QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rivera, J. A. Articles by García-Guerra, A. Search for Related Content PubMed PubMed Citation Articles by Rivera, J. A. Articles by García-Guerra, A.

---

Supplement: Animal Source Foods to Improve Micronutrient Nutrition in Developing Countries

The Effect of Micronutrient Deficiencies on Child Growth: A Review of Results from Community-Based Supplementation Trials¹

Centro de Investigación en Nutrición y Salud, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, México

² To whom correspondence should be addressed. E-mail: jrivera{at}insp.mx.

	ABSTRACT

TOP ABSTRACT METHODS RESULTS AND DISCUSSION LITERATURE CITED

 
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 and poor growth. Therefore, evidence from community-based, randomized, placebo-controlled, micronutrient supplementation trials was reviewed to determine which micronutrient deficiencies have been found to be causal to growth faltering. Although correction of growth-limiting nutrient deficiencies may be achieved through provision of pharmacological 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 contribution of 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 the deficiency state of these nutrients is severe. Several controlled, community-based intervention trials that have included animal source foods, either together with additional micronutrient supplements or with other supplemental food 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 the latter three trials was limited, and it remains unclear to what extent supplemental animal source foods alone and which 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 countries (1) and is associated with several adverse outcomes throughout life (2). Inadequate intakes of dietary energy and protein and frequent infections are well-known causes of growth retardation (3–5). However, the role of specific micronutrient deficiencies in the etiology of growth retardation has gained attention more recently (6–8). Micronutrient deficiencies are highly prevalent in low-income countries, and the most probable causes are low content in the diet and poor bioavailability. More than half of preschool children are anemic, and an estimated 75 million and 140 million preschool children have clinical and subclinical vitamin A deficiencies, respectively (9). Less information is available on the prevalence of zinc deficiency, although it has been estimated recently that about half of the world's population is at risk of inadequate intake of absorbable zinc (10).

Attained height is the result of the interaction between genetic endowment and both macro- and micronutrient availability during the growth period. Longitudinal growth occurs through a process of cell proliferation, the addition of new cells to the growth plate of the bone and hypertrophy, resulting in the expansion of the growth plate (11). Although the control of bone growth in its different phases is not entirely understood, the key roles of growth hormone (GH)³ and insulin-like growth factor I (IGF-I) have been identified. IGF-I receptors are found predominantly in proliferating bone chondrocytes (11), and IGF-I itself stimulates synthesis of collagen and proteoglycans. These physiological functions explain the role of IGF-I in linear growth. Furthermore, GH itself and its effect on IGF-I synthesis exert a direct effect on growth.

Nutrition plays a key role in the control of linear growth through a variety of mechanisms. Evidence from animal models indicates that energy and protein restriction reduces IGF-I plasma concentration, which returns to normal after replenishment. The impact of reduced protein intake appears to be larger than that observed with energy restriction (12). The association between nutritional status and the IGF-I system also has been observed in humans: IGF-I is reduced during acute protein deficiency (kwashiorkor) and protein-energy malnutrition in children (12). Some micronutrients also affect the IGF-I system. For example, it is well documented that zinc deficiency in rats causes not only growth retardation but also a decrease in both IGF-I plasma concentration and GH receptors, which return to normal after zinc repletion (13). Additionally, through its influence on the GH/IGF-I system, zinc deficiency has been observed to affect bone metabolism (14). The role of zinc in growth also may be explained in part through its participation in DNA synthesis (15).

Studies on rats also have shown similar decreases in plasma IGF-I concentrations with depletion of potassium, magnesium or thiamine, which return to normal after repletion of these nutrients (12). Copper also is involved in growth through its role in cross-linking collagen fibers, and manganese deficiency is associated with skeletal abnormalities, including retarded growth, which may be mediated through defects in proteoglycan physiology in the growth plate (11). Vitamin D and calcium deficiencies also affect bone development, as manifested through the condition known as rickets (16).

Vitamin A was first identified as the growth-promoting factor "A." Studies in the 1920s–1930s demonstrated arrested growth, especially of weight in rats, after acute vitamin A depletion (17–20). However, even today effects of vitamin A on linear growth, bone formation and body composition in animals are less clear (21). Judisch et al. (22) found that anemic children were small for their age and that their growth rates accelerated when treated with iron. Since then, however, evidence for the effect of iron deficiency on growth has been equivocal.

Deficiencies of some micronutrients, such as iron, magnesium and zinc, result in anorexia (15,23). Therefore, these nutrient deficiencies also may contribute to growth retardation indirectly by reducing the intake of other growth-limiting factors, such as energy and protein. Also, several micronutrients, including zinc, iron and vitamin A, are associated with immune function and risk of morbidity, which in turn affect growth (4). Therefore, micronutrient deficiencies may have an indirect effect on growth by increasing the prevalence or severity of morbidity and anorexia.

Several approaches may be taken to improve the intake of growth-limiting nutrients, including administration of micronutrient supplements, fortification of food with micronutrients or improved dietary intake. In populations where dietary quality is poor, it is likely that several micronutrient deficiencies co-occur (24–26), in which case growth may be affected by more than one growth-limiting nutrient. Therefore, interventions designed to increase the intake of several common growth-limiting nutrients may be more effective in preventing growth retardation than those that increase the intake of only one problem nutrient. In general, animal source foods contain higher concentrations of several micronutrients that may be limiting to growth (e.g., calcium, zinc, iron and certain amino acids), and micronutrients in animal source foods also tend to be more readily available than micronutrients from plant foods. Indeed, results from observational studies conducted in Mexico and Peru have suggested that intake of animal source foods is associated positively with growth. In Mexico, a higher consumption of animal products between 18 and 30 mo of age was associated with greater weight and length at 30 mo (27). In Peru, intake of animal source foods was associated with greater growth among infants who were either breastfed less frequently or weaned, or whose intake of complementary foods was low (28). These cross-sectional studies suggest that relatively small increases in the intake of animal source foods may reduce the prevalence of growth stunting in populations at risk. However, as these cross-sectional studies cannot confirm a direct impact of animal source food intake on growth, it will be necessary to consider results from experimental studies using animal source food supplements.

The objectives of this review are as follows: 1) to summarize evidence in the literature regarding the effects of common micronutrient deficiencies on child growth derived from community-based, randomized controlled supplementation trials using either single or multiple micronutrients; and 2) to summarize evidence of the effects of interventions that included animal source foods in the prevention of growth retardation in community-based intervention trials.

