Risk factors for anaemia among women and their young children hospitalised with suspected thiamine deficiency in northern Lao PDR.

Anaemia among women and young children remains a major public health concern. This secondary study describes the anaemia prevalence among young hospitalised children and their mothers in northern Lao People's Democratic Republic and explores possible nutritional causes and risk factors for anaemia. Hospitalised children (ages 21 days to <18 months) with clinical symptoms suggestive of thiamine deficiency disorders were eligible along with their mothers. Venous blood was collected for determination of haemoglobin, ferritin, soluble transferrin receptor (sTfR), retinol-binding protein (RBP), erythrocyte glutathione reductase activation coefficient (EGRac), thiamine diphosphate (ThDP) and acute phase proteins. Risk factors for anaemia were modelled using minimally adjusted logistic regression controlling for age. Haemoglobin results were available for 436 women (mean ± SD age 24.7 ± 6.4 years; 1.6% pregnant) and 427 children (4.3 ± 3.5 months; 60.3% male). Anaemia prevalence (Hb < 120 g/L for nonpregnant women and <110 g/L for pregnant women and children) was 30.7% among women and 55.2% among children. In bivariate analyses, biomarkers significantly associated with anaemia in women were ferritin, sTfR, RBP, EGRac and ThDP. Other risk factors for women were lower BMI, mid-upper arm circumference < 23.5 cm, lower education, lower socioeconomic index, food insecurity, Hmong ethnicity, not/rarely having attended antenatal care, not having taken antenatal iron-containing supplements and not meeting minimum dietary diversity. Risk factors for anaemia among children were older age, male sex, stunting, sTfR, ThDP and alpha-1-acid-glycoprotein. Anaemia was common among women and their hospitalised children and was associated with micronutrient deficiencies and socioeconomic, dietary and health care-seeking risk factors, suggesting that multiple strategies are required to prevent anaemia among women and children.

Insulin-like Growth Factor 1 (IGF1), IGF Binding Protein-3 (IGFBP3) and Growth Response to Daily Zinc Supplementation: A Randomized Trial in Rural Laotian Children.

OBJECTIVES: To assess (a) the impact of daily preventive zinc tablets (7 mg; PZ), zinc-containing multiple micronutrient powder (10 mg zinc, and 13 other micronutrients; MNP) or placebo, delivered for 9 months, on Insulin-like Growth Factor 1 (IGF1) and IGF Binding Protein 3 (IGFBP3) among Laotian children 6-23 months, and (b) whether the effects of PZ and MNP on length-for-age z-scores (LAZ) and weight-for-age z-scores (WAZ) are modified by baseline IGF1 and IGFBP3. DESIGN: A double-blind, placebo-controlled trial (N = 419). METHODS: Plasma IGF1 and IGFBP3 concentrations at baseline and 36 weeks were analyzed by automated chemiluminescent assay. Anthropometry was assessed at baseline, at 18 and 36 weeks. Intervention effects were estimated using ANCOVA. RESULTS: At 36 weeks, geometric mean IGF1 (~39.0-39.2 ng/mL; p = 0.99) and IGFBP3 (2038-2076 ng/mL; p = 0.83) did not differ by group. At 18 weeks (but not at 36 weeks), LAZ in the PZ group (-1.45) was higher than the MNP (-1.70) and control (-1.55) groups (p = 0.01) among children in the highest baseline IGF1 tertile (p for interaction = 0.006). At 36 weeks (but not at 18 weeks), WAZ in the PZ group (-1.55) was significantly higher than the MNP (-1.75) and control (-1.65) groups (p = 0.03), among children in the lowest baseline IGFBP3 tertile (p for interactions = 0.06). CONCLUSIONS: Although IGF1 and IGFBP3 did not respond to PZ and MNP, baseline IGF1 and IGFBP3 significantly modified the impact of PZ on linear and ponderal growth, suggesting that IGF1 bioavailability may drive catch-up growth in zinc-supplemented children.

