Effect of fatty acid profiles in varying recipes of ready-to-use therapeutic foods on neurodevelopmental and clinical outcomes of children (6-59 months) with severe wasting: a systematic review.

CONTEXT: In 2020, 13.6 million children under 5 years suffered from severe acute malnutrition (SAM)/wasting. Standard ready-to-use therapeutic foods (RUTFs) improve polyunsaturated fatty acid (PUFA) status but contain suboptimal amounts of omega-3 (n-3) PUFAs with unbalanced n-6-to-n-3 PUFA ratios. OBJECTIVES: The aim was to compare the effects of RUTFs with different essential fatty acid contents on PUFA status, neurodevelopmental, and clinical outcomes (mortality, comorbidities, and recovery) of children with severe wasting. DATA SOURCES: Twelve databases, trial repositories, and article references with no publication limitations. DATA EXTRACTION: Ten studies from randomized, quasi, and cluster-randomized controlled trials providing RUTFs as home treatment to children 6-59 months with SAM/wasting were included. DATA ANALYSIS: Plasma phospholipid eicosapentaenoic acid content was higher in children receiving RUTF with altered essential fatty acid contents compared with standard RUTF (0.20 [0.15-0.25], P < 0.00001). Docosahexaenoic acid (DHA) status only improved in children receiving RUTF with added fish oil (0.33 [0.15-0.50], P = 0.0003). The Malawi Developmental Assessment tool (MDAT) global development and problem-solving assessment scores were higher in global assessment and gross motor domains in children receiving added fish oil compared with standard formulation (0.19 [0.0-0.38] and 0.29 [0.03-0.55], respectively). Children receiving high-oleic-acid RUTF (lowering the n-6:n-3 PUFA ratio of the RUTF) with or without fish oil had significantly higher scores in social domains compared with those receiving the standard formulation (0.16 [0.00-0.31] and 0.24 [0.09-0.40]). Significantly higher mortality risk was found in children receiving a standard formulation compared with RUTF with a lower n-6:n-3 PUFA ratio (0.79 [0.67-0.94], P = 0.008). CONCLUSION: Although lowering n-6:n-3 PUFA ratios did not increase plasma DHA, it improved specific neurodevelopmental scores and mortality due to lower linoleic acid (high-oleic-acid peanuts), higher alpha-linolenic acid (altered oil), or both. Additional preformed n-3 long-chain PUFAs (fish oil) with RUTF improved the children's DHA status, neurodevelopmental outcomes, and weight-for-height z score. More research is needed regarding cost, availability, stability, acceptability, and the appropriate amount of n-3 long-chain PUFAs required in RUTFs for the best clinical outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022303694.

Ready-to-use therapeutic food (RUTF) for home-based nutritional rehabilitation of severe acute malnutrition in children from six months to five years of age.