	METHODS

TOP ABSTRACT METHODS RESULTS AND DISCUSSION LITERATURE CITED

 
We conducted a literature review using the PubMed electronic system. No language restriction was imposed on the search, and articles published after 1989 were identified. Relevant studies published before 1989 were identified through bibliographies of the obtained published articles. For the micronutrient studies, only randomized, placebo-controlled supplementation trials were included. The food-based intervention trials had to have included a concurrently enrolled control group. Only studies conducted for a minimum of 8 wk were accepted, as we consider this the minimum necessary to observe an impact of supplementation on growth.

	RESULTS AND DISCUSSION

TOP ABSTRACT METHODS RESULTS AND DISCUSSION LITERATURE CITED

 
Randomized trials of the effect of micronutrient supplementation on child growth

    Single micronutrients Community-based, randomized controlled supplementation trials were identified for zinc, iron and vitamin A. The findings from these studies are described in detail below, and a summary of the results is presented in Table 1.

Results of one zinc supplementation trial conducted in West Java, Indonesia met the criteria described above and was published after the meta-analysis was completed (29). No differences were found among the groups in height-for-age, weight-for-age or weight-for-height Z-scores (HAZ, WAZ and WHZ, respectively) and in plasma IGF-I concentrations in a subsample. The effect size for length was estimated by us to be 0.09 and was not significant. The authors concluded that there must have been additional underlying factors, including other nutritional deficiencies, that impaired the growth of these children. Nonetheless, the general conclusions of the meta-analysis remain valid, as the authors indicated that >500 studies with no effect of zinc supplementation on growth would be required to invalidate their findings (8).

Iron Twelve iron supplementation trials were identified, which provided sufficient information to determine whether there was a statistically significant difference in growth response. These studies included children between 2 mo and 13.5 y of age, receiving 10–80 mg of iron/d for at least 2 mo and up to 1 y. These studies were conducted in Asia (n = 5), Africa (n = 4) and Latin America (n = 2). Three of these studies selected children who were anemic (30–32). All three studies showed that provision of iron supplements to the anemic infants or young children resulted in improved growth. The two studies that measured length or height demonstrated greater linear growth (31,32), whereas the third study that did not measure length showed significantly greater weight gain (30). It also was noted in the Indonesian study (31) that a decrease in morbidity was observed among the anemic children who received iron.

Four studies enrolled children from communities that were not selected based on their iron status, but baseline measurements indicated that at least 50% of the children were anemic (23,33,34,35). One group of Kenyan schoolchildren demonstrated significant gains in height and weight, as well as increased food intake, after 14 wk of treatment with iron (23). Another study, also conducted among Kenyan schoolchildren, resulted in increased weight, weight-for-height, arm circumference and skinfolds, but no increase in height was observed after 7 mo of intermittent iron supplementation (33). A study conducted in Benin among preschool children showed no change in height or weight, although hemoglobin concentration was noted to increase significantly after treatment (35). Treatment for intestinal helminthes with albendazole also had no effect on growth in the latter study; therefore, it is possible that some other growth-limiting nutrient was severely deficient in this group. Rosado et al. (34) also reported no effect of iron treatment on growth among preschoolers in Mexico. However, it was noted that several multiple-micronutrient deficiencies were present, including zinc, vitamin A and vitamin B-12. One further study conducted in Indonesia did not measure baseline prevalence of anemia, but after 6 mo of iron treatment, 66% of infants in the placebo group were anemic compared to 28% in the group that received iron (29). No effect on growth was observed in the iron-supplemented group nor were any differences in IGF-1 concentrations found. Zinc supplementation in the same study also did not improve growth. The authors concluded that there must have been other underlying growth-limiting deficiencies present.

There also were four iron supplementation trials that selected only children who were nonanemic (31,36–38). None of these studies demonstrated an effect of iron on growth. In fact, the study conducted in Indonesia demonstrated a significantly lower rate of weight gain among children who received iron compared to controls (36).

In summary, 11 trials that reported information necessary to judge the effect of iron supplementation on growth were reviewed. Four selected anemic infants or young children and one analyzed the subgroup of anemic infants separately. The three that selected only anemic subjects all demonstrated positive effects on growth. Two of five studies that did not select for iron status but noted a high (>50%) prevalence of anemia showed a growth response after iron supplementation. On the other hand, none of the four trials that selected only nonanemic children showed an effect on growth. We concluded that there is substantial evidence indicating that iron supplementation of anemic infants or young children has effects on growth. Although the mechanisms by which anemia causes growth retardation are not clear, it may result from reduced oxidation reactions that occur when the functional iron compartment is depleted, from increased morbidity or from decreased appetite. Discrepancies in results in some of the trials conducted in communities with a high prevalence of anemia may be due to the presence of concurrent deficiencies of other growth-limiting nutrients. Available evidence suggests that iron supplementation has no effect on the growth of nonanemic children.

Vitamin A Ramakrishnan and Martorell (39) conducted a literature review of vitamin A supplementation trials that measured impact on growth. They reported on nine randomized, double-blind trials (40–48), seven of which were placebo-controlled. The trials were conducted in India (n=3), Indonesia (n=2), China, Tanzania, Ghana and Nepal. Seven of the trials provided high vitamin A doses every 4 or 6 mo, and two of them provided daily amounts that were close to the recommended daily allowance (RDA). All trials were conducted among children <3 y of age in populations with evidence of vitamin A deficiency and high risk of growth retardation. The follow-up period (1 y) would have been sufficient to find impacts on growth. Most of these trials found that vitamin A reduced mortality; however, eight of the nine studies did not find any effects on length or weight. The two studies that reported effects on growth, one in length (40) and one in weight (46), were the only ones that did not have placebo groups.

Since the publication of the review, results of four additional vitamin A supplementation trials meeting the requirements for inclusion in this review were published from Indonesia (49), Sudan (50), Tanzania (51) and Zaire (52). These studies were community-based, high-dose vitamin A supplementation trials that followed children under 6 y of age for 1–2 y. Two of these studies examined the effects of supplementation on growth according to initial serum retinol concentrations in the children (49,52). Children with severe vitamin A deficiency (serum retinol <0.35 µmol/L) demonstrated improved growth among those who received the vitamin A supplement compared to control children with severe vitamin A deficiency. The third study (50) observed the impact of vitamin A supplementation on weight gain only in girls 1–3 y of age but not in the other age groups (6 mo–1 y and 3–6 y) or in boys, but results were not analyzed according to baseline serum retinol concentrations. The study conducted in Tanzania (51) was the only study prospectively designed to evaluate factors that modify the effect of vitamin A supplementation on growth. Children hospitalized with pneumonia were admitted to the study and received either repeated high-dose vitamin A treatment over 8 mo or a placebo. No overall effect of the treatment was observed in these children. However, treatment had a significant positive effect on the linear growth in subgroups of children of low socioeconomic status and in children with HIV infection. Among those who received vitamin A treatment, risk of stunting after 1 y was significantly lower among children with poor water supply, and in those who were exclusively breastfed for 4–6 mo (but not <4 mo). Finally, treatment attenuated the negative effect of persistent diarrhea on stunting.

