Atoms for Nutrition: IAEA's Contribution to Tackling Malnutrition.

Nuclear techniques, including stable isotope techniques, provide great potential for understanding nutrition and human health with better accuracy and precision compared with other routine techniques. The International Atomic Energy Agency (IAEA) has been at the forefront for more than 25 y to offer guidance and support on the use of nuclear techniques. This article demonstrates how the IAEA has enabled its Member States to contribute to good health and well-being in their countries and to assess progress toward achieving global nutrition and health targets to combat malnutrition in all its forms. Support is provided in several ways including research, capacity building, education, and training as well as the provision of guidance materials. The nuclear techniques help to objectively measure nutritional and health-related outcomes such as body composition, energy expenditure, nutrient uptake, and body stores and assess breastfeeding practices as well as environmental interactions. These techniques are continuously improved to make nutritional assessments more affordable and less invasive with wide use in field settings. New research areas are emerging to assess diet quality with changing food systems and to explore stable isotope-assisted metabolomics to address key questions on nutrient metabolism. Through a deeper understanding of mechanisms, nuclear techniques can contribute to eradicating malnutrition worldwide.

Approaches to Address the Anemia Challenge.

Anemia is a multifactorial condition; approaches to address it must recognize that the causal factors represent an ecology consisting of internal (biology, genetics, and health) and external (social/behavioral/demographic and physical) environments. In this paper, we present an approach for selecting interventions, followed by a description of key issues related to the multiple available interventions for prevention and reduction of anemia. We address interventions for anemia using the following 2 main categories: 1) those that address nutrients alone, and, 2) those that address nonnutritional causes of anemia. The emphasis will be on interventions of public health relevance, but we also consider the clinical context. We also focus on interventions at different stages of the life course, with a particular focus on women of reproductive age and preschool-age children, and present evidence on various factors to consider when selecting an intervention-inflammation, genetic mutations, nutrient delivery, bioavailability, and safety. Each section on an intervention domain concludes with a brief discussion of key research areas.

Association between Biomarkers of Inflammation and Total Liver Vitamin A Reserves Estimated by 13C-Retinol Isotope Dilution among Preschool Children in 5 African Countries.

BACKGROUND: Vitamin A (VA) assessment is important for targeting public health programs. Retinol isotope dilution (RID) is a sensitive method to estimate total body VA stores (TBSs) and total liver reserves (TLRs), but the impact of subclinical inflammation on RID is unclear. OBJECTIVE: We determined the association between TBSs and TLRs, estimated by RID, and inflammation among preschool children without clinical infection in Burkina Faso, Cameroon, Ethiopia, South Africa, and Tanzania. METHODS: Five studies (n = 532; 47.9 ± 8.3 mo; 49.0% male) included 13C-RID and measurement of inflammation markers, CRP, and α1-acid glycoprotein (AGP). Spearman correlations were used to evaluate TBSs and TLRs with inflammation biomarkers. Wilcoxon and Kruskal-Wallis tests were used to compare TBSs and TLRs by inflammation categories [normal vs. elevated CRP (>5 mg/L) or AGP (>1 g/L)] and inflammation stage [reference, incubation (elevated CRP), early convalescence (elevated CRP and AGP), and late convalescence (elevated AGP)]. RESULTS: Complete data were available for 439 children. Median (Q1, Q3) TLRs ranged from 0.12 (0.07, 0.18) µmol/g in Ethiopia to 1.10 (0.88, 1.38) µmol/g in South Africa. Elevated CRP ranged from 4% in Burkina Faso to 42% in Cameroon, and elevated AGP from 20% in Tanzania to 58% in Cameroon. Pooled analysis (excluding Cameroon) showed a negative correlation between TBSs and AGP (ρ = -0.131, P = 0.01). Children with elevated AGP had higher probability of having lower TBSs (probability = 0.61, P = 0.002). TBSs differed among infection stages (P = 0.020). Correlations between TLRs and CRP or AGP were not significant. CONCLUSIONS: No indication of systematic bias in RID-estimated TLRs was found due to subclinical inflammation among preschool children. The inverse relationship between TBSs and AGP may reflect decreased stores after infection or an effect of inflammation on isotope partitioning. Further research should investigate potential confounding variables to improve TBS-estimate validity.

