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.

The cost-effectiveness of small-quantity lipid-based nutrient supplements for prevention of child death and malnutrition and promotion of healthy development: modelling results for Uganda.

OBJECTIVE: Recent meta-analyses demonstrate that small-quantity lipid-based nutrient supplements (SQ-LNS) for young children significantly reduce child mortality, stunting, wasting, anaemia and adverse developmental outcomes. Cost considerations should inform policy decisions. We developed a modelling framework to estimate the cost and cost-effectiveness of SQ-LNS and applied the framework in the context of rural Uganda. DESIGN: We adapted costs from a costing study of micronutrient powder (MNP) in Uganda, and based effectiveness estimates on recent meta-analyses and Uganda-specific estimates of baseline mortality and the prevalence of stunting, wasting, anaemia and developmental disability. SETTING: Rural Uganda. PARTICIPANTS: Not applicable. RESULTS: Providing SQ-LNS daily to all children in rural Uganda (> 1 million) for 12 months (from 6 to 18 months of age) via the existing Village Health Team system would cost ∼$52 per child (2020 US dollars) or ∼$58·7 million annually. SQ-LNS could avert an average of > 242 000 disability-adjusted life years (DALYs) annually as a result of preventing 3689 deaths, > 160 000 cases of moderate or severe anaemia and ∼6000 cases of developmental disability. The estimated cost per DALY averted is $242. CONCLUSIONS: In this context, SQ-LNS may be more cost-effective than other options such as MNP or the provision of complementary food, although the total cost for a programme including all age-eligible children would be high. Strategies to reduce costs, such as targeting to the most vulnerable populations and the elimination of taxes on SQ-LNS, may enhance financial feasibility.

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.

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.

Development of a plasma zinc concentration cutoff to identify individuals with severe zinc deficiency based on results from adults undergoing experimental severe dietary zinc restriction and individuals with acrodermatitis enteropathica.

Plasma zinc concentration (PZC) is a recommended biomarker to assess zinc status and the risk of zinc deficiency in populations. However, the relation between PZC and clinical signs of zinc deficiency remains uncertain. These analyses were conducted to evaluate the relation between PZC and clinical signs of zinc deficiency and to determine a cutoff for PZC below which individuals would have an increased likelihood of having clinical signs associated with zinc deficiency. Electronic bibliographic searches were conducted of literature indexed in PubMed, Embase, CINAHL Plus, and EBSCO and related to experimental zinc depletion studies in adults and case reports in children and adults (ages <1 mo-43 y) with acrodermatitis enteropathica (AE). Data extracted included demographic characteristics, PZCs, and the presence or absence of clinical signs likely associated with zinc deficiency (e.g., dermatitis, diarrhea). Mean PZC was significantly lower among adults consuming severely zinc-restricted diets (<1 mg Zn/d) who developed clinical signs compared with those who remained asymptomatic (36.0 ± 16.8 vs. 67.9 ± 13.3 µg/dL, P < 0.034). Likewise, patients with AE had a lower mean PZC when symptomatic compared with post-treatment PZC when they were asymptomatic (38.2 ± 20.7 vs. 102 ± 34.7 µg/dL, P < 0.01). Among individuals with restricted dietary zinc intake, PZC predicted clinical signs with 82% sensitivity and 92% specificity when using a cutoff of 50 µg/dL. Among individuals with AE, PZC predicted clinical signs with 80% sensitivity and 89% specificity when applying a cutoff of 50 µg/dL. These analyses demonstrate a clear relation between PZC and the presence of clinical signs associated with zinc deficiency among presumably healthy individuals undergoing periods of dietary zinc restriction, as well as in individuals with AE, further validating the usefulness of PZC as a biomarker of severe zinc deficiency.

Asymptomatic malaria infection affects the interpretation of biomarkers of iron and vitamin A status, even after adjusting for systemic inflammation, but does not affect plasma zinc concentrations among young children in Burkina Faso.

