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.

Perinatal intervention strategies providing food with micronutrients to pregnant and breastfeeding women in low- and middle-income countries: A scoping review.

In resource-constrained settings, pregnant and breastfeeding women and girls (PBW/G) are particularly vulnerable to undernutrition. Micronutrient-fortified balanced energy protein (BEP) supplementation may be provided to boost maternal nutritional status and improve birth and infant outcomes. We conducted a scoping review of the published literature to determine the impact of BEP and other related nutrition interventions that provided fortified food or cash along with a minimum of 3 micronutrients on maternal, birth, and infant/child outcomes in low- and middle-income countries. We conducted a PubMed search using pre-defined keywords and controlled vocabulary search terms. All titles and abstracts were reviewed for eligibility by two independent reviewers, and data were extracted according to outcome type. We identified 149 eligible research articles that reported on a total of 21 trials and/or programme evaluations which assessed the health impact of one or more products (fortified lipid-based nutrient supplement [LNS, n = 12], fortified blended flours [n = 5], milk-based beverages [n = 2], and local food/snacks [n = 3]) that provided 118-750 kcal/day and varying levels of protein and micronutrients. Only one of these programme evaluations assessed the impact of the provision of cash and fortified food. Effects on maternal outcomes such as gestational weight gain and duration of gestation were promising but inconsistent. Birth outcomes were reported in 15 studies, and the effects on birthweight and birth length were generally positive. Seven studies demonstrated sustained benefits on infant and child growth out of the 15 studies that reported at least one of these outcomes, although data were sparse. Additional research is needed to investigate issues of dose, cost-effectiveness, and incorporation into multi-component interventions.

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.

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.

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.

Prevalence and determinants of gestational weight gain among pregnant women in Niger.

Low gestational weight gain (GWG) and low mid-upper arm circumference (MUAC) are associated with adverse pregnancy outcomes. We aimed to assess the prevalence and determinants of low GWG and low MUAC among pregnant women in rural Zinder, Niger. A community-based survey was conducted among 1,384 pregnant women in the catchment areas of 18 integrated health centers in the region of Zinder, Niger. Weight and MUAC were measured during an in-home visit and again 1 month later, when haemoglobin concentration and micronutrient status were also assessed. The prevalence of low GWG was defined based on the 2009 United States Institute of Medicine (U.S. IOM) guidelines (<0.35 kg/week) and less than the third centile of the International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) standards. Factors associated with GWG and MUAC were identified using logistic regression models adjusting for season, village, and gestational age. The median (interquartile range) age was 25.0 (20.7, 30.0) years, and 16.4% were ≤19 years. The prevalence of low GWG were 62.9% and 27.5% according to 2009 IOM and less than the third INTERGROWTH-21st centile, respectively; 24.9% had low MUAC. Higher α-1-acid glycoprotein (OR = 1.7, 95% CI [1.1, 2.8]) and C-reactive protein (OR = 1.2, 95% CI [1.02, 1.50]) increased the odds of low GWG. Adolescents (OR = 2.7, 95% CI [1.8, 4.0]), housewives (OR = 1.97, 95% CI [1.36, 2.86]), and those who reported recent food assistance (OR = 1.80, 95% CI [1.04, 3.11]) had higher odds of low MUAC. Prevalence of low GWG and low MUAC was high among pregnant women. Determinants of GWG and MUAC included socio-economic, demographic, and biological factors, although only markers of inflammation were consistent predictors across different definitions of low GWG.

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.

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.

Prevalence of and factors associated with antenatal care seeking and adherence to recommended iron-folic acid supplementation among pregnant women in Zinder, Niger.

The World Health Organization recommends iron and folic acid (IFA) supplementation for pregnant women. The high prevalence of anaemia among pregnant women in Niger warrants better understanding of the utilization of antenatal care (ANC) and IFA. We aimed to assess the prevalence of and factors associated with ANC coverage and adherence to IFA recommendation among pregnant women. Pregnant women (n = 923) from 64 randomly selected villages within the catchment area of 12 health centres were interviewed during a baseline household survey in Zinder, Niger. ANC and IFA coverage were 60.1% and 43.6%, respectively. Only 71.7% of women who attended ANC received IFA. Of the 401 women who reportedly received any IFA supplements, 99.3% had attended any ANC during their current pregnancy and 68.6% reported adherence to recommended IFA supplementation (i.e., consumed IFA every day in the previous week). Women with gestational age ≥27 weeks were more likely to have attended ANC than women with gestational age <27 weeks (85.9% vs. 27.5%, odds ratio [OR]: 21.81, 95% confidence interval [CI]: 13.81, 34.45). Women who reportedly received husbands' advice about attending ANC were more likely to attend ANC (OR: 1.48, 95% CI [1.03, 2.11]) and adhere to IFA recommendations (OR: 1.80, 95% CI [1.04, 3.13]) compared to those who did not receive any advice. ANC attendance is crucial to ensure distribution of IFA supplementation among pregnant women in Zinder. Interventions to improve ANC and IFA adherence will require promotion of early ANC, ensure availability of IFA at ANC, and involve husbands in ANC.

