A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.

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.

Comparison of Published Estimates of the National Prevalence of Iron, Vitamin A, and Zinc Deficiency and Sources of Inconsistencies.

Micronutrient deficiencies result in a broad range of adverse health and functional consequences, but the true prevalence of specific deficiencies remains uncertain because limited information is available from nationally representative surveys using recommended biomarkers. The present review compares various reported national deficiency prevalence estimates for nutrients and years where the estimates overlap for individual countries that conducted nationally representative surveys and explores possible reasons for any discrepancies discovered. Nationally representative micronutrient status surveys that were conducted since 2000 among preschool-aged children or women of reproductive age and included assessment of iron, vitamin A, or zinc status based on recognized biomarkers were considered eligible for inclusion, along with any modeled deficiency prevalence estimates for these same countries and years. There was considerable variation across different published prevalence estimates, with larger inconsistencies when the prevalence estimate was based on proxies, such as hemoglobin for iron deficiency and dietary zinc availability for zinc deficiency. Numerous additional methodological issues affected the prevalence estimates, such as which biomarker and what cutoff was used to define deficiency, whether the biomarker was adjusted for inflammation, and what adjustment method was used. For some country-years, the various approaches resulted in fairly consistent prevalence estimates. For other country-years, however, the results differed markedly and changed the conclusions regarding the existence and severity of the micronutrient deficiency as a public health concern. In conclusion, to determine micronutrient status, we consider the assessment of one of the recommended biomarkers in a population representative survey as the best available information. If indicated, results should be adjusted for inflammation and generally acceptable cutoffs should be applied to facilitate comparisons, although individual countries may also apply nationally defined cutoffs to determine when and where to intervene. Global consensus is needed on best practices for presenting survey results and defining the prevalence of deficiency.

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.

Accelerating action to reduce anemia: Review of causes and risk factors and related data needs.

Anemia is a major public health concern. Young children, menstruating adolescent girls and women, and pregnant women are among the most vulnerable. Anemia is the consequence of a wide range of causes, including biological, socioeconomic, and ecological risk factors. Primary causes include: iron deficiency; inherited red blood cell disorders; infections, such as soil-transmitted helminthiasis, schistosomiasis, and malaria; gynecological and obstetric conditions; and other chronic diseases that lead to blood loss, decreased erythropoiesis, or destruction of erythrocytes. The most vulnerable population groups in low- and middle-income countries are often at the greatest risk to suffer from several of these causes simultaneously as low socioeconomic status is linked with an increased risk of anemia through multiple pathways. Targeted and effective action is needed to prevent anemia. Understanding the causes and risk factors of anemia for different population subgroups within a country guides the design and implementation of effective strategies to prevent and treat anemia. A coordinated approach across various expert groups and programs could make the best use of existing data or could help to determine when newer and more relevant data may need to be collected, especially in countries with a high anemia burden and limited information on the etiology of anemia.

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).

Preventive small-quantity lipid-based nutrient supplements reduce severe wasting and severe stunting among young children: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting. OBJECTIVES: We aimed to identify the effect of SQ-LNSs on prevalence of severe wasting (weight-for-length z score < -3) and severe stunting (length-for-age z score < -3). METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. RESULTS: SQ-LNS provision led to a relative reduction of 31% in severe wasting [prevalence ratio (PR): 0.69; 95% CI: 0.55, 0.86; n = 34,373] and 17% in severe stunting (PR: 0.83; 95% CI: 0.78, 0.90; n = 36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded (PR: 0.74; 95% CI: 0.57, 0.96; n = 26,327 for severe wasting and PR: 0.88; 95% CI: 0.81, 0.95; n = 28,742 for severe stunting). Study-level characteristics generally did not significantly modify the effects of SQ-LNSs, but results suggested greater effects of SQ-LNSs in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation. CONCLUSIONS: Including SQ-LNSs in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. This meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Small-quantity lipid-based nutrient supplements, with or without added zinc, do not cause excessive fat deposition in Burkinabe children: results from a cluster-randomized community trial.

PURPOSE: Public health interventions to address stunting and wasting should be evaluated for possibly contributing to obesity risk. The present study tested the hypothesis that small-quantity lipid-based nutrient supplements (SQ-LNS) might increase fat deposition, and that additional zinc provided via SQ-LNS or in the form of dispersible tablets would increase fat-free mass (FFM) accretion. METHODS: Using a two-stage, cluster-randomized trial design, 34 communities were randomly assigned to the intervention cohort (IC) or non-intervention cohort (NIC), and family compounds within the IC were randomly assigned to receive different amounts of zinc (0, 5 or 10 mg zinc) incorporated in SQ-LNS or 5 mg zinc in the form of dispersible tablets along with treatment for diarrhea, malaria and fever. Body composition was assessed in a subset of IC (n = 201) and NIC (n = 74) children at 9 and 18 months using the deuterium dilution method. A mixed linear model was used to examine average change in FFM and % fat mass (%FM) among intervention groups and by cohort. RESULTS: Children in the IC had significantly greater change in FFM (Mean (95% Confidence Interval)) (1.57 (1.49, 1.64) kg) compared to the NIC (1.35 (1.23, 1.46) kg; p = 0.005). There were no significant differences in the change in %FM between the NIC and IC or among the intervention groups. CONCLUSION: SQ-LNS, along with morbidity treatment increased weight gain and FFM in young children from 9 to 18 months of age without increasing FM deposition. Additional zinc supplementation did not affect changes in FFM or %FM. TRIAL REGISTRATION: The study was registered as a clinical trial with the US National Institute of Health ( www. CLINICALTRIALS: gov ; NCT00944281).

