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.

Body Composition Changes in Children during Treatment for Moderate Acute Malnutrition: Findings from a 4-Arm Cluster-Randomized Trial in Sierra Leone.

BACKGROUND: Measures that better describe "healthy" and sustainable recovery during nutritional treatment of children with moderate acute malnutrition (MAM) are needed. OBJECTIVES: We compared changes to body composition among children receiving 1 of 4 specialized nutritious food (SNFs) during treatment of MAM and by recovery and relapse outcomes. METHODS: The study was nested within a prospective, cluster-randomized, community-based, cost-effectiveness trial assessing 4 SNFs to treat children aged 6-59 mo with MAM [midupper arm circumference (MUAC) ≥11.5 cm and <12.5 cm without bipedal edema] in Sierra Leone. Biweekly SNF rations (1 of 3 fortified-blended foods or a lipid-based nutrient supplement) were given until children recovered (MUAC ≥12.5 cm), or up to 7 rations (∼12 wk). Deuterium dilution was used to estimate fat-free mass (FFM) and fat mass (FM) at enrollment and after 4 wk of treatment to ensure similar treatment exposure among the participants. Another MUAC measurement was performed among recovered children 4 wk after program exit to determine whether recovery was sustained. ANOVA, paired t tests, and linear regression models were used to determine significant differences in changes from baseline to 4 wk. RESULTS: Among 312 analyzed participants, mean baseline weight comprised ∼80% FFM; mean weight gained after 4 wk comprised ∼82% FFM. Changes in FM and FFM among 4 SNFs were similar. Children who recovered gained more weight (241%), FFM (179%), and weight-for-height z score (0.44 compared with 0) compared with those who did not recover; sustainers gained 150% more weight. FM gains were positive among recovered children and sustainers, as well as negative among those who did not recover or sustain recovery, but not significantly different. CONCLUSIONS: Four SNFs had similar effects on body composition in children after 4 wk of treatment for MAM, showing a healthy pattern of weight gain, the majority being FFM. Differential responses to treatment underscore a need for further research to provide targets for healthy, sustainable recovery. This trial was registered at clinicaltrials.gov as NCT03146897.

Impact of stakeholder perspectives on cost-effectiveness estimates of four specialized nutritious foods for preventing stunting and wasting in children 6-23 months in Burkina Faso.

BACKGROUND: Multiple specialized nutritious food options are programmed for supplementation in humanitarian and development settings. However, comparative cost-effectiveness evidence is lacking, let alone incorporation of perspectives from uncompensated stakeholders. A Burkina Faso trial evaluated the cost-effectiveness of Corn Soy Blend Plus w/ oil (CSB+ w/oil, reference arm), Corn Soy Whey Blend w/oil (CSWB w/oil), Super Cereal Plus (SC+), and Ready-to-Use Supplementary Food (RUSF) in reducing stunting and wasting among children 6-23 months old. This paper presents cost-effectiveness findings from multiple stakeholders' perspectives, including caregivers and program volunteers. METHODS: An activity-based costing with ingredients approach was used to summarize cost of the 18-month-long blanket supplementary feeding for each enrolled child (in 2018 USD). Time data were collected using self-reported and observational instruments. Cost-effectiveness relative to CSB+ w/oil assessed incremental cost per enrolled child against incremental outcomes: prevalence of stunting at 23 months of age and number of months of wasting. Two combined perspectives were compared: program (donor, implementer, and volunteer) versus program and caregiver (adding caregiver). RESULTS: A total of 6112 children were enrolled. While similar effectiveness was found in three arms (CSWB w/oil was less effective), costs differed. Product cost and caregiver time to prepare study foods were major drivers of cross-arm cost differences from the respective combined perspective. The two major drivers were used to construct uncertainty ranges of cost per enrolled child from program and caregiver perspective: $317 ($279- $355) in CSB+ w/oil, $350 ($327- $373) in CSWB w/oil, $387 ($371- $403) in RUSF, and $434 ($365- $503) in SC+. Cost from program and caregiver perspective was a substantial increase from program perspective. CSB+ w/oil was most cost-effective in reducing stunting and wasting, and this main finding was robust to changing perspectives and all corresponding sensitivity analyses when uncompensated time was valued at minimum wage ($0.36/h). The break-even point for uncompensated time valuation is >$0.84/h, where RUSF became the most cost-effective from the program and caregiver perspective. Relative cost-effectiveness rankings among the other three arms depended on choice of perspectives, and were sensitive to values assigned to product cost, international freight cost, opportunity cost of time, and outcomes of a hypothetical control. Volunteer opportunity cost did not affect arm comparisons, but lack of compensation resulted in negative financial consequences for caregivers. CONCLUSIONS: Evaluating cost-effectiveness by incorporating uncompensated stakeholders provided crucial implementation insights around nutrition products and programming. TRIAL REGISTRATION: Trial registration number: NCT02071563. Name of registry: ClinicalTrials.gov URL of registry: https://clinicaltrials.gov/ct2/show/NCT02071563?type=Intr&cond=Malnutrition&cntry=BF&draw=2&rank=9 Date of registration: February 26, 2014. Date of enrollment of first participant: July 2014.

