Supplementation during pregnancy with small-quantity lipid-based nutrient supplements or multiple micronutrients, compared with iron and folic acid, increases women's urinary iodine concentration in semiurban Ghana: A randomized controlled trial.

There is little information on whether prenatal multiple micronutrient (MMN) supplements containing iodine affect women's iodine status. In the International Lipid-based Nutrient Supplements DYAD-Ghana trial, we aimed to assess women's urinary iodine concentration (UIC, µg/L) during pregnancy, as one of the planned secondary outcomes. Women (n = 1,320) <20 weeks of gestation were randomized to consume 60 mg iron and 400 µg folic acid per day (iron and folic acid [IFA]); 18 vitamins and minerals including 250 µg iodine per day (MMN); or 20 g/day of small-quantity lipid-based nutrient supplements (LNS) with the same and additional 4 vitamins and minerals as the MMN (LNS). In a subsample (n = 295), we tested differences in groups' geometric mean UICs at 36 weeks of gestation controlling for baseline UIC and compared the geometric means (approximately median UICs) with the World Health Organization (WHO) cut-offs: median UIC <150, 150-249, and ≥500 reflecting low, adequate, and excessive iodine intakes, respectively. At baseline, overall median UIC was 137. At 36 weeks of gestation, controlling for baseline UIC, geometric mean (95% confidence interval) UICs of the MMN (161 [133, 184]) and LNS (158 [132, 185]) groups did not differ; both values were significantly greater (overall p = .004) than that of the IFA group (116 [101, 135]). The median UICs of the MMN and LNS groups were within the WHO "adequate" range, whereas that of the IFA group was below the WHO adequate range. In this setting, supplementation during pregnancy with small-quantity LNS or MMN providing iodine at the WHO-recommended dose, compared with IFA, increases the likelihood of adequate iodine status.

Co-causation of reduced newborn size by maternal undernutrition, infections, and inflammation.

More than 20 million babies are born with low birthweight annually. Small newborns have an increased risk for mortality, growth failure, and other adverse outcomes. Numerous antenatal risk factors for small newborn size have been identified, but individual interventions addressing them have not markedly improved the health outcomes of interest. We tested a hypothesis that in low-income settings, newborn size is influenced jointly by multiple maternal exposures and characterized pathways associating these exposures with newborn size. This was a prospective cohort study of pregnant women and their offspring nested in an intervention trial in rural Malawi. We collected information on maternal and placental characteristics and used regression analyses, structural equation modelling, and random forest models to build pathway maps for direct and indirect associations between these characteristics and newborn weight-for-age Z-score and length-for-age Z-score. We used multiple imputation to infer values for any missing data. Among 1,179 pregnant women and their babies, newborn weight-for-age Z-score was directly predicted by maternal primiparity, body mass index, and plasma alpha-1-acid glycoprotein concentration before 20 weeks of gestation, gestational weight gain, duration of pregnancy, placental weight, and newborn length-for-age Z-score (p < .05). The latter 5 variables were interconnected and were predicted by several more distal determinants. In low-income conditions like rural Malawi, maternal infections, inflammation, nutrition, and certain constitutional factors jointly influence newborn size. Because of this complex network, comprehensive interventions that concurrently address multiple adverse exposures are more likely to increase mean newborn size than focused interventions targeting only maternal nutrition or specific infections.

Maternal Supplementation with Small-Quantity Lipid-Based Nutrient Supplements Compared with Multiple Micronutrients, but Not with Iron and Folic Acid, Reduces the Prevalence of Low Gestational Weight Gain in Semi-Urban Ghana: A Randomized Controlled Trial.