Based on these clinical trials, we conclude that vitamin A supplementation is unlikely to improve the growth of young children who are only mildly to moderately vitamin A deficient. On the other hand, severe vitamin A deficiency does appear to cause growth retardation, which may be alleviated after vitamin A supplementation. Effects of vitamin A deficiency on growth may be mediated through morbidity, as suggested by the results of the study in Tanzania, where stunting vitamin A deficiency appeared to contribute to stunting among children with serious infections such as HIV or persistent diarrhea. The interaction of breastfeeding with the effect of supplemental vitamin A on growth is equivocal. The results from Tanzania suggest that additional vitamin A enhanced the protective effects of breastfeeding against stunting, whereas the Indonesian study suggested that nonbreastfed children benefited more from supplemental vitamin A in terms of growth.

Other single micronutrients We did not find randomized supplementation trials with other micronutrients. There is a theoretical basis to consider potassium, manganese, thiamin and copper as other micronutrients besides zinc, vitamin A and iron as being growth-limiting nutrients in populations. However it is possible that these nutrients are more often consumed in adequate quantities and/or that there is a lack of information available on the occurrence of these deficiencies in populations.

    Multiple micronutrients To date, limited information is available on the effects of multiple-micronutrient supplementation on growth. For the purpose of this review, multiple-micronutrient supplements were considered to be those that contained at least iron, zinc and a form of vitamin A. Five placebo-controlled trials of supplementation with multiple micronutrients were identified and are summarized in Table 2. Two of these studies were published in peer-reviewed journals, two were published abstracts and another was submitted recently to a journal for peer review. The studies were conducted in Botswana, Tanzania, Guatemala, Mexico and Vietnam. The studies in Botswana and Tanzania were conducted among schoolchildren, whereas the others included infants and preschoolers aged between 6 and 30 mo.

The two African trials provided schoolchildren with beverages with or without multiple-micronutrient mixtures. In the study in Botswana (55), schools were randomized to receive either the fortified or the nonfortified beverage, where seven servings (100 kcal) of the beverage were provided 5 d/wk. The fortified beverage contained varying proportions of RDA for four minerals and eight vitamins. This treatment was provided for 8 wk, and change in weight, but not height, was included as a growth outcome. The children receiving the fortified beverage gained significantly more weight than those receiving the unfortified beverage. The trial conducted in Tanzania reported various outcomes of a similarly designed trial in a series of abstracts (56,57,58). The fortified or nonfortified beverages contained 30–120% of the RDA for three minerals and seven vitamins and were provided on school days for a period of 6 mo. High prevalences of anemia and severe vitamin A deficiency were reported at baseline in this population (56). Children who received the fortified beverage had significantly greater weight and height increments over the study period (58) and a reduced risk of stunting (57) compared to children who received the nonfortified beverage.

Another study worth noting is one conducted among low-income, Chinese schoolchildren aged 6–9 y (59), which looked at the effects of daily supplementation with zinc (20 mg) versus multiple micronutrients (half of the RDA for seven minerals and 10 vitamins and one-quarter of the RDA for folate) with and without zinc for 10 wk. A placebo group was not included, iron was not included in the multiple-micronutrient treatment and only knee height was reported as a growth outcome. The differences in knee height among groups were reported to be statistically significant (p < 0.01), and the largest growth increments occurred in the zinc + micronutrients groups, followed by the group of micronutrients alone and finally, the group of zinc alone. These results suggest that micronutrients other than zinc were limiting bone growth in the study population.

In summary, of the five trials examined, four demonstrated a positive growth response to multiple-micronutrient supplementation. The positive growth response found in the two studies conducted among infants and preschool children was significant only among certain subgroups of children (i.e. those under 12 mo of age in Mexico and those initially stunted in Vietnam). The effect size for change in linear growth in the subgroups for which positive responses were found in these studies (Mexico, 0.29; Vietnam, daily 0.48, weekly 0.37) was in the range of that found in the meta-analysis of zinc supplementation for initially stunted children. The abstract reported from Guatemala did not report specifically on effects among possible vulnerable subgroups of children, but suggested that these factors were controlled for in the analysis.

It is not possible to determine which micronutrients in these studies were limiting to growth, and clearly, this would depend on the existence and severity of various micronutrient deficiencies. Based on the results of the meta-analysis of zinc supplementation on growth, it is clear that zinc is a common growth-limiting nutrient. The conclusions of the single-micronutrient trials confirm that zinc deficiency and severe iron and vitamin A deficiencies are causal to growth retardation. However, the study conducted among schoolchildren in China (59) and others (60) suggest that zinc alone was not the primary growth-limiting nutrient. It is possible that micronutrient deficiencies other than zinc, iron and vitamin A also cause growth faltering as the latter studies did not select for anemia or severe vitamin A deficiency.

Supplementation and/or nutrition education trials including foods of animal origin and their influence on child growth

Perhaps the main question to be asked by the review in this section is whether animal source foods can be used to provide additional micronutrients sufficient to prevent or limit growth faltering in children living in high-risk environments. Very few studies have been designed to answer this question directly. Several studies have used interventions that included increased intake of animal source foods. However, the intervention designs varied greatly and most included components other than provision of animal source foods, such as additional micronutrients or nutrition education, to improve young child feeding practices. The studies included in this review are randomized intervention trials with a concurrently enrolled control group and they lasted at least 8 wk.

    Food supplements containing animal source foods plus additional micronutrients Two studies were identified that provided food supplements plus additional micronutrients in the intervention (2,61). One study was conducted in Guatemala, where four villages received either a skim milk–based, high-protein, high-energy supplement (atole) or a no-protein, low-energy supplement (fresco), where both supplements contained additional micronutrients (2,62). The supplements were distributed in a central location in each village and were available on demand to all members of the community. Intake of the supplements was registered daily for all children under 7 y of age. Supplementation with atole resulted in 2.45 ± 0.10 cm greater length at 3 y of age than in the group receiving fresco. In Colombia, women in their first trimester of pregnancy living in an urban area were selected from low income families in which 50% of the children under 5 y of age in the family had a weight-for-age that was >85% of the Colombian standards (61). Mothers were followed through pregnancy and infants resulting from that pregnancy were followed for 3 y. The families were randomly assigned to receive either no supplement or food supplements consisting of dry skim milk, enriched bread and vegetable oil, plus iron and vitamin A supplementation for the enrolled children. At 3 mo, a difference in weight of 197 g in favor of the supplemented group and at 6 mo a difference in length of 0.9 cm were documented. By 36 mo, the supplemented group had a mean weight that was 476 g (p < 0.05) higher and a mean length that was 2.2 cm (p < 0.005) greater than the control group. Among unsupplemented children, diarrhea was significantly negatively associated with length; however, supplementation completely offset the negative effect of diarrheal disease on growth.

