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Animal Source Foods to Improve Micronutrient Nutrition and Human Function in Developing Countries The Effect of Micronutrient Deficiencies on Child Growth: A Review ofResults from Community-Based Supplementation Trials1 Juan A. Rivera,2 Christine Hotz, Teresa Gonza´lez-Cossı´o, Lynnette Neufeld andArmando Garcı´a-Guerra Centro de Investigacio´n en Nutricio´n y Salud, Instituto Nacional de Salud Pu´blica, Cuernavaca, Morelos, Me´xico Several micronutrients are required for adequate growth among children. However, it has been unclear as to which nutrient deficiencies contribute most often to growth faltering in populations at risk for poor nutrition andpoor growth. Therefore, evidence from community-based, randomized, placebo-controlled, micronutrient supple-mentation trials was reviewed to determine which micronutrient deficiencies have been found to be causal to growthfaltering. Although correction of growth-limiting nutrient deficiencies may be achieved through provision ofpharmacological nutrient supplements, it also was of interest to review evidence for the use of animal source food supplements to improved growth among children in at-risk populations. There is strong evidence for the contributionof zinc deficiency to growth faltering among children; even mild to moderate zinc deficiency may affect growth.
Vitamin A and iron deficiencies also have been demonstrated to cause growth faltering, however only when thedeficiency state of these nutrients is severe. Several controlled, community-based intervention trials that haveincluded animal source foods, either together with additional micronutrient supplements or with other supplementalfood sources, have demonstrated positive growth responses among children. Three trials that used an animal source food alone (skim milk powder) also resulted in a positive growth response. However, the geographic scope of thelatter three trials was limited, and it remains unclear to what extent supplemental animal source foods alone andwhich types of animal source foods can be used to improve growth among children in at-risk populations.
KEY WORDS:  Micronutrients  animal source foods  growth  supplements Growth retardation is highly prevalent in developing about half of the world’s population is at risk of inadequate countries (1) and is associated with several adverse outcomes throughout life (2). Inadequate intakes of dietary energy and Attained height is the result of the interaction between protein and frequent infections are well-known causes of genetic endowment and both macro- and micronutrient growth retardation (3–5). However, the role of specific mi- availability during the growth period. Longitudinal growth cronutrient deficiencies in the etiology of growth retardation occurs through a process of cell proliferation, the addition of new has gained attention more recently (6–8). Micronutrient de- cells to the growth plate of the bone and hypertrophy, resulting ficiencies are highly prevalent in low-income countries, and in the expansion of the growth plate (11). Although the control the most probable causes are low content in the diet and poor of bone growth in its different phases is not entirely understood, bioavailability. More than half of preschool children are the key roles of growth hormone (GH)3 and insulin-like growth anemic, and an estimated 75 million and 140 million preschool factor I (IGF-I) have been identified. IGF-I receptors are found children have clinical and subclinical vitamin A deficiencies, predominantly in proliferating bone chondrocytes (11), and respectively (9). Less information is available on the prevalence IGF-I itself stimulates synthesis of collagen and proteoglycans.
of zinc deficiency, although it has been estimated recently that These physiological functions explain the role of IGF-I in lineargrowth. Furthermore, GH itself and its effect on IGF-I synthesisexert a direct effect on growth.
1 Presented at the conference ‘‘Animal Source Foods and Nutrition in Nutrition plays a key role in the control of linear growth held in Washington, D.C. June 24–26, 2002. The through a variety of mechanisms. Evidence from animal conference was organized by the International Nutrition Program, UC Davis and models indicates that energy and protein restriction reduces was sponsored by Global Livestock-CRSP, UC Davis through USAID grant IGF-I plasma concentration, which returns to normal after number PCE-G-00-98-00036-00. The supplement publication was supported byFood and Agriculture Organization, Land O’Lakes Inc., Heifer International, PondDynamics and Aquaculture-CRSP. The proceedings of this conference arepublished as a supplement to The Journal of Nutrition. Guest editors for this 3 Abbreviations used: GH, growth hormone; IGF-I, insulin-like growth factor I; supplement publication were Montague Demment and Lindsay Allen.
HAZ, height-for-age Z-score; WAZ, weight-for-age Z-score; WHZ, weight-for- 2 To whom correspondence should be addressed. E-mail: [email protected].
height Z-score; RDA, Recommended Daily Allowance.
0022-3166/03 $3.00 Ó 2003 American Society for Nutritional Sciences.
MICRONUTRIENTS, ANIMAL SOURCE FOODS AND GROWTH replenishment. The impact of reduced protein intake appears or weaned, or whose intake of complementary foods was low to be larger than that observed with energy restriction (12).