Childhood BMI and other measures of body composition as a predictor of cardiometabolic non-communicable diseases in adulthood: a systematic review.

OBJECTIVE: There is growing evidence that childhood malnutrition is associated with non-communicable diseases (NCD) in adulthood and that body composition mediates some of this association. This review aims to determine if childhood body composition can be used to predict later-life cardiometabolic NCD and which measures of body composition predicts future NCD. DESIGN: Electronic databases were searched for articles where: children aged under 5 years had body composition measured; cardiometabolic health outcomes were measured a minimum of 10 years later. SETTING: The databases Embase, Medline and Global Health were searched through July 2020. PARTICIPANTS: Children aged under 5 years with a follow-up of minimum 10 years. RESULTS: Twenty-nine studies met the inclusion criteria. Though a poor proxy measure of body composition, body mass index (BMI) was commonly reported (n 28, 97 %). 25 % of these studies included an additional measure (ponderal index or skinfold thickness). Few studies adjusted for current body size (n 11, 39 %). CONCLUSIONS: Many studies reported that low infant BMI and high childhood BMI were associated with an increased risk of NCD-related outcomes in later life but no conclusions can be made about the exact timing of child malnutrition and consequent impact on NCD. Because studies focussed on BMI rather than direct measures of body composition, nothing can be said about which measures of body composition in childhood are most useful. Future research on child nutrition and long-term outcomes is urgently needed and should include validated body composition assessments as well as standard anthropometric and BMI measurements.

Tea Consumption Reduces Iron Bioavailability from NaFeEDTA in Nonanemic Women and Women with Iron Deficiency Anemia: Stable Iron Isotope Studies in Morocco.

BACKGROUND: Available data suggest that polyphenols from tea can inhibit iron absorption from ferric sodium EDTA (NaFeEDTA), but previous studies were done in small groups of mostly nonanemic adults. Morocco recently introduced national wheat flour fortification with NaFeEDTA, but tea is the national beverage and is consumed with most meals. OBJECTIVES: Our objective was to quantify bioavailability of iron from NaFeEDTA when added to a wheat flour-based meal in both nonanemic women and women with iron deficiency anemia (IDA), when consumed with and without traditional Moroccan green tea. METHODS: We recruited 2 groups of healthy Moroccan women (n = 46): women with IDA (n = 25; hemoglobin <12 g/dL,  serum ferritin <15 µg/L) and nonanemic women (n = 21). Each group received in random order 2 standardized test meals containing 6 mg Fe as isotopically labeled NaFeEDTA and either 300 mL of tea or water. Fractional iron absorption (FIA) was measured by the erythrocyte incorporation of stable iron isotopes after 14 d. We performed linear mixed-model analysis and post hoc sample t tests to assess the effects of group and tea on FIA. RESULTS: The polyphenol content of the tea serving was 492 mg. Tea consumption reduced iron absorption from NaFeEDTA by >85% in both IDA and nonanemic women. There were group (P < 0.001) and tea (P < 0.001) effects on FIA, but no group by tea interaction (P = 0.312). Median (IQR) FIA (%) in women with IDA from test meals consumed without and with tea was 36.7 (24.2-39.8) and 4.1 (2.8-6.1), respectively (P < 0.001). Median (IQR) FIA (%) in nonanemic women from test meals consumed without and with tea was 16.7 (9.2-24.2) and 1.4 (0.8-2.9), respectively (P < 0.001). CONCLUSIONS: FIA from wheat flour-based meals without and with tea was ∼2-fold higher in women with IDA than in nonanemic women. Providing fortificant iron as NaFeEDTA cannot overcome the inhibition of tea polyphenols on iron absorption, even in IDA, where iron absorption is strongly upregulated. This trial was registered at www.clinicaltrials.gov as NCT02175888.

Body mass index vs deuterium dilution method for establishing childhood obesity prevalence, Ghana, Kenya, Mauritius, Morocco, Namibia, Senegal, Tunisia and United Republic of Tanzania.