Two other studies that provided food supplements containing animal source foods plus additional micronutrients were identified. Although these did not meet the criteria for inclusion in the review, their results are worth mentioning. A study conducted in a peri-urban area in Guinea-Bissau aimed to determine the effects of a dietary supplement (millet gruel with egg, milk powder, banana, margarine and sugar) plus micronutrients given to children <3 y of age with diarrhea (n = 120) versus the children's typical diet. The supplement was given during the diarrheal episode and for 1 wk during convalescence (63). Although the intervention was administered for a median of only 17 d, the children's growth response was monitored for a median of 6.6 mo. The treatment group had a weight gain exceeding that of the control group by 61.5 g/wk during the intervention period and by 12.5 g/wk during follow-up. Not surprisingly, there was no significant increase in knee-heel height during the intervention period. However, it was significantly greater in the treatment group (7.5 mm/y, p < 0.0001) after the follow-up. Another study was conducted among Ghanaian infants to evaluate the effect of feeding centrally produced infant cereals of varying nutritional composition on nutritional status (64). Unfortunately, it was not possible to include a concurrently enrolled control group, so a separate cross-sectional study was used as a comparison. Breastfed infants received one of the following porridges: a cereal-legume blend (Weanimix), Weanimix + vitamins and minerals, Weanimix + fish powder or koko (a traditionally used fermented maize porridge) + fish powder. No differences were observed in length or weight among the four intervention groups. However, LAZ and WAZ among all of the supplemented infants (pooled) were greater than among those in the cross-sectional study group. It is possible that all of the supplemental food types tested were equally sufficient to increase the intake of growth-limiting nutrients. However, the authors also suggested that the provision of the hygienically prepared supplemental foods in vacuum flasks may have reduced exposure to diarrheal pathogens and that more prompt use of clinic facilities may have been encouraged indirectly due to frequent morbidity monitoring during the intervention. It was not possible to assess the contribution of decreased morbidity rates to the apparently improved growth among the supplemented children.

The three controlled trials described above produced positive effects on growth, and two of the studies (61,63) suggested that the growth impact was at least partially mediated through attenuation of the negative effects of diarrheal morbidity on growth. The main difference between these studies and those that provided micronutrient supplements alone is that these trials also included supplementary energy and protein, which also may be limiting to growth and may contribute to improved catch-up during convalescence. As both food supplements and micronutrients were provided simultaneously in the intervention, it is not possible to ascertain whether the nutritious food supplement alone could produce similar benefits without the provision of additional micronutrients.

    Nutrition education interventions that included increased intake of animal source foods Two studies conducted nutrition education interventions that included a component to increase the intake of animal source foods. A year-long intervention was conducted in China that assessed the impact of nutrition education and growth monitoring activities on growth among children from their first year of life (65). The educational component included specific messages to encourage exclusive breastfeeding for 4–6 mo, after which time, hard-boiled egg yolk should be offered to the infant daily. It was reported that more women in the intervention group could cite important foods to include in the complementary diet and appropriate patterns of breastfeeding, and more children in the intervention group received egg yolk daily. Infants in the intervention group had significantly better growth in weight and length than the control group. (WAZ: -1.17 vs. -1.93, p = 0.004; HAZ: -1.32 vs. -1.96, p = 0.002). The increase in intake of egg yolk by young children may have contributed to increased intake of growth-limiting nutrients in this population. However, it cannot be determined to what extent this, or the other intervention activities, contributed to the greater growth observed.

An intervention conducted in India offered a milk- and cereal-based supplement plus nutrition counseling, or visitation only, for 8 mo among infants recruited at 4 mo of age (66). Children receiving the supplement had a weight increment 0.25 kg greater than that of the control group, but no change in length was observed. However, children in the intervention group also had higher rates of diarrhea and were breastfed less frequently than the control children. In this case, the increased diarrheal infections may have been caused by use of contaminated water needed to dilute the food supplement and possibly by the displacement of breast milk. This study suggests that, in addition to providing increased nutritional intake, simultaneous interventions to improve water quality also may be needed to achieve more effective prevention of morbidity and associated growth faltering.

    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 formula without additional micronutrients, three of which were conducted in the same population group. Malcolm (67) reported results of two food-supplementation trials conducted among children in a boarding school in Bundi, New Guinea. The first study compared changes in height, weight and skinfold thickness between two classes of children receiving their regular diet of 3 meals daily of taro and sweet potato (tubers) or a skim milk powder supplement providing 25 g of protein daily for 5 mo. The schoolchildren receiving the supplement demonstrated significantly greater gains in height (+2.42 cm) and weight (+0.73 kg) compared to the control class (+1.18 cm, p < 0.001 and –0.13 kg, p < 0.01). The second study used a similar design to compare growth response of the schoolchildren to supplemental skim milk powder (270 kcal/d), margarine (270 kcal/d) or two additional meals of taro and sweet potato daily, each provided 5 d/wk for 13 wks. The skim milk–supplemented group demonstrated the largest height and weight increases (+2.32 cm, +1.21 kg) relative to the control group (+1.10 cm, +0.50 kg). Only a small increase in weight (+1.05 kg) occurred in the margarine-supplemented group but skinfolds increased substantially in this group compared to controls. The additional taro and sweet potato resulted in a small increase in height (+1.54 cm) relative to controls. Because the children's normal diet was based almost exclusively on tubers with relatively low protein content, it was hypothesized that protein was limiting to the growth of these children. These results are consistent with protein, or other growth-limiting nutrients in milk, being limiting to the accrual of lean tissues, whereas additional energy provided as fat apparently contributed to fat accumulation. These results were corroborated by a later trial conducted in the same area where children receiving a skim milk powder supplement also demonstrated improvements in indices of skeletal development (68). Walker et al. (69) conducted a randomized intervention trial in Jamaica where a milk-based formula was provided for 1 y to children (9–24 mo) who were initially stunted, and their growth was compared to age- and sex-matched stunted controls who received no food supplement. Supplemented children gained an additional 0.9 cm and 0.31 kg more than that of control children during the first 6 mo of the study, whereas no further benefit was observed in the latter half of the study. It was noted that the gains in growth were greater among younger children than they were among older children. Based on the results of these three trials, it appears that milk supplements may provide a good source of nutrients that are limiting to growth in some settings, although the specific growth-limiting nutrients were not identified.

