .-.- .:-.:. :-:- .~ Socioeconomic Index Low Medium High r l Acceptable 1 Low . Def icient FIGURE 1 Nutritional study in Central America and Panama: Urinary excretion of riboflavin in relation to the socioeconomic index of the families in the rural areas of Central America, 1965-1967, males 0-4 yr. Dietary studies revealed an even higher incidence of inadequate nutrient intakes than was evident from the biochemical and clinical studies. The results of the biochemical analyses and dietary studies (with excep- tion of vitamin A and riboflavin) indicated that the average consumption of essential nutrients in each country would have been enough if the distribu- tion of the foods had been equitable. Important differences in the average consumption of various foods per person per day was observed between countries. Likewise, these differences were observed between rural and urban families within each country. The basic dietary data correlated with biochemical estimates for those groups at "risk" or at "moderate risk" developing "malnutrition." No attempt to

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214 A. E. SCHAEFER directly relate individual dietary intake to biochemical data was done nor should it have been done. For defining the problems and potential solutions, it made no difference whatever which set of dietary intake data were used. Bangladesh Nutrition Survey Correlation of Diet and Biochemical Assessment In the 1960-62 nutrition survey conducted in Bangladesh (then East Pakis- tan) (Pakistan, 1969), in which over 25,000 individuals were studied over a 2-year cycle, seasonal variations of intake of leafy green and yellow vegeta- bles and fruits correlated with seasonal variations in serum vitamin A levels and the prevalence of keratomalacia. During the season when leafy green vegetables and yellow fruits were in short supply with an average daily consumption of only 12 g per day, 42 percent of the people had serum vitamin A levels of less than 20 mcg per 100 ml (Figure 2~. Likewise, the percent of total cases seen at the Dacca medical college eye clinic with keratomalacia increases from 0.5 to 3.0 percent during the period of low intake of leafy green and yellow vegetables and fruits. A similar type correlation was noted on the influence of pulse consump- tion on serum albumin levels (Figure 31. When intake reached a low level of 12 g of pulses per day, 58 percent of the population had "low" serum albumin levels of less than 3.5 g per 100 ml, whereas during periods of the year when pulse consumption reached 40 g per day, only 28 percent had "low" serum albumin levels. Ecuador ICNND Nutrition Survey The Ecuador nutrition survey conducted in 1959 employed three methods of obtaining food consumption data: 24-hour recall, 24-hour recipe food weighing, and food composite chemical analysis. Comparisons of the nu- trients consumed in two major regions (coastal and sierra) are given in Tables 8 and 9. The amounts of food consumed per person per day as determined by the direct recipe weighing method in the home and.the 24- hour recall were in remarkably close agreement. The data illustrated that the results obtained from the recall questionnaire can be considered essentially as valid as the data obtained from direct weighings. The same number of personnel were required to obtain data from 28 families by the recipe weighing method as it took to obtain data from 341 families by the recall method. Food composites structured after the data obtained by the recipe method were analyzed by two laboratories. The study revealed that in general the dietary recall method slightly un-

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Can Nutritional Status Be Determinedfrom Food Consumption? 215 ,,, 50 _ UJ O ~ ~ 40 UJ Z 30 2 o ~ IL ~ Z O ~ ~ 20 ~ O z ~ I= ~ ~ ~ 10 UJ ~ O INTAKE (%) 50 ~ 1- - ~1 At' if\ ~ Jan Mar May (Fete) Apr Jun Mar May Jul _ __ ___% % " Def icient or `' Low" Serum Vitamin A's 4 ~30 20 _ 10 Intake of Leafy Green Vegetables and Ripe Fruit (ems) I I I I . Jul Sep Nov Jan Aug (Oct) Dee ( Feb) Sep Nov Jan Mar O FIGURE 2 East Pakistan Nutrition Survey. Seasonal correlation of intake of leafy green vegetables and ripe fruit with serum vitamin A levels, 3-monthly averages. 60 1 an J 2 5o z J 1- Z 40 m car J O ~ ~ ~ 30 0 ~ LL Z Oh 2~ ~ ~ v cay ~ 0 ~ 'a ~ 1 0 i, _` O I I I I 1 1 1 1 1 1 1 1 Dec ( Feb) Apr Jun Aug (Oct.) Dec Jan Mar May Jul Sep Nov Jan (Fete) Apr Jun Aug (Oct) Dec (Fete) ~ , ~-'_~` . ' ~ = %"Deficient" or "Low" Serum Albumin Levels Intake of Pulses (Gms) PULSE INTAKE (Gms) 60 50 40 _ 30 _ 20 10 O FIGURE 3 East Pakistan Nutrition Survey. Seasonal correlation of pulse intake with serum albumin levels, 3-monthly averages.

