A Systematic Review on the Optimal Dose and Duration of Ready-to-Use Therapeutic Food (RUTF) for 6-59-Month-Old Children with Severe Wasting or Oedema.

The World Health Organisation (WHO) recommends that severe wasting and/or oedema should be treated with ready-to-use therapeutic food (RUTF) at a dose of 150-220 kcal/kg/day for 6-8 weeks. Emerging evidence suggests that variations of RUTF dosing regimens from the WHO recommendation are not inferior. We aimed to assess the comparative efficacy and effectiveness of different RUTF doses and durations in comparison with the current WHO RUTF dose recommendation for treating severe wasting and/or oedema among 6-59-month-old children. A systematic literature search identified three studies for inclusion, and the outcomes of interest included anthropometric recovery, anthropometric measures and indices, non-response, time to recovery, readmission, sustained recovery, and mortality. The study was registered with PROSPERO, CRD 42021276757. Only three studies were eligible for analysis. There was an overall high risk of bias for two of the studies and some concerns for the third study. Overall, there were no differences between the reduced and standard RUTF dose groups in all outcomes of interest. Despite the finding of no differences between reduced and standard-dose RUTF, the studies are too few to conclusively declare that reduced RUTF dose was more efficacious than standard RUTF.

The potential of spot urine as a biomarker for zinc assessment in Malawian children and adults.

Population-level assessment of zinc deficiency remains a challenge due to the lack of suitable biomarkers. Spot urinary zinc concentration (UZC) has the potential to provide information on population zinc status in large-scale surveys, but there is no established cut-off point indicating deficiency. A strong correlation between this biomarker and an established biomarker such as serum zinc concentration (SZC) in paired samples (i.e., from the same individual), could identify the thresholds indicating zinc deficiency. This study, therefore, aimed to regress spot UZC from school-aged children and women from the Malawi micronutrient survey with paired SZC data using a linear mixed-effects model. The nested variance components indicated no linear relationship between the UZC and SZC data, irrespective of adjustments for inflammation and hydration. Thresholds of urinary zinc excretion that have been suggested by expert panels were applied to the spot UZC data, as a post-hoc analysis. The zinc deficiency prevalence estimates derived from these suggested thresholds were not similar to the estimates from the SZC data, and further research is required to understand whether spot UZC can still provide useful information in population zinc assessment.

Re-Defining the Population-Specific Cut-Off Mark for Vitamin A Deficiency in Pre-School Children of Malawi.

Retinol Binding Protein (RBP) is responsible for the transport of serum retinol (SR) to target tissue in the body. Since RBP is relatively easy and cheap to measure, it is widely used in national Micronutrient Surveys (MNS) as a proxy for SR to determine vitamin A status. By regressing RBP concentration against SR concentration measured in a subset of the survey population, one can define a population-specific threshold concentration of RBP that indicates vitamin A deficiency (VAD). However, the relationship between RBP and SR concentrations is affected by various factors including inflammation. This study, therefore, aimed to re-define the population-specific cut-off for VAD by examining the influence of inflammation on RBP and SR, among pre-school children (PSC) from the 2015-16 Malawi MNS. The initial association between RBP and SR concentrations was poor, and this remained the case despite applying various methods to correct for inflammation. The World Health Organization (WHO) recommends the threshold of 0.7 µmol/L to define VAD for SR concentrations. Applying this threshold to the RBP concentrations gave a VAD prevalence of 24%, which reduced to 10% after inflammation adjustments following methods developed by the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA). Further research is required to identify why SR and RBP were poorly associated in this population. Future MNS will need to account for the effect of inflammation on RBP to measure the prevalence of VAD in Malawi.

Zinc deficiency is highly prevalent and spatially dependent over short distances in Ethiopia.