It is difficult to summarize interventions studying the efficacy of supplementary animal source foods on prevention of growth faltering because of the many different study designs used and because most of the interventions included other components that may have contributed to the effects observed. The only examples of animal source foods solely contributing to growth promotion are the trials that provided milk supplements alone: all four trials produced positive effects on growth; however, it is not possible to determine what specific micro- or macronutrients contributed to the growth response. It also is unclear to what extent additional micronutrients would have provided further benefits to growth. In any case, all of the trials that included food supplements, with or without additional micronutrients, reported positive impacts on growth.

Conclusions

The essential role for several micronutrients in growth has been demonstrated clearly by both animal- and clinical-based human trials of supplementation with single micronutrients. The three micronutrients with the strongest relationship to growth, iron, zinc and vitamin A, are commonly deficient in low-income populations where dietary quality often is poor. The positive impact of community-based supplementation trials reviewed in this article indeed confirms that iron, zinc and vitamin A are common growth-limiting nutrients. However, iron and vitamin A appear to be limiting to growth only when deficiencies of these nutrients are severe, whereas growth may be limited only by mild to moderate deficiency of zinc. This is consistent with the known metabolic and physiologic activity of these nutrients: zinc has direct effects on the primary hormonal system (IGF-I/GH) that controls growth in the postnatal phase when the majority of stunting occurs. On the other hand, iron and vitamin A do not appear to influence this system directly, but more likely exert their effects on growth when their functional stores have been depleted and/or when deficiencies of these nutrients result in increased morbidity, which in turn contributes to growth faltering. Although single-micronutrient supplementation trials have been useful to confirm the effects of specific micronutrients on growth outcomes, programs that provide supplements of only one nutrient may not be the most cost-effective way of preventing growth faltering and associated adverse health outcomes because of the co-existence of multiple-micronutrient deficiencies in many populations.

Multiple-micronutrient supplements are expected to be more efficacious in preventing growth faltering in at-risk populations, as all possible growth-limiting micronutrient deficiencies may be corrected simultaneously. Although the few available multiple-micronutrient supplementation trials have demonstrated positive effects on growth, in some cases these effects were limited to specific subgroups of the study population. Also, the interaction of various micronutrients and the potential negative effect of some minerals on the absorption of others (e.g., iron, zinc and copper, calcium) when combined in a single supplement requires further assessment.

From a programmatic perspective, it may be more desirable to consider intervention options other than supplement use. Food-based interventions may have several advantages, including the provision of additional nutrients in a familiar form that can be integrated with the usual diet and the provision of an additional source of energy and high-quality protein, which also have direct effects on the IGF-I/GH hormone system (70). Animal source foods provide the richest and most bioavailable sources of several micronutrients. Some of the food-based trials have demonstrated that at least part of the positive effects of the intervention on growth occurred by improving catch-up growth after diarrheal illness (61,63). Although it is conceivable that the additional micronutrients (provided by the pharmacological supplements or animal source food) supported catch-up growth during convalescence, the supplemental foods also would have provided additional energy and protein, which may contribute to improved growth in the face of frequent infections (71,72).

Unfortunately, very few studies have been reported that confirm the evidence from cross-sectional studies suggesting that intake of animal source foods is associated with better growth in children. Several intervention studies have included both food supplements and additional multiple micronutrients, but it remains uncertain as to whether the supplemental food source alone could have been equally effective at preventing growth faltering. The few interventions that provided animal source foods alone were restricted to those that provided milk powder. Although milk powder may provide some additional micronutrients, it is not as good a source of readily available iron and zinc or of vitamin A, as compared to beef for example. Most of the studies that reported positive effects of milk-powder supplementation were conducted in Papua, New Guinea, where protein was likely to be a major growth-limiting nutrient in this population because low-protein tubers are the main staple food. However, in many populations where protein intakes are sufficient, such as those that rely on cereal grains, milk powder may not be as effective in preventing growth faltering. Clearly, more studies are needed to determine the efficacy of different animal source foods, including meat and fish, in a variety of geographical settings.

With respect to program development, it would be useful to compare directly the relative impact of micronutrients and nutritious food supplements in the prevention of growth faltering. If food supplements prove to be comparably effective for many children in a particular setting, greater confidence may be placed in the efficacy of food-based approaches, thus providing another feasible option. A useful study design to determine whether micronutrients from animal source foods can improve growth relative to pharmacological micronutrients alone would be to employ a four-cell design with an animal source food, micronutrients alone, an animal source food supplement plus additional micronutrients and a parallel control group.

	FOOTNOTES

 
¹ Presented at the conference "Animal Source Foods and Nutrition in Developing Countries" held in Washington, D.C. June 24–26, 2002. The conference was organized by the International Nutrition Program, UC Davis and was sponsored by Global Livestock-CRSP, UC Davis through USAID grant number PCE-G-00-98-00036-00. The supplement publication was supported by Food and Agriculture Organization, Land O'Lakes Inc., Heifer International, Pond Dynamics and Aquaculture-CRSP. The proceedings of this conference are published as a supplement to The Journal of Nutrition. Guest editors for this supplement publication were Montague Demment and Lindsay Allen.

³ Abbreviations used: GH, growth hormone; IGF-I, insulin-like growth factor I; HAZ, height-for-age Z-score; WAZ, weight-for-age Z-score; WHZ, weight-for-height Z-score; RDA, Recommended Daily Allowance.

	LITERATURE CITED

TOP ABSTRACT METHODS RESULTS AND DISCUSSION LITERATURE CITED

 

1. de Onís, M. (2000) Measuring nutritional status in relation to mortality. Bull. World Health Organization. 78: 1271–1274.

2. Martorell, R. (1995) Results and implications of the INC AP follow-up study. J. Nutr. 125: 1127S–1138S.

3. Mora, J. O., Herrera, M. G., Suescun, J., de Navarro, L. & Wagner, M. (1981) The effects of nutritional supplementation on physical growth of children at risk of malnutrition. Am. J. Clin. Nutr. 34: 1885–1892.[Free Full Text]

4. Rivera, J. & Martorell, R. (1988) Nutrition, infection and growth. Part I: Effects of infection on growth. Clin. Nutr. 7: 156–162.

5. Habicht, J. P., Martorell, R. & Rivera, J. A. (1995) Nutritional impact of supplementation in the INCAP longitudinal study: analytic strategies and inferences. J. Nutr. 125: 1042S–1050S.

6. Allen, L. H. (1994) Nutritional influences on linear growth: a general review. Eur. J. Clin. Nutr. 48: S75–S89.

7. Gibson, R. S. & Hotz, C. (2001) Nutritional causes of linear growth faltering in infants during the complementary feeding period. In: Nutrition and Growth. Nestle Nutrition Workshop Series No. 47 (Martorell, R. & Haschke, F., eds.), pp. 159–192. Nestec Inc, Vevey/Lippincott, Williams & Wilkins, Philadelphia, PA.