Determinants of oxidative stress among indigenous populations in Northern Laos: Trace element exposures and dietary patterns.

OBJECTIVES: To investigate determinants of oxidative stress in an indigenous population, we examined associations of trace element exposures and dietary patterns with three oxidative stress-related biomarkers among indigenous populations in Northern Laos. METHODS: This cross-sectional study included 341 adults from three villages with different levels of modernization. We used three oxidative stress-related biomarkers: urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-isoprostane concentrations, which were measured using liquid chromatography-tandem mass spectrometry, and blood telomere lengths, which were measured using a quantitative polymerase chain reaction method. We used multilevel analysis to examine associations of urinary arsenic, cadmium, and selenium concentrations, their interaction terms, and wild-plant-food scores (principal component scores calculated from food consumption frequencies) with oxidative stress-related biomarkers. RESULTS: Urinary arsenic and cadmium concentrations were positively associated with urinary 8-isoprostane concentrations. Urinary selenium concentrations were positively associated with urinary 8-OHdG concentrations. Interaction terms ([arsenic or cadmium] × selenium) showed negative associations with urinary 8-OHdG and 8-isoprostane concentrations, respectively. Urinary cadmium concentrations were negatively associated with telomere lengths. Wild-plant-food scores did not exhibit associations with oxidative stress-related biomarkers. CONCLUSION: Our findings imply that exposure to arsenic and cadmium is associated with greater oxidative lipid damage, whereas selenium may attenuate arsenic-induced oxidative DNA damage and cadmium-induced oxidative lipid damage. Cadmium exposure may accelerate telomere attrition. Trace element exposure may be a determinant of oxidative stress among indigenous populations in Northern Laos.

Nutrition and health-seeking practices during pregnancy and lactation and potential strategies to increase micronutrient intakes among women in northern Lao PDR.

Access to and utilisation of antenatal care (ANC) is important for optimising health and nutrition during pregnancy. This study aimed to assess adherence to and factors associated with ANC and antenatal supplement use among Laotian women, and consider culturally appropriate strategies to increase micronutrient intakes. Mother-child (aged 21 d to <18 months) dyads (n 699) enrolled in a hospital-based prospective cohort study with the community comparison group in Luang Prabang province were interviewed about their antenatal history, supplement use, household sociodemographic and dietary practices, including postpartum food avoidances. Ninety percent of women (mean age 24⋅7 ± 6⋅3 years) reported receiving ANC during their pregnancy, with the majority reporting four to seven contacts, while 84⋅6 and 17⋅3 % reported supplement use during pregnancy and lactation, respectively. Adequate ANC contacts (≥8) and supplement use was more likely among women with complete primary education and from higher socioeconomic status households, and less likely among women belonging to ethnic minority populations and those who delivered their child at home. All women continued to consume salt while adhering to postpartum food avoidances; however, 58⋅5 and 38⋅7 % of habitual consumers restricted fish and soy sauces, respectively. Eighty-six percent of women reported they would be willing to take supplements when adhering to postpartum dietary restrictions. Overall, women's reported ANC attendance and antenatal supplement use was suboptimal. Understanding predictors of and barriers to ANC and supplement use may help implement effective public health strategies to improve adherence. Alongside targeted supplementation, salt fortification with micronutrients may be a viable population-wide intervention that needs further evaluation.

Daily preventive zinc supplementation increases the antibody response against pathogenic Escherichia coli in children with zinc insufficiency: a randomised controlled trial.