(28). These cross-sectional studies suggest that relatively small The association between nutritional status and the IGF-I increases in the intake of animal source foods may reduce the system also has been observed in humans: IGF-I is reduced prevalence of growth stunting in populations at risk. However, during acute protein deficiency (kwashiorkor) and protein- as these cross-sectional studies cannot confirm a direct impact energy malnutrition in children (12). Some micronutrients also of animal source food intake on growth, it will be necessary to affect the IGF-I system. For example, it is well documented that consider results from experimental studies using animal source zinc deficiency in rats causes not only growth retardation but also a decrease in both IGF-I plasma concentration and GH The objectives of this review are as follows: 1) to summarize receptors, which return to normal after zinc repletion (13).
evidence in the literature regarding the effects of common Additionally, through its influence on the GH/IGF-I system, micronutrient deficiencies on child growth derived from zinc deficiency has been observed to affect bone metabolism community-based, randomized controlled supplementation (14). The role of zinc in growth also may be explained in part trials using either single or multiple micronutrients; and 2) to through its participation in DNA synthesis (15).
summarize evidence of the effects of interventions that in- Studies on rats also have shown similar decreases in plasma cluded animal source foods in the prevention of growth re- IGF-I concentrations with depletion of potassium, magnesium tardation in community-based intervention trials.
or thiamine, which return to normal after repletion of thesenutrients (12). Copper also is involved in growth through itsrole in cross-linking collagen fibers, and manganese deficiency is associated with skeletal abnormalities, including retardedgrowth, which may be mediated through defects in pro- We conducted a literature review using the PubMed electronic system. No language restriction was imposed on the search, and teoglycan physiology in the growth plate (11). Vitamin D and articles published after 1989 were identified. Relevant studies Downloaded from calcium deficiencies also affect bone development, as ma- published before 1989 were identified through bibliographies of the nifested through the condition known as rickets (16).
obtained published articles. For the micronutrient studies, only Vitamin A was first identified as the growth-promoting randomized, placebo-controlled supplementation trials were included.
factor ‘‘A.’’ Studies in the 1920s–1930s demonstrated arrested The food-based intervention trials had to have included a concurrently growth, especially of weight in rats, after acute vitamin A enrolled control group. Only studies conducted for a minimum of 8 wk depletion (17–20). However, even today effects of vitamin A were accepted, as we consider this the minimum necessary to observe jn.nutrition.org on linear growth, bone formation and body composition in an impact of supplementation on growth.
animals are less clear (21). Judisch et al. (22) found that anemicchildren were small for their age and that their growth ratesaccelerated when treated with iron. Since then, however, evidence for the effect of iron deficiency on growth has been Randomized trials of the effect of micronutrient Deficiencies of some micronutrients, such as iron, magne- sium and zinc, result in anorexia (15,23). Therefore, these Single micronutrients. Community-based, randomized con- nutrient deficiencies also may contribute to growth retarda- trolled supplementation trials were identified for zinc, iron and tion indirectly by reducing the intake of other growth- vitamin A. The findings from these studies are described in de- limiting factors, such as energy and protein. Also, several tail below, and a summary of the results is presented in Table 1.
micronutrients, including zinc, iron and vitamin A, are Zinc. A meta-analysis of the effects of zinc supplementation associated with immune function and risk of morbidity, which on the growth of prepubertal children was published recently in turn affect growth (4). Therefore, micronutrient deficiencies (8); therefore, the results of this analysis are summarized here.
may have an indirect effect on growth by increasing the The studies in this analysis included the following: 1) ran- prevalence or severity of morbidity and anorexia.
domized, placebo-controlled intervention trials in which the Several approaches may be taken to improve the intake of supplemented and controlled groups were enrolled con- growth-limiting nutrients, including administration of micro- currently; 2) children ,12 y of age or specifically stated to be nutrient supplements, fortification of food with micronutrients prepubertal throughout the period of intervention; 3) no pre- or improved dietary intake. In populations where dietary quality mature infants; 4) subjects free of chronic diseases (e.g., is poor, it is likely that several micronutrient deficiencies co- marasmus and cystic fibrosis); 5) zinc as the only component of occur (24–26), in which case growth may be affected by more the supplement that differed between treatment groups; than one growth-limiting nutrient. Therefore, interventions 6) supplementation that was provided for at least 8 wk; and designed to increase the intake of several common growth- 7) information on the body weight and/or height that was limiting nutrients may be more effective in preventing growth collected during the period of supplementation and reported in retardation than those that increase the intake of only one sufficient detail. A total of 33 studies were considered to be problem nutrient. In general, animal source foods contain acceptable, where 13 of the studies were conducted in Latin higher concentrations of several micronutrients that may be America/Caribbean, 8 in Asia, 8 in North America/Europe and limiting to growth (e.g., calcium, zinc, iron and certain amino 4 in Africa. There were positive effect sizes for 25 out of 33 acids), and micronutrients in animal source foods also tend to studies that measured height and 25 out of 32 studies that be more readily available than micronutrients from plant foods.
measured body weight. The overall effect size (expressed in Indeed, results from observational studies conducted in Mexico standard deviation units) in height was 0.350 (CI ¼ 0.189, and Peru have suggested that intake of animal source foods is 0.511; p , 0.0001) and weight was 0.309 (CI ¼ 0.178, 0.439; associated positively with growth. In Mexico, a higher con- p , 0.0001). The growth responses were greater in children sumption of animal products between 18 and 30 mo of age was with low initial weight-for-age Z-scores and in those aged $6 associated with greater weight and length at 30 mo (27). In mo with initial low height-for-age Z-scores.
