Evaluation of pharmacokinetics of single-dose primaquine in undernourished versus normally nourished children diagnosed with Plasmodium vivax malaria in Mumbai.

BACKGROUND: The pharmacokinetics of primaquine [PQ] have been the subject of studies in both adults and healthy participants. However, there is no study on its pharmacokinetics in a setting of undernourishment. In India, there is evidence to show considerable malnourishment in children that in turn can affect drug pharmacokinetics. Given that the country is moving towards malaria elimination, the present study was planned with the objective of comparing pharmacokinetics of the drug in undernourished children relative to normally nourished children. MATERIALS AND METHODS: After Institutional Ethics Committee approval, children of either gender between the ages of 5 and 12 years and smear-positive for Plasmodium vivax malaria were included. Nourishment status was determined using the Indian Academy of Pediatrics classification of protein energy malnutrition based on Khadilkar's growth charts. Twelve children each were enrolled in the two groups. PQ was given in the dose of 0.3 mg/kg/d and blood collections were made at 0, 1, 2, 3, 4, 6, 8 and 24 hours post-dosing. Levels were estimated by high-performance liquid chromatography. Chloroquine in the dose of 25 mg/kg was given over three days along with supportive care. RESULTS: Of the 24 children, there were 17 boys and 7 girls. There was a statistically significant difference in the body weight between the undernourished and the normally nourished children [21.5 ± 5.52 vs. 28.8 ± 8.84, P < 0.05]. PQ levels showed wide inter-individual variation in both groups. No significant difference was seen in any pharmacokinetic parameter between the two groups. DISCUSSION: This study adds to the limited body of evidence on the pharmacokinetics of PQ in children with malaria and indicates that the dosing of primaquine could potentially be independent of the nourishment status.

Whole-blood PUFA and associations with markers of nutritional and health status in acutely malnourished children in Cambodia.

OBJECTIVE: To measure fatty acid composition, particularly whole-blood PUFA content, in acutely malnourished children and identify associations with markers of nutritional and health status. DESIGN: PUFA were assessed in dried blood spots obtained from a cross-sectional study. Nutritional and health status were assessed by anthropometry, haemoglobinopathies, inflammation and blood counts. SETTING: Cambodia. PARTICIPANTS: The study was conducted with 174 children aged 0·5-18 years with acute malnutrition. RESULTS: Among total fatty acids (FA), the relative percentage of total PUFA was 20 % FA, with 14 % of the children having very low PUFA (mead acid (MA):arachidonic acid (AA) >0·02, n-6 docosapentaenoic acid:DHA >0·2 and total n-6:n-3 PUFA >10·5). Wasting was not associated with any PUFA. Stunting and low height were consistently positively associated with total PUFA and positively with n-6 PUFA. Height was positively associated with n-3 long-chain PUFA (LCPUFA). The presence of haemoglobinopathies or inflammation was positively associated with MA:AA, but not total PUFA. Elevated blood platelet counts were positively correlated with linoleic acid and appeared to be influenced by anaemia (P = 0·010) and inflammation (P = 0·002). Monocyte counts were high during inflammation (P = 0·052) and correlated positively with n-6 LCPUFA and n-3 LCPUFA. CONCLUSIONS: Children with acute malnutrition or stunting had low PUFA, while elevated platelets and monocytes were associated with high PUFA. In acutely malnourished children, inflammation could lead to elevated blood cell counts resulting in increased whole-blood PUFA which does not reflect dietary intake or nutritional status.

Association of vitamin D and diarrhoea in children aged less than five years at Muhimbili national hospital, Dar es Salaam: an unmatched case control study.