Zinc deficiency impairs the antibody-mediated immune response and is common in children from lower-income countries. This study aimed to investigate the impact of different zinc supplementation regimens (7, 10 or 20 mg/day elemental zinc)-therapeutic dispersible zinc tablets (TZ), daily multiple micronutrient powder (MNP), daily preventive zinc tablets (PZ) and placebo powder (control)-and compare between baseline and endline antibody production against pathogenic Escherichia coli in Laotian children (aged 6-23 months). Fifty representative plasma samples of each treatment group were randomly selected from 512 children to determine anti-E. coli IgG antibody levels and avidity. Of the 200 children, 78.5% had zinc deficiency (plasma zinc concentration < 65 µg/dL) and 40% had anaemia before receiving zinc supplementation. aAfter receiving the TZ, MNP or PZ regimen, the plasma anti-E. coli IgG levels were significantly increased compared with baseline; the effect on the antibody level was more pronounced in children with zinc deficiency. Interestingly, there was increased anti-E. coli IgG avidity in the control and PZ groups. This study suggests that PZ might be the optimal zinc supplementation regimen to increase both the quantity and quality of antibody responses in children with zinc deficiency. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT02428647 (NCT02428647, 29/04/2015).

Daily supplementation of a multiple micronutrient powder improves folate but not thiamine, riboflavin, or vitamin B12 status among young Laotian children: a randomized controlled trial.

PURPOSE: To assess the effects of intervention with a daily multiple micronutrient powder (MNP) on thiamine, riboflavin, folate, and B12 status among young Laotian children. METHODS: Children (n = 1704) aged 6-23 mo, participating in a double-blind placebo-controlled randomized trial were individually randomized to receive daily either MNP (containing 0.5 mg of thiamine, 0.5 mg riboflavin, 150 µg folic acid, and 0.9 µg vitamin B12 along with 11 other micronutrients) or placebo and followed for ~ 36 weeks. In a randomly selected sub-sample of 260 children, erythrocyte thiamine diphosphate (eThDP), plasma folate and B12 concentrations, and erythrocyte glutathione reductase activation coefficient (EGRac; riboflavin biomarker) were assessed at baseline and endline. RESULTS: There was no treatment effect on endline eThDP concentrations (110.6 ± 8.9 nmol/L in MNP vs. 109.4 ± 8.9 nmol/L in placebo group; p = 0.924), EGRac (1.46 ± 0.3 vs. 1.49 ± 0.3; p = 0.184) and B12 concentrations (523.3 ± 24.6 pmol/L vs. 515.9 ± 24.8 pmol/L; p = 0.678). Likewise, the prevalence of thiamine, riboflavin, and B12 deficiencies did not differ significantly between the two groups. However, endline folate concentration was significantly higher in the MNP compared to the placebo group (28.2 ± 0.8 nmol/L vs 19.9 ± 0.8 nmol/L, respectively; p < 0.001), and correspondingly, the prevalence of folate deficiency was significantly lower in the MNP group (1.6% vs 17.4%; p = 0.015). CONCLUSIONS: Compared to a placebo, daily MNP for 9 months increased only folate but not thiamine, riboflavin, or B12 status in young Laotian children. TRIAL REGISTRATION: The trial was registered at www. CLINICALTRIALS: gov (NCT02428647) on April 29 2015.

Impact of modernization on urinary concentrations of arsenic, cadmium, lead, and selenium in rural residents of Northern Laos.

OBJECTIVES: The impacts of modernization on toxic heavy metal exposure and essential trace element intake in indigenous populations of subsistence societies are unknown. We assessed urinary trace element concentrations in rural residents of Northern Laos and examined associations with levels of modernization. METHODS: A cross-sectional study was conducted comprising 380 residents of three villages in Northern Laos with different levels of modernization. We surveyed general characteristics and measured the weight and height of 341 participants. Arsenic, cadmium, lead, and selenium concentrations were measured in spot urine samples by inductively coupled plasma mass spectrometry. We examined associations between urinary trace element concentrations and variables related to modernization (village, roofing material, possessions index [total number of possessions], and body mass index [BMI]) using multilevel analyses with household as a random effect, after adjusting for sex, age, and smoking status. RESULTS: Urinary concentrations of arsenic and cadmium were high, while those of lead and selenium were low in comparison to previous reports of populations in non-contaminated regions or without excess/deficiency. We observed associations between urinary trace element concentrations and village-level modernization: lead and selenium concentrations were higher in more modernized villages and cadmium concentration was highest in the least modernized village. Urinary arsenic concentration was not predicted by the modernization level of a village, although we observed significant differences among villages. In addition, urinary selenium concentration was higher in participants inhabiting more modernized houses. CONCLUSION: Modernization of villages may impact toxic heavy metal exposure and selenium intake in rural residents of Northern Laos.

