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.

The International Atomic Energy Agency International Doubly Labelled Water Database: Aims, Scope and Procedures.

BACKGROUND: The doubly labelled water (DLW) method is an isotope-based technique that quantifies total energy expenditure (TEE) over periods of 1-3 weeks from the differential elimination of stable isotopes of oxygen and hydrogen. The method was invented in the 1950s, but limited ability to measure low isotope enrichments combined with the high cost of isotopes meant it only became feasible to use in humans in the 1980s. It is still relatively expensive to use, and alone small samples are unable to tackle some of the important questions surrounding energy balance such as how have expenditures changed over time and how do expenditures differ with age, between sexes and in different environments? SUMMARY: By combining information across studies, answers to such questions may be possible. The International Atomic Energy Agency (IAEA) DLW database was established to pool DLW data across multiple studies. It was initiated by the main labs currently using the method and is hosted by the IAEA. At present, the database contains 6,621 measures of TEE by DLW from individuals in 23 countries, along with various additional data on the study participants. Key Messages: The IAEA DLW database is a key resource enabling future studies of energy demands.

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.

Moderate acute malnutrition: uncovering the known and unknown for more effective prevention and treatment.

With a fast-approaching post-Millennium Development Goal era, there is an urgent need to boost global investment in efforts to reduce child malnutrition. Critical to the management of moderate malnutrition, and therefore to the new Sustainable Development Goals, is addressing severe acute malnutrition (SAM) and moderate acute malnutrition (MAM). Despite the considerable difference in the approximate number of children affected by MAM (33 million) compared with SAM (19 million), there is currently no standardized approach to the management of MAM. In partnership with Valid International, the World Food Programme, and the Micronutrient Initiative, the International Atomic Energy Agency hosted the International Symposium on Understanding Moderate Malnutrition in Children for Effective Interventions in Vienna, Austria, 26-29 May 2014. This symposium focused on the management (prevention and treatment) of MAM in children. The symposium convened over 350 participants from 63 countries, the majority of whom represented governments responding to moderate malnutrition in their populations, nearly 70 national and international organizations from the United Nations and nongovernmental sectors, and universities from around the world, as well as donor governments and private-sector entities. The symposium was structured around nine sessions over a 3-day period, progressing from a global analysis of the scale of the problem to recent research findings relevant to designing effective interventions. This Supplement contains a series of papers that summarize the symposium sessions and other fundamental aspects important to improving the management of moderate malnutrition in children.

Health and nutrition knowledge, attitudes and practices of pregnant women attending and not-attending ANC clinics in Western Kenya: a cross-sectional analysis.

BACKGROUND: Antenatal care (ANC) is a key strategy to decreasing maternal mortality in low-resource settings. ANC clinics provide resources to improve nutrition and health knowledge and promote preventive health practices. We sought to compare the knowledge, attitude and practices (KAP) among women seeking and not-seeking ANC in rural Kenya. METHODS: Data from a community-based cross-sectional survey conducted in Western Province, Kenya were used. Nutrition knowledge (NKS), health knowledge (HKS), attitude score (AS), and dietary diversity score (DDS) were constructed indices. χ2 test and Student's t-test were used to compare proportions and means, respectively, to assess the difference in KAP among pregnant women attending and not-attending ANC clinics. Multiple regression analyses were used to assess the impact of the number of ANC visits (none, <4, ≥4) on knowledge and practice scores, adjusting for maternal socio-demographic confounders, such as age, gestational age, education level and household wealth index. RESULTS: Among the 979 pregnant women in the survey, 59% had attended ANC clinics while 39% had not. The mean (±SD) NKS was 4.6 (1.9) out of 11, HKS was 6.2 (1.7) out of 12, DDS was 4.9 (1.4) out of 12, and AS was 7.4 (2.2) out of 10. Nutrition knowledge, attitudes, and DDS were not significantly different between ANC clinic attending and non-attending women. Among women who attended ANC clinics, 82.6% received malaria and/or antihelmintic treatment, compared to 29.6% of ANC clinic non-attendees. Higher number of ANC clinic visits and higher maternal education level were significantly positively associated with maternal health knowledge. CONCLUSIONS: Substantial opportunities exist for antenatal KAP improvement among women in Western Kenya, some of which could occur with greater ANC attendance. Further research is needed to understand multi-level factors that may affect maternal knowledge and practices.