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.

Traditional prenatal and postpartum food restrictions among women in northern Lao PDR.

Culturally determined food restrictions are common among pregnant and postpartum women in Asia. This study aimed to describe perinatal dietary restrictions, factors associated with food avoidances and attainment of minimum dietary diversity (MDD-W) among women in Lao PDR. Mother-child (aged 21 days to <18 months) dyads (n = 682) were enrolled into a cohort study in northern Lao PDR and interviewed at one time point postpartum. During pregnancy and postpartum, 1.6% and 97% of women reported following dietary restrictions, respectively. Cluster analysis identified four distinct postpartum dietary patterns: most restrictive (throughout first 2 months postpartum); least restrictive; 2 weeks highly restrictive and 1 month highly restrictive, followed by 19%, 15%, 5% and 62% of women, respectively. Greater maternal age, gravidity and higher household socioeconomic status were associated with allowing more diverse foods, while women from food insecure households followed more restrictive diets for longer. Women belonging to the Hmong ethnic group followed a highly restrictive diet of white rice and chicken for the first month postpartum. MDD-W was achieved by 10% of women restricting their diet at the time of the interview compared with 17% of women who were consuming their normal diet (p = 0.04). Postpartum dietary restrictions are widespread among women in northern Lao PDR. These highly restrictive diets, low dietary diversity and food insecurity likely contribute to micronutrient deficiencies in women that may have important consequences for their breastfed infants through reduced breastmilk micronutrient content, which requires further exploration. Culturally appropriate strategies to increase micronutrient intakes among women should be considered.

Basis for changes in the disease burden estimates related to vitamin A and zinc deficiencies in the 2017 and 2019 Global Burden of Disease Studies.

BACKGROUND: The Global Burden of Disease (GBD) Study provides estimates of death and disability from eighty-seven risk factors, including some micronutrient deficiencies. OBJECTIVES: To review methodological changes that led to large differences in the disease burden estimates for vitamin A and Zn deficiencies between the GBD 2017 and 2019 Studies. METHODS: GBD publications were reviewed; additional information was provided by GBD researchers. RESULTS: Vitamin A deficiency prevalence is based on plasma retinol concentration, whereas the estimate for Zn deficiency prevalence uses dietary adequacy as a proxy. The estimated global prevalence of vitamin A deficiency for children aged 1-4 years in the year 2017 decreased from 0·20 (95 % CI 0·17, 0·24) in GBD 2017 to 0·16 (95 % CI 0·15, 0·19) in GBD 2019, while the global prevalence of Zn deficiency did not change between the two studies (0·09 (95 % CI 0·04, 0·17) and 0·09 (95 % CI 0·03, 0·18)). New to 2019 was that meta-analyses were performed using Meta Regression - Bayesian, Regularized, Trimmed, a method developed for GBD. Due to this and multiple other methodological changes, the estimated number of deaths due to vitamin A deficiency dropped from 233 000 (179 000-294 000) to 24 000 (3000-50 000) from GBD 2017 to 2019, and for Zn deficiency from 29 000 (1000-77 000) to 2800 (700-6500), respectively. CONCLUSION: The changes in the estimated disease burdens due to vitamin A and Zn deficiencies in the GBD reports from 2017 to 2019 are due primarily to changes in the analytical methods employed, so may not represent true changes in disease burden. Additional effort is needed to validate these results.

A multicenter analytical performance evaluation of a multiplexed immunoarray for the simultaneous measurement of biomarkers of micronutrient deficiency, inflammation and malarial antigenemia.