Prevalence of Anemia and Its Associate Factors among Women of Reproductive Age in Lao PDR: Evidence from a Nationally Representative Survey.

INTRODUCTION: Anemia continues to be a major public health problem significant among women of reproductive age (WRA) in developing countries, including Lao People's Democratic Republic (Lao PDR), where the prevalence of anemia among women remains high. This study aimed to assess the prevalence of anemia and its associated factors among WRA 15-49 years in Lao PDR. METHODS: We conducted a cross-sectional study, using the Lao Social Indicator Survey II, 2017 dataset. A total of 12,519 WRA tested for anemia were included in this study, through multistage sampling approaches. Binary logistic regression was used to determine the associated factors of anemia. RESULTS: Of 12,519 women, 4,907 (39.2%) were anemic. Multivariate logistic regression revealed that living in central provinces (aOR: 2.16, 95% CI: 1.96-2.38), rural area (aOR: 1.1, 95% CI: 1.00-1.20), large family size with more than 6 persons (aOR: 1.14, 95% CI: 1.01-1.29), pregnancy (aOR: 1.46, 95% CI: 1.22-1.74), having any adverse pregnancy outcomes (aOR: 1.14, 95% CI: 1.03-1.25), poor drinking water (aOR: 1.24, 95% CI: 1.10-1.39), and poor sanitation facility (aOR: 1.15, 95% CI: 1.03-1.28) were significantly associated with an increased risk of anemia. Conversely, four factors were associated with anemia preventively, including being aged 25-34 years (aOR: 0.81, 95% CI: 0.74-0.90), postsecondary education (aOR: 0.76, 95% CI: 0.60-0.97), Hmong-Mien ethnicity (aOR: 0.48, 95% CI: 0.39-0.59), and watching television almost daily (aOR: 0.84, 95% CI: 0.75-0.95). CONCLUSION: Anemia continues to be a major public health challenge in Lao PDR. Interventions should be considered on geographic variations, improving safe water and sanitation facility, promoting of iron supplements during pregnancy, and health education through mass media for women in rural areas.

Plasma and Nail Zinc Concentrations, But Not Hair Zinc, Respond Positively to Two Different Forms of Preventive Zinc Supplementation in Young Laotian Children: a Randomized Controlled Trial.

Plasma zinc concentrations (PZC) have been shown to significantly increase during zinc supplementation. This study investigated the effects of daily preventive zinc supplementation on hair and nail zinc concentrations compared with a control group. In a randomized controlled trial, 6- to 23-month-old children (n = 3407) in Lao PDR were randomly assigned to one of four groups and followed for ~ 36 weeks: daily preventive zinc dispersible tablet (7 mg/d; PZ), daily micronutrient powder (10 mg zinc/d; MNP), therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days; TZ), or daily placebo powder (Control). Plasma, hair, and nail zinc concentrations were assessed in a sub-sample of participants (n = 457) at baseline and endline. At baseline, 75% of children had low PZC (< 65 µg/dL). At endline, geometric mean (95% CI) PZC were greater in the PZ and MNP groups compared with the TZ and control groups (P < 0.01), but hair zinc concentrations did not differ among groups (P = 0.99). Nail zinc concentrations were marginally higher in the PZ (115.8 (111.6, 119.9) µg/g) and the MNP (117.8 (113.3, 122.3) µg/g) groups than in the TZ group (110.4 (106.0, 114.8) µg/g; P = 0.055) at endline. This study does not support the use of hair zinc as a biomarker of zinc exposure in young children. However, it provides some evidence that zinc concentrations in nails may respond to supplemental zinc interventions and supports the need for collecting additional data on this emerging biomarker.