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.

Introduction of ß-carotene-rich orange sweet potato in rural Uganda resulted in increased vitamin A intakes among children and women and improved vitamin A status among children.

Vitamin A deficiency (VAD) persists in Uganda and the consumption of ß-carotene-rich orange sweet potato (OSP) may help to alleviate it. Two large-scale, 2-y intervention programs were implemented among Ugandan farmer households to promote the production and consumption of OSP. The programs differed in their inputs during year 2, with one being more intensive (IP) and the other being reduced (RP). A randomized, controlled effectiveness study compared the impact of the IP and RP with a control on OSP and vitamin A intakes among children aged 6-35 mo (n = 265) and 3-5 y (n = 578), and women (n = 573), and IP compared with control on vitamin A status of 3- to 5-y-old children (n = 891) and women (n = 939) with serum retinol <1.05 µmol/L at baseline. The net OSP intake increased in both the IP and RP groups (P < 0.01), accounting for 44-60% of vitamin A intake at follow-up. The prevalence of inadequate vitamin A intake was reduced in the IP and RP groups compared with controls among children 6-35 mo of age (>30 percentage points) and women (>25 percentage points) (P < 0.01), with no differences between the IP and RP groups of children (P = 0.75) or women (P = 0.17). There was a 9.5 percentage point reduction in prevalence of serum retinol <1.05 µmol/L for children with complete data on confounding factors (n = 396; P < 0.05). At follow-up, vitamin A intake from OSP was positively associated with vitamin A status (P < 0.05). Introduction of OSP to Ugandan farming households increased vitamin A intakes among children and women and was associated with improved vitamin A status among children.

A large-scale intervention to introduce orange sweet potato in rural Mozambique increases vitamin A intakes among children and women.

ß-Carotene-rich orange sweet potato (OSP) has been shown to improve vitamin A status of infants and young children in controlled efficacy trials and in a small-scale effectiveness study with intensive exposure to project inputs. However, the potential of this important food crop to reduce the risk of vitamin A deficiency in deficient populations will depend on the ability to distribute OSP vines and promote its household production and consumption on a large scale. In rural Mozambique, we conducted a randomised, controlled effectiveness study of a large-scale intervention to promote household-level OSP production and consumption using integrated agricultural, demand creation/behaviour change and marketing components. The following two intervention models were compared: a low-intensity (1 year) and a high-intensity (nearly 3 years) training model. The primary nutrition outcomes were OSP and vitamin A intakes by children 6-35 months and 3-5·5 years of age, and women. The intervention resulted in significant net increases in OSP intakes (model 1: 46, 48 and 97 g/d) and vitamin A intakes (model 1: 263, 254 and 492 µg retinol activity equivalents/d) among the younger children, older children and women, respectively. OSP accounted for 47-60 % of all sweet potato consumed and, among reference children, provided 80 % of total vitamin A intakes. A similar magnitude of impact was observed for both models, suggesting that group-level trainings in nutrition and agriculture could be limited to the first project year without compromising impact. Introduction of OSP to rural, sweet potato-producing communities in Mozambique is an effective way to improve vitamin A intakes.

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.

Human total, basal and activity energy expenditures are independent of ambient environmental temperature.

Lower ambient temperature (Ta) requires greater energy expenditure to sustain body temperature. However, effects of Ta on human energetics may be buffered by environmental modification and behavioral compensation. We used the IAEA DLW database for adults in the USA (n = 3213) to determine the effect of Ta (-10 to +30°C) on TEE, basal (BEE) and activity energy expenditure (AEE) and physical activity level (PAL). There were no significant relationships (p > 0.05) between maximum, minimum and average Ta and TEE, BEE, AEE and PAL. After adjustment for fat-free mass, fat mass and age, statistically significant (p < 0.01) relationships between TEE, BEE and Ta emerged in females but the effect sizes were not biologically meaningful. Temperatures inside buildings are regulated at 18-25°C independent of latitude. Hence, adults in the US modify their environments to keep TEE constant across a wide range of external ambient temperatures.

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.].