Peru, intake of animal source foods was associated with greater Results of one zinc supplementation trial conducted in West growth among infants who were either breastfed less frequently Java, Indonesia met the criteria described above and was Randomized, placebo-controlled, single-micronutrient supplementation trials and effects on child growth WAZ, and children $ 6 mo of age with , ÿ2 HAZ No difference in HAZ, WAZ, WHZ, prevalence Effect size for HAZ not significant (p = 0.09) No difference in plasma IGF-I concentration Significantly greater rate of weight gain showing greatest increase in hemoglobin(p  0.05) Weight, height and arm circumference increased significantly in the anemic group after iron Morbidity scores significantly lower in anemicchildren after iron treatment No growth effect among nonanemic children Change in height and HAZ significantly greater Change in WHZ significantly greater incontrol group WAZ were significantly greater after iron (severe anemiaand heavy hookwormexcluded) Total food (g) and energy intake significantlyincreased after iron treatment—anorexia mayhave partly caused poor growth in untreatedchildren Changes in weight, weight-for-height, arm circumference and skinfolds were significantly indicators did not improve significantly afteriron treatment Multiple-micronutrient deficiencies were noted inthe children (see Rivera et al., 2001) No significant differences in changes in weight, height or arm circumference observed after irontreatment, nor among those initially stuntedor anemic Hemoglobin increased significantly afteriron treatment Parallel study with albendazole treatment also didnot improve growth No difference in HAZ, WAZ, WHZ or knee-heel The rate of weight gain was significantly greater No significant differences in length gain or armcircumference No significant differences in weight or height Vitamin A, 10 mg ofcholecalciferol and50 mg of Vitamin C) Significant decline in hemoglobin observedin controls but not in those treated with iron Vitamin A supplementation unlikely to improve the growth of young children who have only mild Significant height and weight increases observed only in nonbreastfed children and those with low Significantly greater weight observed only in girls Linear growth increased significantly among children of low socioeconomic status or with HIV Risk of stunting was significantly reduced amongchildren with poor water supply, those who wereexclusively breastfed 4–6 mo and those who hadpersistent diarrhea Significantly greater increases in weight and arm circumference increments in children with initially 1 Initial status refers to nutritional status (biochemical or anthropometric) or physiological status (presence of infections) of the subjects at baseline, where this information was provided or relevant.
Where no information is provided, this indicates that subjects were not selected on the basis of their initial status.
published after the meta-analysis was completed (29). No one analyzed the subgroup of anemic infants separately. The differences were found among the groups in height-for-age, three that selected only anemic subjects all demonstrated weight-for-age or weight-for-height Z-scores (HAZ, WAZ and positive effects on growth. Two of five studies that did not WHZ, respectively) and in plasma IGF-I concentrations in select for iron status but noted a high (>50%) prevalence of a subsample. The effect size for length was estimated by us to be anemia showed a growth response after iron supplementation.
0.09 and was not significant. The authors concluded that there On the other hand, none of the four trials that selected only must have been additional underlying factors, including other nonanemic children showed an effect on growth. We con- nutritional deficiencies, that impaired the growth of these cluded that there is substantial evidence indicating that iron children. Nonetheless, the general conclusions of the meta- supplementation of anemic infants or young children has effects analysis remain valid, as the authors indicated that .500 on growth. Although the mechanisms by which anemia causes studies with no effect of zinc supplementation on growth would growth retardation are not clear, it may result from reduced oxi- be required to invalidate their findings (8).
dation reactions that occur when the functional iron compar- Iron. Twelve iron supplementation trials were identified, tment is depleted, from increased morbidity or from decreased which provided sufficient information to determine whether appetite. Discrepancies in results in some of the trials cond- there was a statistically significant difference in growth response.
ucted in communities with a high prevalence of anemia may be These studies included children between 2 mo and 13.5 y of age, due to the presence of concurrent deficiencies of other growth- receiving 10–80 mg of iron/d for at least 2 mo and up to 1 y.
limiting nutrients. Available evidence suggests that iron suppl- These studies were conducted in Asia (n ¼ 5), Africa (n ¼ 4) ementation has no effect on the growth of nonanemic children.