BACKGROUND: Biomarkers of iron [plasma ferritin (pF)], vitamin A [retinol binding protein (RBP)], and zinc status [plasma zinc (pZn)] are affected by the acute phase response, independent of micronutrient status. OBJECTIVE: The objective of these analyses was to assess how asymptomatic malaria infection affects the interpretation of these biomarkers after adjustment for elevated acute phase proteins (APPs). METHODS: Soluble transferrin receptor (sTfR), pF, RBP, and pZn concentrations were measured among 451 asymptomatic children aged 6-23 mo in Burkina Faso and adjusted for elevated APP (C-reactive protein ≥5 mg/L and/or α-1-acid-glycoprotein ≥1 g/L) based on a 4-group categorical model. Plasma histidine-rich protein II (HRP2) concentrations ≥0.75 µg/L were considered indicative of current or recent malaria parasitemia. RESULTS: Of the children in the study, 57.4% had at least 1 elevated APP, and 48.5% had elevated HRP2. After adjusting for APP, children with elevated HRP2 had higher pF (23.5 ± 1.5 µg/L vs. 11.1 ± 0.8 µg/L; P < 0.001) and lower RBP (0.79 ± 0.01 µmol/L vs. 0.92 ± 0.01 µmol/L; P < 0.001) than those without, but there were no differences in pZn among those with and without elevated HRP2 (64.9 ± 12.7 µg/dL vs. 64.9 ± 11.1 µg/dL; P = 0.98). Children with elevated HRP2 had higher sTfR than those without (17.6 ± 0.5 mg/L vs. 12.3 ± 0.4 mg/L; P < 0.0001). After adjusting for HRP2, along with APP, the estimated prevalence of iron deficiency (pF < 12 µg/L) increased from 38.7% to 50.6% and vitamin A deficiency (RBP < 0.84 µmol/L) decreased from 33.4% to 27.7%. CONCLUSIONS: Asymptomatic malaria is associated with indicators of micronutrient status, even after adjusting for APP. Adjusting indicators of iron and vitamin A status based only on APP may inaccurately estimate the prevalence of micronutrient deficiencies in settings with a high prevalence of malaria and inflammation. This trial was registered at clinicaltrials.gov as NCT00944853.

Mandatory large-scale food fortification programmes can reduce the estimated prevalence of inadequate zinc intake by up to 50% globally.

Large-scale food fortification (LSFF) can increase dietary micronutrient intake and improve micronutrient status. Here we used food balance sheet data from the Food and Agriculture Organization of the United Nations to estimate current country-specific prevalences of inadequate zinc intake. We assessed the potential effects of improving existing LSFF programmes for cereal grains or implementing new programmes in 40 countries where zinc deficiency is a potential public health problem. Accounting for LSFF programmes as currently implemented, 15% of the global population (1.13 billion individuals) is estimated to have inadequate zinc intake. In countries where zinc deficiency is a potential public health problem, the implementation of high-quality mandatory LSFF programmes that include zinc as a fortificant would substantially increase the availability of zinc in the national food supply, reducing the estimated prevalence of inadequate zinc intake by up to 50% globally. Investments in strong LSFF programmes could have a substantial impact on population zinc status.

Consumption of Discretionary Salt and Salt from Bouillon among Households, Women, and Young Children in Northern Region, Ghana: A Mixed-Methods Study with the Condiment Micronutrient Innovation Trial (CoMIT) Project.

Background: Information on salt consumption patterns is needed to inform the need for and design of salt reduction strategies. Objectives: In northern Ghana, this study aimed to estimate household consumption of salt, including salt from bouillon, and compare (estimated) women and children's salt intake to global recommendations; to estimate the proportion of salt consumed from bouillon; and to identify factors, including knowledge, attitudes, and practices, associated with household salt consumption. Methods: Employing mixed-methods methodology, we conducted a pilot survey (n = 369 households enrolled) and focus group discussions (FGDs; n = 20) in Tolon and Kumbungu districts (14 urban, 14 rural clusters) (clinicaltrials.gov registry: NCT04632771). Households reported purchases of discretionary salt (DS, "table salt") and bouillon cubes. DS and total salt (TS; DS+salt from bouillon) consumption for women (15-49 y) and children (2-5 y) were estimated using the Adult Male Equivalent method and compared with global recommendations (<5 g/d women; <3.75 g/d children). Women's salt intake was also predicted from urinary sodium excretion (INTERSALT equation). Associations between DS and TS consumption, as well as household and women's characteristics, were tested with minimally adjusted and multivariable linear mixed-effects models. Qualitative FGD themes were generated using the Framework Method. Results: From household purchase data, estimated TS consumption exceeded global recommendations for 44% of children [median: 2.9 (IQR: 1.9, 5.2) g/d] and 60% of women [6.0 (4.0, 10.2) g/d]; 35% of children and 50% of women exceeded recommendations from DS alone. Bouillon contributed <25% of households' TS consumption. Few characteristics were associated with DS or TS consumption. Salient qualitative themes that shaped salt consumption behaviors included salt's ubiquity as a seasoning, key household members' influence on food procurement and preparation, and perceptions about health. Conclusions: Purchase data suggest salt consumption among women and children exceeds recommendations, even when excluding salt from bouillon; food prepared outside the home likely further contributes. Salt reduction interventions may be warranted in this context.