Background: It is unclear whether maternal supplementation with small-quantity lipid-based nutrient supplements (SQ-LNSs; 118 kcal/d) affects maternal weight.Objective: We compared several secondary anthropometric measures between 3 groups of women in the iLiNS (International Lipid-based Nutrient Supplements)-DYAD trial in Ghana.Methods: Women (n = 1320; <20 wk of gestation) were randomly assigned to receive 60 mg Fe + 400 µg folic acid/d (IFA), 18 vitamins and minerals/d [multiple micronutrients (MMNs)], or 20 g SQ-LNSs with 22 micronutrients/d (LNS) during pregnancy and a placebo (200 mg Ca/d), MMNs, or SQ-LNSs, respectively, for 6 mo postpartum. Weight, midupper arm circumference (MUAC), and triceps skinfold (TSF) thickness at 36 wk of gestation and 6 mo postpartum were analyzed, as were changes from estimated prepregnancy values. We assessed the adequacy of estimated gestational weight gain (GWG) by using Institute of Medicine (IOM) and International Fetal and Newborn Growth Standards for the 21st Century (INTERGROWTH-21st) guidelines.Results: The estimated prepregnancy prevalence of overweight or obesity was 38.5%. By 36 wk of gestation, women (n = 1015) had a mean ± SD weight gain of 7.4 ± 3.7 kg and changes of -1.0 ± 1.7 cm in MUAC and -2.8 ± 4.1 mm in TSF thickness. The LNS group had a lower prevalence of inadequate GWG on the basis of IOM guidelines (57.4%) than the MMN (67.2%) but not the IFA (63.1%) groups (P = 0.030), whereas the prevalence of adequate (26.9% overall) and excessive (10.4% overall) GWG did not differ by group. The percentages of normal-weight women (in kg/m2: 18.5 < body mass index < 25.0; n = 754) whose GWG was less than the third centile of the INTERGROWTH-21st standards were 23.0%, 28.7%, and 28.5% for the LNS, MMN, and IFA groups, respectively (P = 0.36). At 6 mo postpartum, the prevalence of overweight or obesity was 45.3%, and the risk of becoming overweight or obese did not differ by group.Conclusion: SQ-LNS supplementation is one potential strategy to address the high prevalence of inadequate GWG in women in settings similar to Ghana, without increasing the risk of excessive GWG. This trial was registered at clinicaltrials.gov as NCT00970866.

Impact of small-quantity lipid-based nutrient supplement on hemoglobin, iron status and biomarkers of inflammation in pregnant Ghanaian women.

We examined hemoglobin (Hb, g/L), iron status (zinc protoporphyrin, ZPP, µmol/mol heme, and transferrin receptor, TfR, mg/L) and inflammation (C-reactive protein, CRP and alpha-1 glycoprotein, AGP) in pregnant Ghanaian women who participated in a randomized controlled trial. Women (n = 1320) received either 60 mg Fe + 400-µg folic acid (IFA); 18 micronutrients including 20-mg Fe (MMN) or small-quantity lipid-based nutrient supplements (SQ-LNS, 118 kcal/d) with the same micronutrient levels as in MMN, plus four additional minerals (LNS) daily during pregnancy. Intention-to-treat analysis included 349, 354 and 354 women in the IFA, MMN and LNS groups, respectively, with overall baseline mean Hb and anemia (Hb <100) prevalence of 112 and 13.3%, respectively. At 36 gestational weeks, overall Hb was 117, and anemia prevalence was 5.3%. Compared with the IFA group, the LNS and MMN groups had lower mean Hb (120 ± 11 vs. 115 ± 12 and 117 ± 12, respectively; P < 0.001), higher mean ZPP (42 ± 30 vs. 50 ± 29 and 49 ± 30; P = 0.010) and TfR (4.0 ± 1.3 vs. 4.9 ± 1.8 and 4.6 ± 1.7; P < 0.001), and greater prevalence of anemia (2.2% vs. 7.9% and 5.8%; P = 0.019), elevated ZPP (>60) [9.4% vs. 18.6% and 19.2%; P = 0.003] and elevated TfR (>6.0) [9.0% vs. 19.2% and 15.1%; P = 0.004]. CRP and AGP concentrations did not differ among groups. We conclude that among pregnant women in a semi-urban setting in Ghana, supplementation with SQ-LNS or MMN containing 20 mg iron resulted in lower Hb and iron status but had no impact on inflammation, when compared with iron (60 mg) plus folic acid (400 µg). The amount of iron in such supplements that is most effective for improving both maternal Hb/iron status and birth outcomes requires further evaluation. This trial was registered at ClinicalTrials.gov as: NCT00970866.

Lipid-Based Nutrient Supplements Providing Approximately the Recommended Daily Intake of Vitamin A Do Not Increase Breast Milk Retinol Concentrations among Ghanaian Women.