Using formative research to promote antenatal care attendance and iron folic acid supplementation in Zinder, Niger.

In Niger, use of antenatal care (ANC) and iron folic acid (IFA) supplements is suboptimal. The objectives of this paper are as follows: (a) to conduct formative research to understand barriers and beliefs among pregnant women related to ANC, IFA supplementation, and pregnancy outcomes; (b) assess the quality of currently provided ANC services; (c) use the findings to guide the development of programmatic interventions to improve coverage of ANC services and IFA supplementation of pregnant women. Structured in-home interviews (n = 72) and focus groups (n = 4) were conducted with pregnant women in 4 randomly selected villages in rural Zinder. ANC consultations (n = 33) were observed in 5 randomly selected health centres, and exit interviews were conducted with all pregnant women and seven health agents following these observations. During workshops with stakeholders, results of the formative research were interpreted, and programmatic interventions were developed. In home interviews, 72% of women reported having attended at least one ANC visit. They also reported husbands (71%), mothers (40%), and friends (33%) supporting ANC attendance. Among those having attended ANC, only 65% reported taking IFA the day prior to the interview. Three of five health centres visited had IFA in stock. Health staff did not provide IFA supplements during 18 of 33 observed ANC consultations of which only 7 cases could be explained by the lack of IFA supplements in stock. Findings were used to design a 3-pronged intervention: (a) behaviour change communication activities in communities; (b) quality improvement activities in health centres to strengthen ANC; and (c) provision of key supplies required for ANC.

Predictors and pathways of language and motor development in four prospective cohorts of young children in Ghana, Malawi, and Burkina Faso.

BACKGROUND: Previous reviews have identified 44 risk factors for poor early child development (ECD) in low- and middle-income countries. Further understanding of their relative influence and pathways is needed to inform the design of interventions targeting ECD. METHODS: We conducted path analyses of factors associated with 18-month language and motor development in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements (iLiNS) Project in Ghana (n = 1,023), Malawi (n = 675 and 1,385), and Burkina Faso (n = 1,122). In two cohorts, women were enrolled during pregnancy. In two cohorts, infants were enrolled at 6 or 9 months. In multiple linear regression and structural equation models (SEM), we examined 22 out of 44 factors identified in previous reviews, plus 12 additional factors expected to be associated with ECD. RESULTS: Out of 42 indicators of the 34 factors examined, 6 were associated with 18-month language and/or motor development in 3 or 4 cohorts: child linear and ponderal growth, variety of play materials, activities with caregivers, dietary diversity, and child hemoglobin/iron status. Factors that were not associated with child development were indicators of maternal Hb/iron status, maternal illness and inflammation during pregnancy, maternal perceived stress and depression, exclusive breastfeeding during 6 months postpartum, and child diarrhea, fever, malaria, and acute respiratory infections. Associations between socioeconomic status and language development were consistently mediated to a greater extent by caregiving practices than by maternal or child biomedical conditions, while this pattern for motor development was not consistent across cohorts. CONCLUSIONS: Key elements of interventions to ensure quality ECD are likely to be promotion of caregiver activities with children, a variety of play materials, and a diverse diet, and prevention of faltering in linear and ponderal growth and improvement in child hemoglobin/iron status.

Urinary iodine concentration identifies pregnant women as iodine deficient yet school-aged children as iodine sufficient in rural Niger.

OBJECTIVE: To assess iodine status among pregnant women in rural Zinder, Niger and to compare their status with the iodine status of school-aged children from the same households. DESIGN: Seventy-three villages in the catchment area of sixteen health centres were randomly selected to participate in the cross-sectional survey. SETTING: Salt iodization is mandatory in Niger, requiring 20-60 ppm iodine at the retail level. SUBJECTS: A spot urine sample was collected from randomly selected pregnant women (n 662) and one school-aged child from the same household (n 373). Urinary iodine concentration (UIC) was assessed as an indicator of iodine status in both groups. Dried blood spots (DBS) were collected from venous blood samples of pregnant women and thyroglobulin (Tg), thyroid-stimulating hormone and total thyroxine were measured. Iodine content of household salt samples (n 108) was assessed by titration. RESULTS: Median iodine content of salt samples was 5·5 ppm (range 0-41 ppm), 98 % had an iodine content 40 µg/l. CONCLUSIONS: In this region of Niger, most salt is inadequately iodized. UIC in pregnant women indicated iodine deficiency, whereas UIC of school-aged children indicated marginally adequate iodine status. Thus, estimating population iodine status based solely on monitoring of UIC among school-aged children may underestimate the risk of iodine deficiency in pregnant women.

Small-quantity lipid-based nutrient supplements containing different amounts of zinc along with diarrhea and malaria treatment increase iron and vitamin A status and reduce anemia prevalence, but do not affect zinc status in young Burkinabe children: a cluster-randomized trial.