and Latin America (n ¼ 2). Three of these studies selected Vitamin A. Ramakrishnan and Martorell (39) conducted children who were anemic (30–32). All three studies showed a literature review of vitamin A supplementation trials that that provision of iron supplements to the anemic infants or measured impact on growth. They reported on nine random- young children resulted in improved growth. The two studies ized, double-blind trials (40–48), seven of which were placebo- that measured length or height demonstrated greater linear controlled. The trials were conducted in India (n¼3), growth (31,32), whereas the third study that did not measure Indonesia (n¼2), China, Tanzania, Ghana and Nepal. Seven length showed significantly greater weight gain (30). It also was of the trials provided high vitamin A doses every 4 or 6 mo, and noted in the Indonesian study (31) that a decrease in morbidity two of them provided daily amounts that were close to the was observed among the anemic children who received iron.
recommended daily allowance (RDA). All trials were con- Four studies enrolled children from communities that were ducted among children ,3 y of age in populations with not selected based on their iron status, but baseline mea- evidence of vitamin A deficiency and high risk of growth surements indicated that at least 50% of the children were retardation. The follow-up period (;1 y) would have been anemic (23,33,34,35). One group of Kenyan schoolchildren sufficient to find impacts on growth. Most of these trials found demonstrated significant gains in height and weight, as well as that vitamin A reduced mortality; however, eight of the nine increased food intake, after 14 wk of treatment with iron (23).
studies did not find any effects on length or weight. The two Another study, also conducted among Kenyan schoolchildren, studies that reported effects on growth, one in length (40) and resulted in increased weight, weight-for-height, arm circum- one in weight (46), were the only ones that did not have ference and skinfolds, but no increase in height was observed after 7 mo of intermittent iron supplementation Since the publication of the review, results of four additional (33). A study conducted in Benin among preschool children vitamin A supplementation trials meeting the requirements for showed no change in height or weight, although hemoglobin inclusion in this review were published from Indonesia (49), concentration was noted to increase significantly after treat- Sudan (50), Tanzania (51) and Zaire (52). These studies were ment (35). Treatment for intestinal helminthes with alben- community-based, high-dose vitamin A supplementation trials dazole also had no effect on growth in the latter study; that followed children under 6 y of age for 1–2 y. Two of these therefore, it is possible that some other growth-limiting studies examined the effects of supplementation on growth nutrient was severely deficient in this group. Rosado et al.
according to initial serum retinol concentrations in the children (34) also reported no effect of iron treatment on growth (49,52). Children with severe vitamin A deficiency (serum among preschoolers in Mexico. However, it was noted that retinol ,0.35 mmol/L) demonstrated improved growth among several multiple-micronutrient deficiencies were present, those who received the vitamin A supplement compared to including zinc, vitamin A and vitamin B-12. One further control children with severe vitamin A deficiency. The third study conducted in Indonesia did not measure baseline study (50) observed the impact of vitamin A supplementation prevalence of anemia, but after 6 mo of iron treatment, 66% on weight gain only in girls 1–3 y of age but not in the other age of infants in the placebo group were anemic compared to 28% groups (6 mo–1 y and 3–6 y) or in boys, but results were not in the group that received iron (29). No effect on growth analyzed according to baseline serum retinol concentrations.
was observed in the iron-supplemented group nor were any The study conducted in Tanzania (51) was the only study differences in IGF-1 concentrations found. Zinc supplemen- prospectively designed to evaluate factors that modify the effect tation in the same study also did not improve growth. The of vitamin A supplementation on growth. Children hospitalized authors concluded that there must have been other underlying with pneumonia were admitted to the study and received either growth-limiting deficiencies present.
repeated high-dose vitamin A treatment over 8 mo or a placebo.
There also were four iron supplementation trials that No overall effect of the treatment was observed in these selected only children who were nonanemic (31,36–38).
children. However, treatment had a significant positive effect None of these studies demonstrated an effect of iron on on the linear growth in subgroups of children of low socio- growth. In fact, the study conducted in Indonesia demonstrated economic status and in children with HIV infection. Among a significantly lower rate of weight gain among children who those who received vitamin A treatment, risk of stunting after received iron compared to controls (36).
1 y was significantly lower among children with poor water sup- In summary, 11 trials that reported information necessary to ply, and in those who were exclusively breastfed for 4–6 mo judge the effect of iron supplementation on growth were (but not ,4 mo). Finally, treatment attenuated the negative ef- reviewed. Four selected anemic infants or young children and fect of persistent diarrhea on stunting.
MICRONUTRIENTS, ANIMAL SOURCE FOODS AND GROWTH Based on these clinical trials, we conclude that vitamin A receive either the fortified or the nonfortified beverage, where supplementation is unlikely to improve the growth of young seven servings (100 kcal) of the beverage were provided 5 d/wk.
children who are only mildly to moderately vitamin A deficient.