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266 VICTOR HERBERT pregnancy, to 800 ,ug daily. Data presented at the 1975 Folate Workshop of the National Academy of Sciences suggest that such an amount could not easily be achieved without supplementation. Oral contraceptives reduce monthly blood loss, thereby reducing the frequency of iron deficiency. The question of whether the existing iron fortification of American flour should be increased (AMA Council on Foods and Nutrition, 1972: Wintrobe, 1973) has been decided in the negative on grounds of inadequate information to make an adequate risk:benefit assessment. In this connection, it should be noted that American breads are now mainly fortified with ferrous sulfate, with a trend to ferrum reductum, and American spaghettis and pastas with the less absorbable ferrous pyrophosphate (Dudley Titus, personal com- munication). Canada requires that more than 90 percent of ferrum reductum fortification be the more absorbable less than 10 micron particle size, but the United States has no size requirements. Several surveys have shown lower serum and red cell folate in women taking oral contraceptives, but a daily fresh uncooked vegetable, fruit, or fruit juice would probably prevent folate deficiency in this group as well as many other groups. INTRODUCTION Anemia is defined as a reduction below normal in the amount of red blood that occurs when the equilibrium between blood production and loss (through bleeding or destruction) is disturbed (Dorland's Illustrated Medi- cal Dictionary, 1974~. By World Health Organization criteria (1968; Baker and DeMaeyer, 1979), anemia is considered to exist when the nonpregnant adult female has a hemoglobin below 12 and the pregnant adult female a hemoglobin below 11 g/100 ml of venous blood (when at sea level; normal values are higher at higher altitudes). The observations of Scott et al. ( 1970) indicate that the hemoglobin concentration of healthy nonpregnant young women without iron deficiency will almost always be 12 g/100 ml or more, that at mid-pregnancy this value will practically always be at least 10 g/100 ml, but fairly often may be less than 11 g/100 ml, and late in pregnancy this figure will almost always be 10 g/100 ml or more, and most often 11 g/100 ml or more, in the absence of iron deficiency. The normal fall of hemoglo- bin during pregnancy is simply pregnancy hypervolemia (which increases both the plasma and red cell volume, with a greater increase in the former). Nutritional anemia is defined as a condition in which the hemoglobin content of the blood is lower than normal as a result of deficiency of one or more essential nutrients. To delineate a given anemia as nutritional, two criteria must be met: lack of the nutrient must produce, and providing the

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Relation of Nutritional Anemias to Food Consumption Patterns 267 nutrient must correct, the anemia. By these two criteria, there are only three unequivocal nutritional anemias: those due to lack of iron, folate, or vitamin BE (Herbert, 19701. These three anemias reflect an important nutritional problem affecting large population groups, particularly the poverty-stricken and those under metabolic stress. Iron deficiency and folate deficiency are more common in women be- cause of two forms of metabolic stress peculiar to women: the monthly blood loss in premenopausal women and the drain on maternal nutrient stores imposed by pregnancy. The fetus will take from the mother whatever it needs in order to be born normal, even if this produces severe nutrient deficiency in the mother (Committee on Maternal Nutrition, 19701. Since anemia is a relatively late manifestation of nutritional deficiency, those patients diagnosed as having nutritional anemia are the "tip of the iceberg" part of a larger group suffering from nutrient depletion of more moderate degree, which is not yet manifest by unequivocal anemia. The