Program changes are effective and cost-effective in increasing the amount of oil used in preparing corn soy blend porridge for treatment of moderate acute malnutrition in Malawi.

Corn Soy Blend (CSB) porridge is commonly prepared with oil for treatment of moderate acute malnutrition (MAM). A recent review recommended that 30 g of oil be used with 100 g of CSB to increase energy density and micronutrient absorption. This study assessed the effectiveness and cost-effectiveness of program changes aimed at achieving that target oil:CSB ratio in prepared porridge. Caregivers of children in MAM supplementary feeding programs were assigned to three groups: a control group received monthly rations of 1 L oil, 8 kg CSB in bulk, and social and behavior change communication (SBCC); intervention groups received 2.6 L oil, 8 kg CSB provided either in bulk (Group 1) or four 2-kg packages with printed messages (Group 2), and enhanced SBCC emphasizing the target oil:CSB ratio. Compared to the control, both intervention groups had higher mean added oil per 100 g CSB (18 g, p < 0.01, and 13 g, p= 0.04, higher in groups 1 and 2, respectively), and greater odds of meeting or exceeding the target ratio (28.4, p< 0.01, and 12.7, p= 0.02, in groups 1 and 2, respectively). Cost per caregiver reaching the target ratio was most favorable in Group 1 ($391 in Group 1, $527 in Group 2, and $1,666 in the control). Enhanced SBCC combined with increased oil ration resulted in increased use of oil in CSB porridge in a supplementary feeding program. Modified packaging did not improve effectiveness. However, both interventions were more cost-effective than standard programming.

Effects of Different Processing Methods on the Micronutrient and Phytochemical Contents of Maize: From A to Z.

Maize is a staple human food eaten by more than a billion people around the world in a variety of whole and processed products. Different processing methods result in changes to the nutritional profile of maize products, which can greatly affect the micronutrient intake of populations dependent on this crop for a large proportion of their caloric needs. This review summarizes the effects of different processing methods on the resulting micronutrient and phytochemical contents of maize. The majority of B vitamins are lost during storage and milling; further loss occurs with soaking and cooking, but fermentation and nixtamalization (soaking in alkaline solution) can increase bioavailability of riboflavin and niacin. Carotenoids, found mainly in the kernel endosperm, increase in concentration after degermination, while other vitamins and minerals, found mainly in the germ, are reduced. Mineral bioavailability can be improved by processing methods that reduce phytic acid, such as soaking, fermenting, cooking, and nixtamalization. Losses of micronutrients during processing can be mitigated by changes in methods of processing, in addition to encouraging consumption of whole-grain maize products over degermed, refined products. In some cases, such as niacin, processing is actually necessary for nutrient bioavailability. Due to the high variability in the baseline nutrient contents among maize varieties, combined with additional variability in processing effects, the most accurate data on nutrient content will be obtained through analysis of specific maize products and consideration of in vivo bioavailability.

Optimization of the nutrient content and protein quality of cereal-legume blends for use as complementary foods in Ghana.