BACKGROUND: Vitamin A deficiency remains a global public health problem. Daily supplementation with a lipid-based nutrient supplement (LNS) has potential for increasing milk vitamin A concentrations. OBJECTIVE: The objective of this study was to determine whether daily supplementation with approximately the recommended daily intake of vitamin A in an LNS or a multiple-micronutrient supplement (MMN) during pregnancy and the first 6 mo postpartum has an effect on breast milk retinol concentration at 6 mo postpartum. METHODS: Women ≤20 wk pregnant (n = 1320) were randomly assigned to receive either the MMN providing 18 micronutrients, including 800 µg retinol equivalents of vitamin A, or the LNS with the same nutrients as the MMN group, plus 4 minerals and macronutrients, until 6 mo postpartum; a control group received iron and folic acid during pregnancy and a placebo (calcium tablet) during the first 6 mo postpartum. Breast milk samples collected at 6 mo postpartum were analyzed for retinol and fat concentrations by HPLC and creamatocrit, respectively, in a subsample of 756 women. RESULTS: The breast milk retinol concentration was (mean ± SD) 56.3 ± 2.1 nmol/g fat, with no significant differences between groups [iron and folic acid (n = 243): 59.1 ± 2.8; MMN (n = 260): 55.4 ± 2.5; LNS (n = 253): 54.7 ± 2.5 nmol/g fat; P = 0.45], regardless of whether the woman had or had not received a high-dose vitamin A supplement (200,000 IU) soon after childbirth. Around 17% of participants had low milk retinol (≤28 nmol/g fat). We estimated that 41% of infants were potentially receiving vitamin A at amounts above the Tolerable Upper Intake Level (600 µg retinol activity equivalents/d), with no group differences in percentages with low or high milk retinol concentration. CONCLUSION: Daily consumption of approximately the recommended intake of vitamin A did not increase breast milk retinol concentrations in this sample of Ghanaian women. This trial was registered at clinicaltrials.gov as NCT00970866.

A mixed method study exploring adherence to and acceptability of small quantity lipid-based nutrient supplements (SQ-LNS) among pregnant and lactating women in Ghana and Malawi.

BACKGROUND: Supplementing pregnant and lactating mothers with small quantity lipid-based nutrient supplements (SQ-LNS) has resulted in improvements in birth outcomes in some low-income settings. In order to be effective, SQ-LNS must be consumed regularly over sustained periods. METHODS: The objective was to assess and compare acceptability of and adherence to SQ-LNS consumption among pregnant and lactating women in Ghana and Malawi throughout 12 months of supplementation. We enrolled women before 20 gestation weeks into randomized trials in Ghana (n = 1320) and Malawi (n = 869). In the SQ-LNS group participants received a 20 g sachet of supplement per day during pregnancy and the first 6 months of lactation. In the control groups participants received multiple micronutrients (MMN) during pregnancy and lactation or iron and folic acid (IFA) during pregnancy and calcium during lactation. We used questionnaires to collect data on self-reported adherence to daily use of supplements and conducted in-depth interviews with women in the SQ-LNS group to examine acceptability. RESULTS: The mean self-reported adherence during the supplementation period was lower in Ghana (79.9 %) than in Malawi (91.7 %) for all supplements (difference 11.8 %, P < 0.001). Over time, adherence increased in Malawi but decreased in Ghana. In both countries, adherence in the SQ-LNS group was non-inferior to that in the control groups. Participants typically reported consuming SQ-LNS as instructed but when interviewers queried about experiences, most of the women described incidents of non-adherence. A usual reason for not consuming SQ-LNS was nausea and vomiting during pregnancy. Especially in Malawi, women reported sharing SQ-LNS with families and friends. Sustained use of SQ-LNS was attributed to expected health benefits and favorable sensory attributes. Often women compared their pregnancy to previous ones, and were of the view that SQ-LNS made a positive difference. CONCLUSION: Self-reported sustained adherence to consume SQ-LNS daily was high in both sites but lower in Ghana than in Malawi. In Ghana, adherence decreased over time whereas in Malawi adherence increased. Acceptability and adherence appeared interlinked, complex and context-related. Sustained consumption of SQ-LNS may require tailoring interventions by context. TRIAL REGISTRATION: The Ghana trial was registered at clinicaltrials.gov as NCT00970866 , and the Malawi trial as NCT01239693 .

Malawian Mothers Consider Lipid-Based Nutrient Supplements Acceptable for Children throughout a 1-Year Intervention, but Deviation from User Recommendations Is Common.

