K. Michael Hambidge

Low Levels of Zinc in Hair, Anorexia, Poor Growth, and Hypogeusia in Children

Extract: Concentrations of zinc in hair were determined for 338 apparently normal subjects living in Denver with ages ranging from 0–40 years. Mean concentrations of zinc in hair were: neonates (25) 174 ± 8 (1 sem); 3 months-4 years (93) 88 ± 5; 4–17 years (132) 153 ± 5, and 17–40 years (88) 180 ±4. Ten children more than 4 years of age had levels of zinc in hair of less than 70 ppm. Seven of these ten children had a history of poor appetite and eight had heights on or below the 10th percentile; the high incidence of low growth percentiles was not explicable on a familial basis. Taste acuity was tested in six of these children, and five had evidence of objective hypogeusia. After supplementing the diet with small quantities of zinc, taste acuity was normalized in each of these children and levels of zinc in hair increased.Speculation: The correlation between low levels of zinc in hair, anorexia, and low growth percentiles in these children indicates that poor appetite and growth, in addition to the hypogeusia, may have been attributable to zinc deficiency. The low mean concentration of zinc in hair of infants and children under 4 years of age indicates that stores of zinc in the body may be low in this age group.

A population-based, multifaceted strategy to implement antenatal corticosteroid treatment versus standard care for the reduction of neonatal mortality due to preterm birth in low-income and middle-income countries: The ACT cluster-randomised trial

BACKGROUND Antenatal corticosteroids for pregnant women at risk of preterm birth are among the most effective hospital-based interventions to reduce neonatal mortality. We aimed to assess the feasibility, effectiveness, and safety of a multifaceted intervention designed to increase the use of antenatal corticosteroids at all levels of health care in low-income and middle-income countries. METHODS In this 18-month, cluster-randomised trial, we randomly assigned (1:1) rural and semi-urban clusters within six countries (Argentina, Guatemala, India, Kenya, Pakistan, and Zambia) to standard care or a multifaceted intervention including components to improve identification of women at risk of preterm birth and to facilitate appropriate use of antenatal corticosteroids. The primary outcome was 28-day neonatal mortality among infants less than the 5th percentile for birthweight (a proxy for preterm birth) across the clusters. Use of antenatal corticosteroids and suspected maternal infection were additional main outcomes. This trial is registered with ClinicalTrials.gov, number NCT01084096. FINDINGS The ACT trial took place between October, 2011, and March, 2014 (start dates varied by site). 51 intervention clusters with 47,394 livebirths (2520 [5%] less than 5th percentile for birthweight) and 50 control clusters with 50,743 livebirths (2258 [4%] less than 5th percentile) completed follow-up. 1052 (45%) of 2327 women in intervention clusters who delivered less-than-5th-percentile infants received antenatal corticosteroids, compared with 215 (10%) of 2062 in control clusters (p<0·0001). Among the less-than-5th-percentile infants, 28-day neonatal mortality was 225 per 1000 livebirths for the intervention group and 232 per 1000 livebirths for the control group (relative risk [RR] 0·96, 95% CI 0·87-1·06, p=0·65) and suspected maternal infection was reported in 236 (10%) of 2361 women in the intervention group and 133 (6%) of 2094 in the control group (odds ratio [OR] 1·67, 1·33-2·09, p<0·0001). Among the whole population, 28-day neonatal mortality was 27·4 per 1000 livebirths for the intervention group and 23·9 per 1000 livebirths for the control group (RR 1·12, 1·02-1·22, p=0·0127) and suspected maternal infection was reported in 1207 (3%) of 48,219 women in the intervention group and 867 (2%) of 51,523 in the control group (OR 1·45, 1·33-1·58, p<0·0001). INTERPRETATION Despite increased use of antenatal corticosteroids in low-birthweight infants in the intervention groups, neonatal mortality did not decrease in this group, and increased in the population overall. For every 1000 women exposed to this strategy, an excess of 3·5 neonatal deaths occurred, and the risk of maternal infection seems to have been increased. FUNDING Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Iron absorption and iron status are reduced after Roux-en-Y gastric bypass