BACKGROUND: There has been a growing interest in the non-skeletal roles of vitamin D particularly its immune-modulatory properties which has been shown to influence the susceptibility and severity to infections. There is insufficient data globally on the association between Vitamin D levels and Diarrhoea in children. The objective of the study was to determine the association between vitamin D levels and diarrhoea in children aged less than five years. METHODS: Hospital based unmatched case-control study was carried out at MNH between September 2015 and January 2016. Cases were defined as patients with diarrhoea, Sick controls were patients who did not have diarrhoea but were admitted for other illnesses and Healthy controls were children who had neither diarrhoea nor other co-morbid conditions. Structured questionnaires were used to capture the demographic data and anthropometric measurements. Blood samples of study participants were tested for serum vitamin D levels and grouped as vitamin D sufficient, insufficient or deficient (VDD). SPSSv.20 was used to carry out the Statistical analysis. Binary logistic regression, Mann-Whitney and Kruskal-Wallis tests were used, a p-value≤ 0.05 was considered to be statistically significant. RESULTS: A total of 188 children under five were recruited in the study at the ratio of 1 case: 3 controls, of these 47 were Cases, 94 were Sick controls and remaining 47 were Healthy controls. The mean age was 17.01 ± 14.8 months. The mean vitamin D level was 51.18 ± 21.97 nmol/l. Majority of the participants 101 (53.7%) were vitamin D deficient, 64 (34%) were insufficient and 23 (12.2%) had sufficient vitamin D levels. Sick controls were 3.2 times more likely to be VDD compared to cases [95% CI 0.14-0.69; p = 0.0015] and 5.03 times when compared to Healthy controls [95% CI 2.22-11.55; p = 0.000]. Severe acute malnutrition (SAM) was independently associated with diarrhoea (95% CI: 1.26-5.39, p 0.01). CONCLUSIONS: High prevalence of vitamin D deficiency was found in the children under five years studied. Vitamin D levels was not found to be specifically associated with diarrhoea in children under five years of age.

Gut microbiota dysbiosis is associated with malnutrition and reduced plasma amino acid levels: Lessons from genome-scale metabolic modeling.

Malnutrition is a severe non-communicable disease, which is prevalent in children from low-income countries. Recently, a number of metagenomics studies have illustrated associations between the altered gut microbiota and child malnutrition. However, these studies did not examine metabolic functions and interactions between individual species in the gut microbiota during health and malnutrition. Here, we applied genome-scale metabolic modeling to model the gut microbial species, which were selected from healthy and malnourished children from three countries. Our analysis showed reduced metabolite production capabilities in children from two low-income countries compared with a high-income country. Additionally, the models were also used to predict the community-level metabolic potentials of gut microbes and the patterns of pairwise interactions among species. Hereby we found that due to bacterial interactions there may be reduced production of certain amino acids in malnourished children compared with healthy children from the same communities. To gain insight into alterations in the metabolism of malnourished (stunted) children, we also performed targeted plasma metabolic profiling in the first 2 years of life of 25 healthy and 25 stunted children. Plasma metabolic profiling further revealed that stunted children had reduced plasma levels of essential amino acids compared to healthy controls. Our analyses provide a framework for future efforts towards further characterization of gut microbial metabolic capabilities and their contribution to malnutrition.

The Plasma Proteome Is Associated with Anthropometric Status of Undernourished Nepalese School-Aged Children.

Background: Malnutrition affects body growth, size, and composition of children. Yet, few functional biomarkers are known to be associated with childhood morphology.Objective: This cross-sectional study examined associations of anthropometric indicators of height, musculature, and fat mass with plasma proteins by using proteomics in a population cohort of school-aged Nepalese children.Methods: Height, weight, midupper arm circumference (MUAC), triceps and subscapular skinfolds, upper arm muscle area (AMA), and arm fat area (AFA) were assessed in 500 children 6-8 y of age. Height-for-age z scores (HAZs), weight-for-age z scores (WAZs), and body mass index-for-age z scores (BAZs) were derived from the WHO growth reference. Relative protein abundance was quantified by using tandem mass spectrometry. Protein-anthropometry associations were evaluated by linear mixed-effects models and identified as having a false discovery rate (q) <5%.Results: Among 982 proteins, 1, 10, 14, and 17 proteins were associated with BAZ, HAZ, MUAC, and AMA, respectively (q < 0.05). Insulin-like growth factor (IGF)-I, 2 IGF-binding proteins, and carnosinase-1 were associated with both HAZ and AMA. Proteins involved in nutrient transport, activation of innate immunity, and bone mineralization were associated with HAZ. Several extracellular matrix proteins were positively associated with AMA alone. The proteomes of MUAC and AMA substantially overlapped, whereas no proteins were associated with AFA or triceps and subscapular skinfolds. Myosin light-chain kinase, possibly reflecting leakage from muscle, was inversely associated with BAZ. The proteome of WAZ was the largest (n = 33) and most comprehensive, including proteins involved in neural development and oxidative stress response, among others.Conclusions: Plasma proteomics confirmed known biomarkers of childhood growth and revealed novel proteins associated with lean mass in chronically undernourished children. Identified proteins may serve as candidates for assessing growth and nutritional status of children in similar undernourished settings. The antenatal micronutrient supplementation trial yielding the study cohort of children was registered at clinicaltrials.gov as NCT00115271.

