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We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a global challenge; thus, to achieve goals for anemia reduction and assess progress, standardized approaches are required for the assessment of anemia and its causes. We first provide a brief review of how to assess anemia, based on hemoglobin concentrations and cutoffs that correspond to age, sex, and physiologic status. Next, we discuss how to assess the likely causes of anemia in different settings. The causes of anemia are classified as non-nutritional (for example, because of infection, inflammation, blood loss, or genetic disorders) or nutrition-specific (for example, because of deficiencies of iron, vitamin A, riboflavin, vitamin B12, or folate). There is an important overlap between these 2 categories, such as the increased likelihood of iron deficiency in the context of inflammation. Given the multifaceted nature of anemia etiology, we introduce a framework for anemia assessment based on the “ecology of anemia,” which recognizes its many overlapping causes. This conceptual framework is meant to inform what data on anemia causes may need to be collected in population surveys. The framework has a supporting table with information on the diagnostic tests, biomarkers and proposed cutoffs, characteristics, and feasibility of collecting the myriad information that can help elucidate the anemia etiology. We also provide examples of how this framework can be applied to interpret the anemia risk factor data from population-based surveys that can inform decisions about context-specific interventions. Finally, we present research gaps and priorities related to anemia assessment.

Growth faltering in children (low length for age or low weight for length) during the first 1,000 days of life (from conception to 2 years of age) influences short-term and long-term health and survival1,2. Interventions such as nutritional supplementation during pregnancy and the postnatal period could help prevent growth faltering, but programmatic action has been insufficient to eliminate the high burden of stunting and wasting in low- and middle-income countries. Identification of age windows and population subgroups on which to focus will benefit future preventive efforts. Here we use a population intervention effects analysis of 33 longitudinal cohorts (83,671 children, 662,763 measurements) and 30 separate exposures to show that improving maternal anthropometry and child condition at birth accounted for population increases in length-for-age z-scores of up to 0.40 and weight-for-length z-scores of up to 0.15 by 24 months of age. Boys had consistently higher risk of all forms of growth faltering than girls. Early postnatal growth faltering predisposed children to subsequent and persistent growth faltering. Children with multiple growth deficits exhibited higher mortality rates from birth to 2 years of age than children without growth deficits (hazard ratios 1.9 to 8.7). The importance of prenatal causes and severe consequences for children who experienced early growth faltering support a focus on pre-conception and pregnancy as a key opportunity for new preventive interventions.

Sustainable Development Goal 2.2—to end malnutrition by 2030—includes the elimination of child wasting, defined as a weight-for-length z-score that is more than two standard deviations below the median of the World Health Organization standards for child growth1. Prevailing methods to measure wasting rely on cross-sectional surveys that cannot measure onset, recovery and persistence—key features that inform preventive interventions and estimates of disease burden. Here we analyse 21 longitudinal cohorts and show that wasting is a highly dynamic process of onset and recovery, with incidence peaking between birth and 3 months. Many more children experience an episode of wasting at some point during their first 24 months than prevalent cases at a single point in time suggest. For example, at the age of 24 months, 5.6% of children were wasted, but by the same age (24 months), 29.2% of children had experienced at least one wasting episode and 10.0% had experienced two or more episodes. Children who were wasted before the age of 6 months had a faster recovery and shorter episodes than did children who were wasted at older ages; however, early wasting increased the risk of later growth faltering, including concurrent wasting and stunting (low length-for-age z-score), and thus increased the risk of mortality. In diverse populations with high seasonal rainfall, the population average weight-for-length z-score varied substantially (more than 0.5 zin some cohorts), with the lowest mean z-scores occurring during the rainiest months; this indicates that seasonally targeted interventions could be considered. Our results show the importance of establishing interventions to prevent wasting from birth to the age of 6 months, probably through improved maternal nutrition, to complement current programmes that focus on children aged 6–59 months.

Globally, 149 million children under 5 years of age are estimated to be stunted (length more than 2 standard deviations below international growth standards)1,2. Stunting, a form of linear growth faltering, increases the risk of illness, impaired cognitive development and mortality. Global stunting estimates rely on cross-sectional surveys, which cannot provide direct information about the timing of onset or persistence of growth faltering—a key consideration for defining critical windows to deliver preventive interventions. Here we completed a pooled analysis of longitudinal studies in low- and middle-income countries (n= 32 cohorts, 52,640 children, ages 0–24 months), allowing us to identify the typical age of onset of linear growth faltering and to investigate recurrent faltering in early life. The highest incidence of stunting onset occurred from birth to the age of 3 months, with substantially higher stunting at birth in South Asia. From 0 to 15 months, stunting reversal was rare; children who reversed their stunting status frequently relapsed, and relapse rates were substantially higher among children born stunted. Early onset and low reversal rates suggest that improving children’s linear growth will require life course interventions for women of childbearing age and a greater emphasis on interventions for children under 6 months of age.

Background: Zinc plays an important role in antioxidant defense and the maintenance of cellular DNA integrity. However, no experimental human studies have been performed to examine the role of zinc status on DNA damage. Objective: We evaluated the effects of dietary zinc depletion and repletion on DNA strand breaks, oxidative stress, and antioxidant defenses in healthy men. Design: Nine healthy men with reported mean daily zinc intakes > 11 mg/d were recruited. Subjects completed 3 consecutive dietary periods: baseline (days 1 to 13, 11 mg Zn/d), zinc depletion (days 14 to 55; 0.6 mg Zn/d for 1 wk and 4 mg Zn/d for 5 wk), and zinc repletion (days 56 to 83, 11 mg Zn/d for 4 wk with 20 mg supplemental Zn for first 7 d). Blood samples were collected on days l, 13, 35, 55, and 83. DNA damage in peripheral blood cells, plasma oxidative stress, and antioxidant defense biomarkers were assessed. Results: Dietary zinc depletion (6 wk) was associated with increased DNA strand breaks in peripheral blood cells (day 13 compared with day 55; P < 0.05), changes that were ameliorated by zinc repletion (day 55 compared with day 83; P < 0.05). Plasma zinc concentrations were negatively correlated with DNA strand breaks (r = -0.60, P = 0.006) during the zinc-depletion period. Plasma [alpha]- and [gamma]-tocopherol concentrations, plasma total antioxidant capacity, and erythrocyte superoxide dismutase activity did not change significantly, and plasma [F.sub.2]-isoprostanes were unaffected by dietary period. Conclusions: Changes in dietary zinc intake affected DNA single-strand breaks. Zinc appears to be a critical factor for maintaining DNA integrity in humans. Am J Clin Nutr 2009;90:321-8.

Background: Iron deficiency (ID) can occur among exclusively breastfed infants before 6 mo of age. Objective: The objective was to determine which subgroups of fully breastfed infants are at highest risk of ID. Design: We assessed the prevalence of ID (ferritin < 12 [micro]g/L) and iron deficiency anemia (IDA; ferritin < 12 [micro]g/L and hemoglobin < 105 g/L) and risk factors associated with ID and IDA at 6 mo among 404 fully breastfed infants with a birth weight >2500 g from 6 studies in Ghana, Honduras, Mexico, and Sweden. Infants with an elevated C-reactive protein concentration (8%) were excluded. Results: The percentages of infants with ID were 6% in Sweden, 17% in Mexico, 13-25% in Honduras, and 12-37% in Ghana. The percentages with IDA were 2% in Sweden, 4% in Mexico, 5-11% in Honduras, and 8-16% in Ghana. With data pooled, the key predictors of ID (20%) were male sex [adjusted odds ratio (AOR): 4.6; 95% CI: 2.5, 8.5] and birth weight 2500-2999 g (AOR: 2.4; 95% CI: 1.4, 4.3). The predictors of IDA (8%) were male sex (AOR: 7.6; 95% CI: 2.5, 23.0), birth weight of 2500-2999 g (AOR: 3.4; 1.5, 7.5), and weight gain above the median since birth (AOR: 3.4; 95% CI: 1.3, 8.6). The combination of birth weight 2500-2999 g or male sex had a sensitivity of 91% for identifying ID and of 97% for identifying IDA. Conclusions: Among fully breastfed infants with a birth weight >2500 g, IDA is uncommon before 6 mo, but male infants and those with a birth weight of 2500-2999 g are at higher risk of ID and IDA.