BACKGROUND: Lipid-based nutrient supplements (LNSs) offer a vehicle to improve children's diets in low-income countries where complementary foods are typically deficient in essential nutrients. Sustained acceptability by the intended users is essential for achieving growth-promoting effects. OBJECTIVE: We aimed to determine the sustained acceptability of LNSs among 6- to 18-mo-old children in Malawi. METHODS: In the context of a trial testing the growth-promoting effect of different formulations and doses of LNSs, we delivered LNSs to the homes of the children biweekly according to the randomization protocol. We defined acceptability to include adherence to feeding recommendations and mothers' experiences of feeding LNSs to their child. We conducted brief interviews each week with the mothers. At 2 time points we conducted knowledge, attitudes, and practices (KAP) interviews. In addition, we conducted repeated in-depth interviews with a subset of mothers. RESULTS: Of the 1612 children who received the LNS intervention, we analyzed adherence data from 1478 (91.7%) children and KAP data at 2 time points (child's age of 12 and 18 mo) from 839 (52.1%) of the children. The mean ± SD overall adherence (proportion of days when the study child reportedly consumed LNSs considering only those weeks when the supplement had been successfully delivered to the home) was 92.4 ± 9.6%, and there was no difference between children receiving milk-containing or milk-free LNSs. There was also no increasing or decreasing trend over time in any of the groups. Sharing and deviation from other feeding recommendations were common. Maternal experiences were mostly very positive. CONCLUSIONS: The acceptability of LNS products was good and was sustained for 12 mo in this rural Malawian population. However, sharing of the products with family members and deviation from other feeding recommendations were frequent, which means that individually targeted children were likely to receive less than the intended dose of the LNS. This trial was registered at clinicaltrials.gov as NCT00945698.

Supplementation of Maternal Diets during Pregnancy and for 6 Months Postpartum and Infant Diets Thereafter with Small-Quantity Lipid-Based Nutrient Supplements Does Not Promote Child Growth by 18 Months of Age in Rural Malawi: A Randomized Controlled Trial.

BACKGROUND: Intrauterine growth restriction may be reduced by supplementing maternal diets during pregnancy, but few studies have assessed the impact of combined prenatal and postnatal interventions on child growth. OBJECTIVE: We tested a hypothesis that provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) to mothers in pregnancy and 6 mo postpartum and to their infants from 6 to 18 mo of age would promote infant and child growth in the study area in rural Malawi. METHODS: We enrolled 869 pregnant women in a randomized trial in Malawi. During pregnancy and 6 mo thereafter, the women received daily 1 capsule of iron-folic acid (IFA), 1 capsule containing 18 micronutrients (MMN), or one 20-g sachet of SQ-LNS [lipid-based nutrient supplements (LNS), containing 21 MMN, protein, carbohydrates, essential fatty acids, and 118 kcal]. Children in the IFA and MMN groups received no supplementation; children in the LNS group received SQ-LNSs from 6 to 18 mo. Primary outcome was child length at 18 mo. RESULTS: At 18 mo, the mean length in the IFA, MMN, and LNS groups was 77.0, 76.9, and 76.8 cm (P = 0.90), respectively, and the prevalence of stunting was 32.7%, 35.6%, and 37.9% (P = 0.54), respectively. No intergroup differences were found in the mean weight, head circumference, or midupper arm circumference or the proportions with low z scores for these variables (P > 0.05). Covariate adjustment did not change the analysis results, and the associations between the intervention and child length were not modified by maternal parity, age, or nutritional status (P > 0.10). CONCLUSIONS: The findings do not support a hypothesis that provision of SQ-LNSs to women in pregnancy and postpartum and to children from 6 to 18 mo of age would promote child growth in this Malawian study area. This trial was registered at clinicaltrials.gov as NCT01239693.

Provision of 10-40 g/d Lipid-Based Nutrient Supplements from 6 to 18 Months of Age Does Not Prevent Linear Growth Faltering in Malawi.