metabolic stress of menstrual blood loss is increased by the use of some intrauterine contraceptive devices (Anonymous, 1974, 1975) and de- creased by the use of oral contraceptives (Anonymous, 1973~. In fact, ad- vertising of "unique vitamin-mineral formulas for the special needs of patients taking oral contraceptives" are misleading because it has not been established that there is any such special need (Anonymous, 1973; Sym- posium, 1975~. IRON- DEFI CIENCY ANEMIA Fairbanks et al. (1971) tabulated the approximate frequency of iron deple- tion as 50 percent of infants, 50 percent of premenopausal women, and 100 percent of pregnant women. They tabulated the frequency of iron-deficiency anemia (the end product of prolonged iron depletion) as 25 percent of in- fants, 0-5 percent of children (higher frequency was in economically de- prived children), 15 percent of premenopausal women, and 30 percent of pregnant women not receiving iron supplementation. About one-third to one-half of apparently healthy young American women have laboratory evidence of iron depletion (Monsen et al., 1967; Scott and Pritchard, 1967; Sturgeon and Shoden, 19711. Sturgeon and Sho- den (1971) found less than 5 mg of iron/100 g liver tissue in 40 percent of women age 20 to 50, indicative of iron depletion. This was true of only 13 percent of women over age 50 (and less than 10 percent of all men). It should be noted that iron depletion (loss of body iron stores) precedes anemia. While a majority of women who are anemic have iron deficiency, this is not always the case, so self-administration of medicinal iron may be

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268 VICTOR HERBERT unwise, and blanket treatment of every anemic woman with iron, without ascertaining that she, in fact, has iron deficiency, can do positive harm (as, for example, in women with sickle-cell or other hemolytic anemias with increased iron stores, in whom the giving of iron may produce "iron over- load" syndrome). Nevertheless, the incidence of anemia in venous groups of pregnant American women has ranged from 10 to 60 percent, most of which could be prevented by prophylactic iron therapy (AMA Council on Foods and Nutrition, 19681. Menstrual loss of iron is the main source of the iron losses in nonpregnant women in the fertile age-group (Rybo, 1970; Fairbanks et al., 19711. The average menstrual blood loss is about 40 ml/cycle (Fairbanks et al., 1971), representing a loss of about 20 mg of iron per cycle. About 10 percent of women have menorrhagia, with a blood loss exceeding 80 ml/cycle (Hallberg et al., 1966), making them particularly susceptible to iron defi- ciency. The use of more than 12 pads during a menstrual period, of the damming up of blood behind tampons, often suggests excessive menstrual bleeding (More and Dubach, 1956: Fairbanks et al., 1971~. An understanding of the situation of American women with respect to iron balance is more clearly made by reference to Tables 1 and 2, which present respectively the estimated dietary iron requirements of Americans (Table 1) and the iron requirements of pregnant Amencan women (Table 2~. The adsorbability of iron from different food sources is highly variable, averag- ing out to about 10 percent of iron in the total diet being absorbed (Layrisse, 1975; Cook, 19781. Therefore, the amount of iron ingested must be 10-fold TABLE 1 Estimated Dietary Iron Requirements Absorbed Iron Requirement, mg/day Normal men and nonmenstruating women 0.5-1.0 5-10 Menstruating women 0.7 -2.0 7 -20 Pregnant women 2.0-4.8 20-48b Adolescents 1 . 0-2.0 10-20 Children 0.4-1.0 4-10 Infants 0.5-1.5 1.5 mg/kgC Dietary Iron Requirement, a mg/day a Assuming 10 percent absorption. b This amount of iron cannot be derived from diet and should be met by iron supplementation in the latter half of pregnancy. c To a maximum of 15 ma. SOURCE: After Council on Foods and Nutrition, 1968. Courtesy of the Journal of the American Medical Association.