Acceptability of Multiple Micronutrient-Fortified Bouillon Cubes among Women and Their Households in 2 Districts in The Northern Region of Ghana.

Background: Bouillon is a promising large-scale food fortification vehicle, but there is uncertainty regarding the types and concentrations of micronutrients that are feasible to add without compromising consumer acceptability. Objective: The objective of this study was to evaluate the acceptability of 2 different multiple micronutrient-fortified bouillon cube formulations, compared with a bouillon cube fortified with iodine only. Methods: We conducted a double-blind, randomized, controlled acceptability study in 2 districts in northern Ghana. Two nonproprietary, noncommercialized formulations of multiple micronutrient-fortified bouillon cubes containing iron, zinc, folic acid, vitamins A and B12, and iodine at "upper-level" (45-125% CODEX NRV/2.5g) or "lower-level" (15-50% CODEX NRV/2.5g) concentrations, and a control cube that contained iodine only (50% CODEX NRV/2.5g) were evaluated. Eligible women (n = 84) were invited to participate in 1) center-based sensory evaluations designed to permit within-individual comparisons among the different study products; and 2) in-home evaluation of bouillon acceptability and use, in which participants were randomized to receive 1 of the 3 study products to use in household cooking for a 2-wk period. Acceptance test ratings were based on a 5-point Likert scale (1 = dislike very much, 5 = like very much). Results: In the center-based evaluations, overall liking of the 3 bouillon cube formulations both dry and in prepared dishes ranged from 4.3 to 4.6 on the 5-point Likert scale and did not differ among formulations (P > 0.05). After the 2-wk in-home trial, 93.8% of index participants (n = 75/80) rated their overall liking of the bouillon product formulation to which they were randomly assigned as "like" or "like very much" (4-5 on the 5-point Likert scale) and median apparent intake of study-provided bouillon over 2 wk was 3.6 g/capita/d; neither value differed by study group (P = 0.91 for both). Conclusions: All 3 formulations of bouillon cubes assessed were acceptable to women and their households in 2 districts in northern Ghana.This trial was registered at www.clinicaltrials.gov as NCT05177614.

Effect of multiple micronutrient-fortified bouillon on micronutrient status among women and children in the Northern Region of Ghana: Protocol for the Condiment Micronutrient Innovation Trial (CoMIT), a community-based randomized controlled trial.

INTRODUCTION: Micronutrient deficiencies are prevalent in West Africa, particularly among women of reproductive age (WRA) and young children. Bouillon is a promising food fortification vehicle due to its widespread consumption. This study aims to evaluate the impact of multiple micronutrient-fortified bouillon cubes, compared to control bouillon cubes (fortified with iodine only), on micronutrient status and hemoglobin concentrations among lactating and non-lactating WRA and young children in northern Ghana. METHODS: This randomized, controlled doubly-masked trial will be conducted in the Kumbungu and Tolon districts in the Northern Region of Ghana, where prior data indicate multiple micronutrient deficiencies are common. Participants will be: 1) non-pregnant non-lactating WRA (15-49 y), 2) children 2-5 y, and 3) non-pregnant lactating women 4-18 months postpartum. Eligible participants will be randomly assigned to receive household rations of one of two types of bouillon cubes: 1) a multiple micronutrient-fortified bouillon cube containing vitamin A, folic acid, vitamin B12, iron, zinc, and iodine, or 2) a control cube containing iodine only. Each participant's household will receive a ration of bouillon cubes every 2 weeks, and households will be advised to prepare meals as usual, using the study-provided cubes. The trial duration will be 9 months for non-pregnant non-lactating WRA and children, and 3 months for lactating women. The primary outcomes will be changes in biomarkers of micronutrient status and hemoglobin among WRA and children and milk micronutrient concentrations among lactating women. Secondary outcomes will include change in prevalence of micronutrient deficiency and anemia; dietary intake of bouillon and micronutrients; inflammation, malaria, and morbidity symptoms; and child growth and development. DISCUSSION: Evidence from this study will inform discussions about bouillon fortification in Ghana and West Africa. TRIAL REGISTRATION: The trial was registered on ClinicalTrials.gov (NCT05178407) and the Pan-African Clinical Trial Registry (PACTR202206868437931). This manuscript reflects protocol version 4 (August 29, 2022).