Anaemia among adolescents: assessing a public health concern in Lao PDR.

BACKGROUND: Lao PDR has identified the need to target adolescent public health concerns. Adolescents suffering from poor health and nutrition during rapid growth and development may be at risk of anaemia due to high iron requirements and the rapid depletion of body iron stores. OBJECTIVE: This study assessed the prevalence and severity of anaemia among school adolescents in Pholhong district, Vientiane province, Lao PDR. METHODS: A school-based cross-sectional study was conducted among 405 randomly selected school adolescents across 8 high schools in a rural district of Vientiane province. Adolescents aged 10-18, both male and female, were recruited. Haemoglobin concentration from capillary blood was measured. Descriptive statistics were computed for prevalence of anaemia, anthropometric measurements, socio-economic and socio-demographic variables. Multivariate logistic regression analysis was performed to identify determinants of anaemia among subjects. Results were expressed as odds ratios and 95% confidence intervals. RESULTS: The prevalence of anaemia among adolescents in the study area was 19.4%. There was no difference in the prevalence of anaemia between younger and older adolescents, but the prevalence of anaemia was higher in female adolescents than among males (crude OR = 3.91, 95% CI 2.20 to 6.96). On univariate analysis, coming from an ethnic minority household was found to be significantly associated with anaemia among these adolescents (p < 0.05). After adjusting for other variables, only the effect of sex remained significant. Other factors showing no significant association with anaemia included parents' employment status, family size, and living conditions. CONCLUSIONS: The prevalence of anaemia in this population is of public health concern with adolescents of both sexes at risk of developing anaemia. The national nutrition programme to control and manage anaemia by distributing a weekly iron and folate supplement for adolescent girls together with a deworming programme twice per year appears to have partly successful but could be strengthened.

Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial.

BACKGROUND: Diarrhea and respiratory tract infections are leading causes of childhood morbidity and mortality. This individually randomized, double-blind placebo-controlled trial was designed to evaluate the effects of different zinc supplementation regimens on the incidence and duration of diarrhea and acute lower (ALRI) and upper (AURI) respiratory tract infections among rural Laotian children. The study included 3407 children, 6-23 months at enrollment. METHODS: Children were randomized to one of four study groups: therapeutic zinc supplements for diarrhea treatment (20 mg/d for 10 days with each episode; TZ), daily preventive zinc tablets (7 mg/d; PZ), daily multiple micronutrient powder (10 mg/d zinc, 6 mg/d iron and 13 other micronutrients; MNP), or daily placebo powder for 9 months. Incidence and duration of diarrhea (≥3 liquid stools/24 hours), ALRI (persistent cough with wheezing, stridor or chest in-drawing) and AURI (purulent nasal discharge with cough) were assessed by parental report during weekly home visits and analyzed using negative binomial models. RESULTS: Baseline mean age was 14.2 ± 5.1 months, and 71% had low plasma zinc (<65 µg/dL). Overall diarrhea incidence (0.61 ± 0.01 episodes/100 days at risk) and duration (2.12 ± 0.03 days/episode) did not differ by study group. Age modified the impact of the interventions on diarrhea incidence (P = 0.06) and duration (P = 0.01). In children >18 months, TZ reduced diarrhea incidence by 24% vs MNP (P = 0.035), and 36% vs Control (P = 0.004), but there was no difference with PZ. This patterned remained when analyses were restricted to diarrhea episode occurring after the first treatment with TZ. Also, in children >18 months, TZ reduced diarrhea duration by 15% vs PZ (P = 0.03), and 16% vs Control (P = 0.03), but there was no difference with MNP. There were no overall effects of study group on incidence of ALRI (overall mean 0.005 ± 0.001 episodes/100 days, P = 0.14) or AURI (overall mean 0.09 ± 0.01 episodes/100 days, P = 0.72). CONCLUSIONS: There was no overall impact of TZ, PZ or MNP on diarrhea, ALRI and AURI. However, in children >18 months, TZ significantly reduced both the duration of diarrhea episodes and the incidence of future diarrhea episodes compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02428647.