BACKGROUND: Management of severe acute malnutrition (SAM) in children comprises two potential phases: stabilisation and rehabilitation. During the initial stabilisation phase, children receive treatment for dehydration, electrolyte imbalances, intercurrent infections and other complications. In the rehabilitation phase (applicable to children presenting with uncomplicated SAM or those with complicated SAM after complications have been resolved), catch-up growth is the main focus and the recommended energy and protein requirements are much higher. In-hospital rehabilitation of children with SAM is not always desirable or practical - especially in rural settings - and home-based care can offer a better solution. Ready-to-use therapeutic food (RUTF) is a widely used option for home-based rehabilitation, but the findings of our previous review were inconclusive. OBJECTIVES: To assess the effects of home-based RUTF used during the rehabilitation phase of SAM in children aged between six months and five years on recovery, relapse, mortality and rate of weight gain. SEARCH METHODS: We searched the following databases in October 2018: CENTRAL, MEDLINE, Embase, six other databases and three trials registers. We ran separate searches for cost-effectiveness studies, contacted researchers and healthcare professionals in the field, and checked bibliographies of included studies and relevant reviews. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs, where children aged between six months and five years with SAM were, during the rehabilitation phase, treated at home with RUTF compared to an alternative dietary approach, or with different regimens and formulations of RUTF compared to each other. We assessed recovery, deterioration or relapse and mortality as primary outcomes; and rate of weight gain, time to recovery, anthropometrical changes, cognitive development and function, adverse outcomes and acceptability as secondary outcomes. DATA COLLECTION AND ANALYSIS: We screened for eligible studies, extracted data and assessed risk of bias of those included, independently and in duplicate. Where data allowed, we performed a random-effects meta-analysis using Review Manager 5, and investigated substantial heterogeneity through subgroup and sensitivity analyses. For the main outcomes, we evaluated the quality of the evidence using GRADE, and presented results in a 'Summary of findings' table per comparison. MAIN RESULTS: We included 15 eligible studies (n = 7976; effective sample size = 6630), four of which were cluster trials. Eight studies were conducted in Malawi, four in India, and one apiece in Kenya, Zambia, and Cambodia. Six studies received funding or donations from industry whereas eight did not, and one study did not report the funding source.The overall risk of bias was high for six studies, unclear for three studies, and low for six studies. Among the 14 studies that contributed to meta-analyses, none (n = 5), some (n = 5) or all (n = 4) children were stabilised in hospital prior to commencement of the study. One small study included only children known to be HIV-infected, another study stratified the analysis for 'recovery' according to HIV status, while the remaining studies included HIV-uninfected or untested children. Across all studies, the intervention lasted between 8 and 16 weeks. Only five studies followed up children postintervention (maximum of six months), and generally reported on a limited number of outcomes.We found seven studies with 2261 children comparing home-based RUTF meeting the World Health Organization (WHO) recommendations for nutritional composition (referred to in this review as standard RUTF) with an alternative dietary approach (effective sample size = 1964). RUTF probably improves recovery (risk ratio (RR) 1.33; 95% confidence interval (CI) 1.16 to 1.54; 6 studies, 1852 children; moderate-quality evidence), and may increase the rate of weight gain slightly (mean difference (MD) 1.12 g/kg/day, 95% CI 0.27 to 1.96; 4 studies, 1450 children; low-quality evidence), but we do not know the effects on relapse (RR 0.55, 95% CI 0.30 to 1.01; 4 studies, 1505 children; very low-quality evidence) and mortality (RR 1.05, 95% CI 0.51 to 2.16; 4 studies, 1505 children; very low-quality evidence).Two quasi-randomised cluster trials compared standard, home-based RUTF meeting total daily nutritional requirements with a similar RUTF but given as a supplement to the usual diet (213 children; effective sample size = 210). Meta-analysis showed that standard RUTF meeting total daily nutritional requirements may improve recovery (RR 1.41, 95% CI 1.19 to 1.68; low-quality evidence) and reduce relapse (RR 0.11, 95% CI 0.01 to 0.85; low-quality evidence), but the effects are unknown for mortality (RR 1.36, 95% CI 0.46 to 4.04; very low-quality evidence) and rate of weight gain (MD 1.21 g/kg/day, 95% CI - 0.74 to 3.16; very low-quality evidence).Eight studies randomised 5502 children (effective sample size = 4456) and compared standard home-based RUTF with RUTFs of alternative formulations (e.g. using locally available ingredients, containing less or no milk powder, containing specific fatty acids, or with added pre- and probiotics). For recovery, it made little or no difference whether standard or alternative formulation RUTF was used (RR 1.03, 95% CI 0.99 to 1.08; 6 studies, 4188 children; high-quality evidence). Standard RUTF decreases relapse (RR 0.84, 95% CI 0.72 to 0.98; 6 studies, 4188 children; high-quality evidence). However, it probably makes little or no difference to mortality (RR 1.00, 95% CI 0.80 to 1.24; 7 studies, 4309 children; moderate-quality evidence) and may make little or no difference to the rate of weight gain (MD 0.11 g/kg/day, 95% CI -0.32 to 0.54; 6 studies, 3807 children; low-quality evidence) whether standard or alternative formulation RUTF is used. AUTHORS' CONCLUSIONS: Compared to alternative dietary approaches, standard RUTF probably improves recovery and may increase rate of weight gain slightly, but the effects on relapse and mortality are unknown. Standard RUTF meeting total daily nutritional requirements may improve recovery and relapse compared to a similar RUTF given as a supplement to the usual diet, but the effects on mortality and rate of weight gain are not clear. When comparing RUTFs with different formulations, the current evidence does not favour a particular formulation, except for relapse, which is reduced with standard RUTF. Well-designed, adequately powered, pragmatic RCTs with standardised outcome measures, stratified by HIV status, and that include diarrhoea as an outcome, are needed.