Progressive Changes in the Plasma Metabolome during Malnutrition in Juvenile Pigs.

Severe acute malnutrition (SAM) is one of the leading nutrition-related causes of death in children under five years of age. The clinical features of SAM are well documented, but a comprehensive understanding of the development from a normal physiological state to SAM is lacking. Characterizing the temporal metabolomic change may help to understand the disease progression and to define nutritional rehabilitation strategies. Using a piglet model we hypothesized that a progressing degree of malnutrition induces marked plasma metabolite changes. Four-week-old weaned pigs were fed a nutrient-deficient maize diet (MAL) or nutritionally optimized reference diet (REF) for 7 weeks. Plasma collected weekly was subjected to LC-MS for a nontargeted profiling of metabolites with abundance differentiation. The MAL pigs showed markedly reduced body-weight gain and lean-mass proportion relative to the REF pigs. Levels of eight essential and four nonessential amino acids showed a time-dependent deviation in the MAL pigs from that in the REF. Choline metabolites and gut microbiomic metabolites generally showed higher abundance in the MAL pigs. The results demonstrated that young malnourished pigs had a profoundly perturbed metabolism, and this provides basic knowledge about metabolic changes during malnourishment, which may be of help in designing targeted therapeutic foods for refeeding malnourished children.

Metabolomic Changes in Serum of Children with Different Clinical Diagnoses of Malnutrition.

BACKGROUND: Mortality in children with severe acute malnutrition (SAM) remains high despite standardized rehabilitation protocols. Two forms of SAM are classically distinguished: kwashiorkor and marasmus. Children with kwashiorkor have nutritional edema and metabolic disturbances, including hypoalbuminemia and hepatic steatosis, whereas marasmus is characterized by severe wasting. The metabolic changes underlying these phenotypes have been poorly characterized, and whether homeostasis is achieved during hospital stay is unclear. OBJECTIVES: We aimed to characterize metabolic differences between children with marasmus and kwashiorkor at hospital admission and after clinical stabilization and to compare them with stunted and nonstunted community controls. METHODS: We studied children aged 9-59 mo from Malawi who were hospitalized with SAM (n = 40; 21 with kwashiorkor and 19 with marasmus) or living in the community (n = 157; 78 stunted and 79 nonstunted). Serum from patients with SAM was obtained at hospital admission and 3 d after nutritional stabilization and from community controls. With the use of targeted metabolomics, 141 metabolites, including amino acids, biogenic amines, acylcarnitines, sphingomyelins, and phosphatidylcholines, were measured. RESULTS: At admission, most metabolites (128 of 141; 91%) were lower in children with kwashiorkor than in those with marasmus, with significant differences in several amino acids and biogenic amines, including those of the kynurenine-tryptophan pathway. Several phosphatidylcholines and some acylcarnitines also differed. Patients with SAM had profiles that were profoundly different from those of stunted and nonstunted controls, even after clinical stabilization. Amino acids and biogenic amines generally improved with nutritional rehabilitation, but most sphingomyelins and phosphatidylcholines did not. CONCLUSIONS: Children with kwashiorkor were metabolically distinct from those with marasmus, and were more prone to severe metabolic disruptions. Children with SAM showed metabolic profiles that were profoundly different from stunted and nonstunted controls, even after clinical stabilization. Therefore, metabolic recovery in children with SAM likely extends beyond discharge, which may explain the poor long-term outcomes in these children. This trial was registered at isrctn.org as ISRCTN13916953.