The fortified beverage contained varying proportions of RDA On the other hand, severe vitamin A deficiency does appear to for four minerals and eight vitamins. This treatment was cause growth retardation, which may be alleviated after vitamin provided for 8 wk, and change in weight, but not height, was A supplementation. Effects of vitamin A deficiency on growth included as a growth outcome. The children receiving the may be mediated through morbidity, as suggested by the results fortified beverage gained significantly more weight than those of the study in Tanzania, where stunting vitamin A deficiency receiving the unfortified beverage. The trial conducted in appeared to contribute to stunting among children with serious Tanzania reported various outcomes of a similarly designed trial infections such as HIV or persistent diarrhea. The interaction in a series of abstracts (56,57,58). The fortified or nonfortified of breastfeeding with the effect of supplemental vitamin A on beverages contained 30–120% of the RDA for three minerals growth is equivocal. The results from Tanzania suggest that and seven vitamins and were provided on school days for additional vitamin A enhanced the protective effects of a period of 6 mo. High prevalences of anemia and severe breastfeeding against stunting, whereas the Indonesian study vitamin A deficiency were reported at baseline in this pop- suggested that nonbreastfed children benefited more from ulation (56). Children who received the fortified beverage had supplemental vitamin A in terms of growth.
significantly greater weight and height increments over the Other single micronutrients. We did not find randomized study period (58) and a reduced risk of stunting (57) compared supplementation trials with other micronutrients. There is to children who received the nonfortified beverage.
a theoretical basis to consider potassium, manganese, thiamin Another study worth noting is one conducted among low- and copper as other micronutrients besides zinc, vitamin A and income, Chinese schoolchildren aged 6–9 y (59), which looked iron as being growth-limiting nutrients in populations. However at the effects of daily supplementation with zinc (20 mg) versus it is possible that these nutrients are more often consumed in multiple micronutrients (half of the RDA for seven minerals Downloaded from adequate quantities and/or that there is a lack of information and 10 vitamins and one-quarter of the RDA for folate) with available on the occurrence of these deficiencies in populations.
and without zinc for 10 wk. A placebo group was not included, Multiple micronutrients. To date, limited information is iron was not included in the multiple-micronutrient treatment available on the effects of multiple-micronutrient supplemen- and only knee height was reported as a growth outcome. The tation on growth. For the purpose of this review, multiple- differences in knee height among groups were reported to be micronutrient supplements were considered to be those that statistically significant (p , 0.01), and the largest growth incre- jn.nutrition.org contained at least iron, zinc and a form of vitamin A. Five ments occurred in the zinc 1 micronutrients groups, followed placebo-controlled trials of supplementation with multiple by the group of micronutrients alone and finally, the group of micronutrients were identified and are summarized in Table zinc alone. These results suggest that micronutrients other than 2. Two of these studies were published in peer-reviewed zinc were limiting bone growth in the study population.
journals, two were published abstracts and another was In summary, of the five trials examined, four demonstrated submitted recently to a journal for peer review. The studies a positive growth response to multiple-micronutrient supple- were conducted in Botswana, Tanzania, Guatemala, Mexico mentation. The positive growth response found in the two and Vietnam. The studies in Botswana and Tanzania were studies conducted among infants and preschool children was conducted among schoolchildren, whereas the others included significant only among certain subgroups of children (i.e. those infants and preschoolers aged between 6 and 30 mo.
under 12 mo of age in Mexico and those initially stunted in The three studies conducted among infants and preschool Vietnam). The effect size for change in linear growth in the children varied somewhat in design. The study in Mexico (26) subgroups for which positive responses were found in these supplemented 8- to 14-mo-old children daily for 1 y with a fla- studies (Mexico, 0.29; Vietnam, daily 0.48, weekly 0.37) was vored beverage containing 1–1.5 times the RDA of six minerals in the range of that found in the meta-analysis of zinc and 13 vitamins. This population of children was reported to supplementation for initially stunted children. The abstract have multiple-micronutrient deficiencies. Supplemented in- reported from Guatemala did not report specifically on effects fants initially aged ,12 mo had significantly greater length gains among possible vulnerable subgroups of children, but suggested than the placebo group, with a difference of 0.29 length-for-age that these factors were controlled for in the analysis.