OBJECTIVE: To compare the World Health Organization (WHO) body mass index (BMI)-for-age definition of obesity against measured body fatness in African children. METHODS: In a prospective multicentre study over 2013 to 2017, we recruited 1516 participants aged 8 to 11 years old from urban areas of eight countries (Ghana, Kenya, Mauritius, Morocco, Namibia, Senegal, Tunisia and United Republic of Tanzania). We measured height and weight and calculated BMI-for-age using WHO standards. We measured body fatness using the deuterium dilution method and defined excessive body fat percentage as > 25% in boys and > 30% in girls. We calculated the sensitivity and specificity of BMI z-score > +2.00 standard deviations (SD) and used receiver operating characteristic analysis and the Youden index to determine the optimal BMI z-score cut-off for classifying excessive fatness. FINDINGS: The prevalence of excessive fatness was over three times higher than BMI-for-age-defined obesity: 29.1% (95% CI: 26.8 to 31.4; 441 children) versus 8.8% (95% CI: 7.5 to 10.4; 134 children). The sensitivity of BMI z-score > +2.00 SD was low (29.7%, 95% CI: 25.5 to 34.2) and specificity was high (99.7%, 95% CI: 99.2 to 99.9). The receiver operating characteristic analysis found that a BMI z-score +0.58 SD would optimize sensitivity, and at this cut-off the area under the curve was 0.86, sensitivity 71.9% (95% CI: 67.4 to 76.0) and specificity 91.1% (95% CI: 89.2 to 92.7). CONCLUSION: While BMI remains a practical tool for obesity surveillance, it underestimates excessive fatness and this should be considered when planning future African responses to the childhood obesity pandemic.

In Haitian women and preschool children, iron absorption from wheat flour-based meals fortified with sodium iron EDTA is higher than that from meals fortified with ferrous fumarate, and is not affected by Helicobacter pylori infection in children.

Fe fortification of wheat flour was proposed in Haiti to combat Fe deficiency, but Fe bioavailability from fortificants has never been investigated in Haitian women or preschool children, two key target groups. We aimed to investigate the bioavailability of ferrous fumarate (FeFum), NaFeEDTA and their combination from fortified wheat flour. We recruited twenty-two healthy mother-child pairs in Port au Prince, Haiti, for an Fe-absorption study. We administered stable Fe isotopes as FeFum or NaFeEDTA individually in low-extraction wheat flour bread rolls consumed by all participants in a randomised, cross-over design. In a final, identical meal, consumed only by the women, FeFum+NaFeEDTA was administered. We measured Fe absorption by using erythrocyte incorporation of stable isotopes 14 d after consumption of each meal, and determined Fe status, inflammatory markers and Helicobacter pylori infection. Fe absorption (geometric mean was 9·24 (95 % CI 6·35, 13·44) and 9·26 (95 % CI 7·00, 12·31) from FeFum and 13·06 (95 % CI 9·23, 19·10) and 12·99 (95 % CI 9·18, 18·39) from NaFeEDTA in mothers and children, respectively (P<0·05 between compounds). Fe absorption from FeFum+NaFeEDTA was 11·09 (95 % CI 7·45, 17·34) and did not differ from the other two meals. H. pylori infection did not influence Fe absorption in children. In conclusion, in Haitian women and children, Fe absorption from NaFeEDTA was 40 % higher than from FeFum, and the combination FeFum+NaFeEDTA did not significantly increase Fe absorption compared with FeFum alone. In the context of Haiti, where the high costs of NaFeEDTA may not be affordable, the use of FeFum at 60 mg Fe/kg flour may be a preferable, cost-effective fortification strategy.

Stable Isotope Techniques for the Assessment of Host and Microbiota Response During Gastrointestinal Dysfunction.