Stunting is associated with blood lead concentration among Bangladeshi children aged 2-3 years.

BACKGROUND: Lead toxicity is of particular public health concern given its near ubiquitous distribution in nature and established neurotoxicant properties. Similar in its ubiquity and ability to inhibit neurodevelopment, early childhood stunting affects an estimated 34 % of children under 5 in low- and middle-income countries. Both lead and stunting have been shown to be associated with decreased neurodevelopment, although the relationship between these childhood burdens is underexplored. The association between lead exposure and stunting has been previously established, yet limited data are available on susceptibility windows. METHODS: Whole blood lead samples were collected from rural Bangladeshi children at delivery (umbilical cord blood) and at age 20-40 months (fingerstick blood). Stunting was determined using the Child Growth Standards developed from the World Health Organization Multicentre Growth Reference Study. Children with height for age < -2 z-scores below the median of the WHO Child Growth Standards were classified as stunted in all analyses. RESULTS: Median (IQR) umbilical cord and fingerstick blood lead levels were 3.1 (1.6-6.3) µg/dl and 4.2 (1.7-7.6) µg/dl, respectively. In adjusted multivariable regression models, the odds of stunting at 20-40 months increased by 1.12 per µg/dl increase in blood lead level (OR = 1.12, 95 % CI: 1.02-1.22). No association was found between cord blood lead level and risk of stunting (OR = 0.97, 95 % CI: 0.94-1.00). CONCLUSIONS: There is a significant association between stunting and concurrent lead exposure at age 20-40 months. This association is slightly attenuated after controlling for study clinic site. Additional research including more precise timing of lead exposure during these critical 20-40 months is needed.

Assessment of Nutritional Status in Children With Cancer and Effectiveness of Oral Nutritional Supplements.

Malnutrition is a common consequence of cancer in children, but the most effective methods of nutrition intervention are under debate. We aimed to evaluate the nutritional status of children diagnosed with cancer, and to investigate the effect of oral nutritional supplements on anthropometric measurements, biochemical parameters, and outcome. A randomized clinical study of 45 newly diagnosed cancer patients was performed. Anthropometric and biochemical data and related factors were assessed at 0, 3, and 6 months after diagnosis. On initial anthropometric assessment, prevalence of malnutrition by weight or height was found to be lower as compared with body mass index (BMI), or weight for height (WFH), or arm anthropometry. Twenty-six of the patients (55%) received oral nutritional supplement. During the second 3 months after diagnosis, there was a statistically significant decrease in number of the patients with WFH <90th percentile and BMI <5th percentile (P = .003 and P = .04, respectively). Infectious complications occurred more frequently in malnourished patients during first 3 months, and survival of children who were malnourished at the 6th month was significantly lower than that of well-nourished children (P = .003). On laboratory assessment, serum prealbumin levels of the all subjects were below normal ranges, but no relation was found for serum prealbumin or albumin levels in patients who were malnourished or not at diagnosis. Nutritional intervention is necessary to promote normal development and increase functional status as a child receives intensive treatment. Protein- and energy-dense oral nutritional supplements are effective for preventing weight loss in malnourished children.

Reduced prevalence of Giardia duodenalis in iron-deficient Rwandan children.

OBJECTIVE: Acute symptomatic infection with Giardia duodenalis impairs iron absorption, but iron deficiency may protect against infections caused by various micro-organisms including parasites. We therefore examined the association of G. duodenalis infection and iron deficiency in 575 Rwandan children under 5 years of age. METHODS: Giardia duodenalis infection was diagnosed by triplicate microscopy and PCR assays, and iron deficiency was defined as a ferritin concentration <12 ng/ml. RESULTS: Largely asymptomatic G. duodenalis infection was seen in 65.3% of the children and iron deficiency in 17.4%. G. duodenalis infection was less common in iron-deficient children (51%) than in non-deficient children (68%, P = 0.002). In multivariate analysis, the odds of G. duodenalis infection were almost halved in iron-deficient children (adjusted odds ratio, 0.54; 95% confidence interval, 0.33-0.86). CONCLUSION: In this highly endemic setting, there was no evidence that Giardia infection impairs iron status. Rather, iron deficiency appeared to protect against infection with this parasite.