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Relation of Nutritional Anemias to Food Consumption Patterns 269 TABLE 2 Iron Requirements for Pregnancy Average, mg Range, mg External iron loss 170 15(}200 Expansion of red-blood-cell mass 450 20~600 Fetal iron 270 20~370 Iron in placenta and cord 90 3~170 Blood loss at delivery 150 9~310 Total requirements 980 58~1,340 Cost of pregnancyb 680 44~1,050 a Blood loss at delivery not included. b Expansion of red-blood-cell mass not included. SOURCE: After Council on Foods and Nutrition, 1968. Courtesy of the Journal of the American Medical Association. the daily requirement, as Table 1 indicates. Since the average American diet provides about 6 mg of iron per thousand kcal (Monsen et al., 1967), iron intake from dietary sources is borderline for teenage girls and women and may be inadequate for infants and pregnant women (AMA Council on Foods and Nutrition, 1968: Committee on Dietary Allowances, 19741. Nevertheless, a woman who has sufficient iron stores to provide for increase in hemoglobin mass during pregnancy and who breast feeds her infant for 6 months (thereby delaying the return of menstruation) will have her iron needs covered by an adequate intake of dietary iron (FAD/WHO Expert Group, 1970~. The diagnostic features of iron deficiency are summarized in Table 1. To this should be added the fact that 5 mg or less of iron/100 g of liver tissue is indicative of depletion of the storage pool to the extent that iron-deficiency anemia may be either present or anticipated with any further depletion (Sturgeon and Shoden, 19711. As stated in footnote b to Table 1, the amount of iron required to meet the needs of pregnancy should usually be met by iron supplementation in the latter half of pregnancy, since it cannot usually be derived from diet. The Committee on Maternal Nutrition (1970) recommends supplementation with 30-60 mg of iron daily (i.e., 15~300 mg of ferrous sulfate) during preg- nancy. The physician should use his judgment in this regard, based on knowledge of the patient, the dietary habits, the fact that iron deficiency is frequent in pregnant women, and his evaluation of the blood and iron status of the particular patient (Herbert, 1975a). He may routinely give iron (Wal- lerstein, 1973~. In general, oral ferrous sulfate, the least expensive iron preparation, is the drug of choice for treating iron deficiency. A detailed discussion of iron

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270 VICTOR HERBERT therapy is presented elsewhere (Herbert, 1972; Herbert, 1975a). It is im- portant to remember that the duration of oral therapy for iron deficiency should be approximately 6 months, since a lesser duration will not adequately replete body iron stores. The physician must remember that the iron deficiency may have developed in association with menorrhagia; if that menorrhagia persists, iron therapy may have to persist as well so that the iron loss in blood does not again produce a negative iron balance. About 3 - percent of the iron in vegetable foods and 15-20 percent of the iron in animal foods is absorbed. Heme iron accounts for about one-third the iron in animal tissues, but the heme in a moderate portion of meat, fish, or poultry may supply up to one-third of the daily requirement because it is 5 to 10 times as absorbable as inorganic iron in food (Cook, 1978~. Nonheme iron absorption is enhanced by vitamin C and a "meat tissue factor" (not found in milk, eggs, or cheese); it is inhibited by eggs, bran, tea, EDTA, and calcium phosphate (Cook, 1978~. Thus, the amount of iron absorbed from a particular meal is dependent largely on its proportion of heme and nonheme iron, and its content of ascorbic acid and animal food, and iron deficiency, is much more frequent in vegetarians. The high frequency of iron deficiency in infants correlates with diets consisting largely of milk, so the maximum incidence is between 6 months and 2 years of age, and it is corrected by eating a mixed diet, so by age 5 it has fallen considerably. The 0.2-0.3 ,ug Fe/ml breast milk is adequate to the requirements of the exclusively breast-fed infant until birth weight is tripled. When breast feeding is discontinued before age 6 months, the use of formula rather than fresh cow's milk reduces the risk of intestinal blood loss. Cow's milk is higher in iron and lower in lactoferrin than human milk, but the iron in breast milk is better absorbed (Lockhart, 19791. Bothwell and Charlton note (1973) that use of the traditional iron pot instead of aluminum cookware to prepare their predominantly cereal diet (and traditional drinks) made iron deficiency anemia very infrequent in Bantu women, but made iron overload disease frequent in Bantu men. The striking effect of cooking in an iron skillet on iron content of food is illus- trated by them in Table 3. FOLATE-DEFICIENCY ANEMIA Studies carried out under the aegis of the World Health Organization (1968) and by Baker and DeMaeyer (1979) in various countries suggest that up to a third of all the pregnant women in the world have folate deficiency. In a recent study in a New York City municipal clinic, our group (Herbert et al., 1975) found tissue deficiency of folio acid, as measured by a red-cell folate