BACKGROUND: Nutritionally adequate complementary foods made from locally available ingredients are of high priority in developing countries, including Ghana. The majority of complementary foods in these countries are cereal-based and are unable to meet the nutrient intakes recommended by the World Health Organization. OBJECTIVE: To evaluate the nutrient content and protein quality of local cereal-legume blends for complementary foods against recommendations and to determine the quantities of additional ingredients required to meet needs by using linear programming. METHODS: Nine cereal-legume combinations (maize, sorghum, or millet combined with cowpea, peanut, or soybean) and koko (a traditional Ghanaian maize-based complementary food) were evaluated based on the macronutrient targets for a daily ration of complementary food for the age group 12 to 24 months: 264 kcal, 6.5 g of protein, and 8.2 to 11.7 g of fat. Protein quality was assessed by the Protein Digestibility Corrected Amino Acid Score (PDCAAS). Linear programming was then used to determine the amounts of additional oil, sugar, and lysine needed to meet macronutrient requirements. RESULTS: No traditional cereal-legume food met all complementary food macronutrient requirements on its own. Cereal-legume blends made with peanut or cowpeas were low in quality protein, while those with soybean were low in fat. Lysine was the limiting amino acid (PDCAAS 0.50 to 0.82) in all blends. Adding lysine increased utilizable protein by 1% to 10% in soybean blends, 35% to 40% in peanut blends, and 14% to 24% in cowpea blends. Peanut-maize, peanut-millet, and all soybean-cereal blends were able to meet macronutrient targets; most micronutrients remained below recommended levels. CONCLUSIONS: Traditional cereal-legume blends made from locally available ingredients do not meet energy, quality protein, and fat recommendations for complementary foods; however, such complementary food blends may be optimized to meet nutrient requirements by using linear programming as a tool to determine the exact levels of fortificants to be added (including, but not limited to, added fat, amino acids, and micronutrients).

Driving social impact with common global indicators for healthy lifestyle programs: lessons learned.

BACKGROUND: Partnerships between corporate entities and non-governmental organizations (NGOs) involved in delivering community focused health and well-being programs are becoming increasingly valuable especially in the context of promoting healthy lifestyles around the globe. The Mondelez International Foundation (MIF) has funded healthy lifestyles community based programs targeting children and youth through partnership with seven global NGOs. To assess collective impact of these programs, it is crucial to identify best practices and common impact indicators that can be measured across programs. MIF therefore organized the Healthy Lifestyles Evaluation Workshop to explore these pertinent questions. OBJECTIVE: Share best practices and identify common impact indicators to measure the success of current and future MIF funded healthy lifestyles programs. METHODS: Analysis of the Program Impact Pathways (PIPs) and measured output of each of the seven programs. RESULTS: Individual and combined analysis of PIPs of the seven NGO programs led to identification of three critical impact indicators: nutrition knowledge, physical activity, and healthier eating, and also enabled NGOs to identify pathways to improve program delivery among the target population. CONCLUSIONS: This workshop enabled MIF and partner NGOs to came together to align on metrics and future engagement approaches for promoting and evaluating community based healthy lifestyles programs.

Assessment of protein adequacy in developing countries: quality matters.

Dietary protein and amino acid requirement recommendations for normal "healthy" children and adults have varied considerably with 2007 FAO/WHO protein requirement estimates for children lower, but dietary essential AA requirements for adults more than doubled. Requirement estimates as presented do not account for common living conditions, which are prevalent in developing countries such as energy deficit, infection burden and added functional demands for protein and AAs. This study examined the effect of adjusting total dietary protein for quality and digestibility (PDCAAS) and of correcting current protein and AA requirements for the effect of infection and a mild energy deficit to estimate utilizable protein (total protein corrected for biological value and digestibility) and the risk/prevalence of protein inadequacy. The relationship between utilizable protein/prevalence of protein inadequacy and stunting across regions and countries was examined. Data sources (n = 116 countries) included FAO FBS (food supply), UNICEF (stunting prevalence), UNDP (GDP) and UNSTATS (IMR) and USDA nutrient tables. Statistical analyses included Pearson correlations, paired-sample/non-parametric t-tests and linear regression. Statistically significant differences were observed in risk/prevalence estimates of protein inadequacy using total protein and the current protein requirements versus utilizable protein and the adjusted protein requirements for all regions (p < 0·05). Total protein, utilizable protein, GDP per capita and total energy were each highly correlated with the prevalence of stunting. Energy, protein and utilizable protein availability were independently and negatively associated with stunting (p < 0·001), explaining 41 %, 34 % and 40 % of variation respectively. Controlling for energy, total protein was not a statistically significant factor but utilizable protein remained significant explaining~45 % of the variance (p = 0·017). Dietary utilizable protein provides a better index of population impact of risk/prevalence of protein inadequacy than crude protein intake. We conclude that the increased demand for protein due to infections and mild to moderate energy deficits, should be appropriately considered in assessing needs of populations where those conditions still prevail.