Associations between intestinal mucosal function and changes in plasma zinc concentration following zinc supplementation.

OBJECTIVES: Subclinical environmental enteropathy is associated with malabsorption of fats, carbohydrates, and vitamins A, B12, and folate; however, little information is available on mineral absorption. We therefore investigated the relation between intestinal mucosal function (measured by the lactulose:mannitol permeability test and plasma citrulline concentration), and zinc (Zn) absorption, as estimated by the change in plasma Zn concentration (PZC) following short-term Zn or placebo supplementation. METHODS: We conducted a randomized, partially masked, placebo-controlled trial among 282 apparently healthy children 6 to 23 months of age in Burkina Faso. After completing baseline intestinal function tests, participants received either 5 mg Zn, as zinc sulfate, or placebo, daily for 21 days. RESULTS: At baseline, mean ± standard deviation PZC was 62.9 ± 11.9 µg/dL; median (interquartile range) urinary lactulose:mannitol (L:M) recovery ratio and plasma citrulline concentrations were 0.04 (0.03-0.07) and 11.4 (9.0-15.6) µmol/L, respectively. Change in PZC was significantly greater in the Zn-supplemented versus placebo group (15.6 ± 13.3 vs 0.02 ± 10.9 µg/dL; P < 0.0001), and was negatively associated with initial urinary L:M recovery ratio (-1.1 µg/dL per 50% increase in urinary L:M recovery ratio; P = 0.014); this latter relation did not differ between supplementation groups (P = 0.26). Baseline plasma citrulline concentration was not associated with change in PZC. CONCLUSIONS: Although altered intestinal permeability may reduce dietary Zn absorption, it likely does not undermine the efficacy of Zn supplementation, given the large increases in PZC following short-term Zn supplementation observed in this study, even among those with increased urinary L:M recovery ratios.

Lipid-based nutrient supplements for prevention of child undernutrition: when less may be more.

BACKGROUND: Both small-quantity and medium-quantity lipid-based nutrient supplements (LNS) have been used for the prevention of child undernutrition. A meta-analysis of 14 trials of small-quantity lipid-based nutrient supplements (SQ-LNS) - no LNS showed effects on length-for-age z-score {LAZ, +0.14 [95% confidence interval (CI): 0.11, 0.16]} and weight-for-length z-score [WLZ, +0.08 (0.06, 0.10)] z-scores, as well as prevalence ratios (95% CI) for stunting [LAZ < -2, 0.88 (0.85, 0.91)] and wasting [WLZ < -2, 0.86 (0.80, 0.93)]. However, little is known about the effects of medium-quantity lipid-based nutrient supplements (MQ-LNS) on growth. OBJECTIVES: We aimed to examine the effects of preventive MQ-LNS (∼250-499 kcal/d) provided at ∼6-23 mo of age on growth outcomes - no LNS or provision of SQ-LNS. METHODS: We conducted a systematic review of studies of MQ-LNS for prevention, and categorized them as providing <6 mo - ≥6 mo of supplementation; for the latter category, we conducted a meta-analysis, with the main outcomes being change in WLZ and LAZ, and prevalence of wasting and stunting. RESULTS: Three studies provided MQ-LNS for 3-5 mo (seasonal) for children 6-36 mo of age, and did not show consistent effects on growth outcomes. Eight studies provided MQ-LNS for 6-18 mo, generally starting at 6 mo of age; in the meta-analysis (max total n = 13,954), MQ-LNS increased WLZ [+0.09 (95% CI: 0.05, 0.13)] and reduced wasting [0.89 (0.81, 0.97)], but had no effect on LAZ [+0.04 (-0.02, 0.11)] or stunting [0.97 (0.92, 1.02)] - no LNS. Two studies directly compared SQ-LNS and MQ-LNS and showed no significant differences in growth outcomes. CONCLUSIONS: The current evidence suggests that MQ-LNS offer no added benefits over SQ-LNS, although further studies directly comparing MQ-LNS with SQ-LNS would be useful. One possible explanation is incomplete consumption of the MQ-LNS ration and thus lower than desirable intake of certain nutrients. TRIAL REGISTRATION NUMBER: Registry and registry number for systematic reviews or meta-analyses: Registered with PROSPERO as CRD42022382448 on December 18, 2022: =https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382448.

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.