Changes in polyunsaturated fatty acids during treatment of malnourished children may be insufficient to reach required essential fatty acid levels - A randomised controlled trial.

BACKGROUND & AIMS: Severe acute malnutrition (SAM) is a global concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on polyunsaturated fatty acids (PUFA) are almost non-existent. The aim was to investigate the change in whole-blood PUFA and nutrition and health markers among Cambodian children with SAM after treatment with RUTFs. METHODS: The trial was an 8-week randomised clinical trial of the effectiveness of locally produced fish-based RUTF (L-RUTF) vs standard milk-based RUFT (S-RUTF). Whole-blood fatty acids were analysed using dried blood spots. Nutrition and health markers were assessed using anthropometric assessment and blood samples for markers of inflammation. The trial was conducted at the National Pediatric Hospital, Phnom Penh, Cambodia, with one hundred and twenty-one 6-59-month-old children in treatment for SAM. RESULTS: L-RUTF had a higher content of n-3 PUFA and a higher content of arachidonic acid (AA) and docosahexaenoic acid (DHA), while S-RUTF had the highest content of n-6 PUFA. At baseline, the children presented with a Mead acid level in whole-blood of around 0.08% of total fatty acids (FA%) and an omega-3 index of ∼0.91 ± 0.44. After eight weeks of S-RUTF treatment, linoleic acid (LA), AA, n-6/n-3 PUFA ratio, and Mead acid levels were increased. The L-RUTF intervention did not change the whole-blood PUFAs from baseline. At discharge, the children in the L-RUTF group had a lower n-6/n-3 PUFA ratio than the children in the S-RUTF group, driven by a lower alpha-linolenic acid (ALA) (0.20 vs 0.27 FA%, p = 0.004) and lower LA (15.77 vs 14.21 FA%, p = 0.018) with no significant differences in AA or DHA levels. Weight-for-height z-score at discharge was negatively associated with total PUFA (ß -1.4 FA%, 95%CI. -2.7; -0.1), n-6 LCPUFA (ß -1.3 FA%, 95%CI. -1.3; -0.3), and AA (ß -0.6 FA%, 95%CI. -1.0; -0.2). Age-adjusted height was negatively associated with the Mead acid:AA ratio (ß -1.2 FA%, 95%CI. -2.2; -0.2). No significant change was seen in inflammation markers within groups or between groups during treatment, and n-3 and n-6 PUFAs were not associated with markers of inflammation or haemoglobin status at discharge. CONCLUSION: The trial found that whole-blood markers of PUFA status were low in children at admission and discharge from SAM treatment, indicating that the currently recommended composition of RUTFs are not able to correct their compromised essential fatty acid status. The higher content of DHA and AA in L-RUTF did not give rise to any improvement in PUFA status. No changes in health markers or associations between PUFA and health markers were found. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02907424.

Ready-to-Use Therapeutic Foods Fail to Improve Vitamin A and Iron Status Meaningfully during Treatment for Severe Acute Malnutrition in 6-59-Month-old Cambodian Children.

Severe acute malnutrition (SAM) remains a global health concern. Studies on the impact of ready-to-use therapeutic foods (RUTFs) on micronutrient status during SAM treatment are almost nonexistent. The objective was to investigate the impact of RUTFs on the iron and vitamin A status of 6-59-month-old children receiving SAM treatment. Biomarkers of vitamin A status (retinol-binding protein, RBP), iron status (ferritin and soluble transferrin receptor, sTfR), and inflammation (C-reactive protein, CRP, and alpha-1 acid glycoprotein, AGP) were collected at admission and discharge (week 8) during an RUTF effectiveness trial. Vitamin A deficiency was defined as RBP <0.70 µmol/L, low body iron as body iron (BI) <0 mg/kg and deficient iron stores as ferritin <12 µg/L. Data were available for 110 and 75 children at admission and discharge, respectively. There was no significant difference in haemoglobin, ferritin, sTfR, BI or RBP concentrations between admission and discharge. At discharge, BI was 0.2 mg/kg lower, and there was a tendency towards a slightly lower RBP concentration, but the prevalence of vitamin A deficiency was low at admission and discharge (6% and 3%, respectively). The small impact of both RUTFs on improving vitamin A and iron status during SAM treatment calls for further research on the bioavailability of micronutrients to enhance the effectiveness of SAM treatment on micronutrient 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.

Development and testing of locally-produced ready-to-use therapeutic and supplementary foods (RUTFs and RUSFs) in Cambodia: lessons learned.