Low plasma selenium concentrations in critically ill children: the interaction effect between inflammation and selenium deficiency.

INTRODUCTION: Low plasma selenium concentrations are frequent in critically ill patients. However, whether this is due to systemic inflammation, a deficient nutritional state or both is still not clear. We aimed to determine the factors associated with low plasma selenium in critically ill children while considering the inflammatory response and nutritional status. METHOD: A prospective study was conducted in 173 children (median age 34 months) with systemic inflammatory response who had plasma selenium concentrations assessed 48 hours after admission and on the 5th day of ICU stay. The normal reference range was 0.58 µmol/L to 1.6 µmol/L. The outcome variable was 'low plasma selenium', which was defined as plasma selenium values below the distribution median during this period. The main explanatory variables were age, malnutrition, sepsis, C-reactive protein (CRP), and clinical severity scores. The data were analyzed using a Binomial Generalized Estimating Equations model, which includes the correlation between admission and 5th day responses. RESULTS: Malnutrition and CRP were associated with low plasma selenium. The interaction effect between these two variables was significant. When CRP values were less than or equal to 40 mg/L, malnutrition was associated with low plasma selenium levels (odds ratio (OR) = 3.25, 95% confidence interval (CI) 1.39 to 7.63, P = 0.007; OR = 2.98, 95% CI 1.26 to 7.06, P = 0.013; OR = 2.49, 95% CI 1.01 to 6.17, P = 0.049, for CRP = 10, 20 and 40 mg/L, respectively). This effect decreased as CRP concentrations increased and there was loose significance when CRP values were >40 mg/L. Similarly, the effect of CRP on low plasma selenium was significant for well-nourished patients (OR = 1.13; 95% CI 1.06 to 1.22, P <0.001) but not for the malnourished (OR = 1.03; 95% CI 0.99 to 1.08, P = 0.16). CONCLUSIONS: There is a significant interaction between the magnitude of the inflammatory response and malnutrition on low plasma selenium. This interaction should be considered when interpreting plasma concentrations as an index of selenium status in patients with systemic inflammation as well as in the decision on selenium supplementation.

Hematologic and bone marrow changes in children with protein-energy malnutrition.

BACKGROUND: All systems in an organism are affected by protein-energy malnutrition (PEM), but one of the worst affected is the hematopoietic system. Today PEM remains a very serious problem in developing countries. We examined the relationships between clinical features, hematological, and bone marrow changes with severe PEM from Turkey. METHOD: We evaluated 34 (11 females and 23 males) consecutive cases of severe PEM, with no underlying diseases aged 3-20 months. The clinical nutritional conditions of the patients were determined using the Wellcome-Trust PEM classification. Ten of the patients were in the Marasmic-Kwashiorkor (M-K) group, 10 were in the Kwashiorkor (KW) group, and 14 were in the Marasmic (M) group. Full blood count, protein, albumin, serum iron (SI), iron-binding capacity (TIBC), ferritin, vitamin B12, folic acid, complement-3 (C3), complement-4 (C4), and bone marrow were investigated in all groups. RESULTS: Anemia was detected in 97% of patients. We determined serum iron levels were low in 67.6% of the patients, TS levels were low in 76.4% of the patients and ferritin levels were low in 20.5%. The level of vitamin B12 was normal in all patients. Bone marrow analysis showed erythroid series hypoplasia in 28.5% of patients in the M group, 50% in the KW group, and 30% in the M-K group. Marrow iron was absent in 58.8% of patients. CONCLUSION: The most common hematologic change in the children with PEM was anemia and major cause of anemia was iron deficiency in this study. Patients with severe PEM have normal Vit B12 and serum folate levels. Most of the patients with severe PEM had normal cellularity with megaloblastic and dysplastic changes in bone marrow due to the inadequate and imbalanced intake of protein and energy.

Statistical inference from multiple iTRAQ experiments without using common reference standards.

