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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 childrens 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 (

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 participants 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).

BackgroundSmall-quantity lipid-based nutrient supplements (SQ-LNS) during pregnancy and postnatally were previously shown to improve high-density lipoprotein (HDL) cholesterol efflux capacity (CEC) and length in the children of supplemented mothers at 18 mo of age in the International Lipid-Based Nutrient Supplements (iLiNS) DYAD trial in Ghana. However, the effects of SQ-LNS on maternal HDL functionality during pregnancy are unknown.ObjectiveThe goal of this cross-sectional, secondary outcome analysis was to compare HDL function in mothers supplemented with SQ-LNS vs. iron and folic acid (IFA) during gestation.MethodsHDL CEC and the activities of 3 HDL-associated enzymes were analyzed in archived plasma samples (N = 197) from a subsample of females at 36 weeks of gestation enrolled in the iLiNS-DYAD trial in Ghana. Correlations between HDL function and birth outcomes, inflammatory markers C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP), and the effects of season were explored to determine the influence of these factors on HDL function in this cohort of pregnant females.ResultsThere were no statistically significant differences in HDL CEC, plasma lecithin-cholesterol acyltransferase (LCAT) activity, cholesteryl ester transfer protein (CETP) activity, or phospholipid transfer protein (PLTP) activity between mothers supplemented with SQ-LNS compared with IFA control, and no statistically significant relationships between maternal HDL function and childbirth outcomes. LCAT activity was negatively correlated with plasma AGP (R = -0.19, P = 0.007) and CRP (R = -0.28, P < 0.001), CETP and LCAT activity were higher during the dry season compared to the wet season, and PLTP activity was higher in the wet season compared to the dry season.ConclusionsMothers in Ghana supplemented with SQ-LNS compared with IFA during gestation did not have measurable differences in HDL functionality, and maternal HDL function was not associated with childbirth outcomes. However, seasonal factors and markers of inflammation were associated with HDL function, indicating that these factors had a stronger influence on HDL functionality than SQ-LNS supplementation during pregnancy.Clinical trial registry numberThe study was registered as NCT00970866. https://clinicaltrials.gov/study/NCT00970866.

BACKGROUND: Provision of small-quantity lipid-based nutrient supplements (SQ-LNSs) during early life improves growth and development. In the International Lipid-Based Nutrient Supplements DYAD-Ghana trial, prenatal and postnatal SQ-LNS reduced social-emotional difficulties at age 5 y, with greater effects among children in less-enriched home environments. OBJECTIVES: We aimed to investigate the effect of prenatal and postnatal SQ-LNS on childrens social-emotional problems at age 9-11 y. METHODS: In 2009-2011, 1320 pregnant women ≤20 wk gestation were randomly assigned to receive the following daily until 6 mo postpartum: 1) iron and folic acid until delivery, then placebo, 2) multiple micronutrients (MMNs), or 3) SQ-LNS (20 g/d). Children in group 3 received SQ-LNS from 6 to 18 mo. In 2021, we evaluated childrens social-emotional outcomes with 6 assessment tools that used caregiver, teacher, and/or self-report to measure socioemotional difficulties, conduct problems, temperament, mood, anxiety, and emotion management. RESULTS: We assessed outcomes in 966 children, comprising 79.4% of 1217 participants eligible for re-enrolment. No significant differences were found between the SQ-LNS and control (non-LNS groups combined) groups. Few children (

Little is known about the impact of small-quantity lipid-based nutrient supplements (SQ-LNSs) on maternal morbidity. This secondary outcome analysis aimed to compare morbidity symptoms among women in two trials evaluating the efficacy of SQ-LNSs. From enrolment (≤20-week gestation) to 6 months postpartum, Ghanaian (n = 1320) and Malawian (n = 1391) women were assigned to consume daily: 60 mg iron and 400 µg folic acid until childbirth and placebo thereafter (iron and folic acid [IFA] group); or multiple micronutrients (MMN); or 20 g/day SQ-LNSs. Within country, we used repeated measures logistic regression and analysis of variance models to compare group differences in the period prevalence and percentage of days of monitoring when women had fever, gastrointestinal, reproductive, and respiratory symptoms during the second and third trimesters of pregnancy (n ~ 1243 in Ghana, 1200 in Malawi) and 0-3 and 3-6 months postpartum (n ~ 1212 in Ghana, 730 in Malawi). Most outcomes did not differ significantly among groups, with the following exceptions: in Ghana, overall, the prevalence of vomiting was lower in the LNS (21.5%) than MMN (25.6%) group, with the IFA group (23.2%) in-between (p = 0.046); mean ± SD percentage of days with nausea was greater in the LNS (3.5 ± 10.3) and MMN (3.3 ± 10.4) groups than the IFA (2.7 ± 8.3) group (p = 0.002). In Malawi, during 3-6 month postpartum, the prevalence of severe diarrhoea was greater in the LNS (8.1%) than the MMN (2.9%) group, with IFA (4.6%) in-between, p = 0.041). We conclude that the type of nutrient supplement received during pregnancy and lactation generally does not influence morbidity symptoms in these settings. Clinicaltrials.gov identifiers: NCT00970866; NCT01239693.