BACKGROUND: Rates of childhood undernutrition are persistently high in Cambodia. Existing ready-to-use supplementary and therapeutic foods (RUSFs and RUTFs) have had limited acceptance and effectiveness. Therefore, our project developed and trialled a locally-produced, multiple micronutrient fortified lipid-based nutrient supplement (LNS) with therapeutic and supplementary versions. This ready-to-use food (RUF) is innovative in that, unlike many RUFs, it contains fish instead of milk. Development began in 2013 and the RUF was finalised in 2015. From 2015 until the present, both the RUTF and the RUSF versions were trialled for acceptability and effectiveness. METHODS: This paper draws on project implementation records and semi-structured interviews to describe the partnership between the Cambodian Ministries of Health and Agriculture, Forestry and Fisheries, UNICEF, the French National Research Institute for Sustainable Development (IRD), universities, and Vissot factory. It discusses the project implementation and lessons learned from the development and trialling process, and insights into positioning nutrition on the health agenda in low and middle-income countries. RESULTS: The lessons learned relate to the importance of project planning, management, and documentation in order to seize opportunities in the research, policy, advocacy, and programming environment while ensuring adequate day-to-day project administration and resourcing. CONCLUSIONS: We conclude that projects such as ours, that collaborate to develop and test novel, locally-produced RUTFs and RUSFs, offer an exciting opportunity to respond to both local programmatic and broader research needs.

Development and Acceptability of Locally Made Fish-Based, Ready-to-Use Products for the Prevention and Treatment of Malnutrition in Cambodia.

BACKGROUND: Cambodia has a high prevalence of moderate acute malnutrition and severe acute malnutrition (SAM). The SAM treatment requires ready-to-use therapeutic foods (RUTFs), whereas ready-to-use supplementary foods (RUSFs) are used for prevention of acute malnutrition. Three locally produced fish-based products were developed: an RUTF paste (NumTrey-Paste) for treatment and 2 wafer versions, one for prevention (NumTrey-RUSF) and one for treatment (NumTrey-RUTF). OBJECTIVE: To assess the acceptability of NumTrey-Paste and NumTrey-RUSF in comparison to a standard biscuit product (BP-100) used for the treatment of SAM. METHODS: Acceptability of NumTrey-RUSF and NumTrey-Paste was tested in a nonblinded crossover taste trial among children (n = 52), aged ≥ 6 months to 18 years, and their caregivers. Eight organoleptic qualities were assessed on a 5-point hedonic scale, as well as a ranking test. A score of 1 to 3 was categorized as acceptable. The acceptability of NumTrey-RUTF was assessed using the caregivers' perception during an SAM treatment intervention. RESULTS: Taste trial: The proportion of children categorizing products as overall acceptable was lowest for NumTrey-Paste compared to for BP-100 and NumTrey-RUSF (21% vs 43% [BP-100] and 36% [NumTrey-RUSF]). No difference was found in the proportion of children who ranked BP-100 or NumTrey-RUSF as "liked most" ( P > .05). Acceptability of NumTrey-RUSF ranked highest in appearance and taste (caregiver), whereas acceptability of NumTrey-Paste was ranked lowest in appearance and smell among the products. Intervention trial: The acceptability of NumTrey-RUTF increased from 72% to 86%. CONCLUSIONS: The overall acceptability was ranked lowest for a pure paste product. However, filling the paste into a wafer made the product more acceptable.

Effectiveness of a Locally Produced, Fish-Based Food Product on Weight Gain among Cambodian Children in the Treatment of Acute Malnutrition: A Randomized Controlled Trial.

Cambodia continues to have a high prevalence of acute malnutrition. Low acceptability has been found for standard ready-to-use-therapeutic-food (RUTF) products. Therefore, NumTrey, a locally-produced fish-based RUTF, was developed. The objective was to evaluate the effectiveness of NumTrey compared to an imported milk-based RUTF for weight gain among children aged 6⁻59 months in the home-treatment for acute malnutrition. Effectiveness was tested in a single-blinded randomized controlled trial with weight gain as the primary outcome. Anthropometry was assessed at baseline and bi-weekly follow-ups until endline at Week 8. In total, 121 patients were randomized into BP-100TM (n = 61) or NumTrey (n = 60). There was no statistical difference in mean weight gain between the groups (1.06 g/kg/day; 95% CI (0.72, 1.41) and 1.08 g/kg/day; 95% CI (0.75, 1.41) for BP-100™ and NumTrey, respectively). In addition, no statistically significant differences in secondary outcomes were found. Although the ability to draw conclusions was limited by lower weight gain than the desired 4 g/kg/day in both groups, no superiority was found for eitherRUTF. A locally produced RUTF is highly relevant to improve nutrition interventions in Cambodia. A locally produced fish-based RUTF is a relevant alternative to imported milk-based RUTF for the treatment of SAM in Cambodia.