A case report and literature review of olanzapine-associated hyperglycemia with previous history of gestational diabetes.

BACKGROUND: Olanzapine (Zyprexa) package labeling includes a warning for hyperglycemia, stating physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus or having borderline increased blood glucose levels. A case report of olanzapine-associated hyperglycemia in a patient with a history of gestational diabetes mellitus (GDM) is presented and literature review is discussed. CASE REPORT: A 33-year-old female with a past medical history of bipolar disorder, cocaine and amphetamine use disorder, hypertension, and GDM was initiated on olanzapine 5 mg PO daily which was subsequently titrated to 25 mg daily. On day 15 of admission, she developed signs and symptoms of hyperglycemia, with blood glucose readings >500 mg/dL. Insulin was initiated, olanzapine was discontinued, and her blood glucose began improving. She was later discharged on ziprasidone 20 mg PO twice daily. DISCUSSION: There have been several case reports published on olanzapine-induced hyperglycemia. This is the first case report to specifically recognize a history of GDM as a potential risk factor for developing olanzapine-associated hyperglycemia. CONCLUSION: Adverse effect profiles and patient-specific risk factors should be considered when selecting appropriate antipsychotic treatment. Olanzapine may not be an ideal medication choice for a person with a history of GDM; however, if olanzapine is indicated, then close blood glucose monitoring is recommended.

Chronic and acute hypervitaminosis A are associated with suboptimal anthropometric measurements in a cohort of South African preschool children.

BACKGROUND: Excessive vitamin A (VA) can cause bone resorption and impair growth. Government-mandated VA supplementation (VAS) and adequate intake through dietary fortification and liver consumption led to excessive VA in South African children. OBJECTIVES: We evaluated the relation between VAS and underlying hypervitaminosis A assessed by retinol isotope dilution (RID) with measures of growth and bone turnover in this cohort. METHODS: Primary outcomes in these children (n = 94, 36-60 mo) were anthropometric measurements [height-for-age (HAZ), weight-for-age (WAZ), and weight-for-height (WHZ) z scores], serum bone turnover markers [C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (P1NP)], and inflammation defined as C-reactive protein (CRP; ≥5 mg/L) and/or α1-acid glycoprotein (AGP; ≥1 g/L). VA status was previously measured by RID-estimated total body VA stores (TBSs) and total liver VA reserves (TLRs), and serum retinol and carotenoid concentrations, before and 4 wk after children were administered 200,000 IU VAS. Serum 25-hydroxyvitamin D3 was measured by ultra-performance LC. RESULTS: In this largely hypervitaminotic A cohort, HAZ, WAZ, and WHZ were negatively associated with increasing TLRs, where TLRs predicted 6-10% of the variation before VAS (P < 0.05), increasing to 14-19% 4 wk after VAS (P < 0.01). Bone resorption decreased after VAS (P < 0.0001), whereas formation was unaffected. Neither CTX nor P1NP were correlated with TLRs at either time. Serum carotenoids were low. One child at each time point was vitamin D deficient (<50 nmol/L). CRP and AGP were not associated with growth measurements. CONCLUSIONS: Excessive TLRs due to dietary VA intake and VAS are associated with lower anthropometric measures and bone resorption decreased after supplementation. VA supplementation programs should monitor VA status with biomarkers sensitive to TLRs to avoid causing negative consequences in children with hypervitaminosis A. This trial is registered at clinicaltrials.gov as NCT02915731.