Z-score at the end of supplementation, whereas no effects were It is not possible to determine which micronutrients in these observed in children aged $ 12 mo at baseline. The study in studies were limiting to growth, and clearly, this would depend Vietnam (53) supplemented children 6–24 mo of age for 3 mo on the existence and severity of various micronutrient de- with either of the following: 1) daily supplements with 8 mg of ficiencies. Based on the results of the meta-analysis of zinc iron, 5 mg of zinc, 333 mg of retinol and 20 mg of vitamin C, supplementation on growth, it is clear that zinc is a common 5 d/wk; 2) weekly supplements with 20 mg of iron, 17 mg of zinc, growth-limiting nutrient. The conclusions of the single- 1700 mg of retinol and 20 mg of vitamin C; or 3) a placebo.
micronutrient trials confirm that zinc deficiency and severe Positive impacts on HAZ were documented both in the daily iron and vitamin A deficiencies are causal to growth retarda- (10.48, p , 0.001) and weekly (10.37, p , 0.001) groups, but tion. However, the study conducted among schoolchildren in only in infants who were stunted at baseline. Limited infor- China (59) and others (60) suggest that zinc alone was not the mation is as yet available for the study conducted in Guatemala primary growth-limiting nutrient. It is possible that micro- (54). The supplements provided either whey protein concen- nutrient deficiencies other than zinc, iron and vitamin A also trate or bovine serum concentrate, both with or without cause growth faltering as the latter studies did not select for multiple micronutrients (composition not reported), for ;7 mo.
anemia or severe vitamin A deficiency.
There were no differences in length or weight between the pro- Supplementation and/or nutrition education trials tein-supplemented groups and the groups containing micronu- including foods of animal origin and their influence The two African trials provided schoolchildren with beverages with or without multiple-micronutrient mixtures.
Perhaps the main question to be asked by the review in this In the study in Botswana (55), schools were randomized to section is whether animal source foods can be used to provide Randomized, placebo-controlled, single-micronutrient supplementation trials and effects on child growth Weight and weight-for-age Z-scores increased significantly after supplementation with the multiple micronutrient–containing beverage (effect size forweight-for-age Z-score = 0.36) Mean change in weight was 0.8 kg greater (p , 0.001) and mean change in height was 0.7 cm greater (p , 0.001) in the group that received micronutrients Stunting was significantly reduced (odds ratio 0.52) No difference among groups in changes in length, Impact of supplementation on length-for-age in infants ,12 mo of age at recruitment (effect size = 0.30;p , 0.05) Effect size on children $12 mo of age: 0.10 (N.S.) No significant differences in growth among groups Among those stunted at baseline, HAZ increased significantly after daily (effect size 0.48) and MICRONUTRIENTS, ANIMAL SOURCE FOODS AND GROWTH additional micronutrients sufficient to prevent or limit growth Breastfed infants received one of the following porridges: faltering in children living in high-risk environments. Very few a cereal-legume blend (Weanimix), Weanimix 1 vitamins and studies have been designed to answer this question directly.
minerals, Weanimix 1 fish powder or koko (a traditionally used Several studies have used interventions that included increased fermented maize porridge) 1 fish powder. No differences were intake of animal source foods. However, the intervention observed in length or weight among the four intervention designs varied greatly and most included components other groups. However, LAZ and WAZ among all of the sup- than provision of animal source foods, such as additional plemented infants (pooled) were greater than among those in micronutrients or nutrition education, to improve young child the cross-sectional study group. It is possible that all of the feeding practices. The studies included in this review are supplemental food types tested were equally sufficient to in- randomized intervention trials with a concurrently enrolled crease the intake of growth-limiting nutrients. However, the control group and they lasted at least 8 wk.
authors also suggested that the provision of the hygienically Food supplements containing animal source foods plus prepared supplemental foods in vacuum flasks may have additional micronutrients. Two studies were identified that reduced exposure to diarrheal pathogens and that more prompt provided food supplements plus additional micronutrients use of clinic facilities may have been encouraged indirectly due in the intervention (2,61). One study was conducted in to frequent morbidity monitoring during the intervention. It Guatemala, where four villages received either a skim milk– was not possible to assess the contribution of decreased based, high-protein, high-energy supplement (atole) or a no- morbidity rates to the apparently improved growth among the protein, low-energy supplement (fresco), where both sup- plements contained additional micronutrients (2,62). The The three controlled trials described above produced posi- supplements were distributed in a central location in each tive effects on growth, and two of the studies (61,63) suggested village and were available on demand to all members of the that the growth impact was at least partially mediated through community. Intake of the supplements was registered daily for attenuation of the negative effects of diarrheal morbidity on Downloaded from all children under 7 y of age. Supplementation with atole growth. The main difference between these studies and those resulted in 2.45 6 0.10 cm greater length at 3 y of age than in that provided micronutrient supplements alone is that these the group receiving fresco. In Colombia, women in their first trials also included supplementary energy and protein, which trimester of pregnancy living in an urban area were selected also may be limiting to growth and may contribute to improved from low income families in which 50% of the children under 5 y catch-up during convalescence. As both food supplements and of age in the family had a weight-for-age that was .85% of the micronutrients were provided simultaneously in the interven- jn.nutrition.org Colombian standards (61). Mothers were followed through tion, it is not possible to ascertain whether the nutritious food pregnancy and infants resulting from that pregnancy were supplement alone could produce similar benefits without the followed for 3 y. The families were randomly assigned to receive provision of additional micronutrients.