Isobaric tags for relative and absolute quantitation (iTRAQ) is a prominent mass spectrometry technology for protein identification and quantification that is capable of analyzing multiple samples in a single experiment. Frequently, iTRAQ experiments are carried out using an aliquot from a pool of all samples, or "masterpool", in one of the channels as a reference sample standard to estimate protein relative abundances in the biological samples and to combine abundance estimates from multiple experiments. In this manuscript, we show that using a masterpool is counterproductive. We obtain more precise estimates of protein relative abundance by using the available biological data instead of the masterpool and do not need to occupy a channel that could otherwise be used for another biological sample. In addition, we introduce a simple statistical method to associate proteomic data from multiple iTRAQ experiments with a numeric response and show that this approach is more powerful than the conventionally employed masterpool-based approach. We illustrate our methods using data from four replicate iTRAQ experiments on aliquots of the same pool of plasma samples and from a 406-sample project designed to identify plasma proteins that covary with nutrient concentrations in chronically undernourished children from South Asia.

Serum retinol in 1-6-year-old children from a low socio-economic South African community with a high intake of liver: implications for blanket vitamin A supplementation.

OBJECTIVE: To assess serum retinol, liver intake patterns, breast-feeding history and anthropometric status in pre-school children of a low socio-economic community where liver is regularly consumed. DESIGN: Cross-sectional study. SETTING: Northern Cape Province, South Africa. SUBJECTS: Children aged 1-6 years (n 243) who attended the local primary health-care facility and had not received a vitamin A supplement in the 6 months preceding the study. Non-pregnant female caregivers (n 225), below 50 years of age, were also assessed. RESULTS: Despite stunting, underweight and wasting being prevalent in 40·5%, 23·1% and 8·4% of the children, only 5·8% had serum retinol concentrations < 20 µg/dl, which is in sharp contrast to the national prevalence of 63·6%. None of the caregivers were vitamin A deficient. Liver was eaten by 89·2% of children, with 87% of households eating liver at least once monthly and 30% eating it at least once weekly; liver was introduced into the diet of the children at a median age of 18 months. Ninety-three per cent of the children were being breast-fed or had been breast-fed in the past; children were breast-fed to a median age of 18 months. A significant negative correlation was found between educational level of the caregiver and frequency of liver intake (r = -0·143, P=0·032). There was no correlation between serum retinol and indicators of anthropometric or socio-economic status. CONCLUSIONS: The blanket approach in applying the national vitamin A supplementation programme may not be appropriate for all areas in the country, even though the community may be poor and undernourished.

Prevalence of ocular signs and subclinical vitamin A deficiency and its determinants among rural pre-school children in India.

OBJECTIVE: To assess the magnitude and determinants of vitamin A deficiency (VAD) and coverage of vitamin A supplementation (VAS) among pre-school children. DESIGN: A community-based cross-sectional study was carried out by adopting a multistage, stratified, random sampling procedure. SETTING: Rural areas of eight states in India. SUBJECTS: Pre-school children and their mothers were covered. RESULTS: A total of 71,591 pre-school children were clinically examined for ocular signs of VAD. Serum retinol concentrations in dried blood spots were assessed in a sub-sample of 3954 children using HPLC. The prevalence of Bitot spots was 0·8%. The total ocular signs were significantly higher (P < 0·001) among boys (2·6%) compared with girls (1·9%) and in older children (3-4 years) compared (P < 0·001) with younger (1-2 years), and were also high in children of labourers, scheduled castes and illiterate mothers. The odds of having Bitot spots was highest in children of scheduled caste (OR = 3·8; 95% CI 2·9, 5·0), labourers (OR = 2·9; 95% CI 2·1, 3·9), illiterate mothers (OR = 2·7; 95% CI 2·2, 2·3) and households without a sanitary latrine (OR = 5·9; 95% CI 4·0, 8·7). Subclinical VAD (serum retinol level <20 µg/dl) was observed in 62% of children. This was also relatively high among scheduled caste and scheduled tribe children. The rate of coverage of VAS was 58%. CONCLUSIONS: The study revealed that VAD is a major nutritional problem and coverage of VAS was poor. The important determinants of VAD were illiteracy, low socio-economic status, occupation and poor sanitation. Strengthening the existing VAS programme and focused attention on dietary diversification are essential for prevention of VAD.