Background: Information is needed on the minimum energy density and feeding frequency of complementary foods that can provide adequate energy intakes (EIs) for healthy breastfed children. Objectives: The objectives of the study were to evaluate the effects of various energy densities and feeding frequencies of complementary foods on EI from these foods, breast milk consumption, and total EI from both sources. Design: During 9 separate, randomly ordered dietary periods lasting 3-6 d each, we measured intakes of food and breast milk by 18 healthy breastfed children 8-11 mo of age who, 3, 4, or 5 times/d, were fed porridge with a coded energy density of 0.5, 1.0, or 1.5 kcal/g. Food intake was measured by weighing the feeding bowl before and after meals, and breast milk intake was measured by test weighing. Results: The mean amounts of complementary foods consumed were inversely related to their energy density and positively related to the number of meals/d (P < 0.001 for both); EIs from foods were positively related to both factors. Breast milk intake decreased slightly but progressively, with greater energy density and feeding frequency of complementary foods; total EIs (kcal/d) increased in relation to both factors (P < 0.001 for both). Conclusions: The energy density and feeding frequency of complementary foods affect infants' total daily EI and breast milk consumption. Recommendations can be developed for the appropriate combinations of these dietary factors that are compatible with adequate EI, although longer-term effects of complementary feeding practices on breast milk intake and breasffeeding duration need further community-based studies.

Background: Efforts to develop global programs for the control of iron deficiency require simple, low-cost, and accurate indicators of iron status. Objective: We aimed to compare estimates of body iron (BI) stores, as calculated from either plasma ferritin concentration alone (BI-ferritin) or the ratio of plasma transferrin receptor (TfR) to ferritin (BI-TfR/ferritin). Design: Data were analyzed from 4 previously completed, randomized intervention trials that enrolled infants, schoolchildren, or pregnant women (total n = 1189, after excluding subjects with elevated C-reactive protein). Results: The correlation coefficients between BI-ferritin and BI-TfR/ferritin were >0.95 for all studies. The kappa index ranged from 0.5 to 1.0. All of the sensitivities of Bl-ferritin for identifying persons with low iron stores (defined as BI-TfR/ferritin < 0 mg/kg body wt) were >0.90. All of the specificities were >0.90 except the study of pregnant women (specificity = 0.66). The effect sizes of iron intervention trials were significantly greater for change in iron reserves estimated by BI-TfR/ferritin than by BI-ferritin in 2 studies with larger effect sizes (1.11 compared with 1.00 and 1.56 compared with 1.44, respectively; P < 0.05) and 1 study with medium effect size (0.70 compared with 0.57; P < 0.05). However, there were no significant differences between estimates of these effect sizes for 1 study with a medium effect size and 1 study with a smaller effect size (0.78 compared with 0.83 and 0.37 compared with 0.35, respectively; P > 0.2). Conclusion: Plasma ferritin concentration alone provides a good approximation of total BI reserves, as estimated by BI-TfR/ferritin, on the basis of high correlation, sensitivity, and specificity among nonpregnant persons with unelevated C-reactive protein.

Background: No studies have examined the independent effects of current and longer-term dietary zinc intakes on zinc absorption. Objective: We determined the effects of current compared with longer-term zinc intake on fractional zinc absorption (FZA). Design: We studied 9 men whose usual zinc intakes were > 11 mg/d. FZA was measured at baseline, depletion (0.6 mg Zn/d for 1 wk and 4 mg Zn/d for 5 wk), and repletion (11 mg Zn/d for 4 wk with 20 mg supplemental Zn/d for first 7 d). During 2 successive days after each dietary period, subjects consumed either adequate-zinc meals (11 mg Zn/d) with a zinc stable isotope tracer for 1 d, followed by low-zinc meals (4 mg Zn/d) with zinc tracer, or vice versa. Five days after oral dosing, a zinc tracer was infused intravenously. FZA was measured with the use of a modified double isotope tracer ratio method with urine samples collected on days 5-7 and 10-12 of absorption studies. Results: Plasma and urinary zinc did not vary by dietary period. Mean FZA was greater from low-zinc meals than from adequate-zinc meals (60.9% [+ or -] 13.8% compared with 36.1% [+ or -] 8.9%; P < 0.0001), whereas mean total absorbed zinc was greater from adequate-zinc meals than from low-zinc meals (3.60 [+ or -] 0.91 compared with 2.48 [+ or -] 0.56; P < 0.0001), regardless of the longer-term dietary period. Conclusions: FZA was inversely related to current zinc intake, but there was no detectable effect of longer-term dietary zinc. If longer-term zinc intake does modify FZA, such changes are smaller than those caused by current zinc intake, or they occur only after more severe zinc depletion.

Background: Micronutrient deficiencies are common during infancy, and optimal approaches for their prevention need to be identified. Objective: The objective was to compare the efficacy and acceptability of Sprinkles (SP), crushable Nutritabs (NT), and fat-based Nutributter (NB; 108 kcal/d), which provide 6, 16, and 19 vitamins and minerals, respectively, when used for home fortification of complementary foods. Design: Ghanaian infants were randomly assigned to receive SP (n = 105), NT (n = 105), or NB (n = 103) daily from 6 to 12 mo of age. We assessed dietary intake, morbidity, and compliance weekly. Hemoglobin and plasma ferritin, TfR, C-reactive protein, and zinc were measured at 6 and 12 mo. We used an exit interview to assess acceptability. A randomly selected control group of infants who received no intervention (NI; n = 96) were assessed at 12 mo. Results: All supplements were well accepted, and the mean percentage of days that supplements were consumed (87%) did not differ between groups. At 12 mo, all 3 intervention groups had significantly higher ferritin and lower TfR concentrations than did the NI control group. Mean ([+ or -] SD) hemoglobin was significantly higher in NT (112 [+ or -] 14 g/L) and NB (114 [+ or -] 14 g/L) but not in SP (110 [+ or -] 14 g/L) infants than in NI infants (106 [+ or -]14 g/L). The prevalence of iron deficiency anemia was 31% in the NI control group compared with 10% in the intervention groups combined (P < 0.0001). Conclusion: All 3 options for home fortification of complementary foods are effective for reducing the prevalence of iron deficiency in such populations.

Background: Multiple studies have shown the benefits of zinc supplementation among young children in high-risk populations. However, the optimal dose and safe upper level of zinc have not been determined. Objectives: The objectives of this study were to measure the effects of different doses of supplemental zinc on the plasma zinc concentration, morbidity, and growth of young children; to detect any adverse effects of 10 mg supplemental Zn on markers of copper or iron status; and to determine whether any adverse effects are alleviated by providing copper with zinc. Design: This randomized, double-masked, community-based intervention trial was conducted in 631 Ecuadorian children who were 12-30 mo old at baseline and who had initial length-for-age z scores < - 1.3. Children received 1 of 5 daily supplements for 6 mo: 3, 7, or 10 mg Zn as zinc sulfate, 10 mg Zn + 0.5 mg Cu as copper sulfate, or placebo. Results: The change in plasma zinc concentration from baseline was positively related to the zinc dose (P < 0.001). Zinc supplementation, including doses as low as 3 mg/d, reduced the incidence of diarrhea by 21-42% (P < 0.01). There were no other significant group-wise differences. Conclusions: Zinc supplementation with a dose as low as 3 mg/d increased plasma zinc concentrations and reduced diarrhea incidence in the study population. There were no observed adverse effects of 10 mg Zrdd on indicators of copper or iron status. The current tolerable upper level of zinc recommended by the Institute of Medicine should he reassessed for young children. KEY WORDS Zinc, copper, dose response, tolerable upper level, diarrhea, lipoprotein concentration, iron, growth response

Background: Leptin, ghrelin, and insulin are hormonal regulators of energy balance and, therefore, may be related to growth during infancy. Zinc is essential for growth, and its growth effects may be mediated through these hormones. Objective: We examined the effects of supplemental zinc on plasma leptin, ghrelin, and insulin concentrations among young children at risk of zinc deficiency and examined the relations between these hormones and physical growth. Design: Children (n = 142) aged 6-8 mo were randomly assigned to receive 3 mg Zn/d as a supplement, in a fortified food, or as a placebo for 6 mo. Relations between hormones and anthropometric z scores, body composition, and growth rates were examined at baseline and 3 and 6 mo after the start of the intervention. Results: No treatment group-related differences were found in plasma leptin, ghrelin, or glucose concentrations or in anthropometric z scores at 3 or 6 mo after the start of the zinc intervention. Neither plasma leptin nor ghrelin concentrations at baseline or 3 mo were predictive of subsequent changes in growth. However, changes in weight-for-age z scores over the two 3-mo time intervals were positively associated with subsequent leptin concentrations and inversely associated with subsequent plasma ghrelin concentrations. Conclusions: Supplemental zinc did not affect the children's growth, anthropometric indexes, or plasma hormone concentrations in this study population. Our results suggest that plasma leptin and ghrelin concentrations in later infancy are a consequence of previous weight changes rather than predictors of short-term growth. KEY WORDS Zinc, leptin, ghrelin, insulin, growth, infants

