Adherence and acceptability of multiple micronutrient supplementation during pregnancy: Study protocol for a cluster-randomized non-inferiority trial in Cambodia.

BACKGROUND: Iron and folic acid (IFA) supplements are currently provided to Cambodian women during pregnancy. However, recent research has found benefits of a multiple micronutrient supplement (MMS) over just IFA alone on several outcomes of perinatal and infant health. The Ministry of Health in Cambodia has proposed a transition from IFA to MMS but to effectively guide this transition requires implementation research on the acceptability and adherence to MMS (over IFA). METHODS: This non-inferiority trial aims to assess the adherence and acceptability of IFA (60 mg elemental iron and 400 µg folic acid) compared to MMS (standard UNIMMAP formulation including 15 micronutrients) during antenatal care in Cambodia. A prospective cohort of 1545 pregnant women will be assigned to one of three trial arms: (1) IFA for 90 days [IFA-90]; (2) MMS for 180 days with two distributions of 90-count tablet bottles [MMS-90]; or (3) MMS for 180 days with one 180-count tablet bottle [MMS-180]. Each arm will enroll 515 women across 48 health centers (clusters) in Kampong Thom Province in Cambodia. The primary outcome is the non-inferiority of adherence rates of MMS-180 compared to IFA-90, as assessed by tablet counts. Mixed-effects logistic and linear regression models will be used to estimate the difference in the adherence rate between the two groups, with an 'a priori' determined non-inferiority margin of 15%. Acceptability of MMS and IFA will be measured using a quantitative survey conducted with enrolled pregnant women at 30-day, 90-day, and 180-day time-points. DISCUSSION: Findings from this study will guide an effective and feasible MMS scale-up strategy for Cambodia. Additionally, the findings will be shared globally with other stakeholders planning to scale up MMS in other countries. TRIAL REGISTRATION: NCT05867836 ( ClinicalTrials.gov , registered May 18, 2023).

National nutrition surveillance programmes in 18 countries in South-East Asia and Western Pacific Regions: a systematic scoping review.

Objective: To identify and analyse ongoing nutrition-related surveillance programmes led and/or funded by national authorities in countries in South-East Asian and Western Pacific Regions. Methods: We systematically searched for publications in PubMed® and Scopus, manually searched the grey literature and consulted with national health and nutrition officials, with no restrictions on publication type or language. We included low- and middle-income countries in the World Health Organization South-East Asia Region, and the Association of Southeast Asian Nations and China. We analysed the included programmes by adapting the United States Centers for Disease Control and Prevention's public health surveillance evaluation framework. Findings: We identified 82 surveillance programmes in 18 countries that repeatedly collect, analyse and disseminate data on nutrition and/or related indicators. Seventeen countries implemented a national periodic survey that exclusively collects nutrition-outcome indicators, often alongside internationally linked survey programmes. Coverage of different subpopulations and monitoring frequency vary substantially across countries. We found limited integration of food environment and wider food system indicators in these programmes, and no programmes specifically monitor nutrition-sensitive data across the food system. There is also limited nutrition-related surveillance of people living in urban deprived areas. Most surveillance programmes are digitized, use measures to ensure high data quality and report evidence of flexibility; however, many are inconsistently implemented and rely on external agencies' financial support. Conclusion: Efforts to improve the time efficiency, scope and stability of national nutrition surveillance, and integration with other sectoral data, should be encouraged and supported to allow systemic monitoring and evaluation of malnutrition interventions in these countries.

High consumption of unhealthy commercial foods and beverages tracks across the complementary feeding period in rural/peri-urban Cambodia.

Consumption of unhealthy commercial foods and beverages (UCFB) is common among infants and young children living in low- and middle-income countries. Such foods can displace other nutritious foods, however, there is limited evidence on how this consumption tracks across time. This study assessed and tracked UCFB consumption of children living in rural/peri-urban Cambodia during the complementary feeding period, identified UCFB consumption patterns of these children, and explored the association between UCFB consumption and growth. A 6-month longitudinal cohort study was implemented among 567 caregivers of children aged 10-14 months at recruitment. UCFB consumption was estimated each month via a telephone-administered 7-day food frequency questionnaire, and UCFB consumption patterns were identified based on changes in this frequency of consumption over time. The majority of children either maintained (45.7%, n = 246) or developed (43.5%, n = 234) an unhealthy consumption pattern and only 10.8% (n = 58) of children maintained/transitioned into a healthy consumption pattern. High consumers of UCFB at 10-14 months had a 4.7 (CI: 4.7 [3.1-7.2]) times odds of being high consumers of UCFB at 15-19 months (p < 0.001). There was a trend of lower length-for-age z-scores (LAZ) among children maintaining or developing an unhealthy consumption pattern (~-0. SD LAZ) compared to children maintaining/transitioning into a healthy consumption pattern, however, this association was not statistically significant. Findings indicate that high UCFB consumption begins during infancy and tracks into early childhood. National policies and programmes centred on early interventions addressing the use of UCFB for infant and young child feeding are needed.