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Relation of Nutritional Anemias to Food Consumption Patterns 271 TABLE 3 Effect of Cooking in Iron Skillet (Dutch Oven) on Fe Content of Foods Food Iron Content, mg/100 gm Cooling Time, min Glass Dish Dutch Oven Spaghetti sauce 180 3.0 87.5 Gravy 20 0.43 5.9 Potatoes, fried 30 0.45 3.8 Rice casserole 45 1.4 5.2 Beef hash 45 1.52 5.2 Apple butter 120 0.47 52.5 Scrambled eggs 3 1.7 4. 1 SOURCE: Bothwell and Charlton, 1973. level below 150 ng/ml, present in 16 percent of 110 sequential pregnant women at the time of their first prenatal visit to the clinic. A further 14 percent had red-cell folate levels in the range "suggestive but not conclusive for tissue folate depletion" (150-199 ng/ml). It was suggested that daily ingestion of one fresh or fresh-frozen uncooked fruit or vegetable or fruit juice could have prevented this folate deficiency. These studies add to a growing body of evidence that nutritional defi- ciency of folic acid is prevalent among Americans of poor economic status. Based on findings up until 1970, Pritchard, writing for the Committee on Maternal Nutrition of the Food and Nutrition Board (1970), recommended that folic acid supplements should be taken throughout pregnancy. Sub- sequently, the data of the Ten-State Nutrition Survey (1968-70) became available. Although that survey found that "the mean serum folate values were, with few exceptions, above the acceptable level of 6 ng/ml and the mean red cell folate values were in the acceptable range of 150-650 ng/ml," a more detailed evaluation indicates a real problem in fact exists, obscured by the use of mean values alone (Herbert et al., 19751. The mean values obscured the existence of substantial numbers of actual values sufficiently below the mean as to suggest widespread folio acid deficiency. This is indicated by the data from the Survey Director for Massachusetts of the Ten-State Nutrition Survey (Edozien, 19721. In Massachusetts, serum and red-cell folates were measured on most of the samples collected. Of all the 1,087 Massachusetts blood samples from females on which such estimations were made, 25.6 percent had red-cell folate values below 150 ng/ml. This includes 115 pregnant women, all of whom were receiving prenatal clinic care, in the economically poor

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272 VICTOR HERBERT Roxbury-Dorchester area, and most of whom were receiving vitamin sup- plements, presumably containing folio acid. Among these pregnant women, 7.1 percent had red-cell folate values below 160 ng/ml and 7.1 percent had serum folate levels below 3 ng/ml. It is probably relevant that the over 10,000 individuals surveyed in Massachusetts were randomly selected from enumeration districts with the lowest average income (lowest quartile) ac- cording to the 1960 census (Ten-State Survey, 1968-70), and poverty and folate deficiency tend to run hand in hand (Herbert, 1968; Kahn et al., 1970~. As the Massachusetts report noted (Edozien, 1972), "The results suggest that the diets currently eaten by a large segment of the population cannot provide the allowance of folic acid recommended for optimal health and, therefore, that dietary deficiency of folic acid may pose a major nutri- tional problem. Considered together with the finding of a high prevalence of low plasma vitamin A levels, it would appear that these diets contain insuf- ficient amounts of green leafy vegetables which are major sources of both folic acid and provitamin A. Current processes for preservation, storage and preparation of foods may also destroy a high proportion of the folate in foods. " The hazard to mother and fetus of folate deficiency in the absence of frank anemia is unclear and has been extensively reviewed (Rothman, 1970~. Studies from South Africa suggest that folate supplements in this situation decrease the incidence of prematurity (Baumslag et al., 1970) and cause significant elevation of hemoglobin levels (Colman et al., 1975 a, b, c), suggesting that even mild deficiency may limit DNA synthesis. Prospective studies of the effects on the fetus are difficult to interpret because folate administration invariably starts only after the period of maximum fetal sus- ceptibility in the first trimester. However, animal experiments demonstrate a consistent teratogenic effect of folate deprivation from the time of concep- tion, dependent on the duration of the experiment (Herbert et al., 1975~. Thus, in the light of present knowledge it appears appropriate to correct folate deficiency in pregnancy. The implementation of this principle by improving the quality and quantity of available food is a long-term ideal limited by custom and economic circumstances. For this reason, the Joint FAD/WHO Expert Committee on Nutrition has recommended that food for- tification should be considered as an immediate possibility for the improve- ment of intake of any deficient nutrient (FAD/WHO Expert Committee, 19711. A series of studies indicate that fortification of staple foods with folic aicd is feasible, safe, effective, and in accordance with the recommenda- tions of the Expert Committee (Colman et al., 1974a,b,c, 1975a,b,c). With adequate fortification, possible hazards of folate deficiency in early preg- nancy would be averted. Until such fortification is practiced, administration of folic acid tablets, 200-400,ug/day, is appropriate for all pregnant women,