Background: The low micronutrient content of complementary foods is associated with growth faltering in many populations. A potential low-cost solution is the home fortification of complementary foods with Sprinkles (SP) powder, crushable Nutritabs (NT) tablets, or energy-dense (108 kcal/d), fat-based Nutributter (NB). Objective: The objective was to test the hypothesis that multiple micronutrients added to home-prepared complementary foods would increase growth and that the effect would be greatest in the presence of added energy from fat. Design: We randomly assigned 313 Ghanaian infants to receive SP, NT, or NB containing 6, 16, and 19 vitamins and minerals, respectively, daily from 6 to 12 mo of age. We assessed anthropometric status at 6, 9, and 12 mo; micronutrient status at 6 and 12 too; motor development at 12 too; and morbidity weekly. Infants (n = 96) not randomly selected for the intervention (nonintervention; NI) were assessed at 12 too. Results: The groups did not differ significantly at baseline, except that the NB group had a higher proportion of boys and weighed slightly more. The dropout rate (15/313) was low. At 12 mo, after control for initial size, the NB group had a significantly greater weight-for-age z score (WAZ) (-0.49 [+ or 1] 0.54) and length-for-age z score (LAZ) (-0.20 [+ or 1] 0.54) than did the NT group (WAZ: -0.67 [+ or 1] 0.54; LAZ: -0.39 [+ or 1] 0.54) and the NT and SP groups combined (WAZ: -0.65 [+ or 1] 0.54; LAZ: -0.38 [+ or 1] 0.54); the difference with the NI group (WAZ: -0.74 [+ or 1] 1.1; LAZ: -0.40 [+ or 1] 1.0) was not significant. A lower percentage of the NI infants (25%) than of the intervention groups (SP: 39%; NT: 36%; NB: 49%) could walk independently by 12 too. Conclusion: All 3 supplements had positive effects on motor milestone acquisition by 12 mo compared with no intervention, but only NB affected growth. Am J Clin Nutr 2007;86:412-20. KEY WORDS Multiple micronutrient supplements, home fortification, infant growth, motor development, Ghana

Background: Nightblindness affects 16-52% of pregnant women in areas of Nepal and in some cases persists after vitamin A treatment. Iron and riboflavin affect vitamin A utilization and photoreceptor function, respectively, and pilot data in the study population showed a high prevalence of iron and riboflavin deficiencies. Objective: The objective was to assess the effect of supplemental iron and riboflavin on pupillary threshold (PT) and plasma retinol in nightblind, pregnant Nepali women given vitamin A--fortified rice. Design: Nightblind pregnant women were randomly assigned to receive, 6 d/wk under supervision for 6 wk, a vitamin A--fortified rice curry dish providing 850 [micro]g retinal activity equivalents/d with either a 30-mg Fe and 6-mg riboflavin (FeR + VA) capsule or a placebo control (VA only) capsule. Hemoglobin, erythrocyte riboflavin, and plasma ferritin and retinol were measured before and after the intervention. Dark adaptation was assessed by PT score. Results: Women who were iron deficient at baseline (n = 38) had significantly greater improvement in PT score with iron and riboflavin supplementation than without (P = 0.05). Iron and riboflavin supplements significantly reduced the prevalences of riboflavin deficiency (from 60% to 6%; P < 0.0001), iron deficiency anemia (from 35% to 15%; P < 0.007), and abnormal PT (from 87% to 30%; P < 0.05) from baseline. Mean increases in erythrocyte riboflavin (P < 0.0001) and plasma ferritin (P = 0.0l) were greater in the FeR + VA group than in the VA only group. Conclusions: Iron deficiency may limit the efficacy of vitamin A to normalize dark adaptation in pregnant Nepali women. Further studies are needed to assess the effect of simultaneous delivery of iron and vitamin A for the treatment of nightblindness. KEY WORDS Pregnancy, impaired pupillary threshold, nightblindness, iron deficiency, riboflavin, women, Nepal

Background: Zinc supplementation decreases morbidity from infections and increases growth of stunted children, but there is little information on functional responses to zinc delivered in fortified foods. Objective: The aim was to examine the effects of zinc fortification on the growth, morbidity from infections, and plasma zinc concentrations of young children. Design: We compared the physical growth, morbidity, and micro-nutrient status of 6-8-mo-old Peruvian children with initial length-for-age z score (LAZ) < -0.50 who were randomly assigned to receive one of the following treatments daily for 6 mo: 1) 30 g dry weight of an iron-fortified cereal porridge and a separate dose of an aqueous multivitamin (MV) supplement between meals (control group), 2) the same porridge and MV with 3 mg Zn added to the supplement dose (ZnSuppl group), or 3) the porridge with added zinc (150 mg/kg dry weight) and MV without zinc (ZnFort group). Results: The children consumed a mean of 22-26 g dry porridge/d and 96% of the possible MV doses. After adjustment for small baseline differences in socioeconomic status and morbidity, no significant differences in weight or length increments were observed between the groups, even among the subset with an initial LAZ < - 1.5, and no significant differences in the rates of common illnesses were observed. Mean plasma zinc concentrations decreased in the control group (-3.9 [micro]g/dL), increased in the ZnSuppl group (4.3 [micro]g/dL), and did not change significantly in the ZnFort group (-1.5 [micro]g/dL; P < 0.001 for group-wise comparison). Conclusions: Provision of additional zinc, either in an aqueous supplement or a fortified porridge, did not significantly affect the children's physical growth or morbidity from infections, possibly because they were not sufficiently growth-restricted or zinc-deficient initially or because the level of zinc intake or absorption was inadequate. Additional studies of the functional effect of zinc-fortified foods are needed in populations that are known to respond to zinc supplements. KEY WORDS Zinc, fortification, supplementation, growth, diarrhea, infants

Background: Little information on the micronutrient status of HIV-infected (HIV-positive) breastfeeding women is available. Objective: The objective was to compare the protein and micronutrient status of South African breastfeeding women by HIV status. Design: Serum albumin, prealbumin, vitamin B-12, fotate, retinol, [alpha]-tocopherol, hemoglobin, ferritin, and zinc concentrations were compared between 92 HIV-positive and 52 HIV-uninfected (HIV-negative) mothers 6, 14, and 24 wk after delivery. C-reactive protein and [[alpha].sub.1]-acid glycoprotein were used as proxy indicators of an inflammatory process. Results: Mean albumin and prealbumin were significantly lower in HIV-positive mothers, and a higher proportion of HIV-positive mothers had low albumin concentrations ( Conclusions: Deficiencies in vitamins B-12, folate, [alpha]-tocopherol, ferritin, and zinc are common in South African breastfeeding mothers. HIV-positive mothers had lower mean serum concentrations of albumin, prealbumin, folate, retinol, and hemoglobin than did HIV-negative mothers. KEY WORDS HIV infection, breastfeeding women, South Africa, micronutrient status

Background: It has been documented that growth patterns differ between breastfed and formula-fed infants. Some investigators have suggested that these differences may be related to differences in zinc nutriture. Objective: The objective of this study was to examine the effect of zinc supplementation on growth, morbidity, and motor development in healthy, term, breastfed infants. Design: We conducted a randomized double-blind intervention comparing zinc supplementation (5 mg/d as zinc sulfate) with placebo in breastfed infants aged 4-10 mo. Growth and indexes of body composition and gross motor development were measured monthly from 3 to 10 mo. Morbidity data were collected weekly. Results: Eighty-five infants were enrolled, and 70 completed the study. The baseline characteristics, attained weight or length at 10 mo, growth velocity, gross motor development, and morbidity did not differ significantly between groups, even after control for potentially confounding variables. Conclusions: The dietary zinc intake of these breastfed infants appeared to be adequate, given that zinc supplementation did not affect growth, development, or risk of infection (although sample size for detection of differences in development or infection was limited). Previously described differences in growth between breastfed and formula-fed infants in such populations do not appear to be due to differences in zinc nutriture. KEY WORDS Zinc. randomized supplementation trial, infant growth, motor development, breastfeeding