Impact of Different Strategies for Delivering Supplemental Zinc on Selected Fecal Markers of Environmental Enteric Dysfunction among Young Laotian Children: A Randomized Controlled Trial.

The objective of this study was to assess the impact of different strategies for delivering supplemental zinc on fecal myeloperoxidase (MPO), neopterin (NEO), and calprotectin (CAL) among young Laotian children. In a double-blind controlled trial, children aged 6-23 months were randomized to receive either daily preventive zinc (PZ) tablets (7 mg/day), daily micronutrient powder (MNP; containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days), or daily placebo powder and followed for ∼36 weeks. Stool samples were collected at baseline and endline. Fecal MPO, NEO, and CAL concentrations were determined in a randomly selected subsample of 720 children using commercially available ELISA kits. At baseline, the mean age was 14.1 ± 4.9 months and prevalence of stunting was 39%. The endline prevalence of stunting was 43%; there was no overall treatment effect on physical growth in the parent trial. At endline, the mean (95% CI) MPO in the PZ group was 1,590 [1,396; 1,811] ng/mL and did not differ from that in the MNP (1,633 [1,434; 1,859] ng/mL), TZ (1,749 [1,535; 1,992] ng/mL), and control (1,612 [1,415; 1,836] ng/mL) groups (P = 0.749). Similarly, there was no overall treatment effect on NEO and CAL concentrations (P = 0.226 and 0.229, respectively). In this population, the provision of PZ or TZ supplements or MNP had no impact on growth or environmental enteric dysfunction (EED) as assessed by fecal MPO, NEO, and CAL. Additional research is needed to better understand the etiology and proposed mechanisms of EED pathogenesis.

Daily Preventive Zinc Supplementation Decreases Lymphocyte and Eosinophil Concentrations in Rural Laotian Children from Communities with a High Prevalence of Zinc Deficiency: Results of a Randomized Controlled Trial.

BACKGROUND: Zinc deficiency impairs immune function and is common among children in South-East Asia. OBJECTIVES: The effect of zinc supplementation on immune function in young Laotian children was investigated. METHODS: Children (n = 512) aged 6-23 mo received daily preventive zinc tablets (PZ; 7 mg Zn/d), daily multiple micronutrient powder (MNP; 10 mg Zn/d, 6 mg Fe/d, plus 13 other micronutrients), therapeutic dispersible zinc tablets only in association with diarrhea episodes (TZ; 20 mg Zn/d for 10 d after an episode), or daily placebo powder (control). These interventions continued for 9 mo. Cytokine production from whole blood cultures, the concentrations of T-cell populations, and a complete blood count with differential leukocyte count were measured at baseline and endline. Endline means were compared via ANCOVA, controlling for the baseline value of the outcome, child age and sex, district, month of enrollment, and baseline zinc status (below, or above or equal to, the median plasma zinc concentration). RESULTS: T-cell cytokines (IL-2, IFN-γ, IL-13, IL-17), LPS-stimulated cytokines (IL-1ß, IL-6, TNF-α, and IL-10), and T-cell concentrations at endline did not differ between intervention groups, nor was there an interaction with baseline zinc status. However, mean ± SE endline lymphocyte concentrations were significantly lower in the PZ than in the control group (5018 ± 158 compared with 5640 ± 160 cells/µL, P = 0.032). Interactions with baseline zinc status were seen for eosinophils (Pixn = 0.0036), basophils (Pixn = 0.023), and monocytes (P = 0.086) but a significant subgroup difference was seen only for eosinophils, where concentrations were significantly lower in the PZ than in the control group among children with baseline plasma zinc concentrations below the overall median (524 ± 44 compared with 600 ± 41 cells/µL, P = 0.012). CONCLUSIONS: Zinc supplementation of rural Laotian children had no effect on cytokines or T-cell concentrations, although zinc supplementation affected lymphocyte and eosinophil concentrations. These cell subsets may be useful as indicators of response to zinc supplementation.This trial was registered at clinicaltrials.gov as NCT02428647.