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Relation of Nutritional Anemias to Food Consumption Patterns 273 with 300 ,ug probably adequate for any pregnant population group (Herbert, 1977). The evidence relating folate deficiency in pregnancy to presence in the offspring of mental retardation and other defects in central nervous system function and development is reviewed elsewhere (Herbert and Tisman, 1973~. This evidence is, as yet, far from conclusive but does constitute one more slight increment in the balance favoring the concept of daily folate supplementation throughout pregnancy. In 1975, there was a National Academy of Sciences "Workshop on Human Folate Requirements," whose proceedings were published in 1977. That workshop included papers presenting the latest information on dis- tribution of folates in food, food folate availability, results of several sur- veys to detect folate deficiency in certain American population groups, and reviews of the folic acid requirement in children, adults, and in situations of increased need. To briefly summarize the findings most pertinent to nutri- tional anemias: Measurement of serum and red-cell folate together constitute the best method for delineating the existence of folate deficiency; food folate availability is affected by various constituents present in different foodstuffs; pregnancy increases folate requirement. The minimal daily adult requirement for folic acid, which must be ab- sorbed from food to sustain normality, is in the range of 50 ,ug daily (Her- bert, 1968), and the Food and Nutrition Board (1974) recommends that the diets of adults contain 400 ,ug daily. This requirement appears to be ap- proximately doubled by pregnancy. Thus, if a woman is absorbing from her food in the range of 100 ,ug of folio acid daily from the start of pregnancy, she may not need supplementation, but assuming lesser stores than normal at the start of pregnancy, 20~300 ,ug of folate supplementation daily may be necessary (Herbert, 1975; Herbert, 1977~. The Food and Nutrition Board (1974) recommends a daily dietary intake of 800 ,ug during pregnancy and 600 ,ug during lactation. Although serum and red-cell folate may be lowered by the use of oral contraceptives (Smith et al., 1975; Prasad et al., 1975), it is not yet clear that folate supplementation is needed by women taking such products (Anonymous, 1973; Lindenbaum, 1975~. This folate need would probably be adequately met by one fresh uncooked vegetable, fruit, or fruit juice daily (Herbert, 1975b). VITAMIN Bi2 Although serum vitamin BE level falls in pregnancy (Cooper, 1973) and may also fall with the use of oral contraceptives (Wertalik et al., 1972; Smith et al., 1975), tissue levels of vitamin BE may remain normal and vitamin BE

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274 VICTOR HERBERT deficiency anemia has not seemed to be a problem (Wertalik et al., 1972~. From evidence so far, vitamin BE deficiency anemia is rarely a dietary problem in the United States (Herbert, 1975b). In population groups where vitamin B,2 deficiency is common due to vegetarianism, such vitamin BE deficiency would be increased by the metabolic stress in pregnancy, including the fetal drain on maternal stores of about 0.3 ,ug B~2/day (Herbert, 1968; WHO, 1970) and by a mean of 0.3 ,ug B~2/day lost in breast milk during lactation (WHO, 1970~. It is for these reasons that the recommended dietary allowance (Food and Nutrition Board, 1974) for vitamin B ~2 was raised from the 3 ,ug for adults in general to 4 ,ug for pregnant or lactating females. Certain microorganisms and all animal protein are the sole source of dietary vitamin Bit. Thus, any diet devoid of animal protein, or not con- taining microorganisms that synthesize the vitamin, will eventually produce vitamin BE deficiency, unless the diet is supplemented with the vitamin. Certain seaweeds and legume nodules contain microorganisms that syn- thesize the vitamin; eating these foods and unwashed food contaminated with fecal microorganisms that synthesize the vitamin delays the onset of vitamin BE deficiency. REFERENCES AMA Council on Foods and Nutrition. 1968. Iron deficiency in the United States. JAMA 203:407-412. AMA Council on Foods and Nutrition. 1972. Iron in enriched wheat flour, farina, bread, buns and rolls. JAMA 220:855 - 859. Anonymous. 1973. Feminins and other vitamin-mineral supplements for women taking oral contraceptives. Med. Lett. 15:81-82. Anonymous. 1974. Topical and systematic contraceptive agents. Med. Lett. 16:37-40. Anonymous. 1975. Cu-7, a copper containing IUD. Med. Lett. 17:26-27. Baker, S. J., and E. M. DeMaeyer. 1979. Nutritional anemia: Its understanding and control with special reference to the work of the World Health Organization. Am. J. Clin. Nutr. 32:368-417. Baumslag, N., T. Edelstein, and J. Metz. 1970. Reduction of incidence of prematurity by folic acid supplementation in pregnancy. Br. Med. J. 1:16-17. Bothwell, T. H., and R. W. Charlton. 1973. Iron deficiency geographically speaking. In W. H. Crosby, ed. Iron. Medcom, New York. Colman, N., M. Barker, R. Green, and J. Metz. 1974a. Prevention of folate deficiency in pregnancy by food fortification. Am. J. Clin. Nutr. 27:339. Colman, N., J. V. Larsen, M. Barker, E. A. Barker, R. Green, and J. Metz. 1974b. Preven- tion of folate deficiency by food fortification. V. A pilot field trial of folic acid-fortified maize meal. S. Afr. Med. J. 48:1763. Colman, N., R. Green, K. Stevens, and J. Metz. 1974c. Prevention of folate deficiency by food fortification. VI. The antimegaloblastic effect of folic acid-fortified maize meal. S. Afr. Med. J. 48:1795. Colman, N., R. Green, and J. Metz. 1975a. Prevention of folate deficiency by food fortifica- tion. II. Absorption of folic acid from fortified staple foods. Arn. J. Clin. Nutr. 28:459-464.