Background: Information is needed to design studies of the effects of complementary feeding regimens on children's intakes of complementary foods (CFs) and breast milk. Objective: We evaluated the effects of varied energy density of CFs on the time until stabilization of dietary intakes and on total daily energy intakes (EIs) and breast-milk intakes. Design: CFs with low [0.4 kcal/g (LD)] and high [1.5 kcal/g (HD)] energy density were fed 3 times/d to 10 children (aged 9-18 mo) during 2 randomly assigned sequences of three 8-d diet periods (HD-LD-HD or LD-HD-LD) along with ad libitum breastfeeding. CF and breast-milk intakes were measured. Results: Intakes of the HD diet and breast milk did not vary by day of period, but intake of the LD diet increased progressively. During days 5-7 of the last 2 diet periods in each sequence, more of the LD than of the HD diet was consumed (752 [+ or -] 252 and 439 [+ or -] 111 g/d, respectively; P < 0.001), but EIs from CFs were greater with the HD diet. Breast-milk consumption was slightly less (192 [+ or -] 115 and 234 [+ or -] 121 g/d, respectively; P = 0.03) but total daily El was greater (774 [+ or-] 175 and 441 [+ or -] 85 kcal/d, respectively: P < 0.001) during the HD than during the LD diet period. Conclusions: New information on the effects of newly introduced diets on daily intakes of these diets and of breast milk can be used to design future studies. Total daily Els were greater with the HD diet despite its negative effects on breast-milk intakes. KEY WORDS Infant feeding, complementary food, energy density, breast milk, breastfeeding

Background: The effect of breastfeeding on the nutrition of HIV-infected (HIV+) mothers is unknown. Simple, valid methods are needed for body-composition assessment of HIV+ women. Objective: We compared the ability of bioimpedance spectroscopy (BIS) and anthropometry with that of isotope dilution ([sup.2][H.sub.2]O) to measure fat-free mass (FFM) and fat mass (FM) in HIV+ and HIV-uninfected (HIV-) breastfeeding South African mothers. Design: Total body water (TBW) content of 68 lactating mothers (20 HIV +, 48 HIV-) was measured 10 wk after delivery by using B IS and [sup.2][H.sub.2]O to measure FFM and FM. Anthropometric measurements included body mass index (BMI; in kg/[m.sup.2]), midupper ann circumference (MUAC), and 4 skinfold thicknesses. Results: TBW, FFM, and FM measurements determined by BIS were correlated with [sup.2][H.sub.2]O measurements in HIV+ (r = 0.664, 0.621, and 0.872, respectively: P < 0.01) and HIV- (r = 0.876, 0.868, and 0.932, respectively: P < 0,001) mothers. TBW measured by BIS was greater than that measured by the [sup.2][H.sub.2]O method in both HIV+ (1.8 L) and HIV- (1.5 L) women: FM or FFM did not differ significantly by method. BMI, MUAC, and all skinfold-thickness measurements correlated strongly (r > 0.62, P < 0.001) with FM measured by [sup.2][H.sub.2]O in both groups. BMI and MUAC correlated (r > 0.64, P < 0.001) with FFM in HIV- mothers but not in HIV+ mothers. Conclusions: In HIV+ and HIV- breastfeeding mothers, BIS provides an estimate of body composition comparable to that obtained with the [sup.2][H.sub.2]O method. BMI and MUAC are useful in predicting FM in both groups but are not valid measures of FFM in HIV+ mothers. KEY WORDS HIV, breastfeeding, body composition, South Africa, fat mass, fat-free mass, anthropometry, isotope dilution, women, AIDS, lactation, bioimpedance spectroscopy

Background: Information is needed on the fractional absorption of zinc (FAZ) and absorbed zinc (AZ) during prolonged exposure to zinc-fortified foods. Objective: The objective was to measure FAZ and AZ from diets fortified with different amounts of zinc and to determine whether zinc absorption changes over [approximately equal to] 7 wk. Design: Forty-one stunted, moderately anemic children received daily, at breakfast and lunch, 100 g wheat products fortified with 3 mg Fe (ferrous sulfate) and 0 (group Zn-0), 3 (group Zn-3), or 9 (group Zn-9) mg Zn (zinc sulfate) per 100 g flour. FAZ was measured on days 2-3 and 51-52; meal-specific AZs were calculated as the product of FAZ and zinc intake. Results: For the breakfast and lunch meals combined, mean total zinc intakes were 2.14, 4.72, and 10.04 mg/d in groups Zn-0, Zn-3, and Zn-9, respectively, during the initial absorption studies; mean ([+ or -] SD) FAZ values were 0.341 [+ or -] 0. l 11,0.237 [+ or -] 0.052, and 0.133 [+ or -] 0.041, respectively, on days 2-3 (P < 0.001) and did not change significantly on days 51-52 in the subset of 31 children studied twice. Mean initial AZ was positively related to zinc intake (0.71 [+ or -] 0.18, 1.11 [+ or -] 0.21, and 1.34 [+ or -] 0.47 mg/d, respectively; P < 0.001); final values did not differ significantly from the initial values. Conclusions: AZ from meals containing zinc-fortified wheat products increases in young children relative to the level of fortification and changes only slightly during [approximately equal to] 7-wk periods of consumption. Although consumption of zinc-fortified foods may reduce FAZ, zinc fortification at the levels studied positively affects total daily zinc absorption, even after nearly 2 mo of exposure to zinc-fortified diets. KEY WORDS Zinc, iron, wheat, fortification, absorption, stable isotopes, children

Background: It is not known whether daily consumption of vitamin A-containing foods is efficacious for treating nightblindness. Objective: We assessed the effect of supplementation with vitamin A from food or synthetic sources on dark adaptation and plasma retinol concentrations in nightblind pregnant Nepali women. Design: Nightblind pregnant women were randomly assigned to 1 of 6 treatment groups to receive 6 d/wk for 6 wk either 850 [micro]g retinol equivalents/d as retinyl palmitate, vitamin A-fortified rice, goat liver, amaranth leaves, or carrots or 2000 [micro]g retinol equivalents/d as retinyl palmitate. Dark adaptation was assessed weekly by using the pupillary threshold (PT) test: plasma retinol concentrations were measured before and after the intervention. These outcomes were also assessed in a comparison group of nonnightblind pregnant women. Results: In the nightblind women, the mean PT improved significantly (P < 0.0001) from -0.71 [+ or -] 0.04 to -1.42 [+ or -] 0.02 log cd/[m.sup.2], and the final mean PT did not differ significantly from that in the nonnightblind women (-1.43 [+ or -] 0.04: P = 0.55). Improvement in dark adaptation was greater in the liver group than in the vitamin A-fortified rice group (P < 0.02). Plasma retinol concentrations increased significantly (P < 0.0001) from 0.95 [+ or -] 0.05 to 1.07 [+ or -] 0.05 [micro]mol/L. The plasma retinol response was greater in the higher-dose capsule and liver groups than in the vegetable groups and significantly greater in the liver group than in the vitamin A-fortified rice group (both: P < 0.05). Conclusion: Improvement in dark adaptation did not differ significantly between women who received vitamin A as liver, amaranth leaves, carrots, or retinyl palmitate. KEY WORDS Nightblindness, pregnancy, vitamin A status, supplementation, pupillary threshold, dark adaptation, Nepal, vitamin A, [beta]-carotene, food-based interventions

Background: Recent evidence suggests that the vitamin A equivalency of [beta]-carotene from plant sources is lower than previously estimated. Objective: We assessed the effect of 60 d of daily supplementation with 750 [micro]g retinol equivalents (RE) of either cooked, pureed sweet potatoes; cooked, pureed Indian spinach (Basella alba); or synthetic sources of vitamin A or [beta]-carotene on total-body vitamin A stores in Bangladeshi men. Design: Total-body vitamin A stores in Bangladeshi men (n = 14/group) were estimated by using the deuterated-retinol-dilution technique before and after 60 d of supplementation with either 0 [micro]g RE/d (white vegetables) or 750 [micro]g RE/d as sweet potatoes, Indian spinach, retinyl palmitate, or [beta]-carotene (RE = 1 [micro]g retinol or 6 [micro]g [beta]-carotene) in addition to a low-vitamin A diet providing [approximately equal to] 200 [micro]g RE/d. Mean changes in vitamin A stores in the vegetable and [beta]-carotene groups were compared with the mean change in the retinyl palmitate group to estimate the relative equivalency of these vitamin A sources. Results: Overall geometric mean ([+ or -] SD) initial vitamin A stores were 0.108 [+ or -] 0.067 mmol. Relative to the low-vitamin A control group, the estimated mean changes in vitamin A stores were 0.029 mmol for sweet potato (P = 0.21), 0.041 mmol for Indian spinach (P = 0.033), 0.065 mmol for retinyl palmitate (P < 0.001), and 0.062 mmol for [beta]-carotene (P < 0.002). Vitamin A equivalency factors ([beta]-carotene:retinol, wt:wt) were estimated as [approximately equal to] 13:1 for sweet potato, [approximately equal to]10:1 for Indian spinach, and [approximately equal to]6:1 for synthetic [beta]-carotene. Conclusion: Daily consumption of cooked, pureed green leafy vegetables or sweet potatoes has a positive effect on vitamin A stores in populations at risk of vitamin A deficiency. Am J Clin Nutr 2004;80:705-14. KEY WORDS Deuterated retinol dilution, stable isotope, bioavailability, vitamin A status, [beta]-carotene, vitamin A stores, green leafy vegetables, sweet potatoes, Bangladesh