The International Atomic Energy Agency convened a technical meeting on environmental enteric dysfunction (EED) in Vienna (October 28-30, 2015; https://nucleus.iaea.org/HHW/Nutrition/EED_Technical_Meeting/index.html) to bring together international experts in the fields of EED, nutrition, and stable isotope technologies. Advances in stable isotope-labeling techniques open up new possibilities to improve our understanding of gastrointestinal dysfunction and the role of the microbiota in host health. In the context of EED, little is known about the role gut dysfunction may play in macro- and micronutrient bioavailability and requirements and what the consequences may be for nutritional status and linear growth. Stable isotope labeling techniques have been used to assess intestinal mucosal injury and barrier function, carbohydrate digestion and fermentation, protein-derived amino acid bioavailability and requirements, micronutrient bioavailability and to track microbe-microbe and microbe-host interactions at the single cell level. The noninvasive nature of stable isotope technologies potentially allow for low-hazard, field-deployable tests of gut dysfunction that are applicable across all age groups. The purpose of this review is to assess the state-of-the-art use of stable isotope technologies and to provide a perspective on where these technologies can be exploited to further our understanding of gut dysfunction in EED.

Body composition from birth to 2 years.

Providing all infants with the best start to life is a universal but challenging goal for the global community. Historically, the size and shape of infants, quantified by anthropometry and commencing with birthweight, has been the common yardstick for physical growth and development. Anthropometry has long been considered a proxy for nutritional status during infancy when, under ideal circumstances, changes in size and shape are most rapid. Developed from data collected in the Multicentre Growth Reference Study (MGRS), WHO Child Growth Standards for healthy infants and children have been widely accepted and progressively adopted. In contrast, and somewhat surprisingly, much less is understood about the 'quality' of growth as reflected by body composition during infancy. Recent advances in body composition assessment, including the more widespread use of air displacement plethysmography (ADP) across the first months of life, have contributed to a progressive increase in our knowledge and understanding of growth and development. Along with stable isotope approaches, most commonly the deuterium dilution (DD) technique, the criterion measure of total body water (TBW), our ability to quantify lean and fat tissue using a two-compartment model, has been greatly enhanced. However, until now, global reference charts for the body composition of healthy infants have been lacking. This paper details some of the historical challenges associated with the assessment of body composition across the first two years of life, and references the logical next steps in growth assessments, including reference charts.

Body composition reference charts for infants from birth to 24 months: Multicenter Infant Body Composition Reference Study.

BACKGROUND: Body composition assessment in the first 2 y of life provides important insights into child nutrition and health. The application and interpretation of body composition data in infants and young children have been challenged by a lack of global reference data. OBJECTIVES: We aimed to develop body composition reference charts of infants aged 0-6 mo based on air displacement plethysmography (ADP) and those aged 3-24 mo based on total body water (TBW) by deuterium dilution (DD). METHODS: Body composition was assessed by ADP in infants aged 0-6 mo from Australia, India, and South Africa. TBW using DD was assessed for infants aged 3-24 mo from Brazil, Pakistan, South Africa, and Sri Lanka. Reference charts and centiles were constructed for body composition using the lambda-mu-sigma method. RESULTS: Sex-specific reference charts were produced for FM index (FMI), FFM index (FFMI), and percent FM (%FM) for infants aged 0-6 mo (n = 470 infants; 1899 observations) and 3-24 mo (n = 1026 infants; 3690 observations). When compared with other available references, there were observable differences but similar patterns in the trajectories of FMI, FFMI, and %FM. CONCLUSIONS: These reference charts will strengthen the interpretation and understanding of body composition in infants across the first 24 mo of life.

Birth Weight and Body Composition as Determined by Isotopic Dilution with Deuterium Oxide in 6- to 8-Year-Old South African Children.

Low and high birth weight (BW) are associated with obesity later in life; however, this association has not been extensively studied in African countries. This study determines the association between BW and body composition derived from deuterium oxide (D2O) dilution in 6- to 8-year-old South African children (n = 91; 40 boys, 51 girls). BW was recorded retrospectively from the children's Road-to-Health cards. Weight and height were measured using standard procedures, and D2O dilution was used to determine total body water and, subsequently, to determine body fat. Fatness was classified using the McCarthy centiles, set at 2nd, 85th, and 95th (underfat, overfat and obese). BW correlated with body composition measures, such as body weight (r = 0.23, p = 0.03), height (r = 0.33, p < 0.001), and fat free mass (FFM; r = 0.27, p = 0.01). When multiple regression analysis was employed, BW significantly and positively associated with FFM (ß = 0.24, p = 0.013; 95% CI: 0.032; 0.441) and fat mass (ß = 0.21, p = 0.02, 95%CI: 0.001; 0.412) in girls and boys combined. A total of 13% of the children had a low BW, with 21% being overweight and 17% obese. More girls than boys were overweight and obese. Intervention strategies that promote healthy uterine growth for optimal BW are needed in order to curb the global obesity pandemic.