BACKGROUND: Complementing infant diets with lipid-based nutrient supplements (LNSs) has been suggested to improve growth and reduce morbidity, but the daily quantity and the milk content of LNSs affect their cost. OBJECTIVE: We tested the hypotheses that the change in mean length-for-age z score (LAZ) for infants provided with 10-40 g LNSs/d from ages 6 to 18 mo would be greater than that for infants receiving no dietary intervention at the same age and that provision of LNSs that did not contain milk would be as good as milk-containing LNSs in promoting linear growth. METHODS: We enrolled in a randomized single-blind trial 6-mo-old infants who were allocated to 1 of 6 groups to receive 10, 20, or 40 g LNSs/d containing milk powder; 20 or 40 g milk-free LNSs/d; or no supplement until 18 mo of age. The primary outcome was change in LAZ. RESULTS: Of the 1932 enrolled infants, 78 (4.0%) died and 319 (16.5%) dropped out during the trial. The overall reported supplement consumption was 71.6% of days, with no difference between the groups (P = 0.26). The overall mean ± SD length and LAZ changes were 13.0 ± 2.1 cm and -0.45 ± 0.77 z score units, respectively, which did not differ between the groups (P = 0.66 for length and P = 0.74 for LAZ). The difference in mean LAZ change in the no-milk LNS group compared with the milk LNS group was -0.02 (95% CI: -0.10, 0.06; P = 0.72). CONCLUSION: Our results do not support the hypothesis that LNS supplementation during infancy and childhood promotes length gain or prevents stunting between 6 and 18 mo of age in Malawi. This trial was registered at clinicaltrials.gov as NCT00945698.

High-Oleic Ready-to-Use Therapeutic Food Maintains Docosahexaenoic Acid Status in Severe Malnutrition.

OBJECTIVES: Ready-to-use therapeutic food (RUTF) is the preferred treatment for uncomplicated severe acute malnutrition. It contains large amounts of linoleic acid and little α-linolenic acid, which may reduce the availability of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the recovering child. A novel high-oleic RUTF (HO-RUTF) was developed with less linoleic acid to determine its effect on DHA and EPA status. METHODS: We conducted a prospective, randomized, double-blind clinical effectiveness trial treating rural Malawian children with severe acute malnutrition. Children were treated with either HO-RUTF or standard RUTF. Plasma phospholipid fatty acid status was measured on enrollment and after 4 weeks and compared between the 2 intervention groups. RESULTS: Among the 141 children enrolled, 48 of 71 receiving HO-RUTF and 50 of 70 receiving RUTF recovered. Plasma phospholipid samples were analyzed from 43 children consuming HO-RUTF and 35 children consuming RUTF. The change in DHA content during the first 4 weeks was +4% and -25% in the HO-RUTF and RUTF groups, respectively (P = 0.04). For EPA, the change in content was 63% and -24% in the HO-RUTF and RUTF groups, respectively (P < 0.001). For arachidonic acid, the change in content was -3% and 13% in the HO-RUTF and RUTF groups, respectively (P < 0.009). CONCLUSIONS: The changes in DHA and EPA seen in the children treated with HO-RUTF warrant further investigation because they suggest that HO-RUTF support improved polyunsaturated fatty acid status, necessary for neural development and recovery.

Ready-to-use foods for management of moderate acute malnutrition: considerations for scaling up production and use in programs.

Ready-to-use foods are one of the available strategies for the treatment of moderate acute malnutrition (MAM), but challenges remain in the use of these products in programs at scale. This paper focuses on two challenges: the need for cheaper formulations using locally available ingredients that are processed in a safe, reliable, and financially sustainable local production facility; and the effective use of these products in large-scale community-based programs. Linear programming tools can be used successfully to design local compositions that are in line with international guidelines, low in cost, and acceptable, and the efficacy of these local formulations in the treatment of MAM was recently demonstrated in Malawi. The production of local formulations for programs at scale relies on the existence of a reliable and efficient local production facility. Technical assistance may be required in the development of sustainable business models at an early stage in the process, taking into account the stringent product quality and safety criteria and the required investments. The use of ready-to-use products, as of any food supplement, in programs at scale will be affected by the practice of household sharing and diversion of these products for other uses. Additional measures can be considered to account for sharing. These products designed for the treatment and prevention of MAM are to be used in community-based programs and should therefore be used in conjunction with other interventions and designed so that they do not replace the intake of other foods and breastmilk. Remaining challenges and implications for the (operations) research agenda are discussed.

Considerations in developing lipid-based nutrient supplements for prevention of undernutrition: experience from the International Lipid-Based Nutrient Supplements (iLiNS) Project.