Changes of Plasma Amino Acid Profiles in Infants With a Nutrient-Fortified Complementary Food Supplement: Evidence From a 12-Month Single-Blind Cluster-Randomized Controlled Trial.

Stunting is reportedly associated with low circulating levels of essential amino acids (EAAs). This study examined the effect of a macronutrient- and micronutrient-fortified complementary food supplement (KOKO Plus) on specific plasma EAA levels and stunting in infants aged 6-18 months. In a single-blind cluster-randomized controlled trial conducted in Ghana, infants were enrolled at 6 months and followed until 18 months. Thirty-eight communities were randomly assigned to receive KOKO Plus (KP, fourteen communities, n = 321), multiple-micronutrient powder (MN, thirteen communities, n = 327), or only nutritional education as control group (NE, eleven communities, n = 318), and all groups received nutrition education. Plasma amino acids (AAs) were measured at 6, 12, and 18 months (end point). Mixed-effects models were used to assess the effect of the intervention on plasma AAs, and the relationship between plasma branched-chain AAs (BCAAs) and the risk of stunting was assessed. At the end point, total BCAA concentrations (±standard error) significantly exceeded baseline in the KP (284.2 ± 4.3 µM) and NE (289.1 ± 4.4 µM) groups but not the MN group (264.4 ± 4.1 µM). After adjustment for compliance at 200 sachets, plasma BCAAs exceeded in the KP group (284.5 ± 4.2 µM) compared to the MN group (264.6 ± 4 µM). Plasma BCAAs were positively correlated with changes in length-for-age Z-score from baseline (R = 0.327, p = 0.048). In conclusion, the plasma BCAA concentrations of infants that received KP and the NE group was significantly higher compared to the MN group but there were no differences between the KP and NE group at end point. Improved plasma BCAAs may be due to improved nutrient intake by infants exposed to KP or NE. Low BCAAs were associated with stunting, replicating the previous finding. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03181178?term=NCT03181178&draw=2&rank=1, identifier: NCT03181178.

Inflammation Adjustments to Serum Retinol and Retinol-Binding Protein Improve Specificity but Reduce Sensitivity when Estimating Vitamin A Deficiency Compared with the Modified Relative Dose-Response Test in Ghanaian Children.

BACKGROUND: Serum retinol and retinol-binding protein (RBP) concentrations are commonly used biomarkers of vitamin A deficiency (VAD); however, evidence indicates that they are not always accurate, especially in populations with high exposure to inflammation. OBJECTIVE: The aim was to assess sensitivity and specificity of serum retinol and RBP concentrations to predict VAD, with and without adjustment for inflammation (using categorical and regression-adjusted approaches), using the modified relative dose-response (MRDR) as the reference standard for liver reserves. METHODS: This secondary analysis of diagnostic accuracy used inflammation and RBP data and analyzed serum retinol and MRDR from a subsample of women of reproductive age (n = 178) and preschool children (n = 166) in the cross-sectional 2017 Ghana Micronutrient Survey. RESULTS: Inflammation (elevated C-reactive protein and/or α1-acid glycoprotein) was present in 41% of children and 16% of women. Among children, estimates of VAD prevalence were as follows: 7% (MRDR), 40% (serum retinol), 29% (categorical-adjusted serum retinol), 24% (RBP), 13% (categorical-adjusted RBP), and 7% (regression-adjusted RBP). Sensitivity (95% CI) ranged from 22.2% (2.81%, 60.0%; both adjusted RBPs) to 80.0% (44.4%, 97.5%; serum retinol), whereas specificity ranged from 63.3% (54.7%, 71.3%; serum retinol) to 93.5% (88.0%, 97.0%; regression-adjusted RBP). Among women, VAD prevalence ranged from 1% (RBP) to 4% (all others); sensitivity was 0% and specificity was >96% for all indicators. CONCLUSIONS: Serum retinol and RBP had varying accuracy in estimating VAD, especially in children; adjustment for inflammation increased accuracy by increasing specificity at the expense of sensitivity. Effects of inflammation adjustment in the context of high inflammation and VAD prevalence need to be further explored. Especially in populations with high inflammation, the MRDR test should accompany serum retinol or RBP measurements in a subsample of subjects in population-based surveys. This trial was registered with the Open Science Framework registry (doi: 10.17605/OSF.IO/J7BP9).