Erratum: Level of agreement between objectively determined body composition and perceived body image in 6- to 8-year-old South African children: The Body Composition-Isotope Technique study.

[This corrects the article DOI: 10.1371/journal.pone.0237399.].

Level of agreement between objectively determined body composition and perceived body image in 6- to 8-year-old South African children: The Body Composition-Isotope Technique study.

To assess the level of agreement between body size self-perception and actual body size determined by body mass index (BMI) z-score and body fatness measured by the deuterium dilution method (DDM) in South African children aged 6-8 years. A cross-sectional sample of 202 children (83 boys and 119 girls) aged 6-8 years from the Body Composition-Isotope Technique study (BC-IT) was taken. Subjective measures of body image (silhouettes) were compared with the objective measures of BMI z-score and body fatness measured by the DDM. The World Health Organization BMI z-scores were used to classify the children as underweight, normal, overweight, or obese. DDM-measured fatness was classified based on the McCarthy centile curves set at 2nd, 85th and 95th in conjunction with fatness cut-off points of 25% in boys and 30% in girls. Data were analyzed using SPSS v26. Of 202 children, 32.2%, 55.1%, 8.8%, and 2.4% perceived their body size as underweight, normal, overweight, and obese, respectively. Based on BMI z-score, 18.8%, 72.8%, 6.9%, and 1.5% were classified as underweight, normal, overweight, and obese, respectively. Body fatness measurement showed that 2.5%, 48.0%, 21.8%, and 29.7% were underweight, normal weight, overweight, and obese, respectively. The application of silhouettes and BMI z-scores resulted in either overestimation or underestimation of own body size. Overall, the levels of agreements (kappa, κ) between body size perception, body fatness, and BMI for age respectively, were small (κ = 0.083, p = 0.053 and κ = 0.154, p<0.001). Level of agreement between body size perception, body fatness, and BMI z-score was poor. The use of silhouettes made children either overestimate their own body size while being underweight or underestimate their own body size while being overweight or obese. Given the potential health implications associated with misclassification of body size during childhood, correct self-assessment of body size is important, and may be key to the adoption of weight control strategies directed at curbing the escalating obesity epidemic in the country. Scalable measures to allow for more accurate self-assessment are urgently needed-one approach is behavior change communication at all levels.

Using programme theory to assess the feasibility of delivering micronutrient Sprinkles through a food-assisted maternal and child health and nutrition programme in rural Haiti.

This paper uses programme theory to assess, in the context of an effectiveness evaluation, the feasibility and acceptability of distributing micronutrient Sprinkles through a food-assisted maternal and child health and nutrition programme in rural Haiti. We laid out the steps related to programme delivery and household utilization of Sprinkles and used qualitative and quantitative methods to gather data on these steps. Methods included structured observations, checks of beneficiary ration cards, exit interviews, focus group discussions (FGD), individual interviews and survey data from the effectiveness evaluation. Results are as follows: (1) information on use of Sprinkles was provided before mothers first received them, as planned; (2) Sprinkles were re-packaged and distributed as planned and in the appropriate amount; (3) almost all mothers (96%) received two monthly rations of Sprinkles and received timely information on their use; (4) mothers understood instructions about use of Sprinkles and acceptance was high, and no selling of the product was reported or observed; and (5) mothers reported using Sprinkles as instructed, every day (63% in survey; 86% at exit interviews), and for the child only (99%). FGD with staff highlighted the acceptance of the intervention, with a reported 'modest' increase in workload. Within this well-established programme, it proved feasible to distribute Sprinkles and to ensure appropriate use by beneficiary mothers. Existing programme venues were suitable for distributing Sprinkles and educating mothers about their use. Use of programme theory helped to assess feasibility and acceptability of the Sprinkles intervention and provided useful information for programme replication or scale-up.