Background: Zinc supplements reduce childhood morbidity in populations in whom zinc deficiency is common. In such populations, deficiencies in other micronutrients may also occur. Objective: The objective was to determine whether the administration of other micronutrients with zinc modifies the effect of zinc supplementation on children's morbidity and physical growth. Design: Two hundred forty-six children aged 6-35 mb with persistent diarrhea were randomly assigned to 1 of 3 groups to receive a daily supplement of 10 mg Zn alone (Zn; n = 81), zinc plus vitamins and other minerals at 1-2 times recommended daily intakes (Zn+VM; n = 82), or placebo (n = 83) for [approximately equal to] 6 mo after the diarrhea episode ended. Morbidity information was collected on weekdays. Weight, length, and other anthropometric indicators were measured monthly, and plasma zinc and other indicators of micronutrient status were measured at baseline and 6 mo. Results: Supplement consumption was high ([approximately equal to] 90%) in all groups, although slightly more vomiting was reported in the Zn+VM group (P < 0.0001, analysis of variance). The change in plasma zinc from baseline to 6 mo was greater in the 2 zinc groups (6.1, 27.3, and 16.2 [micro] g/dL in the placebo, Zn, and Zn+VM groups, respectively; P < 0.000l, analysis of variance). The Zn group had fewer episodes of diarrhea, dysentery, and respiratory illness and a lower prevalence of fever and cough than did the Zn+VM group and a lower prevalence of cough than did the placebo group (P = 0.05), No significant effects of supplementation on growth were observed. Conclusion: Morbidity was greater after supplementation with zinc plus multivitamins and minerals than it was after supplementation with zinc alone. KEY WORDS Zinc supplementation, zinc deficiency, diarrhea, respiratory infection, growth

Background: Iron, zinc, and calcium can interact with each other in a way that inhibits their respective absorption. On the other hand, mineral fortification has been used to improve simultaneous iron and zinc absorption from food supplements. Objective: We evaluated the effect of a novel fortificant mixture consisting of NaFeEDTA, zinc methionine, ascorbic acid, and citric acid on iron and zinc absorption from a dry food supplement designed for preschool children. Design: The standard food supplement contained cereal and legume flour, dried milk, and a mixture of micronutrients including ferrous sulfate and zinc sulfate as sources of supplemental iron and zinc, respectively. Standard and novel food products were prepared as porridge with or without the addition of 200 mg Ca as calcium phosphate. Iron absorption and zinc absorption from the food products were evaluated simultaneously in 13 nonpregnant, adult women by extrinsically labeling the products with radioisotopes of iron and zinc and carrying out whole-body counting 7 d after the food products were consumed in random order. Results: The absorption of iron from the NaFeEDTA-containing (novel) food product was 1.7 times that from the ferrous sulfate-containing (standard) product (P = 0.015). There was no significant effect of dietary calcium on iron absorption. Zinc absorption was not associated with the form of zinc consumed, but higher dietary calcium was marginally associated with lower zinc absorption (P = 0.071). Conclusions: A mixture of fortificants containing NaFeEDTA, zinc sulfate or zinc methionine, ascorbic acid, and citric acid, but without calcium, can improve iron and zinc absorption from food products. A cost-benefit analysis of the novel fortificant mixture needs to be performed. KEY WORDS Iron, zinc, phytic acid, calcium, iron absorption, zinc absorption, food products

Background: The recent dietary reference intakes publication provides updated information on the physiologic and dietary requirements for zinc and proposes new tolerable upper intake levels. Objective: We analyzed dietary intake data of US preschool children to determine the prevalence of inadequate and excessive intakes of zinc. Design: Diets of 7474 nonbreastfeeding preschool children in the Continuing Survey of Food Intakes by Individuals (1994-1996 and 1998) were analyzed for the intakes of zinc and other dietary components, and factors associated with zinc intake were examined. Results: The mean intakes of zinc by children aged < 1 y, 1-3 y, and 4-5 y were 6.6, 7.6, and 9.1 mg/d, respectively. Less than 1% of children had usual zinc intakes below the adequate intake or estimated average requirement. The percentages of children with intakes exceeding the tolerable upper intake level were 92% (0-6 mo), 86% (7-12 mo), 51% (1-3 y), and 3% (4-5 y). Controlling for age and energy intake, zinc intake was greater in 1998 than in 1994 (P < 0.0001) and was positively associated with participation in the Women, Infants, and Children Program (P < 0.001) and with the lowest income category (P < 0.001). Conclusions: Preschool children in the United States have dietary zinc intakes that exceed the new dietary reference intakes. Zinc intakes increased during the 4 y of the study. The present level of intake does not seem to pose a health problem, but if zinc intake continues to increase because of the greater availability of zinc-fortified foods in the US food supply, the amount of zinc consumed by children may become excessive. KEY WORDS: Zinc, copper, phytate, dietary intake, preschool children, Continuing Survey of Food Intakes by Individuals, CSFII, dietary reference intakes, DRIs

Background: The risk of zinc deficiency in populations can be estimated by comparing serum zinc data with statistically defined lower cutoffs derived from a presumably healthy population. Serum zinc data are available from a large sample of the US population assessed during the second National Health and Nutrition Examination Survey (NHANES II). Although the original analysis of these data considered fasting status and the time of day of blood sampling, it did not account for potentially confounding variables that may affect the serum zinc concentration, such as age, sex, and health status. Objective: The objective was to describe variations in serum zinc concentration by age, sex, and other characteristics and to recommend lower cutoffs for presumably healthy persons. Design: Serum zinc data from NHANES II were analyzed by using analysis of variance and covariance models to identify and describe variables significantly associated with serum zinc concentration; 2.5th percentile curves were produced and used to establish age-and sex-based lower cutoffs. Results: Age and sex were significant confounders of serum zinc concentration, so separate lower cutoffs were derived for children and adolescent and adult males and females. Other minor confounding variables were identified. Tentative lower cutoffs for pregnancy and oral contraceptive use were also derived. Conclusions: The interpretation of population serum zinc data with the use of lower cutoffs should account for the age and sex of the subjects, pregnancy and oral contraceptive use, and fasting status and time of day of blood collection. KEY WORDS Serum zinc, zinc deficiency, second National Health and Nutrition Examination Survey, NHANES II

Background: Several chemical forms of zinc have been proposed for food fortification, but information is needed on their absorption from common cereals having varied phytate content. Objective: The goal was to measure zinc absorption from wheat products fortified with iron sulfate and either zinc sulfate or zinc oxide. Design: Adult volunteers received either low-phytate bread (n = 11) or higher-phytate porridge (n = 11) once weekly on 2 or 3 occasions. The foods were fortified with 1 of the 2 zinc salts (60 mg elemental Zn/kg wheat flour) during week 1 and with the other during week 2, in random order. 65Zn in the same chemical form as the fortificant was incorporated in each food to assess zinc absorption with the use of whole-body counting. The porridge group received an additional test meal fortified with zinc oxide during week 3, but the [sup.65]Zn tracer was given as an oral solution of [sup.65]Zn[Cl.sub.2]. Results: Zinc absorption from bread (13.8%; 95% CI: 11.8%, 16.2%) was significantly (P < 0.001) greater than from porridge (6.4%; 5.5%, 7.6%), presumably because of the greater phytate content of the porridge. With control for food type, there were no significant differences in zinc absorption from meals fortified with zinc sulfate or zinc oxide (P = 0.24). When the porridge was fortified with zinc oxide and labeled with [sup.65]Zn[Cl.sub.2], absorption of the tracer (8.9%; 7.1%, 11.0%) was significantly (P = 0.007) greater than when [sup.65]ZnO was incorporated in the porridge (5.6%; 4.5%, 6.9%). Conclusions: Either zinc oxide or zinc sulfate can be used to fortify wheat products consumed by presumably healthy persons. Isotopic tracers used to assess the absorption of mineral fortificants should have the same chemical form as the fortificant. KEY WORDS Iron, zinc, wheat, fortification, zinc absorption, radioisotopes