Impact of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Plasma Biomarkers of Environmental Enteric Dysfunction among Rural Laotian Children: A Randomized Controlled Trial.

Environmental enteric dysfunction (EED) may be ameliorated by zinc supplementation. The objective of this study was to investigate the impact of different forms of zinc supplementation on biomarkers of EED (i.e., plasma citrulline, kynurenine, and tryptophan concentrations and the kynurenine:tryptophan [KT] ratio) among young Laotian children. In a double-blind randomized controlled trial, 3,407 children aged 6-23 months were randomized into one of four groups: daily preventive zinc dispersible tablets (PZ; 7 mg zinc), daily multiple micronutrient powders (MNP; 10 mg zinc, 6 mg iron, and 13 other micronutrients), therapeutic zinc supplements for diarrhea treatment (TZ; 20 mg/day for 10 days), or daily placebo powder, and followed up for ∼36 weeks. Plasma samples at baseline and endline for 359 children were analyzed for citrulline, kynurenine, and tryptophan concentrations. At baseline, the prevalence of stunting and zinc deficiency was 37% and 76.5%, respectively. The mean plasma citrulline, kynurenine, and tryptophan concentrations were 24.6 ± 5.4 µmol/L, 3.27 ± 0.83 µmol/L, and 72.3 ± 12.9 µmol/L, respectively; the mean KT ratio (×1,000) was 45.9 ± 12.0. At endline, neither plasma citrulline, kynurenine, or tryptophan concentrations, nor the KT ratio differed among intervention groups (P > 0.05). In this population, PZ, MNP, and TZ had no overall effect on plasma concentrations of citrulline, kynurenine, and tryptophan, or the KT ratio. The need remains to better understand the etiology of EED, and the development of biomarkers to diagnose EED and evaluate the impact of interventions.

Iron status and inherited haemoglobin disorders modify the effects of micronutrient powders on linear growth and morbidity among young Lao children in a double-blind randomised trial.

Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6-23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (-1·93 (95 % CI -1·88, -1·97)) v. placebo (-1·88 (95 % CI -1·83, -1·92)), and the opposite occurred among initially anaemic children (final mean LAZ -1·90 (95 % CI -1·86, -1·94) in MNP v. -1·92 (95 % CI -1·88, -1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.

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.

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.

Effects of Daily Zinc, Daily Multiple Micronutrient Powder, or Therapeutic Zinc Supplementation for Diarrhea Prevention on Physical Growth, Anemia, and Micronutrient Status in Rural Laotian Children: A Randomized Controlled Trial.