Assessing supervisory and motivational factors in the context of a program evaluation in rural Haiti.

Staff supervisory and motivational factors were assessed in the context of an ongoing program evaluation in Haiti comparing 2 models of targeting an integrated health and nutrition program. The study objectives were to 1) understand and improve supervisory and motivational factors influencing program implementation and 2) compare these factors between the 2 program models being evaluated. Qualitative methods (focus group discussions and semistructured interviews) were used to understand factors related to supervision and motivation. Quantitative measures of supervisory and motivational factors were designed, and factor analysis was used, to develop summary scales of motivational factors and supervision. T-tests were used to compare mean scores on the scales between the 2 program models. Results from the qualitative research were discussed with program management and staff to help develop solutions to implementation bottlenecks. Staff at all levels of the program seemed motivated and generally well supervised. Constraints to motivation included perceived inadequacy of wages (before changes were made to salaries), heavy workloads, and logistical constraints. We found no salient differences between the 2 program models that could contribute to differential implementation or differences in impact. This lack of salient differences between the program models suggested that supervisory and motivational factors were unlikely to contribute to differences in impact. Assessing supervisory and motivational factors was feasible and desirable in the context of this evaluation and deepened understanding of the program context and constraints to implementation.

Elucidating Adverse Nutritional Implications of Exposure to Endocrine-Disrupting Chemicals and Mycotoxins through Stable Isotope Techniques.

Multiple drivers of the double burden of malnutrition (DBM) include a rapid shift from predominantly plant-based diets to energy-dense foods based on meats, milk, animal fats and vegetable oils. The shift to overweight and obesity is driven by increased exposure to mass media, urbanization, technological advances in food processing, rising income and increased population density associated with increased access to cheap foods. At the same time, undernutrition persists mainly due to food insecurity and lack of access to safe water, sanitation and adequate health care. All known nutrition interventions result in only one third reduction in stunting. Little consideration has been given to hazardous exposure to endocrine disrupting chemicals (EDCs) and microbial toxins as major components of the malnutrition-causal framework. These hazards include microbial toxins, for example, mycotoxins, and environmental pollutants such as persistent organic pollutants (POPs), some of which are known to disrupt the endocrine system. These hazards sit at the cross road of undernutrition and overweight and obesity since the exposure cuts across the critical window of opportunity (the first 1000 days). In this review, we update on the role of food and environmental contaminants, especially EDCs and aflatoxins, in child growth and on the implications for metabolic dysfunction and disease risk in later life, and discuss potential applications of nuclear and isotopic techniques to elucidate the underlying biological mechanisms, outcome indicators, as well as occurrence levels.

Using stable isotope techniques in nutrition assessments and tracking of global targets post-2015.

Stable isotopes are non-radioactive, safe and are applied for various purposes in human health assessment in trace amounts that minimally disturb normal physiology. The International Atomic Energy Agency supports the use of stable isotope techniques to design and evaluate interventions addressing malnutrition in all its forms with focus on infant and young child feeding; maternal and adolescent nutrition; diet quality; prevention and control of non-communicable diseases; healthy ageing and gut function. These techniques can be used to objectively measure: (1) amount of human milk consumed and whether an infant is exclusively breastfed; (2) body composition in the context of re-feeding programmes for moderate and severe acute malnutrition and as an indicator of the risk for obesity; (3) bioavailability and bioconversion of pro-vitamin A and vitamin A body stores following vitamin A intervention programmes; (4) absorption and retention of iron, zinc and protein; (5) total energy expenditure for validation of physical activity measurement and dietary assessment tools and (6) diagnosis of Helicobacter pylori. Stable isotope techniques will be invaluable in the tracking of global targets on exclusive breast-feeding childhood obesity and anaemia among women. Efforts are underway to make nuclear techniques more affordable, field-friendly and less invasive, and to develop less sophisticated but precise equipment. Advocacy for the wide adoption of the techniques is needed.