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Relation of Nutritional Anemias to Food Consumption Patterns 275 Colman, N., J. V. Larsen, M. Barker, E. A. Barker, R. Green, and J. Metz, 1975b. Preven- tion of folate deficiency by food fortification. III. Effect in pregnant subjects of varying amounts of added folic acid. Am. J. Clin. Nutr. 28:465~70. Colman, N., E. A. Barker,~M. Barker, R. Green, and J. Metz. 1975c. Prevention of folate deficiency by food fortification. IV. Identification of target groups in addition to pregnant women in an adult rural population. Am. J. Clin. Nutr. 28:471-476. Cook, J. D. 1978. Food iron availability. Food Nutr. News 49(3):1,4. (National Live Stock and Meat Board, Chicago) Cooper, B. 1973. Folate and vitamin BE in pregnancy. Clin. Haemat. 2:461~76. Committee on Dietary Allowances. 1974. Recommended dietary allowances. Food and Nutri- tion Board, National Research Council, National Academy of Sciences, Washington, D.C. Committee on Maternal Nutrition. 1970. Maternal nutrition and the course of pregnancy. Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, D.C. Dorland's illustrated medical dictionary, 25th ed. 1974. W. B. Saunders, Philadelphia. Edozien, J. C. 1972. National Nutrition Survey, Massachusetts, July 1969-June 1971. Report of the Survey Director to the Commissioner for Public Health, Commonwealth of Mas- sachusetts, Boston. (Kindly supplied to us by Derek Robinson, M.D., Director, Division of Community Operations, Department of Public Health, Commonwealth of Massachusetts.) Fairbanks, V. F., J. L. Fahey, and E. Beutler, eds. l 971. Clinical disorders of iron metabolism, 2d ed. Grune and Stratton, New York and London. FAD/WHO Expert Committee on Nutrition. 1971. Food fortification. WHO Tech. Rep. Ser. No. 477. FAD/WHO Expert Group. 1970. Requirements of ascorbic acid, vitamin D, vitamin Be, folate and iron. WHO Tech. Rep. Ser. No. 452. (Purchasable for $1.25 from WHO in Geneva or American Public Health Association, 1740 Broadway, New York, NY 10019. Available in English, French, Spanish, Russian, and Chinese.) Food and Nutrition Board, National Research Council. 1977. Folic acid: Biochemistry and physiology in relation to the human nutrition requirement. National Academy of Sciences, Washington, D.C. Hallberg, L., A.-M. Hogdahl, L. Nilsson, and G. Rybo. 1966. Menstrual blood loss, a population study: Variation at different ages and attempts to define normality. Herbert, V. 1968. Nutritional requirements of vitamin BE and folic acid. Am. J. Clin. Nutr. 21:743 -752. Herbert, V. 1970. Introduction to the nutritional anemias. Semin. Haemat. 7:2-5. Herbert, V. 1972. Oral iron therapy. In W. H. Crosby, ed. Iron. Medcom, New York. Herbert, V. 1975a. Drugs effective in iron-deficiency and other hypochromic anemias. Pages 1309-1323 in L. S. Goodman and A. Gilman, eds. The pharmacological basis of therapeu- tics, 5th ed. Macmillan, New York. Herbert, V. 1975b. Drugs effective in megaloblastic anemias. Vitamin BE and folic acid. Pages 132~1349 in L. S. Goodman and A. Gilman, eds. The pharmacological basis of therapeutics, 5th ed. Macmillan, New York. Herbert, V. 1977. Folic acid requirements in adults (including pregnant and lactating females). In Folic acid. Food and Nutrition Board, National Academy of Sciences, Washington, D. C. Herbert, V., and G. Tisman.1973. Effects of deficiencies of folic acid and vitamin B ~2 on central nervous system function and development. Pages 373-392 in G. Gaull, ed. Biology of brain dysfunction, vol. 1. Plenum Press, New York and London. Herbert, V., N. Colman, M. Spivack, E. Ocasio, V. Ghanta, K. Kimmel, L. Brenner, J. Freundlich, and J. Scott. 1975. Folic acid deficiency in the United States: Folate assays in a prenatal clinic. Am. J. Obstet. Gynecol. 123:175-179.