Stunting, wasting and breast-feeding as correlates of body composition in Cambodian children at 6 and 15 months of age.

The study aimed at assessing stunting, wasting and breast-feeding as correlates of body composition in Cambodian children. As part of a nutrition trial (ISRCTN19918531), fat mass (FM) and fat-free mass (FFM) were measured using 2H dilution at 6 and 15 months of age. Of 419 infants enrolled, 98 % were breastfed, 15 % stunted and 4 % wasted at 6 months. At 15 months, 78 % were breastfed, 24 % stunted and 11 % wasted. Those not breastfed had lower FMI at 6 months but not at 15 months. Stunted children had lower FM at 6 months and lower FFM at 6 and 15 months compared with children with length-for-age z ≥0. Stunting was not associated with height-adjusted indexes fat mass index (FMI) or fat-free mass index (FFMI). Wasted children had lower FM, FFM, FMI and FFMI at 6 and 15 months compared with children with weight-for-length z (WLZ) ≥0. Generally, FFM and FFMI deficits increased with age, whereas FM and FMI deficits decreased, reflecting interactions between age and WLZ. For example, the FFM deficits were -0·99 (95 % CI -1·26, -0·72) kg at 6 months and -1·44 (95 % CI -1·69; -1·19) kg at 15 months (interaction, P<0·05), while the FMI deficits were -2·12 (95 % CI -2·53, -1·72) kg/m2 at 6 months and -1·32 (95 % CI -1·77, -0·87) kg/m2 at 15 months (interaction, P<0·05). This indicates that undernourished children preserve body fat at the detriment of fat-free tissue, which may have long-term consequences for health and working capacity.

Realistic Food-Based Approaches Alone May Not Ensure Dietary Adequacy for Women and Young Children in South-East Asia.

Objectives Micronutrient deficiencies, in southeast Asia (SE Asia), remain a public health challenge. We evaluated whether promoting the consumption of locally available nutritious foods, which is a low-risk micronutrient intervention, alone can ensure dietary adequacy, for women of reproductive age and 6-23 m old children. Methods Representative dietary data from Cambodia, Indonesia, Lao PDR, Thailand and Vietnam were analysed using linear programming analysis to identify nutrients that are likely low in personal food environments (problem nutrients), and to formulate food-based recommendations (FBRs) for three to six target populations per country. Results The number of problem nutrients ranged from zero for 12-23 m olds in Indonesia, Thailand and Vietnam to six for pregnant women in Cambodia. The FBRs selected for each target population, if adopted, would ensure a low percentage of the population was at risk of inadequate intakes for five to ten micronutrients, depending on the country and target population. Of the 11 micronutrients modelled, requirements for iron, calcium and folate were most difficult to meet (≥ 10 of the 24 target populations), using FBRs alone. The number of individual FBRs selected per set, for each target population, ranged from three to eight; and often included meat, fish or eggs, liver/organ meats, vegetables and fruits. Conclusions for practice Intervention strategies need to increase access to nutritious foods, including products fortified with micronutrients, in SE Asia, when aiming to ensure dietary adequacy for most individuals in the population.

Multi-criteria Mapping of Stakeholders' Viewpoints in Five Southeast Asian Countries on Strategies to Reduce Micronutrient Deficiencies Among Children and Women of Reproductive Age: Findings from the SMILING Project.