either no supplement or food supplements consisting of dry Nutrition education interventions that included increased skim milk, enriched bread and vegetable oil, plus iron and intake of animal source foods. Two studies conducted nutri- vitamin A supplementation for the enrolled children. At 3 mo, tion education interventions that included a component to a difference in weight of 197 g in favor of the supplemented increase the intake of animal source foods. A year-long in- group and at 6 mo a difference in length of 0.9 cm were tervention was conducted in China that assessed the impact documented. By 36 mo, the supplemented group had a mean of nutrition education and growth monitoring activities on weight that was 476 g (p , 0.05) higher and a mean length that growth among children from their first year of life (65). The was 2.2 cm (p , 0.005) greater than the control group. Among educational component included specific messages to encour- unsupplemented children, diarrhea was significantly negatively age exclusive breastfeeding for 4–6 mo, after which time, hard- associated with length; however, supplementation completely boiled egg yolk should be offered to the infant daily. It was offset the negative effect of diarrheal disease on growth.
reported that more women in the intervention group could cite Two other studies that provided food supplements con- important foods to include in the complementary diet and taining animal source foods plus additional micronutrients were appropriate patterns of breastfeeding, and more children in the identified. Although these did not meet the criteria for in- intervention group received egg yolk daily. Infants in the clusion in the review, their results are worth mentioning. A intervention group had significantly better growth in weight study conducted in a peri-urban area in Guinea-Bissau aimed and length than the control group. (WAZ: ÿ1.17 vs. ÿ1.93, to determine the effects of a dietary supplement (millet gruel p ¼ 0.004; HAZ: ÿ1.32 vs. ÿ1.96, p ¼ 0.002). The increase with egg, milk powder, banana, margarine and sugar) plus in intake of egg yolk by young children may have contributed to micronutrients given to children ,3 y of age with diarrhea increased intake of growth-limiting nutrients in this population.
(n ¼ 120) versus the children’s typical diet. The supplement However, it cannot be determined to what extent this, or the was given during the diarrheal episode and for 1 wk during other intervention activities, contributed to the greater growth convalescence (63). Although the intervention was adminis- tered for a median of only 17 d, the children’s growth response An intervention conducted in India offered a milk- and was monitored for a median of 6.6 mo. The treatment group cereal-based supplement plus nutrition counseling, or visitation had a weight gain exceeding that of the control group by 61.5 g/ only, for 8 mo among infants recruited at 4 mo of age (66).
wk during the intervention period and by 12.5 g/wk during Children receiving the supplement had a weight increment follow-up. Not surprisingly, there was no significant increase in 0.25 kg greater than that of the control group, but no change in knee-heel height during the intervention period. However, it length was observed. However, children in the intervention was significantly greater in the treatment group (7.5 mm/y, p , group also had higher rates of diarrhea and were breastfed less 0.0001) after the follow-up. Another study was conducted frequently than the control children. In this case, the increased among Ghanaian infants to evaluate the effect of feeding diarrheal infections may have been caused by use of con- centrally produced infant cereals of varying nutritional taminated water needed to dilute the food supplement and composition on nutritional status (64). Unfortunately, it was possibly by the displacement of breast milk. This study suggests not possible to include a concurrently enrolled control group, so that, in addition to providing increased nutritional intake, a separate cross-sectional study was used as a comparison.
simultaneous interventions to improve water quality also may be needed to achieve more effective prevention of morbidity supplements, with or without additional micronutrients, reported positive impacts on growth.
Interventions with animal source foods alone. Only four studies were identified where a single food supplement was provided to children in the form of milk powder or formulawithout additional micronutrients, three of which were The essential role for several micronutrients in growth has conducted in the same population group. Malcolm (67) been demonstrated clearly by both animal- and clinical-based reported results of two food-supplementation trials conducted human trials of supplementation with single micronutrients.
among children in a boarding school in Bundi, New Guinea.