Evaluation of the cytotoxic properties, gene expression profiles and secondary signalling responses of cultured cells exposed to fumonisin B1, deoxynivalenol and zearalenone mycotoxins.

Mycotoxins are toxic secondary metabolites produced by a range of fungi and are common contaminants of agricultural crops. These toxins are chemically diverse and structurally stable, enabling them to enter the food chain which can lead to numerous adverse health effects in animals and humans. Although mycotoxin exposure is associated with the development of several cancers, it has proved challenging to show a direct connection between exposure and oncogenic change. This study investigates the in vitro cytotoxicity, molecular mechanisms and secondary signalling responses associated with the exposure to three major mycotoxins, fumonisin B1 (FB1), deoxynivalenol (Don) and zearalenone (Zea). The cytotoxicity of FB1, Don and Zea were investigated in cultured HepG2 and Caco-2 cells using cell viability assays as well as flow cytometry. FB1 proved to be less cytotoxic than its counterparts, while Don and Zea demonstrated high cytotoxicity through an apoptotic mechanism. Expression profiles of 84 genes involved in mediating communication between tumour cells and the cellular mediators of inflammation as well as the innate immune system were also studied. The expression profiles associated with the different mycotoxins were further explored for functional networks, biological functions, canonical pathways, toxicological association as well as to predict network associations between the differentially expressed genes. RT-qPCR revealed the significant differential expression of 46 genes, including the expression of several genes strongly associated with cancer and aberrant inflammatory signalling, after mycotoxin exposure. Aberrant inflammatory signalling seems to be a credible contributing factor that initiates the malignant change observed in cells exposed to mycotoxins.

Application and interpretation of multiple statistical tests to evaluate validity of dietary intake assessment methods.

BACKGROUND: Several statistical tests are currently applied to evaluate validity of dietary intake assessment methods. However, they provide information on different facets of validity. There is also no consensus on types and combinations of tests that should be applied to reflect acceptable validity for intakes. We aimed to 1) conduct a review to identify the tests and interpretation criteria used where dietary assessment methods was validated against a reference method and 2) illustrate the value of and challenges that arise in interpretation of outcomes of multiple statistical tests in assessment of validity using a test data set. METHODS: An in-depth literature review was undertaken to identify the range of statistical tests used in the validation of quantitative food frequency questionnaires (QFFQs). Four databases were accessed to search for statistical methods and interpretation criteria used in papers focusing on relative validity. The identified tests and interpretation criteria were applied to a data set obtained using a QFFQ and four repeated 24-hour recalls from 47 adults (18-65 years) residing in rural Eastern Cape, South Africa. RESULTS: 102 studies were screened and 60 were included. Six statistical tests were identified; five with one set of interpretation criteria and one with two sets of criteria, resulting in seven possible validity interpretation outcomes. Twenty-one different combinations of these tests were identified, with the majority including three or less tests. Coefficient of correlation was the most commonly used (as a single test or in combination with one or more tests). Results of our application and interpretation of multiple statistical tests to assess validity of energy, macronutrients and selected micronutrients estimates illustrate that for most of the nutrients considered, some outcomes support validity, while others do not. CONCLUSIONS: One to three statistical tests may not be sufficient to provide comprehensive insights into various facets of validity. Results of our application and interpretation of multiple statistical tests support the value of such an approach in gaining comprehensive insights in different facets of validity. These insights should be considered in the formulation of conclusions regarding validity to answer a particular dietary intake related research question.

Mycotoxin exposure and infant and young child growth in Africa: what do we know?