BACKGROUND: Despite scientific evidence on the potential impact or importance of specific interventions to improve micronutrient status of vulnerable groups, political commitment and extensive support from national stakeholders is paramount to support introduction and implementation of these interventions at national level. In order to develop efficient nutritional strategies to improve the micronutrient status of children < 5 years of age and women of reproductive age that will be supported by a wide range of stakeholders, a better understanding of viewpoints on the nutrition politics and strategies is necessary. Multi-criteria mapping (MCM) was successfully used to assess the stakeholder's viewpoint in a wide variety of contexts since the late 1990s. OBJECTIVE: The objective of the present study was to assess the viewpoints of stakeholders on a wide range of potential nutritional interventions in the five Southeast Asian countries participating in the SMILING project. METHOD: MCM methodology was used to appraise the stakeholder's viewpoints in five countries. RESULTS: The results show that the overall stakeholders' preference was for actions already implemented in their country rather than for new, innovative options, even for supplementation. Indirect interventions such like food fortification (except in Indonesia), delayed cord clamping or food-based approaches were generally less favored by the stakeholders. However, the majority of stakeholders agreed that new approaches should be considered and put in place in the future provided that evidence of their impact was demonstrated, that they received adequate technical support for their implementation and their monitoring, and that they will be accompanied by strong advocacy among decision-makers, civil society and beneficiaries. CONCLUSIONS FOR PRACTICE: To conclude, for the introduction of new, innovative strategies to reduce micronutrient deficiencies in South-East Asia, convincing stakeholders appears to be the first hurdle to be taken.

Effects of animal source food and micronutrient fortification in complementary food products on body composition, iron status, and linear growth: a randomized trial in Cambodia.

BACKGROUND: Poor nutritional quality of complementary foods often limits growth. Animal source foods, such as milk or meat, are often unaffordable. Local affordable alternatives are needed. OBJECTIVE: We evaluate the efficacy of 2 newly developed, rice-based complementary food products: WinFood (WF) with small fish and edible spiders and WinFood-Lite (WF-L) fortified with small fish, against 2 existing fortified corn-soy blend products, CSB+ (purely plant based) and CSB++ (8% dried skimmed milk). DESIGN: In total, 419 infants aged 6 mo were enrolled in this randomized, single-blinded study for 9 mo, designed primarily to assess increments in fat-free mass by a deuterium dilution technique and change in plasma ferritin and soluble transferrin receptor. Secondary endpoints were changes in anthropometric variables, including knee-heel length. Data were analyzed by the intention-to-treat approach. RESULTS: There was no difference in fat-free mass increment in WF or WF-L compared with CSB+ [WF: +0.04 kg (95% CI: -0.20, 0.28 kg); WF-L: +0.14 kg (95% CI: -0.10, 0.38 kg)] or CSB++ [WF: -0.03 kg (95% CI: -0.27, 0.21 kg); WF-L: +0.07 kg (95% CI: -0.18, 0.31 kg)] and no effect on iron status. The 1.7-mm (95% CI: -0.1, 3.5 mm) greater increase in knee-heel length in WF-L than in CSB+ was not significant. CONCLUSIONS: No difference was found between the locally produced products (WF and WF-L) and the CSBs. Micronutrient fortification may be necessary, and small fish may be an affordable alternative to milk to improve complementary foods. The dietary role of edible spiders needs to be further explored. This trial was registered at controlled-trials.com as ISRCTN19918531.

The SMILING project: a North-South-South collaborative action to prevent micronutrient deficiencies in women and young children in Southeast Asia.

BACKGROUND: The "Sustainable Micronutrient Interventions to Control Deficiencies and Improve Nutritional Status and General Health in Asia" project (SMILING), funded by the European Commission, is a transnational collaboration of research institutions and implementation agencies in five Southeast Asian countries--Cambodia, Indonesia, Laos PDR, Thailand, and Vietnam--with European partners, to support the application of state-of-the art knowledge to alleviate micronutrient malnutrition in Southeast Asia. OBJECTIVE: The major expected outcomes are to improve micronutrient status on a large scale, to identify priority interventions in each Southeast Asian country, and to develop a road map for decision makers and donors for inclusion of these priority interventions into the national policy. METHODS: SMILING has been built around a strong project consortium that works on a constant and proactive exchange of data and analyses between partners and allows for the differences in contexts and development stages of the countries, as well as a strong North-South-South collaboration and colearning. RESULTS: The selection of Southeast Asian countries considered the range of social and economic development, the extent of micronutrient malnutrition, and capacity and past success in nutrition improvement efforts. SMILING is applying innovative tools that support nutrition policy-making and programming. The mathematical modeling technique combined with linear programming will provide insight into which food-based strategies have the potential to provide essential (micro) nutrients for women and young children. Multicriteria mapping will offer a flexible decision-aiding tool taking into account the variability and uncertainty of opinions from key stakeholders. The lessons learned throughout the project will be widely disseminated.