Zinc (Zn) is an essential nutrient for human health. In Ethiopia, a high prevalence of Zn deficiency has been reported. To explore demographic variation and spatial dependencies in the Zn status of the Ethiopian population, we analyzed archived serum samples (n = 3373) from the 2015 Ethiopian National Micronutrient Survey (ENMS), a cross-sectional survey of young children, school-age children, women of reproductive age (WRA) and men conducted in all 9 regions and two city administration of Ethiopia. Serum Zn concentrations, measured using inductively coupled plasma-mass spectrometry (ICPMS), were compared to thresholds based on age, sex, fasting status, and time of blood collection, after adjusting for inflammation status. Median serum Zn concentration of the population was 57.5 µg dL-1. Overall, it is estimated that 72% of the population was Zn deficient, with high prevalence in all demographic groups. Spatial statistical analysis showed that there was spatial dependence in Zn status of WRA at distances of up to 45 km. Zinc deficiency is spatially dependent over short distances. Although WRA in most areas are likely to be Zn deficient, prevalence of deficiency varies at regional scale and between rural and urban inhabitants, suggesting there is scope to explore drivers of this variation, prioritize nutritional interventions, and to design more representative surveillance programs.

Biofortified Maize Improves Selenium Status of Women and Children in a Rural Community in Malawi: Results of the Addressing Hidden Hunger With Agronomy Randomized Controlled Trial.

Background: Selenium deficiency is widespread in the Malawi population. The selenium concentration in maize, the staple food crop of Malawi, can be increased by applying selenium-enriched fertilizers. It is unknown whether this strategy, called agronomic biofortification, is effective at alleviating selenium deficiency. Objectives: The aim of the Addressing Hidden Hunger with Agronomy (AHHA) trial was to determine whether consumption of maize flour, agronomically-biofortified with selenium, affected the serum selenium concentrations of women, and children in a rural community setting. Design: An individually-randomized, double-blind placebo-controlled trial was conducted in rural Malawi. Participants were randomly allocated in a 1:1 ratio to receive either intervention maize flour biofortified with selenium through application of selenium fertilizer, or control maize flour not biofortified with selenium. Participant households received enough flour to meet the typical consumption of all household members (330 g capita -1 day-1) for a period of 8 weeks. Baseline and endline serum selenium concentration (the primary outcome) was measured by inductively coupled plasma mass spectrometry (ICP-MS). Results: One woman of reproductive age (WRA) and one school-aged child (SAC) from each of 180 households were recruited and households were randomized to each group. The baseline demographic and socioeconomic status of participants were well-balanced between arms. No serious adverse events were reported. In the intervention arm, mean (standard deviation) serum selenium concentration increased over the intervention period from 57.6 (17.0) µg L-1 (n = 88) to 107.9 (16.4) µg L-1 (n = 88) among WRA and from 46.4 (14.8) µg L-1 (n = 86) to 97.1 (16.0) µg L-1 (n = 88) among SAC. There was no evidence of change in serum selenium concentration in the control groups. Conclusion: Consumption of maize flour biofortified through application of selenium-enriched fertilizer increased selenium status in this community providing strong proof of principle that agronomic biofortification could be an effective approach to address selenium deficiency in Malawi and similar settings. Clinical Trial Registration: http://www.isrctn.com/ISRCTN85899451, identifier: ISRCTN85899451.

Inflammation Adjustment by Two Methods Decreases the Estimated Prevalence of Zinc Deficiency in Malawi.

Serum zinc concentration (SZC) is used widely to assess population-level zinc status. Its concentration decreases during inflammatory responses, which can affect the interpretation of the results. This study aimed to re-estimate the prevalence of zinc deficiency in Malawi based on the 2015-2016 Malawi Micronutrient Survey (MNS) data, by adjusting SZC measures with markers of inflammation. SZC and inflammation data from 2760 participants were analysed. Adjustments were made using: (1) The Internal Correction Factor (ICF) method which used geometric means, and (2) The Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) method, which used linear regression. Mean SZC values increased significantly when adjustments were made by either ICF or BRINDA (p < 0.001). The national prevalence of zinc deficiency decreased from 62% to 59%, after ICF adjustment, and to 52% after BRINDA adjustment. ICF and BRINDA values of SZC were highly correlated (p < 0.001, r = 0.99), but a Bland-Altman plot showed a lack of agreement between the two methods (bias of 2.07 µg/dL). There was no association between the adjusted SZC and stunting, which is a proxy indicator for zinc deficiency. Inflammation adjustment of SZC, using ICF or BRINDA, produces lower estimates of zinc deficiency prevalence, but the lack of agreement between the adjustment methods warrants further research. Furthermore, the lack of association between SZC and stunting highlights the need to explore other biomarkers and proxies of population zinc assessment. This study demonstrates the importance of considering inflammatory confounders when reporting SZC, to ensure accuracy and to support policy decision making.