The three micronutrients with the strongest relationship to The first study compared changes in height, weight and growth, iron, zinc and vitamin A, are commonly deficient in skinfold thickness between two classes of children receiving low-income populations where dietary quality often is poor.
their regular diet of 3 meals daily of taro and sweet potato The positive impact of community-based supplementation (tubers) or a skim milk powder supplement providing 25 g of trials reviewed in this article indeed confirms that iron, zinc and protein daily for 5 mo. The schoolchildren receiving the vitamin A are common growth-limiting nutrients. However, supplement demonstrated significantly greater gains in height iron and vitamin A appear to be limiting to growth only when (12.42 cm) and weight (10.73 kg) compared to the control deficiencies of these nutrients are severe, whereas growth may class (11.18 cm, p , 0.001 and –0.13 kg, p , 0.01). The be limited only by mild to moderate deficiency of zinc. This is second study used a similar design to compare growth response consistent with the known metabolic and physiologic activity of of the schoolchildren to supplemental skim milk powder (270 these nutrients: zinc has direct effects on the primary hormonal kcal/d), margarine (270 kcal/d) or two additional meals of taro system (IGF-I/GH) that controls growth in the postnatal phase and sweet potato daily, each provided 5 d/wk for 13 wks. The when the majority of stunting occurs. On the other hand, iron skim milk–supplemented group demonstrated the largest and vitamin A do not appear to influence this system directly, height and weight increases (12.32 cm, 11.21 kg) relative but more likely exert their effects on growth when their to the control group (11.10 cm, 10.50 kg). Only a small functional stores have been depleted and/or when deficiencies increase in weight (11.05 kg) occurred in the margarine- of these nutrients result in increased morbidity, which in turn supplemented group but skinfolds increased substantially in contributes to growth faltering. Although single-micronutrient this group compared to controls. The additional taro and supplementation trials have been useful to confirm the effects sweet potato resulted in a small increase in height (11.54 cm) of specific micronutrients on growth outcomes, programs that relative to controls. Because the children’s normal diet was provide supplements of only one nutrient may not be the most based almost exclusively on tubers with relatively low protein cost-effective way of preventing growth faltering and associated content, it was hypothesized that protein was limiting to the adverse health outcomes because of the co-existence of growth of these children. These results are consistent with multiple-micronutrient deficiencies in many populations.
protein, or other growth-limiting nutrients in milk, being Multiple-micronutrient supplements are expected to be limiting to the accrual of lean tissues, whereas additional more efficacious in preventing growth faltering in at-risk pop- energy provided as fat apparently contributed to fat accumu- ulations, as all possible growth-limiting micronutrient de- lation. These results were corroborated by a later trial ficiencies may be corrected simultaneously. Although the few conducted in the same area where children receiving a skim available multiple-micronutrient supplementation trials have milk powder supplement also demonstrated improvements in demonstrated positive effects on growth, in some cases these indices of skeletal development (68). Walker et al. (69) effects were limited to specific subgroups of the study popu- conducted a randomized intervention trial in Jamaica where lation. Also, the interaction of various micronutrients and the a milk-based formula was provided for 1 y to children (9–24 potential negative effect of some minerals on the absorption of mo) who were initially stunted, and their growth was others (e.g., iron, zinc and copper, calcium) when combined in compared to age- and sex-matched stunted controls who a single supplement requires further assessment.
received no food supplement. Supplemented children gained From a programmatic perspective, it may be more desirable an additional 0.9 cm and 0.31 kg more than that of control to consider intervention options other than supplement use.
children during the first 6 mo of the study, whereas no further Food-based interventions may have several advantages, in- benefit was observed in the latter half of the study. It was cluding the provision of additional nutrients in a familiar form noted that the gains in growth were greater among younger that can be integrated with the usual diet and the provision of children than they were among older children. Based on the an additional source of energy and high-quality protein, which results of these three trials, it appears that milk supplements also have direct effects on the IGF-I/GH hormone system (70).
may provide a good source of nutrients that are limiting to Animal source foods provide the richest and most bioavailable growth in some settings, although the specific growth-limiting sources of several micronutrients. Some of the food-based trials have demonstrated that at least part of the positive effects of It is difficult to summarize interventions studying the the intervention on growth occurred by improving catch-up efficacy of supplementary animal source foods on prevention growth after diarrheal illness (61,63). Although it is conceiv- of growth faltering because of the many different study able that the additional micronutrients (provided by the designs used and because most of the interventions included pharmacological supplements or animal source food) supported other components that may have contributed to the effects catch-up growth during convalescence, the supplemental foods observed. The only examples of animal source foods solely also would have provided additional energy and protein, which contributing to growth promotion are the trials that provided may contribute to improved growth in the face of frequent milk supplements alone: all four trials produced positive effects on growth; however, it is not possible to determine Unfortunately, very few studies have been reported that what specific micro- or macronutrients contributed to the confirm the evidence from cross-sectional studies suggesting growth response. It also is unclear to what extent additional that intake of animal source foods is associated with better micronutrients would have provided further benefits to growth in children. Several intervention studies have included growth. In any case, all of the trials that included food both food supplements and additional multiple micronutrients, MICRONUTRIENTS, ANIMAL SOURCE FOODS AND GROWTH but it remains uncertain as to whether the supplemental food source alone could have been equally effective at preventing during growth. J. Biol. Chem. 23: 231–254.
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