Thiamine pharmacokinetics in Cambodian mothers and their breastfed infants.

BACKGROUND: Thiamine deficiency is common in parts of Asia and causes beriberi. Pharmacokinetics of thiamine in deficient populations are unknown. OBJECTIVE: We characterized thiamine pharmacokinetics in Cambodian mothers and their breastfed infants. DESIGN: Total plasma thiamine, whole-blood thiamine diphosphate (TDP), and breast milk total thiamine were measured in 16 healthy Cambodian mothers and their infants before and after mothers received oral thiamine hydrochloride (100 mg for 5 d). Assays were also performed in 16 healthy American mothers. RESULTS: On day 1, Cambodian mothers were thiamine deficient, with median (range) total plasma thiamine and TDP concentrations of 2.4 nmol/L (0-4.4 nmol/L) and 58.0 nmol/L (27-98 nmol/L), respectively. After a single oral dose, the mean ± SD maximal concentration of thiamine and net area under the thiamine concentration-time curve were 73.4 ± 45.6 nmol/L and 465 ± 241 h · nmol ∙ L⁻¹. Day 6 median maternal total plasma thiamine and TDP concentrations were normal [18.6 nmol/L (13.4-25.3 nmol/L) and 76.5 nmol/L (48-107 nmol/L), respectively; P ≤ 0.001 compared with day 1]. Median Cambodian total breast milk thiamine concentration increased from 180 nmol/L (85-359 nmol/L) on day 1 to 403 nmol/L (314-415 nmol/L) on day 2 and 503 nmol/L (360-808 nmol/L) on day 6; the corresponding American breast milk value was 500 nmol/L (114-622 nmol/L). Median Cambodian infant total plasma thiamine and TDP concentrations increased from 3.0 nmol/L (0-7.3 nmol/L) and 38.5 nmol/L (23-57 nmol/L), respectively, on day 1 to 5.6 nmol/L (0-9.7 nmol/L) and 45.5 nmol/L (32-70 nmol/L), respectively, on day 6. CONCLUSIONS: Thiamine-deficient Cambodian mothers effectively absorb oral thiamine, with sharp increases in breast milk thiamine concentrations, but their breastfed infants remain thiamine deficient after 5 d of maternal supplementation. Longer-term maternal supplementation may be necessary to correct thiamine deficiency in breastfed infants. This trial was registered at clinicaltrials.gov as NCT01864057.

Effect of micronutrient sprinkles on reducing anemia: a cluster-randomized effectiveness trial.

OBJECTIVE: To evaluate the effectiveness of Sprinkles alongside infant and young child feeding (IYCF) education compared with IYCF education alone on anemia, deficiencies in iron, vitamin A, and zinc, and growth in Cambodian infants. DESIGN: Cluster-randomized effectiveness study. SETTING: Cambodian rural health district. PARTICIPANTS: Among 3112 infants aged 6 months, a random subsample (n = 1350) was surveyed at baseline and 6-month intervals to age 24 months. INTERVENTION: Daily micronutrient Sprinkles alongside IYCF education vs IYCF education alone for 6 months from ages 6 to 11 months. MAIN OUTCOME MEASURES: Prevalence of anemia; iron, vitamin A, and zinc deficiencies; and growth via biomarkers and anthropometry. RESULTS: Anemia prevalence (hemoglobin level <11.0 g/dL [to convert to grams per liter, multiply by 10.0]) was reduced in the intervention arm compared with the control arm by 20.6% at 12 months (95% CI, 9.4-30.2; P = .001), and the prevalence of moderate anemia (hemoglobin level <10.0 g/dL) was reduced by 27.1% (95% CI, 21.0-31.8; P < .001). At 12 and 18 months, iron deficiency prevalence was reduced by 23.5% (95% CI, 15.6-29.1; P < .001) and 11.6% (95% CI, 2.6-17.9; P = .02), respectively. The mean serum zinc concentration was increased at 12 months (2.88 µg/dL [to convert to micromoles per liter, multiply by 0.153]; 95% CI, 0.26-5.42; P = .03). There was no statistically significant difference in the prevalence of zinc and vitamin A deficiencies or in growth at any time. CONCLUSIONS: Sprinkles reduced anemia and iron deficiency and increased the mean serum zinc concentration in Cambodian infants. Anemia and zinc effects did not persist beyond the intervention period. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12608000069358.