BackgroundMeta-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.ObjectivesWe 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).MethodsWe 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.ResultsSQ-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.ConclusionsIncluding 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.

ObjectivesTo investigate several basic psychometric properties, including construct, convergent and discriminant validity, of the tablet-based Rapid Assessment of Cognitive and Emotional Regulation (RACER) among children aged 4-6 years in Ghana.MethodsWe investigated whether RACER tasks administered to children in Ghana could successfully reproduce expected patterns of performance previously found in high-income countries on similar tasks assessing inhibitory control (e.g., slower responses on inhibition trials), declarative memory (e.g., higher accuracy on previously seen items), and procedural memory (e.g., faster responses on sequence blocks). Next, we assessed the validity of declarative memory and inhibitory control scores by examining associations of these scores with corresponding paper-based test scores and increasing child age. Lastly, we examined whether RACER was more sensitive than paper-based tests to environmental risk factors common in low- and middle-income countries (LMICs).ResultsOf the 966 children enrolled, more than 96% completed the declarative memory and inhibitory control tasks; however, around 30% of children were excluded from data analysis on the procedural memory task due to missing more than half of trials. The performance of children in Ghana replicated previously documented patterns of performance. RACER inhibitory control accuracy score was significantly correlated with child age (r (929) = .09, p = .007). However, our findings did not support other hypotheses.ConclusionsThe high task completion rates and replication of expected patterns support that certain RACER sub-tasks are feasible for measuring child cognitive development in LMIC settings. However, this study did not provide evidence to support that RACER is a valid tool to capture meaningful individual differences among children aged 4-6 years in Ghana.

BackgroundPrevious studies show an association between maternal plasma and salivary cortisol and preterm birth but have been primarily conducted in high-income countries. It is unknown whether salivary cortisol is a risk factor for preterm birth in Ghana. Our objective was to determine whether maternal salivary cortisol during pregnancy was associated with pregnancy duration and preterm delivery in Ghana.MethodsWe conducted a cohort study of 783 pregnant women in Ghana. We measured salivary cortisol at baseline (mean 16 wk), 28 wk., and 36 wk. gestation. Pregnancy duration was determined primarily by ultrasound. We used adjusted linear regression models to examine the association between cortisol and pregnancy duration and Poisson regression models to determine the risk of preterm delivery among women with high cortisol at baseline or 28 wk. gestation.ResultsMean pregnancy duration was 39.4 ± 1.8 wk. and 6.6% had a preterm delivery. Mean maternal cortisol increased throughout pregnancy, from 4.9 ± 2.7 nmol/L at baseline (16 wk) to 6.4 ± 3.2 nmol/L at 28 wk. and 7.9 ± 3.0 nmol/L at 36 wk. gestation. In adjusted analyses, higher cortisol concentrations at baseline (β = - 0.39, p = .002) and 28 wk. (β = - 0.49, p = .001), but not 36 wk. (β = - 0.23, p = .084) were associated with a shorter pregnancy duration. Women with high cortisol at baseline (> 6.3 nmol/L) had an increased relative risk of preterm delivery (RR (95% CI): 1.96 (1.13, 3.40)), but the association between high cortisol at 28 wk. and preterm delivery was not significant. There was a significant interaction with fetal sex (p-for-interaction = 0.037): among women carrying male fetuses, high cortisol at baseline increased the risk of preterm delivery threefold (3.18 (1.51, 6.71)) while there was no association (1.17 (0.50, 2.74)) among women carrying female fetuses.ConclusionHigher maternal cortisol is associated with a shorter pregnancy duration and an increased risk of preterm delivery. Subgroup analysis by fetal sex revealed that this association is evident primarily among women carrying male fetuses. Future studies of cortisol and preterm delivery should include consideration of fetal sex as a potential effect modifier.