8. Brown, K. H., Peerson, J. M., Rivera, J. & Allen, L. H. (2002) Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 75: 1062–1071.[Abstract/Free Full Text]

9. ACC/SCN. (2000) Fourth Report on the World Nutrition Situation. ACC/SCN & IFPRI, Geneva, Switzerland.

10. Brown, K. H., Wuehler, S. E. & Peerson, J. M. (2001) The importance of zinc in human nutrition and estimation of the global prevalence of zinc deficiency. Food Nutr. Bull. 22: 113–125.

11. Loveridge, N. & Noble, B. S. (1994) Control of longitudinal growth: the role of nutrition. Eur. J. Clin. Nutr. 48: 75–84.[Medline]

12. Estívariz, C. F. & Ziegler, T. R. (1997) Nutrition and the insulin-like growth factor system. Endocrine 7: 65–71.[Medline]

13. Dorup, I. & Clausen, T. (1991) Effects of magnesium and zinc deficiencies on growth and protein synthesis in skeletal muscle and the heart. Br. J. Nutr. 66: 493–504.[Medline]

14. Nishi, Y. (1996) Zinc and growth. J. Am. Coll. Nutr. 15: 340–344.[Abstract]

15. Clausen, T. & Dorup, I. (1998) Micronutrients, minerals and growth control. Bibl. Nutr. Dieta 54: 84–92.

16. Abrams, S. A. (2002) Nutritional rickets: An old disease returns. Nutr. Rev. 60: 111–115.[Medline]

17. McCollum, E. V. & Davis, M. (1915) The essential factors in the diet during growth. J. Biol. Chem. 23: 231–254.[Free Full Text]

18. Orr, J. B. & Richards, M. B. (1934) Growth and vitamin A deficiency. Biochem. J. 28: 1259–1273.

19. Lamb, A. J., Apiwatanaporn, P. & Olsen, J. A. (1974) Induction of rapid, synchronous vitamin A deficiency in the rat. J. Nutr. 104: 1140–1148.

20. Anzano, M. A., Lamb, A. J. & Olsen, J. A. (1979) Growth, appetite, sequence of pathological signs and survival following the induction of rapid, synchronous vitamin A deficiency in the rat. J. Nutr. 109: 1419–1431.

21. Agarwal, D. K., Pandey, C. M. & Agarwal, K. N. (1994) Vitamin A administration and preschool child mortality. In: Two Decades of Progress: Linking Knowledge to Action. XVI International Vitamin A Consultative Group Meeting. Oct 24–28, 1994. Chiang Rai, Thailand.

22. Judisch, J. M., Naima, J. L. & Oski, F. A. (1966) The fallacy of the fat iron deficient child. Pediatrics. 37: 987–990.[Abstract/Free Full Text]

23. Lawless, J. W., Latham, M. C., Stephenson, L. S., Kinoti, S. N. & Pertet, A. M. (1994) Iron supplementation improves appetite and growth in anemic Kenyan primary school children. J. Nutr. 124: 645–654.

24. Calloway, D., Murphy, S., Balderson, J., Receveur, O., Lein, D. & Hudes, M. (1992) Village Nutrition in Egypt, Kenya and Mexico: Looking across the CRSP projects. Final report to the U.S. Agency for International Development. Cooperative Agreement # DAN 1309-A-00–9090–00, April 1992. University of California, Berkeley, CA.

25. Chusilp, K., Somnasang, P., Kirdpon, W., Wongkham, S., Sribonlue, P., Mahaverawat, U., Yongvanit, P., Sawakontha, S. & Waterlow, J. (1992) Observations on the development of stunting in children of the Khon Kaen region of Thailand. Eur. J. Clin. Nutr. 46: 475–488.[Medline]

26. Rivera, J. A., González-Cossío, T., Flores, M., Romero, M., Rivera, M., Téllez-Rojo, M. M., Rosado, J. L. & Brown, K. H. (2001) Multiple micronutrient supplementation increases the growth of Mexican children. Am. J. Clin. Nutr. 74: 657–663.[Abstract/Free Full Text]

27. Allen, L. H., Backstrand, J. R., Stanek, E. J., Pelto, G. H., Chávez, A., Molina, E., Castillo, J. B. & Mata, A. (1992) The interactive effects of dietary quality on the growth and attained size of young Mexican children. Am. J. Clin. Nutr. 56: 353–364.[Abstract/Free Full Text]

28. Marquis, G. S., Habicht, J. P., Lanata, C. F., Black, R. E. & Rasmussen, K. M. (1997) Breast-milk or animal-product foods improve linear growth of Peruvian toddlers consuming marginal diets. Am. J. Clin. Nutr. 66: 1102–1109.[Abstract/Free Full Text]

29. Dijkhuizen, M. A., Wieringa, F. T., West, C. E., Martuti, S. & Muhilal (2001) Effects of iron and zinc supplementation in Indonesian infants on micronutrient status and growth. J. Nutr. 131: 2860–2865.[Abstract/Free Full Text]

30. Aukett, M. A., Parks, Y. A., Scott, P. H. & Wharton, B. A. (1986) Treatment with iron increases weight gain and psychomotor development. Arch. Dis. Child. 61: 849–857.[Abstract]

31. Chwang, L. C., Soemantri, A. G. & Pollitt, E. (1988) Iron supplementation and physical growth of rural Indonesian children. Am. J. Clin. Nutr. 47: 496–501.[Abstract/Free Full Text]

32. Angeles, I. T., Schultink, W. J., Matulessi, P., Gross, R. & Sastroamidjojo, S. (1993) Decreased rate of stunting among anemic Indonesian preschool children through iron supplementation. Am. J. Clin. Nutr. 58: 339–342.[Abstract/Free Full Text]

33. Latham, M. C., Stephenson, L. S., Kinoti, S. N., Zaman, M. S. & Kurz, K. M. (1990) Improvements in growth following iron supplementation in young Kenyan children. Nutrition 6: 159–165.[Medline]

34. Rosado, J. L., López, P., Muñoz, E., Martinez, H. & Allen, L. H. (1997) Zinc supplementation reduced morbidity, but neither zinc nor iron supplementation affected growth or body composition of Mexican preschoolers. Am. J. Clin. Nutr. 65: 13–19.[Abstract/Free Full Text]

35. Dossa, R. A., Ategbo, E. A., de Koning, F. L., van Raaij, J. M. & Hautvast, J. G. (2001) Impact of iron supplementation and deworming on growth performance in preschool Beninese children. Eur. J. Clin. Nutr. 55: 223–228.[Medline]

36. Idjradinata, P., Watkins, W. E. & Pollitt, E. (1994) Adverse effects of iron supplementation on weight gain of iron-replete young children. Lancet 343: 1252–1254.[Medline]