INTRODUCTION: Infant and young child (IYC) growth impairment remains a public health problem in Africa partly because infants are exposed to staple foods (contaminated with mycotoxins) at an early age. Understanding the role of mycotoxins in IYC growth is vital, and this paper systematically reviews the available knowledge. METHODS: Studies were searched and included if they provided information on African IYC mycotoxin exposure rates and/or growth. Studies were excluded if subjects were older than 15 years, if they were animal studies or focusing on other mycotoxins. Relevant search words were included in search strings. Eight reviews were identified and reference lists scrutinised for additional studies. RESULTS: Ten studies were included; 8 focused on aflatoxin (AF), 2 on fumonisin (FB) and none on deoxynivalenol (DON) and zearalenone (ZEA). AF exposure prevalence reached 100% with levels at 40.4 pg/mg. AF was present in umbilical cords indicating that AF crosses the placenta. Maternal exposure levels were correlated with breast milk levels. The highest levels of serum AF (mean 32.8 pg/mg) were measured in Benin and Togo with 5.4% reaching levels higher than 200 pg/mg. At the end of weaning, children had similar prevalence and exposure levels as adults. RESULTS also indicated that infants with higher levels of maternal exposure had significantly lower height-for-age z-scores (HAZ scores), although there was no significant association between cord AF and infant HAZ scores or AF in cord blood and HAZ scores. Significantly higher mean maternal AF levels related to lower weight-for-age z-scores (WAZ scores) were reported, and infants with higher levels of maternal exposure had significantly lower WAZ scores that decreased over age. Cord AF levels had no effect on infant WAZ scores. One study investigated the association between FB and IYC growth and found that those with FB intakes greater than the provisional maximum tolerable daily intake were significantly shorter (1.3 cm) and lighter (328 g). No studies investigated the role of DON and ZEA. CONCLUSION: A limited number of epidemiological studies have been conducted, and available research indicates extreme exposures to AF. There are strong associations between AF exposure and stunting and wasting. However, more epidemiological research is urgently needed to understand the role of FB, DON and ZEA in IYC growth.

Development and evaluation of a sensitive mycotoxin risk assessment model (MYCORAM).

The differential risk of exposure to fumonisin (FB), deoxynivalenol (DON), and zearalenone (ZEA) mycotoxins to the South African population, residing in the nine Provinces was assessed during a cross-sectional grain consumer survey. The relative per capita maize intake (g/day) was stratified by gender, ethnicity, and Province and the probable daily intake (PDI) for each mycotoxin (ng/kg body weight/day) calculated utilizing SPECIAL and SUPER dry milled maize fractions representing different exposure scenarios. Men consumed on an average more maize (173 g/day) than women (142 g/day) whereas the black African ethnic group had the highest intake (279 g/day) followed by the Colored group (169 g/day) with the Asian/Indian and White groups consuming lower quantities of 101 and 80 g/day, respectively. The estimated mean PDIs for the various subgroups and Provinces, utilizing the different dry milled maize fractions, were below the provisional maximum tolerable daily intake (PMTDI) for each mycotoxin. A distinct and more sensitive mycotoxin risk assessment model (MYCORAM) for exposure, stratified by Province and ethnicity were developed utilizing specific maize intake increments (g/kg body weight/day) that provides information on the percentage of the population exposed above the PMTDI for each mycotoxin. Evaluation of the MYCORAM utilizing commercial and EXPERIMENTALLY DERIVED: SPECIAL milling fractions, containing predefined mycotoxins levels, predicts the percentage of maize consumers exposed above the respective PMTDI. Safety modeling using the MYCORAM could also predict a maximum tolerated level adequate to safeguard all South African maize consumers including the most vulnerable groups.

Introducing Solid Foods

There are recommendations to guide parents to help their infants make the transition from milk to weaning foods; but they differ in their focus in developed or developing countries and on the physiological and behavioural reasons that underlie the introduction of weaning foods. According to recommendations; ideally; term infants should begin weaning at six months; while breastfeeding should continue for two years. The recommendations on nutrients in complementary foods are based on the nutrient gap between the composition and volume of breast milk after approximately six months of exclusive breastfeeding and the physiology of infant nutritional requirements

Understanding Lactose Intolerance and the Dietary Management Thereof

Diets that exclude dairy may decrease gastrointestinal symptoms in symptomatic individuals who have lactose malabsorption or lactose intolerance. However; most lactose-intolerant adults can consume some lactose without experiencing major symptoms; thereby reducing the need for strict elimination of dairy products from the diet