IgA anti-tissue transglutaminase antibodies, first line in the diagnosis of celiac disease.

BACKGROUND: According to the 2008 celiac disease working group run by Dr. A. Fassano under the auspices of the Federation of International Societies of Pediatric Gastroenterology, Hepatology and Nutrition, celiac disease is a chronic immune-mediated enteropathy characterized by gluten sensitivity, which can affect any organ or system, having a wide range of clinical manifestations of variable severity. The serological diagnosis of celiac disease is based on high sensitivity and specificity tests. The measurement of IgA anti-tissue transglutaminase antibodies by ELISA is universally accepted in the screening of celiac disease. METHODS: Using the gold standard represented by IgA anti-endomysium antibodies in a group of 890 children investigated during 2008-2009, we aimed to evaluate IgA anti-tissue transglutaminase antibodies (tTG IgA), as well as to establish their prevalence in associated diseases. RESULTS: Following the measurement of tTG IgA in the entire group, we obtained: sensitivity 773%, positive predictive value 55.2%, specificity 93.1%, negative predictive value 973%, p = 0.000, and in tTG IgA associations we obtained the value 0.51 for the ROC curve area. We found associations of tTG IgA with type 1 diabetes mellitus (235% prevalence), protein-calorie malnutrition (0.89% prevalence), and intestinal malabsorption (0.56% prevalence). CONCLUSIONS: Our results have a high specificity and sensitivity in the screening of celiac disease, while requiring a second method of confirmation.

Correlates of serum IGF-1 in young children with moderate acute malnutrition: a cross-sectional study in Burkina Faso.

BACKGROUND: Serum insulin-like growth factor 1 (sIGF-1) is an important growth factor in childhood. However, studies on sIGF-1 among children from low-income countries are few, and the role of body composition is unknown. OBJECTIVES: To assess the associations of anthropometry, body composition, inflammation, and breastfeeding with sIGF-1 among children with moderate acute malnutrition (MAM). METHODS: A cross-sectional study based on admission data from 6- to 23-mo-old children with MAM participating in a nutrition intervention trial (Treatfood) in Burkina Faso. Linear regression analysis was used to identify correlates of sIGF-1. RESULTS: Among 1546 children, the median (IQR) sIGF-1 was 12 (8.2-18.3) ng/mL. sIGF-1 was highest at 6 mo, with a nadir ∼10-11 mo, and higher in girls than boys. Length-for-age z score (LAZ), weight-for-length z score (WLZ), and midupper arm circumference were positively associated with sIGF-1 (P ≤ 0.001). Fat-free mass (FFM) was also positively associated, as sIGF-1 increased 1.5 (95% CI: 0.5, 2.5) ng/mL for each 1-kg increase in FFM. However, the association disappeared after adjustment for height. Elevated serum C-reactive protein and α1-acid glycoprotein were negatively associated with sIGF-1 (P ≤ 0.001), as was fever (P < 0.001) but not a positive malaria test per se (P = 0.15). Children never breastfed had lower sIGF-1 (-5.1; 95% CI: -9.8, -0.3). CONCLUSIONS: LAZ and WLZ were positively and inflammation negatively associated with sIGF-1. As all children were moderately malnourished and many had inflammation, this probably explains the very low median sIGF-1. The association of FFM with sIGF-1 was fully explained by height. There was a marked age pattern, with a nadir in late infancy, confirming findings from smaller studies from well-nourished populations. There is a need for prospective studies to disentangle the role of sIGF-1 in growth and health. This trial was registered at https://www.isrctn.com as ISRCTN42569496.

Serum Trace Element Levels and Their Correlation with Picky Eating Behavior, Development, and Physical Activity in Early Childhood.