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276 VICTOR HERBERT Kahn, S. B., S. Fein, S. Rigberg, and I. Brodsky. 1970. Correlation of folate metabolism and socioeconomic status in pregnancy and in patients taking oral contraceptives. Am. J. Obstet. Gynecol. 108:931-935. Layrisse, M. 1975. Iron nutriture. Pages 148- 154 in P. L. White and N. Selvey, eds. Pro- ceedings, Western Hemisphere Nutrition Congress IV. Publishing Sciences Group, Acton, Mass. Lindenbaum, J., N. Whitehead, and F. Reyner. 1975. Oral contraceptive hormones, folate metabolism, and the cervical epithelium. Am. J. Clin. Nutr. 28:346-353. Lockhart, J. D. 1979. Breast milk. Contemp. Nutr. 4(1):1-2 (General Mills, Minneapolis). Monsen, E. R., I. N. Kuhn, and C. A. Finch. 1967. Iron status of menstruating women. Am. J. Clin. Nutr. 20:842-849. Moore, C. V., and R. Dubach. 1956. Metabolism and requirements of iron in the human. JAMA 162:197-204. Prasad, A. S., K. Y. Lei, D. Oberleas, K. S. Moghissi, and J. C. Stryker. 1975. Effect of oral contraceptive agents on nutrients II. Vitamins. Am. J. Clin. Nutr. 28:385-391. Rothman, D 1970. Folicacidin pregnancy. Am. J. Obstet. Gynecol. 108:149-175. Rybo, G. 1970. Menstrual loss of iron. Pages 163- 171 in L. Hallberg, H.-G. Harwerth, and A. Vannotti, eds. Iron deficiency. Academic Press, London and New York. Scott, D. E., and J. A. Pritchard, 1967. Iron deficiency in healthy young college women. JAMA 199:897-900. Scott, D. E., J. A. Pritchard, A. S. Saltin, and J. M. Humphreys. 1970. Iron deficiency during pregnancy. Pages 491-503 in L. Hallberg, H.-G. Harwerth, and A. Vannotti, eds. Iron deficiency, Academic Press, London and New York. Smith, J. L., G. A. Goldsmith, and J. D. Lawrence.1975. Effects of oral contraceptive steroids on vitamin and lipid levels in serum. Am. J. Clin. Nutr. 28:377-384. Sturgeon, P., and A . Shoden. 1971. Total liver storage iron in normal populations of the U. S . A. Am. J. Clin. Nutr. 24:469-474. Symposium. 1975. Effects of oral contraceptive hormones on nutrient metabolism. Am. J. Clin. Nutr. 28:333-402, 521-560. Ten-State Nutrition Survey. 1968-70. U.S. Department of Health, Education, and Welfare, Center for Disease Control, Atlanta, Ga. DHEW Publ. No. (HSM) 72-8130 through 8134. Wallerstein, R. O. 1973. Iron metabolism and iron def~ciency during pregnancy. Clin. Haemat. 2:45~460. Wertalik, L. F., E. N. Metz, A. F. LoBuglio, and S. P. Balcerzak. 1972. Decreased serum B~ levels with oral contraceptive use. JAMA 221:1371-1374. WHO Scientific Group. 1968. Nutritional anaemias. WHO Tech. Rep. Ser. No. 405. (Purchasable for $ 1.00 from Publication Distribution and Sales, World Health Organization, 1211 Geneva 27, Switzerland.) Wintrobe, M. M. 1973. The proposed increase in the iron fortification of wheat products. Nutr. Today 8:18-20.