BACKGROUND: We assessed the effects of providing a package of interventions including small-quantity lipid-based nutrient supplements (SQ-LNS) containing 0, 5 or 10 mg zinc and illness treatment to Burkinabe children from 9 to 18 months of age, on biomarkers of zinc, iron and vitamin A status at 18 months and compared with a non-intervention cohort (NIC). METHODS: Using a two-stage cluster randomized trial design, communities were randomly assigned to the intervention cohort (IC) or NIC, and extended family compounds within the IC were randomly assigned to different treatment groups. IC children (n = 2435) were provided with 20 g SQ-LNS/d containing 0, 5 or 10 mg zinc, 6 mg of iron and 400 µg of vitamin A along with malaria and diarrhea treatment. NIC children (n = 785) did not receive the intervention package. At 9 and 18 months, hemoglobin (Hb), zinc, iron and vitamin A status were assessed in a sub-group (n = 404). Plasma concentrations of zinc (pZC), ferritin (pF), soluble transferrin receptor (sTfR) and retinol-binding protein (RBP) were adjusted for inflammation. RESULTS: At baseline, 35% of children had low adjusted pZC (<65 µg/dL), 93% were anemic (Hb <110 g/L), 25% had low adjusted pF (<12 µg/L), 90% had high adjusted sTfR (>8.3 mg/L) and 47% had low adjusted RBP (<0.94 µmol/L), with no group-wise differences. Compared with the NIC, at 18 months IC children had significantly lower anemia prevalence (74 vs. 92%, p = 0.001) and lower iron deficiency prevalence (13% vs. 32% low adjusted pF and 41% vs. 71% high adjusted sTfR, p < 0.001), but no difference in pZC. Mean adjusted RBP was greater at 18 months in IC vs. NIC (0.94 µmol/L vs. 0.86 µmol/L, p = 0.015), but the prevalence of low RBP remained high in both cohorts. Within the IC, different amounts of zinc had no effect on the prevalence of low pZC or indicators of vitamin A deficiency, whereas children who received SQ-LNS with 10 mg zinc had a significantly lower mean pF at 18 months compared to children who received SQ-LNS with 5 mg zinc (p = 0.034). CONCLUSIONS: SQ-LNS regardless of zinc amount and source provided along with illness treatment improved indicators of iron and vitamin A status, but not pZC. TRIAL REGISTRATION: NCT00944281 (July 21, 2009).

Effects of an intervention on infant growth and development: evidence for different mechanisms at work.

Millions of children in low-income and middle-income countries falter in linear growth and neurobehavioral development early in life. This faltering may be caused by risk factors that are associated with both growth and development, such as insufficient dietary intake and infection in infancy. Alternatively, these risk factors may be indicative of an environment that constrains both linear growth and development through different mechanisms. In a cluster-randomized trial in Burkina Faso, we previously found that provision of lipid-based nutrient supplements plus malaria and diarrhoea treatment from age 9 to 18 months resulted in positive effects of ~0.3 standard deviation on length-for-age z-score (LAZ) and of ~0.3 standard deviation on motor, language and personal-social development scores at age 18 months. In this paper, we examined whether the effect of the intervention on developmental scores was mediated by the effect on LAZ, or, alternatively, whether the intervention had independent effects on growth and development. For motor, language, and personal-social z-scores, the effect of the intervention decreased from 0.32 to 0.21, from 0.33 to 0.27 and from 0.35 to 0.29, respectively, when controlling for change in LAZ from 9 to 18 months. All effects remained significant. These results indicate that the intervention had independent positive effects on linear growth and development, suggesting that these effects occurred through different mechanisms. © 2016 John Wiley & Sons Ltd.

Impact of small quantity lipid-based nutrient supplements on infant and young child feeding practices at 18 months of age: results from four randomized controlled trials in Africa.

Optimal infant and young child feeding (IYCF) practices can help ensure nutrient adequacy and support healthy growth and development. Small-quantity lipid-based nutrient supplements (SQ-LNS) have been proposed to help fill nutrient gaps, but little is known about the impact of provision of SQ-LNS on breastfeeding or complementary feeding practices. In the context of four coordinated randomized controlled nutrient supplementation trials in diverse sites in Africa, we compared IYCF practices at infant age 18 months (after 9-12 months of supplementation) between those receiving and not receiving SQ-LNS. Practices were assessed by caregiver recall. Continued breastfeeding ranged from 74% (Ghana site) to 97% (Burkina Faso site) and did not differ between groups in any site; prevalence of frequent breastfeeding also did not differ. In two sites (Burkina Faso and Malawi), infants receiving SQ-LNS were more likely to meet the World Health Organization recommendations for frequency of feeding (percentage point differences of 12-14%, P < 0.0001 and P = 0.005, respectively; the remaining two sites did not have data for this indicator). Most indicators of infant dietary diversity did not differ between groups in any site, but in the same two sites where frequency of feeding differed, infants receiving SQ-LNS were less likely to have low frequency of consumption of animal-source foods in the previous week (percentage point differences of 9-19% for lowest tertile, P = .02 and P = 0.04, respectively). We conclude that provision of SQ-LNS did not negatively impact self-reported IYCF practices and may have positively impacted frequency of feeding.