Background: The deuterated-retinol-dilution technique provides a quantitative estimate of total-body vitamin A (TBVA) stores in adults. To apply the technique to children, information on plasma retinol kinetics in this age group is needed. Objectives: We described the plasma retinol kinetics of an oral dose of [[sup.2][H.sub.4]]retinyl acetate in a population of Peruvian children (12-24 mo of age) in order to examine the relation between TBVA stores and individual plasma isotopic ratios 3 d after the dose and to estimate 1) the time required for the isotope dose to mix with endogenous vitamin A, 2) the fractional catabolic rate for retinol, and 3) TBVA stores. Design: An oral dose of [[sup.2][H.sub.4]]retinyl acetate (14 [micro]mol retinol equivalents) was administered to children (n = 107) to construct a population-level kinetic curve of the plasma ratio of [[sup.2][H.sub.4]]retinol to retinol to estimate equilibration time and the fractional catabolic rate. TBVA stores were estimated by using a modification of the isotope dilution equation for adults. Results: The dose of [[sup.2][H.sub.4]]retinyl acetate fully mixed with endogenous vitamin A 8 d after the dose. The fractional catabolic rate was 0.022/d (95% CI: 0.014, 0.030/d). Mean ([+ or -] SD) TBVA stores were estimated as 0.097 [+ or -] 0.081 mmol (range: 0.016-0.392 mmol). Plasma ratios of [[sup.2][H.sub.4]]retinol to retinol 3 d after the dose were correlated with the inverse of estimated TBVA stores (r = -0.74, P < 0.0001). Conclusions: Compared with previous results in adults, the equilibration time occurred earlier and the estimated system fractional catabolic rate was higher in this population of children. The modified isotope dilution equation provided estimates of hepatic vitamin A concentration that are similar to values reported in US children at autopsy. KEY WORDS Vitamin A stores, children, stable isotope, vitamin A, plasma kinetics, [[sup.2][H.sub.4]]retinyl acetate, Peru

Background: Multiple studies have been carried out to assess the effect of zinc supplementation on children's growth. The results of these studies are inconsistent, and the factors responsible for these varied outcomes are unknown. Objective: Meta-analyses of randomized controlled intervention trials were therefore completed to assess the effect of zinc supplementation on the physical growth and serum zinc concentrations of prepubertal children. Design: A total of 33 acceptable studies with appropriate data were identified by MEDLINE (National Library of Medicine, Bethesda, MD) searches and other methods. Weighted mean effect sizes (expressed in SD units) were calculated for changes in height, weight, weight-for-height, and serum zinc concentration by using random-effects models; factors associated with effect sizes were explored by meta-regression techniques. Results: Zinc supplementation produced highly significant, positive responses in height and weight increments, with effect sizes of 0.350 (95% CI: 0.189, 0.511) and 0.309 (0.178, 0.439), respectively. There was no significant effect of zinc on weight-for-height indexes [weighted mean effect size: -0.018 (-0.132, 0.097)]. Zinc supplementation caused a large increase in the children's serum zinc concentrations, with an effect size of 0.820 (0.499, 1.14). Growth responses were greater in children with low initial weight-for-age z scores and in those aged > 6 mo with low initial height-for-age z scores. Conclusions: Interventions to improve children's zinc nutriture should be considered in populations at risk of zinc deficiency, especially where there are elevated rates of underweight or stunting. The population mean serum zinc concentration is a useful indicator of the successful delivery and absorption of zinc supplements in children. Am J Clin Nutr 2002;75:1062-71. KEY WORDS Zinc, growth, serum zinc, zinc deficiency, nutritional assessment, indicators, children, meta-analysis

Several models have been developed to predict the effects of folic acid fortification programs on prevention of neural tube defects (NTDs), but each relies on different assumptions and data inputs. We identified and reviewed 7 models that predict the effects of folic acid intake or status on NTD risk. We applied 4 of these models [the original and a modified version of the Lives Saved Tool (LiST) and models developed by Arth et al. and Wald et al.] to predict the effect of folic acid fortification of wheat flour on reduction of NTDs using national survey data from Cameroon. The estimated percentage of NTDs averted due to fortified wheat flour (5.0 μg folic acid/g flour) varied by predictive model, with a 21–31% reduction in LiST to 83% in Arth's model, and 15% in Wald's model. As the simulated fortification level was increased from 1.0 to 7.0 μg folic acid/g flour, the pattern of change in estimated numbers of NTDs averted differed due to different model assumptions: the number of NTDs averted increased and then reached a plateau in the modified LiST model (as would be expected in real-world conditions), increased sharply in Arth's model, and increased continuously in Wald's model. This wide variation in predicted effects, and implausible results in some cases, undermines the models’ utility for users of model outputs. Concurrent collection of dietary and biomarker data, including plasma and RBC folate concentrations, and NTD outcomes, is necessary to validate these models and monitor change in folic acid intake, folate-related biomarkers, and reduced NTD risk due to fortification. In the meantime, models based on erythrocyte folate concentration are recommended, based on biological plausibility and consistency with empirical evidence. Where erythrocyte folate data are unavailable, sensitivity analyses (using several models) could be conducted to examine the range of possible outcomes.Statement of Significance: Inconsistent predictions by different models of neural tube defect (NTD) reduction due to folic acid fortification may cause confusion and hamper NTD prevention efforts; this paper offers suggested best practices for modeling.

The development of intervention programs to control zinc deficiency is hampered by the lack of sensitive, specific, low-cost indicators of zinc status. The mean plasma zinc concentration of groups of individuals has been suggested as a possible indicator of a population's zinc status because the plasma zinc concentration seems to predict whether growth will increase in response to zinc supplementation. However, experimental studies in both animal models and adult human volunteers as well as clinical studies of infected and noninfected adults indicate that systemic infections that produce an acute phase response also cause the plasma zinc concentration to fall. Therefore, concerns have been raised about the usefulness of plasma zinc concentration as an indicator of zinc status in populations with high prevalences of infections. By contrast with the aforementioned studies in adults, cross-sectional, community-based surveys of children with and without common infections have not found any association between the presence of infection and plasma zinc concentration, possibly because the severity of those infections observed in children in field settings was less than that of the infections studied in adults. Thus, it appears that the mean plasma zinc concentration may be a useful indicator of population zinc status for children in low-income countries despite the high prevalence of common childhood infections encountered in these settings. Am J Clin Nutr 1998;68(suppl):425S-9S.

To evaluate the effect of introducing complementary foods before 6 mo of age, we randomly assigned 164 infants who had been exclusively breast-fed for 4 mo to continue being exclusively breast-fed until 6 mo (EBF group) or to receive iron-fortified foods in addition to breast milk from 4 to 6 mo (BF+SF group). At 6 mo, the BF+SF group had higher mean iron intake (4 mg/d compared with 0.2 mg/d in EBF infants) and higher hemoglobin, hematocrit, and ferritin values than the EBF group (P [is less than] 0.05). The percentage with low hemoglobin ([is less than] 103 g/L) did not differ significantly between groups, but fewer infants in the BF+SF group had a low hematocrit ([is less than] 0.33; 21.4% compared with 32.0%, respectively; P [is less than] 0.05). The percentage of infants with ferritin concentrations [is less than] 12 [micro]g/L at 6 mo was lower than the percentage with low hemoglobin or hematocrit, raising questions about the validity of the cutoffs at this age. Infants at greatest risk for anemia and low ferritin were those with birth weights [is less than] 2500 g; no infant with a birth weight [is greater than] 3000 g had a low ferritin value at 6 mo. We conclude that the risk of iron deficiency is low among infants with birth weights [is greater than] 3000 g who are exclusively breast-fed for 6 mo. Iron drops are recommended for low-birth-weight infants; for breast-fed infants with birth weights between 2500 and 3000 g, further research is needed to determine whether iron drops are more effective than complementary foods for preventing iron deficiency before 6 mo. Am J Clin Nutr 1998;67:878-84.

Hepatic stores of vitamin A were estimated in 31 Bangladeshi surgical patients (15 males and 16 females) by the deuterated-retinol-dilution (DRD) technique and by analysis of the vitamin A concentration of a liver biopsy specimen obtained during previously scheduled abdominal surgery. Patients ranged in age from 21 to 65 y and had an average body mass index (BMI; in kg/[m.sup.2]) of 17.7 [+ or -] 3.4. They received 0.753 [Mu]mol [[.sup.2][H.sub.4]] retinyl acetate/kg body wt orally 9-11 d before surgery. Hepatic vitamin A reserves were estimated according to Furr et al (Am J Clin Nutr 1989;49:713-6) by using a single plasma isotopic-ratio measurement (18-25 d postdose). Estimated mean hepatic vitamin A stores were similar by both techniques, 0.110 [+ or -] 0.072 mmol (by DRD) compared with 0.100 p[+ or -] 0.067 mmol (by biopsy). Regression analysis was used to compare results of the DRD and biopsy techniques. A significant linear relation was found between the two techniques (r = 0.75, P [is less than] 0.0001), and the least-squares regression line was not significantly different from y = x (P = 0.09). The results indicate that the DRD technique provided a very good estimate of hepatic vitamin A reserves for this population. However, a wide prediction interval was observed for estimates of hepatic vitamin A reserves for individual subjects. Thus, further refinement of the prediction model is necessary to improve estimates of hepatic vitamin A reserves for individual subjects.