The International Lipid-Based Nutrient Supplements (iLiNS) Project began in 2009 with the goal of contributing to the evidence base regarding the potential of lipid-based nutrient supplements (LNS) to prevent undernutrition in vulnerable populations. The first project objective was the development of acceptable LNS products for infants 6-24 months and for pregnant and lactating women, for use in studies in three countries (Burkina Faso, Ghana and Malawi). This paper shares the rationale for a series of decisions in supplement formulation and design, including those related to ration size, ingredients, nutrient content, safety and quality, and packaging. Most iLiNS supplements have a daily ration size of 20 g and are intended for home fortification of local diets. For infants, this ration size is designed to avoid displacement of breast milk and to allow for dietary diversity including any locally available and accessible nutrient-dense foods. Selection of ingredients depends on acceptability of flavour, micronutrient, anti-nutrient and essential fatty acid contents. The nutrient content of LNS designed to prevent undernutrition reflects the likelihood that in many resource-poor settings, diets of the most nutritionally vulnerable individuals (infants, young children, and pregnant and lactating women) are likely to be deficient in multiple micronutrients and, possibly, in essential fatty acids. During ingredient procurement and LNS production, safety and quality control procedures are required to prevent contamination with toxins or pathogens and to ensure that the product remains stable and palatable over time. Packaging design decisions must include consideration of product protection, stability, convenience and portion control.

Multidimensional evaluation of the early emergence of executive function and development in Bangladeshi children using nutritional and psychosocial intervention: A randomized controlled trial protocol.

INTRODUCTION: Reversing malnutrition-induced impairment of cognition and emotional regulation is a critical global gap. We hypothesize that brain-targeted micronutrient supplemented nutritional rehabilitation in children with moderate acute malnutrition, followed by 2 years micronutrient supplementation will impact on the cognition and emotion regulation of these children. METHODS: The primary outcome of this prospective, randomized controlled trial is to study the development of executive functions (EFs) and emotion regulation (ER) in this cohort. Moderate acute malnourished (MAM; WLZ/WHZ <-2 and ≥-3 z-score, and/or 11.5 cm ≤ MUAC < 12.5cm; n = 140)children aged around one year (11m-13m) in Mirpur, Dhaka, Bangladesh will be randomized (1:1) to receive either locally produced Ready to Use Supplementary Food (RUSF) or Enhanced Ready to Use Supplementary Food (E-RUSF) until anthropometric recovery (WLZ/WHZ > -1SD), or for 3 months after enrollment (whichever is earlier). The randomized MAMs groups will be given either Small Quantity Lipid Based Nutrient Supplement (SQLNS) or Enhanced Small Quantity Lipid Based Nutrient Supplement (E-SQLNS), respectively until the end of the 2-year follow up period. Standard psychosocial stimulation will be provided to the MAMs intervention groups. Biological samples will be collected, anthropometric and neurocognitive assessments will be performed at 2 (22m-26m) and 3 (34m-38m) years of age. Two control groups will be recruited: 1), non-malnourished one-year (11m-13m) old children (WLZ/WHZ score>-1SD; n = 70); and 2) three-year (34m-38m) old children (n = 70) with untreated MAM (WHZ <-2 and ≥-3 z-score, and/or 11.5≤MUAC<12.5 cm). The 3-year-old MAM reference group will be assessed once and provided with 2 months of nutritional rehabilitation support (RUSF Nutriset's Plumpy'Sup™).

Acceptability of lipid-based nutrient supplements (LNS) among Ghanaian infants and pregnant or lactating women.

Inadequate micronutrient intake during pregnancy, lactation and infancy is a major problem in many developing countries. Lipid-based nutrient supplements (LNS) can improve micronutrient status, growth and development of infants, and also have potential to improve nutritional status of pregnant and lactating women. The objective of the study was to test the acceptability of LNS designed for infants (LNS-20gM) and pregnant or lactating women (LNS-P&L). Participants were infants (n = 22, mean age = 8 months) and pregnant or lactating women (n = 24) attending routine services at a hospital in Ghana. Infants consumed 45 g of a test meal consisting of one part LNS-20gM and three parts fermented maize porridge, while women consumed 50 g of a similar test meal containing LNS-P&L instead. Participants also used their respective LNS at home for 14 days. Primary outcome was the proportion of the test meal consumed. On average, infants consumed 76.2% of the test meal [95% (confidence interval) CI: 65.7, 86.7], while women consumed 87.1% (95% CI: 82.6, 91.6). During the 14-day period, median daily consumption of LNS-20gM was 19.3 g, very close to the recommended 20 g d(-1), while that of LNS-P&L was one sachet, as recommended. We conclude that LNS-20gM and LNS-P&L were well accepted.

Acceptability of three novel lipid-based nutrient supplements among Malawian infants and their caregivers.