OBJECTIVES: To evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children. STUDY DESIGN: In total, 3407 children aged 6-23 months were randomized to receive either daily preventive zinc tablets (7 mg/d), high-zinc, low-iron micronutrient powder (10 mg/d zinc, 6 mg/d iron, and 13 other micronutrients), therapeutic zinc supplementation for diarrhea (20 mg/d for 10 days per episode), or daily placebo powder; all were followed for ~9 months. Anthropometry, hemoglobin, zinc, and iron status were assessed at baseline and endline. Analyses were by intention-to-treat, using linear and modified Poisson regression. RESULTS: At baseline, mean (±SD) age was 14.2 ± 5.1 months and stunting and anemia prevalence were 37.9% and 55.6%, respectively. At endline, zinc deficiency in the preventive zinc (50.7%) and micronutrient powder (59.1%) groups were significantly lower than in the therapeutic zinc (79.2%) and control groups (78.6%; P < .001), with no impact on stunting (37.1%-41.3% across the groups, P = .37). The micronutrient powder reduced iron deficiency by 44%-55% compared with other groups (P < .001), with no overall impact on anemia (P = .14). Micronutrient powder tended to reduce anemia by 11%-16% among children who were anemic at baseline (P = .06). CONCLUSIONS: Despite improving zinc status, preventive zinc and micronutrient powder had no impact on growth. The micronutrient powder improved iron status and tended to reduce anemia among the subset of previously anemic children. TRIAL REGISTRATION: ClinicalTrials.govNCT02428647.

Impact of Two Forms of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Hair Cortisol Concentrations Among Rural Laotian Children: A Randomized Controlled Trial.

Zinc supplementation has been shown to reduce the morbidity burden among young children, and may reduce chronic stress. Hair cortisol has been promoted as an indicator of chronic stress. We assessed the impact of different strategies for delivering supplementary zinc on hair cortisol concentrations (HCC) in young Laotian children and examined risk factors associated with HCC. In a randomized double-blind controlled trial (NCT02428647), children aged 6⁻23 mo were randomized to one of four intervention groups and followed for ~36 weeks: daily preventive zinc (PZ) tablets (7 mg/day), daily multiple micronutrient powder (MNP) sachets (containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days) or daily placebo powder. HCC of 512 children was assessed at baseline and endline. ANCOVA and linear regression models were used to assess group differences in HCC and to examine the risk factors associated with HCC, respectively. At enrollment, mean HCC was 28.8 ± 43.9 pg/mg. In models adjusted for age at enrollment, health district, and baseline HCC there was no overall effect of the interventions on endline HCC and change in HCC. When controlling for additional predetermined covariates, there was a marginally significant effect on change in HCC (p = 0.075) with a slightly lower reduction of HCC in TZ compared to PZ (mean change (95% CI): -4.6 (-7.0; -2.3) vs. -9.4 (-11.7; -7.0) pg/mg; p = 0.053). At baseline, consumption of iron rich foods was negatively associated with HCC, whereas AGP (α1-acid glycoprotein) levels, elevated AGP and C-reactive protein and high soluble transferrin receptor were positively associated with HCC. In young Laotian children, MNP, PZ and TZ had no impact on HCC. The marginal difference in change in HCC between the PZ and TZ groups was too small to be considered of health significance.

Thiamine deficiency disorders: diagnosis, prevalence, and a roadmap for global control programs.

Thiamine is an essential micronutrient that plays a key role in energy metabolism. Many populations worldwide may be at risk of clinical or subclinical thiamine deficiencies, due to famine, reliance on staple crops with low thiamine content, or food preparation practices, such as milling grains and washing milled rice. Clinical manifestations of thiamine deficiency are variable; this, along with the lack of a readily accessible and widely agreed upon biomarker of thiamine status, complicates efforts to diagnose thiamine deficiency and assess its global prevalence. Strategies to identify regions at risk of thiamine deficiency through proxy measures, such as analysis of food balance sheet data and month-specific infant mortality rates, may be valuable for understanding the scope of thiamine deficiency. Urgent public health responses are warranted in high-risk regions, considering the contribution of thiamine deficiency to infant mortality and research suggesting that even subclinical thiamine deficiency in childhood may have lifelong neurodevelopmental consequences. Food fortification and maternal and/or infant thiamine supplementation have proven effective in raising thiamine status and reducing the incidence of infantile beriberi in regions where thiamine deficiency is prevalent, but trial data are limited. Efforts to determine culturally and environmentally appropriate food vehicles for thiamine fortification are ongoing.