A lack of comparative data across laboratories is often a barrier to the uptake and adoption of new technologies. Furthermore, data generated by different immunoassay methods may be incomparable due to a lack of harmonization. In this multicenter study, we describe validation experiments conducted in a single lab and cross-lab comparisons of assay results to assess the performance characteristics of the Q-plex™ 7-plex Human Micronutrient Array (7-plex), an immunoassay that simultaneously quantifies seven biomarkers associated with micronutrient (MN) deficiencies, inflammation and malarial antigenemia using plasma or serum; alpha-1-acid glycoprotein, C-reactive protein, ferritin, histidine-rich protein 2, retinol binding protein 4, soluble transferrin receptor, and thyroglobulin. Validations included repeated testing (n = 20 separately prepared experiments on 10 assay plates) in a single lab to assess precision and linearity. Seven independent laboratories tested 76 identical heparin plasma samples collected from a cohort of pregnant women in Niger using the same 7-plex assay to assess differences in results across laboratories. In the analytical validation experiments, intra- and inter-assay coefficients of variation were acceptable at <6% and <15% respectively and assay linearity was 96% to 99% with the exception of ferritin, which had marginal performance in some tests. Cross-laboratory comparisons showed generally good agreement between laboratories in all analyte results for the panel of 76 plasma specimens, with Lin's concordance correlation coefficient values averaging ≥0.8 for all analytes. Excluding plates that would fail routine quality control (QC) standards, the inter-assay variation was acceptable for all analytes except sTfR, which had an average inter-assay coefficient of variation of ≥20%. This initial cross-laboratory study demonstrates that the 7-plex test protocol can be implemented by users with some experience in immunoassay methods, but familiarity with the multiplexed protocol was not essential.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child anemia and micronutrient status: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers. RESULTS: SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics. CONCLUSIONS: SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Small-quantity lipid-based nutrient supplements for children age 6-24 months: a systematic review and individual participant data meta-analysis of effects on developmental outcomes and effect modifiers.

BACKGROUND: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development. OBJECTIVES: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024). RESULTS: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11). CONCLUSIONS: Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Characteristics that modify the effect of small-quantity lipid-based nutrient supplementation on child growth: an individual participant data meta-analysis of randomized controlled trials.

BACKGROUND: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design. OBJECTIVES: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes. METHODS: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons. RESULTS: SQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation. CONCLUSIONS: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Increasing the availability and utilization of reliable data on population micronutrient (MN) status globally: the MN Data Generation Initiative.

Micronutrient (MN) deficiencies can produce a broad array of adverse health and functional outcomes. Young, preschool children and women of reproductive age in low- and middle-income countries are most affected by these deficiencies, but the true magnitude of the problems and their related disease burdens remain uncertain because of the dearth of reliable biomarker information on population MN status. The reasons for this lack of information include a limited understanding by policy makers of the importance of MNs for human health and the usefulness of information on MN status for program planning and management; insufficient professional capacity to advocate for this information and design and implement related MN status surveys; high costs and logistical constraints involved in specimen collection, transport, storage, and laboratory analyses; poor access to adequately equipped and staffed laboratories to complete the analyses reliably; and inadequate capacity to interpret and apply this information for public health program design and evaluation. This report describes the current situation with regard to data availability, the reasons for the lack of relevant information, and the steps needed to correct this situation, including implementation of a multi-component MN Data Generation Initiative to advocate for critical data collection and provide related technical assistance, laboratory services, professional training, and financial support.

Out-of-pocket costs and time spent attending antenatal care services: a case study of pregnant women in selected rural communities in Zinder, Niger.

BACKGROUND: Despite an official policy of exemption from health care costs, pregnant women in Niger still face some out-of-pocket costs (OPC) in addition to time costs when they attend antenatal care (ANC) services. We aimed to: 1) assess the OPC for pregnant woman attending ANC, 2) estimate the time spent to attend ANC and the opportunity cost of that time, and 3) assess how OPC and time spent to attend ANC affected ANC attendance. METHODS: Data were obtained from a quasi-experimental descriptive study carried out in the region of Zinder, Niger, which compared pre- and post-intervention cohorts of pregnant women (n = 1736 women who reported attending ANC during their current pregnancy). An ANC attendance score was developed to describe the timing of ANC attendance in regard to the WHO recommendation of attending 4 ANC sessions. OPC and time spent were evaluated separately for associations with ANC attendance using Spearman correlations. RESULTS: The mean (±SD) age of pregnant women was 25.0 ± 6.4 yr, 19.0% were ≤ 19 yr and 99.7% were in their second or third trimester of gestation at the time of the interview. Among those who were > 13 weeks and > 27 weeks of gestation, 4.0 and 74.4% had attended ANC during their first and second trimesters, respectively. The median (1st quartile (Q1), 3rd quartile (Q3)) ANC score was 0 (- 1, 0), reflecting that the majority of women failed to follow the WHO recommendation. More than half of the women (72.5%) experienced OPC related to ANC. The majority of women (> 80%) reported spending ~ 3 h for an ANC visit, including travel and waiting time. Time spent to attend ANC was not associated with ANC attendance score. Women who experienced OPC, and those who received iron folic acid (IFA) or long-lasting insecticide-treated bednets during an ANC visit, were more likely to have a higher ANC attendance score compared to those who did not. CONCLUSION: OPC and time spent were not identified as barriers to ANC visits, and IFA and long-lasting insecticide-treated bednets distribution could be used to motivate pregnant women to attend ANC. TRIAL REGISTRATION: The NiMaNu project was registered at www.clinicaltrials.gov as NCT01832688 . Registered 16 April 2013.