We tested the acceptability of three new lipid-based nutrient supplements (LNSs) in two independent phases among 18 8-12-month-old healthy rural Malawians and their caregivers. In phase 1, acceptability was assessed by offering three new LNSs in random order, and an LNS already determined to be acceptable, Nutributter(®), each added to 30 g of warm maize porridge over three consecutive days. In phase 2, infants from each village were provided one of the new supplements for a 2-week home-use trial. Outcome measures included the amount consumed, time completion of the dose and the maternal rating of likeability on a 5-point scale. The supplements were rated acceptable if consumption was over 50% of the offered dose in phase 1. The mean (95% confidence interval) proportion of the LNS test meals consumed under direct observation was 88% (82-94%) for LNS-10gM, 90% (84-95%) for LNS-20gM, 87% (79-95%) for LNS-20gNoM, and 86% (83-90%) for Nutributter. The median (25th and 75th centile) time (minutes) for completing the offered test meal was 4 (2, 7) for LNS-10gM, 5 (3, 6) for LNS-20gM, 4 (3, 8) for LNS-20gNoM and 4 (2, 6) for Nutributter. During both phases, almost all caregivers rated all study foods very likeable for themselves and their children, with mean scores slightly lower among the caregivers than among the infants. In the home-use phase, the test foods were almost exclusively used by the study participants with minimal sharing with siblings and other household members. Some infants were reported to prefer the new investigational products over traditional complementary food. Considering that the novel LNS was largely acceptable. Efficacy trials are now needed to assess their impact on child growth and development.

Acceptability of zinc-fortified, lipid-based nutrient supplements (LNS) prepared for young children in Burkina Faso.

Micronutrient deficiencies are a public health concern among young children in low-income countries, and novel strategies are needed to improve the nutritional status of children at risk. One promising approach is the use of lipid-based nutrient supplements (LNS), which can be added to complementary food at the time of consumption. The optimal amount of zinc to include in LNS is uncertain, and concerns have been expressed about possible adverse effects of zinc on sensory characteristics of LNS. We conducted a series of acceptability studies of LNS containing either 0 or 10 mg of zinc per daily 20 g LNS dose among Burkinabe children 9-15 months old and their mothers. These acceptability studies included observations of children's consumption, maternal and child sensory reaction to the products using a 5-unit hedonic scale, a triangle test for detection of differences and a review of maternal reports of their child-feeding experiences during a 2-week home-feeding trial. The LNS products were well appreciated by the mothers and children during the sensory trials and the 2-week home-feeding trial. The addition of 10 mg zinc to LNS did not affect the consumed proportion of the offered porridge-LNS-mixture (P = 0.43). Results of the triangle test with mothers confirmed that there was no detectable difference between products containing 0 or 10 mg zinc per 20 g LNS dose. Most importantly, interviews and focus groups following the 2-week home-feeding trial indicated good acceptability of the products by mothers and their children.

Measurement of Saccharin and trans-Resveratrol Metabolites in Urine as Adherence Markers for Small Quantity Lipid-Based Nutrient Supplement Consumption.

Saccharin and trans-resveratrol were incorporated into small quantity lipid-based nutritional supplements (SQ-LNS) to be evaluated as the markers of consumption for nutritional intervention studies. Forty-seven healthy women consumed a single supplement with either 8.6 mg of saccharin or 5 mg of trans-resveratrol, and urine was collected for 4 h. A rapid 11 min method employing multiple reaction monitoring and ultrahigh performance liquid chromatography coupled to a triple quadrupole mass spectrometer was developed to measure saccharin and resveratrol metabolites in urine simultaneously. The linear dynamic range of the method was from 3 to 1000 ng mL-1, with the correlation coefficient of 0.999 and limits of quantification from 15.28 to 53.03 ng mL-1. Sample preparation was simple dilution with an average recovery of 97.8%. Ion suppression was observed with urine concentrations >10%. Mean levels of saccharin and resveratrol-3-O-sulfate in urine were 5.481 ± 4.359 and 3.440 ± 4.160 nmol L-1, respectively. We developed and validated a method to measure saccharin and trans-resveratrol metabolites in urine to objectively corroborate the consumption of SQ-LNS for the first time in nutrition intervention studies.

Evaluation of Saccharin and Resveratrol as Extrinsic Markers of Small-Quantity Lipid-Based Nutrient Supplement Consumption in Healthy Women.