Trace elements are vital components for healthy growth, development, and physical activity. The aim of this study was to investigate the relationship between trace element (iron, zinc, copper) deficiencies and picky eating behavior, development level, and physical activity level. This cross-sectional study involved 203 children aged 4-7 years; picky eating behavior, development level, and physical activity level were assessed through questionnaires. Zinc deficiency has the highest prevalence (37.4%); 67.5% of the children were assessed as picky eaters. Children with picky eating behaviors, poor development level, or poor physical activity level have significantly lower zinc levels, and higher prevalence of zinc deficiency. Pearson's correlation coefficient indicated a positive correlation between serum zinc level and development scores (r = 0.221, p = 0.002) and physical activity scores (r = 0.469, p < 0.001). In multivariate analysis, zinc deficiency independently related to picky eating (OR = 2.124, p = 0.037, CI = 1.042-4.312), developmental level (OR = 0.893, p = 0.022, CI = 0.810-0.984), and physical activity level (OR = 0.785, p < 0.001, CI = 0.700-0.879). In conclusion, the prevalence of zinc deficiency in children aged 4-7 was high, especially in picky eaters. Zinc deficiency was significantly associated with low development and poor physical activity in early childhood.

Biomarkers of environmental enteric dysfunction are differently associated with recovery and growth among children with moderate acute malnutrition in Sierra Leone.

BACKGROUND: Environmental enteric dysfunction (EED) may influence growth during and recovery from moderate acute malnutrition (MAM), however, biomarkers to assess these relations have yet to be identified. OBJECTIVES: The objectives of this study were to: 1) develop a score for EED based on host fecal mRNA transcripts, 2) compare biomarkers of EED with each other, and 3) examine associations between the EED biomarkers and recovery from MAM and growth outcomes. METHODS: In a cohort of 520 Sierra Leonean MAM children, biomarkers of EED included the lactulose: mannitol (L: M) test, 15 host fecal mRNA transcripts, and host fecal proteins [α-1-antitrypsin (AAT), myeloperoxidase (MPO), neopterin (NEO)]. Anthropometry data were also collected and z scores were computed for length-for-age (LAZ) and weight-for-length (WLZ). Recovery from MAM was defined as midupper arm circumference ≥12.5 cm. Factor analysis was used to identify EED scores using the mRNA transcripts, and mixed effects regression was conducted to test for associations. RESULTS: The 15 host fecal mRNA transcripts were clustered into 3 scores: gut inflammation (GI) score, gut structure (GS) score, and gut defense (GD) score. We found agreement between certain inflammation markers (GI score and MPO), and permeability markers (GS score and AAT; AAT and the L: M excretion ratio). Antimicrobial gut defense (GD score) was inversely associated with percent lactulose excreted, a measure of intestinal permeability. LAZ (ß: -0.08; 95% CI: -0.14, -0.02) and WLZ (ß: -0.03; 95% CI: -0.06, -0.01) were negatively associated with GI score. A high GD score (ß: 0.36; 95% CI: 0.08, 0.64) and low AAT (ß: -1.35; 95% CI: -2.35, -0.36) were associated with recovery from MAM. CONCLUSIONS: Scores derived from host fecal mRNA transcript variably correlated with the L: M test and host fecal proteins. Markers of intestinal inflammation, permeability, and defense were associated with growth outcomes and recovery from MAM.

Improved appetite after multi-micronutrient supplementation for six months in HIV-infected South African children.

The aim of the study was to assess the effect of multi-micronutrient supplementation on the appetite of HIV-infected children. HIV-infected children (6-24 months) who had previously been hospitalized were enrolled into a double-blind randomized trial, and given daily multi-micronutrient supplements or placebos for six months. Appetite tests were performed at enrollment and after three and six months. Appetite was measured as ad libitum intake of a commercial cereal test food served after an overnight fast according to standardized procedures. Body weights and total amount of test food eaten were measured. In total, 99 children completed the study (50 on supplements and 49 on placebos). Amounts eaten per kilogram body weight in the supplement group at enrollment and after six months were 36.7+/-17.7 g/kg (mean+/-SD) and 41.3+/-15.0 g/kg respectively, while the amounts in the placebo group were 47.1+/-14.9 g/kg and 45.7+/-13.1g/kg respectively. The change in amount eaten per kilogram body weight over six months was significantly higher in the supplement group (4.7+/-14.7 g/kg) than in the placebo group (-1.4+/-15.1g/kg). Multi-micronutrient supplementation for six months seems to significantly improve the appetite of HIV-infected children.