Host Fecal mRNAs Predicted Environmental Enteric Dysfunction among Children with Moderate Acute Malnutrition in Sierra Leone.

Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference ≥ 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L ≥ 0.2) and severe EED (%L ≥ 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment.

Effectiveness and cost-effectiveness of 4 supplementary foods for treating moderate acute malnutrition: results from a cluster-randomized intervention trial in Sierra Leone.

BACKGROUND: Moderate acute malnutrition (MAM) affects 33 million children annually. Investments in formulations of corn-soy blended flours and lipid-based nutrient supplements have effectively improved MAM recovery rates. Information costs and cost-effectiveness differences are still needed. OBJECTIVES: We assessed recovery and sustained recovery rates of MAM children receiving a supplementary food: ready-to-use supplementary food (RUSF), corn soy whey blend with fortified vegetable oil (CSWB w/oil), or Super Cereal Plus with amylase (SC + A) compared to Corn Soy Blend Plus with fortified vegetable oil (CSB+ w/oil). We also estimated differences in costs and cost effectiveness of each supplement. METHODS: In Sierra Leone, we randomly assigned 29 health centers to provide a supplement containing 550 kcal/d for ∼12 wk to 2691 children with MAM aged 6-59 mo. We calculated cost per enrollee, cost per child who recovered, and cost per child who sustained recovery each from 2 perspectives: program perspective and caregiver perspective, combined. RESULTS: Of 2653 MAM children (98.6%) with complete data, 1676 children (63%) recovered. There were no significant differences in the odds of recovery compared to CSB+ w/oil [0.83 (95% CI: 0.64-1.08) for CSWB w/oil, 1.01 (95% CI: 0.78-1.3) for SC + A, 1.05 (95% CI: 0.82-1.34) for RUSF]. The odds of sustaining recovery were significantly lower for RUSF (0.7; 95% CI 0.49-0.99) but not CSWB w/oil or SC + A [1.08 (95% CI: 0.73-1.6) and 0.96 (95% CI: 0.67-1.4), respectively] when compared to CSB+ w/oil. Costs per enrollee [US dollars (USD)/child] ranged from $105/child in RUSF to $112/child in SC + A and costs per recovered child (USD/child) ranged from $163/child in RUSF to $179/child in CSWB w/oil, with overlapping uncertainty ranges. Costs were highest per sustained recovery (USD/child), ranging from $214/child with the CSB+ w/oil to $226/child with the SC + A, with overlapping uncertainty ranges. CONCLUSIONS: The 4 supplements performed similarly across recovery (but not sustained recovery) and costed measures. Analyses of posttreatment outcomes are necessary to estimate the full cost of MAM treatment. This trial was registered at clinicaltrials.gov as NCT03146897.

Advancing Nutrition in the International Food Assistance Agenda: Progress and Future Directions Identified at the 2018 Food Assistance for Nutrition Evidence Summit.

BACKGROUND: Global food insecurity persists despite continued international attention, necessitating evidence-based food assistance interventions that adequately address nutritional concerns. In June 2018, the US Agency for International Development's Office of Food for Peace through the Food Aid Quality Review (FAQR) project sponsored a "Food Assistance for Nutrition Evidence Summit" to share evidence relevant to policy and programmatic decision-making and to identify critical evidence gaps. OBJECTIVE: This article presents 4 priority areas to advance nutrition in the international food assistance agenda generated through presentations and discussions with the food assistance community at the Evidence Summit. METHODS: Priority areas were identified after the Evidence Summit using a combination of FAQR team discussions, review of presentations and official notes, and supporting literature. RESULTS: Key priority areas to advance nutrition in the international food assistance agenda are as follows: (1) increase research funding for food assistance in all contexts, paying particular attention to emergency settings; (2) research and adopt innovative ingredients, technology, and delivery strategies in food assistance products and programs that encourage long-term well-being; (3) redefine and expand indicators of nutritional status to capture contextual information about the outcomes of food assistance interventions; and (4) augment communication and collaboration across the food assistance ecosystem. CONCLUSIONS: These priorities are critical in a time of increased humanitarian need and will be key to fostering long-term resilience among vulnerable groups.