BACKGROUND Iron deficiency and iron deficiency anemia are common in patients who undergo gastric bypass. The magnitude of change in iron absorption is not well known. OBJECTIVE The objective was to evaluate the effects of Roux-en-Y gastric bypass (RYGBP) on iron status and iron absorption at different stages after surgery. We hypothesized that iron absorption would be markedly impaired immediately after surgery and would not improve after such a procedure. DESIGN Anthropometric, body-composition, dietary, hematologic, and iron-absorption measures were determined in 67 severe and morbidly obese women [mean age: 36.9 +/- 9.8 y; weight: 115.1 +/- 15.6 kg, body mass index (BMI: in kg/m(2)); 45.2 +/- 4.7] who underwent RYGBP. The Roux-en-Y loop length was 125-150 cm. Determinations were carried out before and 6, 12, and 18 mo after surgery. Fifty-one individuals completed all 4 evaluations. RESULTS The hemoglobin concentration decreased significantly throughout the study (repeated-measures analysis of variance). The percentage of anemic subjects changed from 1.5% at the beginning of the study to 38.8% at 18 mo. The proportion of patients with low serum ferritin increased from 7.5% to 37.3%. The prevalence of iron deficiency anemia was 23.9% at the end of the experimental period. Iron absorption from both a standard diet and from a standard dose of ferrous ascorbate decreased significantly after 6 mo of RYGBP to 32.7% and 40.3% of their initial values, respectively. No further significant modifications were noted. CONCLUSION Iron absorption is markedly reduced after RYGBP with no further modifications, at least until 18 mo after surgery.

The Quantity of Zinc Absorbed from Wheat in Adult Women Is Enhanced by Biofortification

Biofortification of crops that provide major food staples to large, poor rural populations offers an appealing strategy for diminishing public health problems attributable to micronutrient deficiencies. The objective of this first-stage human study was to determine the increase in quantity of zinc (Zn) absorbed achieved by biofortifying wheat with Zn. Secondary objectives included evaluating the magnitude of the measured increases in Zn absorption as a function of dietary Zn and phytate. The biofortified and control wheats were extracted at high (95%) and moderate (80%) levels and Zn and phytate concentrations measured. Adult women with habitual diets high in phytate consumed 300 g of 95 or 80% extracted wheat as tortillas for 2 consecutive days using either biofortified (41 mg Zn/g) or control (24 mg Zn/g) wheat. All meals for the 2-d experiment were extrinsically labeled with Zn stable isotopes and fractional absorption of Zn determined by a dual isotope tracer ratio technique. Zn intake from the biofortified wheat diet was 5.7 mg/d (72%) higher at 95% extraction (P < 0.001) and 2.7 mg/d (68%) higher at 80% extraction compared with the corresponding control wheat (P = 0.007). Zn absorption from biofortified wheat meals was (mean +/- SD) 2.1 +/- 0.7 and 2.0 +/- 0.4 mg/d for 95 and 80% extraction, respectively, both of which were 0.5 mg/d higher than for the corresponding control wheat (P < 0.05). Results were consistent with those predicted by a trivariate model of Zn absorption as a function of dietary Zn and phytate. Potentially valuable increases in Zn absorption can be achieved from biofortification of wheat with Zn.

Growth and intakes of energy and zinc in infants fed human milk

The objectives of this study were to examine the growth pattern of healthy infants who were fed human milk exclusively for > or = 5 months and its relationship to intakes of milk, energy, and zinc. Monthly anthropometric measurements were obtained on 71 infants through 7 months of age and on 43 through 9 months. Milk zinc concentrations were determined and milk intake was measured by 3-day test weighing. Mean (+/- SD) calculated energy intake from human milk was 106 +/- 20, 79 +/- 11, 70 +/- 10, and 57 +/- 12 kcal/kg per day at 2 weeks and 3, 5, and 7 months of age, respectively; intake from milk plus solids was 70 +/- 13 kcal/kg at 7 months. Zinc intakes from human milk were 2.3 +/- 0.68, 1.0 +/- 0.43, 0.81 +/- 0.42, and 0.52 +/- 0.31 mg/day at these points. The maximum mean weight-for-age percentile for both sexes was 62 at 2 months; the mean percentile declined to 33 by 7 months and to 25 by 9 months of age. Mean length-for-age percentile declined from 43 at 2 weeks of age to 28 and 26 by 7 and 9 months of age, respectively. Energy intake at 2 weeks of age was positively associated with the weight increment from 2 weeks to 7 months of age (p = 0.003) and with a change in weight-for-age z scores from 2 weeks to 3 months of age (p = 0.028). Mean energy intakes of healthy breast-fed infants are lower through the first 7 months of life than current recommendations. Zinc intakes of breast-fed infants are likely to be adequate, on average, through 5 months of breast-feeding but subsequently are marginal without the introduction of weaning foods. Revision of standards for growth based on observations in breast-fed infants may be appropriate, but the possibility of growth-limiting nutrient deficiencies should also be investigated.

Zinc and diarrhea.