BACKGROUND: Dietary supplements, like small-quantity lipid-based nutrient supplements (SQ-LNS), are used in intervention programs to prevent undernutrition among women and young children in low-income countries. An objective marker is needed to track consumption of supplements to evaluate the effectiveness of these programs. OBJECTIVE: The aim of this study was to evaluate saccharin and resveratrol as potential adherence markers for tracking recent consumption of a single serving of SQ-LNS in women. METHODS: Forty-seven healthy nonpregnant women 18-45 y of age were assigned to consume a single dose of SQ-LNS (20 g) containing either 10 mg sodium saccharin or 5 mg trans-resveratrol, under supervision. On the day before and for 2 d following SQ-LNS consumption, urine samples were collected each day for 24 h as 3 consecutive 4-h collections and one 12-h overnight collection. Urinary concentrations of saccharin and trans-resveratrol-3-O-sulfate, a resveratrol metabolite, were measured by ultra-high-performance liquid chromatography interfaced to a mass spectrometer with electrospray ionization [UHPLC-(ESI-)MS/MS]. Urinary concentrations (µmol/L urine) of saccharin and trans-resveratrol-3-O-sulfate were plotted against time, and receiver operating characteristic (ROC) curves were used to determine the discriminative capacity of each compound, at each post-consumption time point compared with baseline, to detect recent consumption of SQ-LNS. Cutoff values to differentiate supplement consumption from nonconsumption of each marker were developed using the closest-to-(0,1)-corner cut-point approach. RESULTS: Forty-five participants were included in the analysis. Urinary concentrations of saccharin and trans-resveratrol-3-O-sulfate increased within 4 h of SQ-LNS consumption. Urinary concentration cutoff values for saccharin (13.4 µmol/L) and trans-resveratrol-3-O-sulfate (0.7 µmol/L) allowed for 78% and 89% sensitivity, respectively, and 100% specificity in detecting consumption of SQ-LNS within the first 12 h after consumption. CONCLUSIONS: Urinary concentrations of saccharin and trans-resveratrol-3-O-sulfate reflect consumption of SQ-LNS containing those compounds during the first 12 h post-consumption with high sensitivity and specificity in healthy women and may be useful objective adherence markers for tracking consumption of SQ-LNS.

Modeling undernutrition with enteropathy in mice.

Undernutrition is a global health issue leading to 1 out 5 all deaths in children under 5 years. Undernutrition is often associated with environmental enteric dysfunction (EED), a syndrome associated with increased intestinal permeability and gut inflammation. We aimed to develop a novel murine model of undernutrition with these EED features. Post-weaning mice were fed with low-protein diet (LP) alone or combined with a gastrointestinal insult trigger (indomethacin or liposaccharides). Growth, intestinal permeability and inflammation were assessed. LP diet induced stunting and wasting in post-weaning mice but did not impact gut barrier. We therefore combined LP diet with a single administration of indomethacin or liposaccharides (LPS). Indomethacin increased fecal calprotectin production while LPS did not. To amplify indomethacin effects, we investigated its repeated administration in addition to LP diet and mice exhibited stunting and wasting with intestinal hyperpermeability and gut inflammation. The combination of 3-weeks LP diet with repeated oral indomethacin administration induced wasting, stunting and gut barrier dysfunction as observed in undernourished children with EED. As noninvasive methods for investigating gut function in undernourished children are scarce, the present pre-clinical model provides an affordable tool to attempt to elucidate pathophysiological processes involved in EED and to identify novel therapeutic strategies.

Animal Models of Undernutrition and Enteropathy as Tools for Assessment of Nutritional Intervention.

: Undernutrition is a major public health problem leading to 1 in 5 of all deaths in children under 5 years. Undernutrition leads to growth stunting and/or wasting and is often associated with environmental enteric dysfunction (EED). EED mechanisms leading to growth failure include intestinal hyperpermeability, villus blunting, malabsorption and gut inflammation. As non-invasive methods for investigating gut function in undernourished children are limited, pre-clinical models are relevant to elucidating the pathophysiological processes involved in undernutrition and EED, and to identifying novel therapeutic strategies. In many published models, undernutrition was induced using protein or micronutrient deficient diets, but these experimental models were not associated with EED. Enteropathy models mainly used gastrointestinal injury triggers. These models are presented in this review. We found only a few studies investigating the combination of undernutrition and enteropathy. This highlights the need for further developments to establish an experimental model reproducing the impact of undernutrition and enteropathy on growth, intestinal hyperpermeability and inflammation, that could be suitable for preclinical evaluation of innovative therapeutic intervention.