Factors that May Influence the Effectiveness of 4 Specialized Nutritious Foods in the Prevention of Stunting and Wasting in Children Aged 6-23 Months in Burkina Faso.

BACKGROUND: A trial in Burkina Faso compared the cost-effectiveness of 4 specialized nutritious foods (SNFs) used to prevent stunting and wasting in children aged 6-23 mo. OBJECTIVES: This article explores differences in SNF use that may have influenced effectiveness, specifically in relation to consumption by the recipient child and by any other person (i.e., sharing), other diversion from the recipient child, preparation, storage, and hygiene. METHODS: Subsamples from a geographically clustered, longitudinal trial with random assignment to Corn Soy Blend Plus with oil (CSB+ w/oil), Corn Soy Whey Blend with oil (CSWB w/oil), Super Cereal Plus (SC+), or ready-to-use supplementary food (RUSF) were selected for in-depth interviews, in-home observations, and focus group discussions. RESULTS: Sharing was common in all arms, with the highest reported in SC+ (73%) and highest observed in CSWB w/oil (36%). Some reported giving the ration away (highest in SC+ at 17%) or using it for other purposes (highest in CSWB w/oil at 17%). The recipient child was observed consuming the ration in 49% of households on average (38-60% by arm in CSB+ w/oil and RUSF, respectively). Qualitative reports of bitterness and spoilage emerged in the CSWB w/oil arm. Most observed households (excluding RUSF) did not prepare porridge daily as instructed (35-46% by arm). Household water samples showed either high-risk or unsafe contamination with Escherichia coli (72-78% by arm). Low percentages were observed handwashing (both child and server) before consuming the porridge. CONCLUSIONS: The SNFs were not prepared or served as intended and diversion from the recipient was common. Storage conditions may have resulted in spoilage of the ration containing whey before reaching recipients. This article provides context about factors that may have influenced the effectiveness of these SNFs. Programming and household use of SNFs are as important as their nutrient composition. This trial was registered at clinicaltrials.gov as NCT02071563.

Cost-Effectiveness of 4 Specialized Nutritious Foods in the Prevention of Stunting and Wasting in Children Aged 6-23 Months in Burkina Faso: A Geographically Randomized Trial.

BACKGROUND: There is a variety of specialized nutritious foods available for use in programs targeting undernutrition, but evidence supporting the choice of product is limited. OBJECTIVES: We compared the cost-effectiveness of 4 specialized nutritious foods to prevent stunting and wasting in children aged 6-23 mo in Burkina Faso. METHODS: Four geographic regions were randomly assigned to 1 of 4 intervention arms: Corn-Soy Blend Plus (CSB+) programmed with separate fortified vegetable oil (the reference food), Corn-Soy-Whey Blend (CSWB; a new formulation) with oil, SuperCereal Plus (SC+), and ready-to-use supplementary food (RUSF). We compared the effects of each intervention arm on growth (length-for-age z score (LAZ), weight-for-length z score (WLZ), end-line stunting (LAZ < -2), and total monthly measurements of wasting (WLZ < -2). Rations were ∼500 kcal/d, distributed monthly. Children were enrolled in the blanket supplementary feeding program at age ∼6 mo and measured monthly for ∼18 mo. Average costs per child reached were linked with effectiveness to compare the cost-effectiveness of each arm with CSB+ with oil. RESULTS: In our sample of 6112 children (CSB+, n = 1519; CSWB, n = 1503; SC+, n = 1564; RUSF, n = 1526), none of the foods prevented declines in growth. Children in the SC+ and RUSF arms were not significantly different than those in the CSB+ with oil arm. Children in the CSWB with oil arm experienced higher end-line (measurement at age 22.9-23.9 mo) stunting (OR: 2.07; 95% CI: 1.46, 2.94) and more months of wasting (incidence rate ratio: 1.29; 95% CI: 1.09, 1.51). CSB+ with oil was the least-expensive ration in all costing scenarios ($113-131 2018 US dollars/enrolled child) and similar in effectiveness to SC+ and RUSF, and thus the most cost-effective product for the defined purposes. CONCLUSIONS: CSB+ with oil was the most cost-effective ration in the prevention of wasting and stunting in this trial. This trial was registered at clinicaltrials.gov as NCT02071563.