Malnutrition is a major factor in the etiology, management and prognosis of persistent diarrhea in young children. Apart from inadequate energy intake, deficiencies of several specific nutrients have been implicated. Zinc is a micronutrient that appears to be of special interest, at least in some communities. Zinc deficiency has been documented in otherwise normal children. The risk of deficiency, however, is enhanced by diarrhea which is associated with variable but sometimes gross increases in zinc losses in the feces. These losses could contribute to a vicious circle, as there is now evidence that mild as well as severe zinc deficiency states can contribute to the duration and severity of diarrheal disease. During rehabilitation, impaired zinc nutriture could be responsible for slow growth, especially if the rehabilitation diet is high in phytate, a recognized inhibitor of zinc absorption. Research should be directed to a better understanding of zinc metabolism and homeostasis during diarrhea disease, to the consequences of zinc deficiency and to the benefits to be derived from zinc supplementation programs.

The Maternal and Newborn Health Registry Study of the Global Network for Women's and Children's Health Research

To implement a vital statistics registry system to register pregnant women and document birth outcomes in the Global Network for Womens and Childrens Health Research sites in Asia, Africa, and Latin America.

The use of stable isotope techniques to assess zinc metabolism

The refinement of techniques that can accurately measure small changes in zinc stable isotope ratios in biological samples provides new opportunities for advancing our understanding of human zinc metabolism. The feasibility of utilizing more than one zinc stable isotope label simultaneously is invaluable for more complex kinetic studies. These techniques are especially valuable for investigations of the regulation of Zn homeostasis in infants and in women during the reproductive cycle in whom problems with zinc nutriture may be relatively frequent and of concern for preand postnatal growth and development. Initially, these techniques have been applied to studying the role of the intestine in the maintenance of zinc homeostasis and have served to emphasize the importance of the modulation of fecal excretion of endogenous zinc. Application of stable isotope techniques to explore zinc metabolism beyond the intestinal tract is still limited but has considerable potential for advancing our understanding of zinc metabolism in health and disease.

Biofortification of Pearl Millet with Iron and Zinc in a Randomized Controlled Trial Increases Absorption of These Minerals above Physiologic Requirements in Young Children

Millet is unusually drought resistant and consequently there is a progressive increase in the use of these grains as a human food staple, especially in large areas of India and sub-Saharan Africa. The purpose of this study was to determine the absorption of iron and zinc from pearl millet biofortified with 2 micronutrients that are typically deficient in nonfortified, plant-based diets globally. The study was undertaken in 40 children aged 2 y in Karnataka, India (n = 21 test/19 controls). Three test meals providing ∼84 ± 17 g dry pearl millet flour were fed on a single day for zinc and 2 d for iron between 0900 and 1600 h. The quantities of zinc and iron absorbed were measured with established stable isotope extrinsic labeling techniques and analyses of duplicate diets. The mean (± SD) quantities of iron absorbed from test and control groups were 0.67 ± 0.48 and 0.23 ± 0.15 mg/d, respectively (P < 0.001). The quantities of zinc absorbed were 0.95 ± 0.47 and 0.67 ± 0.24 mg/d, respectively (P = 0.03). These data did not include absorption of the modest quantities of iron and zinc contained in snacks eaten before and after the 3 test meals. In conclusion, quantities of both iron and zinc absorbed when iron and zinc biofortified pearl millet is fed to children aged 2 y as the major food staple is more than adequate to meet the physiological requirements for these micronutrients.

Dietary reference intakes for zinc may require adjustment for phytate intake based upon model predictions.

The quantity of total dietary zinc (Zn) and phytate are the principal determinants of the quantity of absorbed Zn. Recent estimates of Dietary Reference Intakes (DRI) for Zn by the Institute of Medicine (IOM) were based on data from low-phytate or phytate-free diets. The objective of this project was to estimate the effects of increasing quantities of dietary phytate on these DRI. We used a trivariate model of the quantity of Zn absorbed as a function of dietary Zn and phytate with updated parameters to estimate the phytate effect on the Estimated Average Requirement (EAR) and Recommended Daily Allowance for Zn for both men and women. The EAR predicted from the model at 0 phytate was very close to the EAR of the IOM. The addition of 1000 mg phytate doubled the EAR and adding 2000 mg phytate tripled the EAR. The model also predicted that the EAR for men and women could not be attained with phytate:Zn molar ratios > 11:1 and 15:1, respectively. The phytate effect on upper limits (UL) was predicted by first estimating the quantity of absorbed Zn corresponding to the UL of 40 mg for phytate-free diets, which is 6.4 mg Zn/d. Extrapolation of the model suggested, for example, that with 900 mg/d phytate, 100 mg dietary Zn is required to attain 6.4 mg absorbed Zn/d. Experimental studies with higher Zn intakes are required to test these predictions.