37. Rahman, M. M., Akramuzzaman, S. M., Mitra, A. K., Fuchs, G. J. & Mahalanabis, D. (1999) Long-term supplementation with iron does not enhance growth in malnourished Bangladeshi children. J. Nutr. 129: 1319–1322.[Abstract/Free Full Text]

38. Aguayo, V. M. (2000) School-administered weekly iron supplementation: Effect on the growth and hemoglobin status on non-anemic Bolivian school-age children. A randomized placebo-controlled trial. Eur. J. Nutr. 39: 263–269.[Medline]

39. Ramakrishnan, U. & Martorell, R. (1998) The role of vitamin A in reducing child mortality and morbidity and improving growth. Salud Publica Mex. 40: 189–198.[Medline]

40. Muhilal, A., Permeisih, D., Idradinata, Y. R., Muherdiyantiningsih & Karyadi, D. (1988) Impact of vitamin A-fortified monosodium glutamate on health, growth and survival of children: A controlled field trial. Am. J. Clin. Nutr. 48: 1271–1276.[Abstract/Free Full Text]

41. Rahamtullah, L., Underwood, B. A., Thulasiraj, R. D. & Milton, R. C. (1991) Diarrhea, respiratory infections and growth are not affected by a weekly low-dose vitamin A supplement: A masked controlled field trial in children in Southern India. Am. J. Clin. Nutr. 54: 568–577.[Abstract/Free Full Text]

42. Lie, C., Ying, C., En-Lin, W., Brun, T. & Geissler, C. (1993) Impact of large dose vitamin A supplementation on childhood diarrhea, respiratory disease and growth. Eur. J. Clin. Nutr. 47: 88–96.[Medline]

43. Ndossi, G. D. (1992) The Impact of Vitamin A Supplementation in Preschool Children in Iringa, Tanzania. Doctoral thesis, Cornell University, Ithaca, NY .

44. Ramakrishnan, U., Latham, M. C., Abel, R. & Frongillo, E. A., Jr. (1995) Vitamin A supplementation and morbidity among preschool children in South India. Am. J. Clin. Nutr. 61: 1295–1303.[Abstract/Free Full Text]

45. Kirkwood, B. R., Ross, D. A., Arthur, P., Morris, S. S., Dollimore, N., Binka, F. N., Shier, R. P., Gyapong, J. O., Addy, H. A. & Smith, P. G. (1996) Effect of vitamin A supplementation on the growth of young children in northern Ghana. Am. J. Clin. Nutr. 63: 773–781.[Abstract/Free Full Text]

46. West, K. P., Jr., Djunaedi, E., Pandji, A., Kusdiono, Tarwotjo, I. & Sommer, A. (1988) Vitamin A supplementation and growth: A randomized community trial. Am. J. Clin. Nutr. 48: 1257–1264.[Abstract/Free Full Text]

47. West, K. P., Jr., LeClerq, S. C., Wu, L. S., Katz, J. & Khatry, S. K. (1997) Can vitamin A be expected to improve child growth. FASEB J. 11: 140 (abs).

48. Bahl, R., Bhandari, N., Taneja, S. & Bhan, M. K. (1997) The impact of vitamin A supplementation on physical growth of children is dependent on season. Eur. J. Clin. Nutr. 51: 26–29.[Medline]

49. Hadi, H., Stoltzfus, J., Dibley, M. J., Moulton, L. H., West, K. P., Jr., Kjolhede, C. L. & Sadjimin, T. (2000) Vitamin A supplementation selectively improves the linear growth of Indonesian preschool children results from a randomized controlled trial. Am. J. Clin. Nutr. 71: 507–513.[Abstract/Free Full Text]

50. Fawzi, W. W., Herrera, G., Willett, W. C., Nestel, P., El Amin, A. & Mohamed, K. A. (1997) The effect of vitamin A supplementation on the growth of preschool children in the Sudan. Am. J. Public Health 87: 1359–1362.[Abstract/Free Full Text]

51. Villamor, E., Mbise, R., Spiegelman, D., Hertzmark, E., Fataki, M., Peterson, K. E., Ndossi, G. & Fawzi, W. W. (2002) Vitamin A supplements ameliorate the adverse effect of HIV-1, malaria, and diarrheal infections on child growth. Pediatrics 109: 1–10.[Abstract/Free Full Text]

52. Donnen, P., Brasseur, D., Dramaix, M., Vertongen, F., Zihindula, M., Muhamiriza, M. & Hennart, P. (1998) Vitamin A supplementation but not deworming improves growth of malnourished preschool children in Eastern Zaire. J. Nutr. 128: 1320–1327.[Abstract/Free Full Text]

53. Thu, B., Schultink, W., Dillon, D., Gross, R., Leswara, N. D. & Khoi, H. H. (1999) Effect of daily and weekly micronutrient supplementation on micronutrient deficiencies and growth in young Vietnamese children. Am. J. Clin. Nutr. 69: 80–86.[Abstract/Free Full Text]

54. Brown, K. H., Santizo, M. C., Begín, F. & Torún, B. (2000) Effect of supplementation with multiple micronutrient (MMN) and/or bovine serum concentrate (BSC) on the growth of low-income, peri-urban Guatemalan infants and young children. FASEB J. 371: 1 (abs.).

55. Abrams, S. A., Mushi, A., Hilmers, D. C., Griffin, I. J., Davila, P. & Allen, L. (2003) A multinutrient-fortified beverage enhances the nutritional status of children in Botswana. J. Nutr. 133: 1834–1840.

56. Ash, D. M., Tatala, S. R., Frongillo, E. A., Jr., Ndossi, G. D. & Latham, M. C. (1998) Effect of a micronutrient fortified beverage on anemia and stunting in Tanzanian schoolchildren. FASEB J. 12: 3768.

57. Ash, D. M., Tatala, S. R., Frongillo, E. A., Jr., Ndossi, G. D., Mehansho, H. & Latham, M. C. (1999) Trial of a micronutrient dietary supplement to control vitamin A, iron and iodine deficiencies in Tanzania. FASEB J. 13: 190.

58. Latham, M. C., Ash, D. M., Tatala, S. R., Ndossi, G. D., Mehansho, H. & Frongillo, E. A., Jr. (1998) Impact of a micronutrient dietary supplement on growth of school children in Tanzania. FASEB J. 12: 3769.

59. Sanstead, H. H., Penland, J. G., Alock, L. W., Dayal, H. H., Chen, X. C., Li, J. S., Zhao, F. & Yang, J. J. (2000) Effects of repletion with zinc and other micronurients on neuropsychologic performance and growth of Chinese children. Am. J. Clin. Nutr. 68: 470S–475S.