Lactational amenorrhea (LA) is associated with postpartum infertility and is known to be related to breast-feeding frequency and duration, but the exact role of complementary feeding of the infant has not been clearly defined. Data on LA were collected during and after a 2-mo intervention trial in which low-income Honduran women who had breast-fed fully for 4 mo were randomly assigned to one of three groups: continued full breast-feeding until 6 mo (FBF, n = 50), introduction of complementary foods at 4 mo with ad libitum breast-feeding from 4 to 6 mo (SF, n = 47), or introduction of complementary foods at 4 mo with maintenance of baseline breast-feeding frequency from 4 to 6 mo (SF-M, n = 44). Women were followed up until the infant was 12 mo of age, or later if menses had not occurred by then. All but six of the women continued to breast-feed for [is greater than or equal to] 12 mon. With the exclusion of those whose menses returned before 18 wk postpartum (which could not have been due to the intervention), the proportion of women who were amenorrheic at 6 mo was 64.5% in the SF group, 80.0% in the FBF group, and 85.7% in the SF-M group (chi-square test = 4.13, P = 0.02; one-tailed test with the latter two groups combined). The total duration of LA did not differ significantly among groups. The most significant determinant of LA was time spent breast-feeding (min/d), which was in turn negatively associated (P = 0.06) with the infant's energy intake from complementary foods in regression analyses. These results indicate that there is a significant effect of introducing foods at 4 mo on the likelihood of amenorrhea at 6 mo postpartum, but not thereafter, and that this effect is not seen in mothers who maintain breast-feeding frequency.

The large within- and between-sample variability in breast milk lipid content greatly complicates the collection of representative samples in field studies. The main purpose of this study was to validate the ability of individual daytime samples to predict the 24-h lipid concentration of breast milk. We also studied maternal, child, and other factors (time of day and interval between feeds) associated with the within- and between-mother variability in milk lipid content. Fifty-two primiparous urban Guatemalan women between 1 and 4 mo postpartum were studied. Milk samples were collected during six 2-h intervals from 0600 to 1800, and throughout the night when the child breast-fed. On average, the 24-h pooled milk samples contained 4.2 [+ or -] 0.92% (x [+ or -] SD) lipids and the best concordance with this value was obtained with samples collected between 0600 and 0800 (concordance correlation coefficient = 0.60, P [is less than] 0.05). None of the regression equations to predict the 24-h lipid content of breast milk based on daytime samples reached a sufficiently high predictive power to be recommended for the estimation of individual child intake. Time of day and time elapsed since the last feeding were significant determinants of diurnal variations in milk lipid content, whereas between-mother variability was explained by maternal weight (P = 0.05) and body mass index (P [is less than] 0.05). For the collection of milk samples in surveys and pre-post studies, we recommend standardization of time of day and interval between feeds.

Seventeen per cent of the world's population is estimated to be at risk of inadequate zinc intake, which could in part be addressed by zinc fortification of widely consumed foods. We conducted a review of efficacy and effectiveness studies to ascertain the effect of zinc fortification [postharvest fortification of an industrially produced food or beverage; alone or with multiple micronutrients (MMN)] on a range of health outcomes. Previous reviews have required that the effect of zinc be isolated; because zinc is always cofortified with MMN in existing fortification programs, we did not impose this condition. Outcomes assessed were zinc-related biomarkers (plasma or serum, hair or urine zinc concentrations, comet assay, plasma fatty acid concentrations, and the proportion of and total zinc absorbed in the intestine from the diet), child anthropometry, morbidity, mortality, cognition, plasma or serum iron and copper concentrations, and for observational studies, a change in consumption of the food vehicle. Fifty-nine studies were included in the review; 54 in meta-analyses, totaling 73 comparisons. Zinc fortification with and without MMN increased plasma zinc concentrations (efficacy, n= 27: 4.68 μg/dL; 95% CI: 2.62–6.75; effectiveness, n= 13: 6.28 μg/dL; 95% CI: 5.03–7.77 μg/dL) and reduced the prevalence of zinc deficiency (efficacy, n= 11: OR: 0.76, 95% CI: 0.60–0.96; effectiveness, n= 10: OR: 0.45, 95% CI: 0.31–0.64). There were statistically significant increases in child weight (efficacy, n= 11: 0.43 kg, 95% CI: 0.11–0.75 kg), improvements in short-term auditory memory (efficacy, n= 3: 0.32 point, 95% CI: 0.13–0.50 point), and decreased incidence of diarrhea (efficacy, n= 3: RR: 0.79, 95% CI: 0.68–0.92) and fever (efficacy, n= 2: RR: 0.85, 95% CI: 0.74–0.97). However, these effects cannot be solely attributed to zinc. Our review found that zinc fortification with or without MMN reduced the prevalence of zinc deficiency and may provide health and functional benefits, including a reduced incidence of diarrhea.Zinc fortification increased plasma/serum zinc concentrations and reduced the prevalence of zinc deficiency; limited evidence indicated that MMN + zinc-fortified food increased body weight and reduced the incidence of fever and diarrhea.

To investigate the potential effects of maternal infection during lactation on breast-milk quantity and composition, we examined low-income Peruvian women who had an acute febrile infection and were exclusively breast-feeding a child from l to 6 mo of age (n = 36). Women who were not ill (n = 38) served as controls; all women had body mass indexes (in kg/[m.sup.2]) > 19.5. Blood and milk samples were collected on days 1, 7, and 14 after identification of the episode of illness. C-reactive protein in maternal serum was significantly elevated by infection, whereas two other acute-phase reactants, ceruloplasmin and [alpha.sub.2]-macroglobulin, showed no change. Serum zinc concentrations were significantly lower in ill women than in women who were not ill, whereas serum copper concentrations were elevated initially in ill women. Serum iron concentrations increased significantly with time, but there was no significant difference between groups. Milk intake, as assessed by 12-h test-weighing, was not affected by the infection. Concentrations of milk total protein, casein, and whey proteins were similar in the two groups and there was no significant effect of illness on milk trace element concentrations. Thus, acute maternal infections during established lactation did not affect milk volume, milk protein, or trace clement concentrations, despite expected changes in serum protein and trace element concentrations.

To develop recommendations for the design of special foods for young children, we measured total daily energy consumption from semisolid food mixtures with energy densities of 1.67, 2.93, 4.18, or 6.28 kJ/g (0.4, 0.7, 1.0, or 1.5 kcal/g) and that were fed ad libitum three, four, or five times per day to 18 fully weaned children from 6 to 18 mo of age who were recovering in the hospital from malnutrition. The diets were generally indistinguishable by sensory qualities, and were fed in a randomized sequence. The mean amounts consumed (g . kg body [wt.sup.-1].[d.sup.-1]) were significantly less with successively greater energy density of the diet (P < 0.001). The total daily consumption was [double tilde]16% more when the number of meals was increased from three to four per day, with energy density controlled for (P < 0.001), and 7% more when the feeding frequency rose from four to five meals per day (P = 0.005). The total daily energy intakes (kJ . kg body [wt.sup.-1].[d.sup.-1]) increased significantly with the more concentrated diets (P < 0.001) and varied positively in relation to feeding frequency (P < 0.001). Approximately 15-20 min were required per meal for the children to reach satiety. The total amount of time required to feed the children each day was related to the number of meals served (P < 0.001) and not to energy density. Implications for child feeding are discussed.