South African preschool children habitually consuming sheep liver and exposed to vitamin A supplementation and fortification have hypervitaminotic A liver stores: a cohort study.

BACKGROUND: In some regions, multiple vitamin A (VA) interventions occur in the same target groups, which may lead to excessive stores. Retinol isotope dilution (RID) is a more sensitive technique than serum retinol to measure VA status. OBJECTIVE: We evaluated VA status before and after a high-dose supplement in preschool children living in a region in South Africa with habitual liver consumption and exposed to VA supplementation and fortification. METHODS: After baseline blood samples, subjects (46.7 ± 8.4 mo; n = 94) were administered 1.0 µmol [14,15]-13C2-retinyl acetate to estimate total liver retinol reserves by RID with a follow-up 14-d blood sample. Liver intake was assessed with a frequency questionnaire. In line with current practice, a routine 200,000 IU VA capsule was administered after the RID test. RID was repeated 1 mo later. Serum retinyl esters were evaluated using ultra-performance liquid chromatography. RESULTS: At baseline, 63.6% of these children had hypervitaminosis A defined as total liver retinol reserves ≥1.0 µmol/g liver, which increased to 71.6% after supplementation (1.13 ± 0.43 to 1.29 ± 0.46 µmol/g; P < 0.001). Total serum VA as retinyl esters was elevated in 4.8% and 6.1% of children before and after supplementation. The odds of having hypervitaminosis A at baseline were higher in children consuming liver ≥1/mo (ratio 3.70 [95% CI: 1.08, 12.6]) and in children receiving 2 (4.28 [1.03, 17.9]) or 3 (6.45 [0.64, 65.41]) supplements in the past 12 mo. Total body stores decreased after the supplement in children in the highest quartile at baseline compared with children with lower stores, who showed an increase (P = 0.007). CONCLUSIONS: In children, such as this cohort in South Africa, with adequate VA intake through diet, and overlapping VA fortification and supplementation, preschool VA capsule distribution should be re-evaluated. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT02915731 as NCT02915731.

A macro- and micronutrient-fortified complementary food supplement reduced acute infection, improved haemoglobin and showed a dose-response effect in improving linear growth: a 12-month cluster randomised trial.

Inadequate protein quality may be a risk factor for poor growth. To examine the effect of a macronutrient-micronutrient supplement KOKO Plus (KP), provided to infants from 6 to 18 months of age, on linear growth, a single-blind cluster-randomised study was implemented in Ghana. A total of thirty-eight communities were randomly allocated to receive KP (fourteen communities, n 322), a micronutrient powder (MN, thirteen communities, n 329) and nutrition education (NE, eleven communities, n 319). A comparison group was followed cross-sectionally (n 303). Supplement delivery and morbidity were measured weekly and anthropometry monthly. NE education was provided monthly. Baseline, midline and endline measurements at 6, 12 and 18 months included venous blood draws, diet, anthropometry, morbidity, food security and socio-economics. Length-for-age Z-score (LAZ) was the primary outcome. Analyses were intent-to-treat using mixed-effects regressions adjusted for clustering, sex, age and baseline. No differences existed in mean LAZ scores at endline (-1·219 (sd 0·06) KP, -1·211 (sd 0·03) MN, -1·266 (sd 0·03) NE). Acute infection prevalence was lower in the KP than NE group (P = 0·043). Mean serum Hb was higher in KP infants free from acute infection (114·02 (sd 1·87) g/l) than MN (107·8 (sd 2·5) g/l; P = 0·047) and NE (108·8 (sd 0·99) g/l; P = 0·051). Compliance was 84·9 % (KP) and 87·2 % (MN) but delivery 60 %. Adjusting for delivery and compliance, LAZ score at endline was significantly higher in the KP v. MN group (+0·2 LAZ; P = 0·026). A macro- and micronutrient-fortified supplement KP reduced acute infection, improved Hb and demonstrated a dose-response effect on LAZ adjusting consumption for delivery.