60. Ronaghy, H. A., Reinhold, J. G., Mahloudji, M., Ghavami, P., Fox, M. R. & Halsted, J. A. (1974) Zinc supplementation of malnourished schoolboys in Iran: increased growth and other effects. Am. J. Clin. Nutr. 27: 112–121.[Abstract]

61. Lutter, C. K., Mora, J. O., Habicht, J.-P., Rasmussen, K. M., Robson, D. S., Sellers, S. G., Super, C. M. & Herrera, M. G. (1989) Nutritional supplementation: effects on child stunting because of diarrhea. Am. J. Clin. Nutr. 50: 1–8.[Abstract/Free Full Text]

62. Rivera, J. A., Habicht, J. P. & Robson, D. S. (1991) Effect of supplementary feeding on recovery from mild-to moderate wasting in preschool children. Am. J. Clin. Nutr. 54: 62–68.[Abstract/Free Full Text]

63. Valentiner-Branth, P., Steinsland, H., Santos, G., Perch, M., Begtrup, K., Bhan, M. K., Dias, F., Aaby, P., Sommerfelt, H. & Mølbak, K. (2001) Community-based controlled trial of dietary management of children with persistent diarrhea: sustained beneficial effect on ponderal and linear growth. Am. J. Clin. Nutr. 73: 968–974.[Abstract/Free Full Text]

64. Lartey, A., Manu, A., Brown, K. H., Peerson, J. M. & Dewey, K. G. (1999) A randomized, community-based trial of the effects of improved, centrally processed complementary foods on growth and micronutrient status of Ghanaian infants from 6 to 12 months of age. Am. J. Clin. Nutr. 70: 391–404.[Abstract/Free Full Text]

65. Guldan, G. S., Fan, H.-C., Ma, X., Ni, Z.-Z., Xiang, X. & Tang, M. Z. (2000) Culturally appropriate nutrition education improves infant feeding and growth in rural Sichuan, China. J. Nutr. 130: 1204–1211.

66. Bhandari, N., Bahl, R., Nayyar, B., Khokhar, P., Rohde, J. E. & Bhan, M. K. (2001) Food supplementation with encouragement to feed it to infants from 4 to 12 months of age has a small impact on weight gain. J. Nutr. 131: 1879–1880.[Free Full Text]

67. Malcolm, L. A. (1970) Growth retardation in a New Guinea boarding school and its response to supplementary feeding. Br. J. Nutr. 24: 297–305.[Medline]

68. Lampl, M., Johnston, F. E. & Malcolm, L. A. (1978) The effects of protein supplementation on the growth and skeletal maturation of New Guinean school children. Ann. Hum. Biol. 3: 219–227.

69. Walker, S. P., Powell, C. A., Grantham-McGregor, S. M., Himes, J. H. & Chang, S. M. (1991) Nutritional supplementation, psychosocial stimulation, and growth of stunted children: the Jamaican study. Am. J. Clin. Nutr. 54: 642–648.[Abstract/Free Full Text]

70. Root, A. W. (1990) Effects of undernutrition on skeletal development, maturation, and growth. In: Nutrition and Bone Development (Simmons, D. J., ed.), pp. 114–130. Oxford University Press, New York, NY.

71. Becker, S., Black, R. E. & Brown, K. H. (1991) Relative effects of diarrhea, fever, and dietary energy intake on weight gain in rural Bangladeshi children. Am. J. Clin. Nutr. 53: 1499–1503.[Abstract/Free Full Text]

72. Brown, K. H., Gastañaduy, A. S., Saavedra, J. M., Lembcke, J., Rivas, D., Robertson, A. D., Yolken, R. & Sack, R. B. (1998) Effect of continued oral feeding on clinical and nutritional outcomes of acute diarrhea in children. J. Pediatr. 112: 191–200.

This article has been cited by other articles:

				D. Moretti, M. B Zimmermann, S. Muthayya, P. Thankachan, T.-C. Lee, A. V Kurpad, and R. F Hurrell Extruded rice fortified with micronized ground ferric pyrophosphate reduces iron deficiency in Indian schoolchildren: a double-blind randomized controlled trial. Am. J. Clinical Nutrition, October 1, 2006; 84(4): 822 - 829. [Abstract] [Full Text] [PDF]

				D. Stifel and H. Alderman The "Glass of Milk" Subsidy Program and Malnutrition in Peru World Bank Econ. Rev., January 1, 2006; 20(3): 421 - 448. [Abstract] [Full Text] [PDF]

				L. E. King, J. W. Frentzel, J. J. Mann, and P. J. Fraker Chronic Zinc Deficiency in Mice Disrupted T Cell Lymphopoiesis and Erythropoiesis While B Cell Lymphopoiesis and Myelopoiesis Were Maintained J. Am. Coll. Nutr., December 1, 2005; 24(6): 494 - 502. [Abstract] [Full Text] [PDF]

				E. Villamor, E. Saathoff, R. J Bosch, E. Hertzmark, A. Baylin, K. Manji, G. Msamanga, D. J Hunter, and W. W Fawzi Vitamin supplementation of HIV-infected women improves postnatal child growth Am. J. Clinical Nutrition, April 1, 2005; 81(4): 880 - 888. [Abstract] [Full Text] [PDF]

				L. Allen and R. Shrimpton The International Research on Infant Supplementation Study: Implications for Programs and Further Research J. Nutr., March 1, 2005; 135(3): 666S - 669S. [Full Text] [PDF]

				C. Lopriore, Y. Guidoum, A. Briend, and F. Branca Spread fortified with vitamins and minerals induces catch-up growth and eradicates severe anemia in stunted refugee children aged 3-6 y Am. J. Clinical Nutrition, October 1, 2004; 80(4): 973 - 981. [Abstract] [Full Text] [PDF]

				U. Ramakrishnan, N. Aburto, G. McCabe, and R. Martorell Multimicronutrient Interventions but Not Vitamin A or Iron Interventions Alone Improve Child Growth: Results of 3 Meta-Analyses J. Nutr., October 1, 2004; 134(10): 2592 - 2602. [Abstract] [Full Text] [PDF]

				J. A. Rivera, D. Sotres-Alvarez, J.-P. Habicht, T. Shamah, and S. Villalpando Impact of the Mexican Program for Education, Health, and Nutrition (Progresa) on Rates of Growth and Anemia in Infants and Young Children: A Randomized Effectiveness Study JAMA, June 2, 2004; 291(21): 2563 - 2570. [Abstract] [Full Text] [PDF]

				M. W. Demment, M. M. Young, and R. L. Sensenig Providing Micronutrients through Food-Based Solutions: A Key to Human and National Development J. Nutr., November 1, 2003; 133(11): 3879S - 3885. [Abstract] [Full Text] [PDF]

M. T. Ruel Operationalizing Dietary Diversity: A Review of Measurement Issues and Research Priorities