As part of a study on the optimal timing of complementary feeding in Honduras, we assessed breast milk volume and composition at 4, 5, and 6 mo in 141 low-income women who were randomly assigned to exclusively breast-feed for the first 6 mo or to complement breast milk with preprepared solid foods beginning at 4 mo. Milk volume averaged 797 [+ or -] 139 g/d at 4 mo. Maternal body mass index was positively associated with infant birth weight and milk energy density. In multivariate analyses in which group assignment was controlled for, milk volume was positively associated with birth weight but negatively associated with milk energy density. Infant breast milk energy intake was positively associated with birth weight and milk energy density. Maternal anthropometric status was not a significant predictor of milk volume or infant energy intake when birth weight and milk energy density were included in the models. These results indicate that infant characteristics, such as birth weight and the ability to self-regulate intake in response to milk energy density, mediate the relationship between maternal anthropometric status and lactation performance. Am J Clin Nutr 1995;61:528-34

To assess the validity of maternal reports of poor infant appetite, these histories were compared with measured energy consumption on 1621 d of observation of 131 Peruvian infants in a low-income community. Mean ([+ or -]SD) total energy intakes on days with reported anorexia were 338 [+ or -] 88 kJ/kg body wt in infants 1--6 mo of age and 299 [+ or -] 92 kJ/kg body wt in infants aged >6 mo compared with 395 [+ or -] 92 and 342 [+ or -] 88 kJ/kg body wt in the respective age groups when appetites were reportedly normal (P < 0.001). Energy intake from non-brest-milk sources was more affected than energy from breast milk. The epidemiology of poor appetite was assessed in 153 infants who were monitored longitudinally during their first year of life. The prevalence of reported anorexia increased progressively from 22 to 317/1000 d of observation from

To examine the effects of concurrent infection on population-based assessment of trace element status, we collected data on clinical signs and laboratory indicators of infection when obtaining blood for serum zinc, copper, and ferritin analyses in 153 Peruvian children aged 11 - 19 mo. Fifty-two (34.7%) of the children had some reported sign of infection and 43 (28.3%) had elevated C-reactive protein concentrations or leukocytosis. Children with any evidence of infection had marginally lower mean ([+ or -] SD) serum zinc concentrations (7.0 [+ or -] 2.3 vs 7.5 [+ or -] 2.0 [micro]mol/L, P = 0.16) and significantly greater serum copper (24.7 [+ or -] 4.7 vs 22.7 [+ or -] 4.2 [micro]mol/L, P = 0.006) and serum ferritin concentrations (10.0 [+ or -] 12.9 vs 3.9 [+ or -] 4.4 [micro]g/L, P < 0.001) than did those without infections. Infection caused an underestimation in the rate of low copper status by 1 percentage point and low iron status by 12 percentage points. Thus, the effect of concurrent infections is of variable magnitude and may differ by nutrient, nutritional status of the population, and prevalence and severity of infections.

To determine the effect of dietary viscosity on energy consumption by young children, 56 Peruvian children 9-20 mo of age with acute diarrhea were randomly assigned to either a liquid or semisolid diet, with or without added amylase to reduce viscosity. Intakes of the study diet, breast milk, and other foods were measured for 2 consecutive d during and again after illness. Total 24-h energy intake ([x bar] [+ or -] SD) during diarrhea, 349.4 [+ or -] 121.8 kJ/kg (83.6 [+ or -] 29.1 kcal/kg) was 18% less than intake after recovery, 428.9 [+ or -] 141.0 kJ/kg (102.6 [+ or -] 33.7), P < 0.001. In the ANOVA breast-fed children consumed significantly less total energy (P = 0.008) and energy from the study diet (P = 0.02) than non-breast-fed children. Breast milk intake did not change with illness. There was no significant relationship between viscosity of the study diet and either total energy intake or intake of energy from the study diet. Energy intake by these children was primarily determined by health status and breast-feeding practice, not by dietary viscosity. Am J Clin Nutr 1993;57:218-23.

We compared growth, dietary intake, and morbidity of infants breast-fed for [is greater than or equal to] 12 mo from two populations: Davis, CA (n = 46) and Huascar, Peru (n = 52). When compared against WHO reference data (based primarily on formula-fed infants), Huascar infants appeared to falter as early as 3-4 mo, but when compared with Davis breast-fed infants, the curves for weight and length were very similar in girls until 10-12 mo and in boys until 6-9 mo. Thereafter, Huascar infants grew less rapidly than did Davis infants. Breast milk intake was very similar between groups, but in Huascar the amount and nutrient density of complementary foods consumed after 6 mo were lower and morbidity rates were much higher than in Davis. These results indicate that growth faltering of Huascar infants, when judged against breast-fed infants in the United States, occurs primarily after the first 6 mo of life and is not due to poor lactation performance. Am J Clin Nutr 1992;56:1012-8.

The observed variances in monthly weight and length gains of 96 Peruvian infants were compared with predicted variances obtained by applying the reference curve-fitting methods to the same Peruvian data. Predicted variance estimates were significantly less (P < 0.0001) than the observed variances from 2 to 12 mo of age. The extent of underestimation in total variance that occurred when 1-mo growth-increment reference data were generated by curve-fitting and interpolation was approximated. This underestimation, caused by not taking into account infants' random deviations from their own growth trajectories. ranged from 59% to 94% and resulted in misclassification of ;w 24-67% of infants as abnormal gainers (below the 5th percentile or above the 95th percentile with respect to existing reference data) in the intervals evaluated. Am J Clin Nutr 1992;56:58-64.

Acute childhood diarrhea is treated by replacing fluid and minerals lost with stool, administering drugs that combat the causative organisms, and supplying sufficient nutrients. A review of the medical literature is presented concerning the dietary management of diarrhea, which is a controversial topic. Many of the studies are highly variable in design and patient selection. Recommendations have included continued, as well as reduced, feeding during the acute stage of diarrhea. The review covers methodologic issues in interpreting clinical studies; the timing of dietary therapy during illness; continuing breast-feeding and feeding nonhuman milks during diarrhea; and the use of mixed diets (consisting of milk with other ingredients, such as wheat noodles). No disadvantages appear to result from continuing to feed infants the same formulas that they received prior to the onset of illness. The reasons such feedings may be beneficial are discussed. Human milk seems to reduce the severity, and possibly the duration, of diarrhea. Nonhuman milks, on the other hand, do not appear to be as beneficial, although most children can safely continue such diets. When milk products are used, patients need close supervision because life-threatening effects can develop rapidly. In several studies, children with diarrhea who were fed milk and noodles had decreased fecal output and a shorter duration of diarrheal disease than those fed only milk. Studies in developing countries have compared several types of staple food (wheat flour, pea flour, potato, carrot) with formulas that lack the milk sugar found in cow's milk (lactose-free); in general, diarrhea in children fed staples resolved more quickly than diarrhea in those fed formulas, and the former group gained more weight. Children accustomed to diets of human milk or solid food should continue their normal diets when they develop diarrhea. Those normally maintained on formula (nonhuman milk diets) should be closely observed and receive a cereal-milk mixture. (Consumer Summary produced by Reliance Medical Information, Inc.)

Infectious diseases play an important role in determining the nutritional status and growth of children in underdeveloped countries. Infectious diseases may alter nutritional status by causing changes in dietary intake and nutrient absorption and retention. To assess the effects of common infections on dietary intake, 131 Peruvian infants were observed. Infants were monitored for symptoms of illness, and food and breast-milk consumption were measured during 1,615 days of observation. The average energy intake on symptom-free days was 557 kilocalories per day for infants 180 days old and younger, and 638 kilocalories per day for infants 181 days and older. Illness did not affect the amount of breast milk consumed, suckling time, or frequency of breast feeding. However, energy intake from other sources decreased by 20 to 30 percent during diarrhea and fever. The decrease in total energy consumed during illness was attributed to decreased consumption of non-breast-milk foods. (Consumer Summary produced by Reliance Medical Information, Inc.)

Malnutrition and infectious diseases are a great threat to the welfare of infants and children in Latin America and other regions of the developing world. They contribute to higher morbidity and mortality than are observed in industrialized countries. A recent survey from Huascar, Peru indicated that more than one-third of the children under three years of age were malnourished, and that the infant mortality rate was roughly 60 deaths per 1,000 live births. Therefore, a study was conducted to determine the consumption of breast milk, liquids, and foods by 131 poor Peruvian infants during their first year of life. Macronutrients were analyzed in milk samples; foods and liquids were weighed at preparation and consumption; and nutrient content was estimated from food composition tables. The average energy intake increased with age, but declined from 95 to 78 percent of the recommended amounts during the first year. Average protein intake was above recommended levels, but more than one-third of the infants received less than 80 percent of the recommended intake from six to twelve months of age. Breast milk provided the major source of energy, and together with cow milk supplied more than half the energy and protein intake during the second six months of life. In addition, cereals were an important source of energy and protein. Calcium, thiamin and ascorbic acid intakes were less than recommended. This study demonstrates the importance of breast milk as a major source of nutrients during the first year of life. It also highlights the need for improvement in the quantity and nutritional quality of complementary foods during the second six months of life. (Consumer Summary produced by Reliance Medical Information, Inc.)