Prenatal plus postnatal small-quantity lipid-based nutrient supplements (SQ-LNS) improved child growth at 18 months in the International Lipid-Based Nutrient Supplements DYAD trial in Ghana. In this secondary outcome analysis, we determined whether SQ-LNS versus prenatal iron and folic acid (IFA) supplementation improves the cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) particles and alters their lipidomic, proteomic, or glycoproteomic composition in a subset of 80 children at 18 months of age. HDL CEC was higher among children in the SQ-LNS versus IFA group (20.9 ± 4.1 vs 19.4 ± 3.3%; one-tailed p = 0.038). There were no differences in HDL lipidomic or proteomic composition between groups. Twelve glycopeptides out of the 163 analyzed were significantly altered by SQ-LNS, but none of the group differences remained significant after correction for multiple testing. Exploratory analysis showed that 6 out of the 33 HDL-associated proteins monitored differed in glycopeptide enrichment between intervention groups, and 6 out of the 163 glycopeptides were correlated with CEC. We conclude that prenatal plus postnatal SQ-LNS may modify HDL protein glycoprofiles and improve the CEC of HDL particles in children, which may have implications for subsequent child health outcomes. This trial was registered at clinicaltrials.gov as NCT00970866.

BackgroundMeta-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.ObjectivesWe aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes.MethodsWe 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.ResultsSQ-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) (

BackgroundSmall-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development.ObjectivesWe 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.MethodsWe 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).ResultsIn 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).ConclusionsChild 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.

BackgroundSmall-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.ObjectivesWe 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.MethodsWe 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.ResultsSQ-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 mo and provided 9 (as opposed to

ObjectivesInadequate iodine intake during pregnancy increases the risk of neonatal morbidity and mortality. We aimed to evaluate whether prenatal supplements containing iodine affect urinary iodine concentrations (UIC) of pregnant women in Malawi.DesignA randomised controlled trial. Pregnant women (n 1391) were assigned to consume 60 mg/d Fe and 400 µg/d folic acid (IFA) or 18 vitamins and minerals including 250 µg/d iodine (MMN) or 20 g/d small-quantity lipid-based nutrient supplements (SQ-LNS) with similar nutrient contents as MMN group, plus macronutrients (LNS) until childbirth. In a sub-study (n 317), we evaluated group geometric mean urinary iodine concentration (UIC) (µg/L) at 36 weeks of gestation controlling for baseline UIC and compared median (baseline) and geometric mean (36 weeks) UIC with WHO cut-offs: UIC < 150, 150-249, 250-499 and ≥500 reflecting insufficient, adequate, above requirements and excessive iodine intakes, respectively.SettingMangochi District, Malawi.ParticipantsWomen ≤20 weeks pregnant.ResultsGroups had comparable background characteristics. At baseline, overall median (Q1, Q3) UIC (319 (167, 559)) suggested iodine intakes above requirements. At 36 weeks, the geometric mean (95 % CI) UIC of the IFA (197 (171, 226)), MMN (212 (185, 243)) and LNS (220 (192, 253)) groups did not differ (P = 0·53) and reflected adequate intakes.ConclusionsIn this setting, provision of supplements containing iodine at the recommended dose to pregnant women with relatively high iodine intakes at baseline, presumably from iodised salt, has no impact on the women's UIC. Regular monitoring of the iodine status of pregnant women in such settings is advisable. Clinicaltrials.gov identifier: NCT01239693.

BackgroundIt is unknown whether prenatal lipid-based nutrient supplements (LNSs) affect blood pressure (BP). Associations between hypertension and birth outcomes using recently updated BP cutoffs are undetermined.ObjectivesWe aimed to assess the impact of LNSs on maternal hypertension and associations between hypertension and birth outcomes.MethodsPregnant Ghanaian women at ≤20 weeks of gestation (n = 1320) were randomly assigned to receive daily 1) iron and folic acid (IFA), 2) multiple micronutrients (MMN), or 3) LNSs until delivery. BP was measured at enrollment and 36 weeks of gestation. We analyzed the effect of LNSs on BP using ANOVA and associations between hypertension [systolic BP (SBP) ≥130 mm Hg or diastolic BP (DBP) ≥80 mm Hg] and birth outcomes by linear and logistic regressions.ResultsMean ± SD SBP and DBP were 110 ± 11 and 63 ± 8 mm Hg at 36 weeks of gestation and did not differ by supplementation group (SBP, P > 0.05; DBP, P > 0.05). At enrollment, higher DBP was associated with lower birth weight and shorter gestation; women with high DBP had greater risk of low birth weight (LBW) [risk ratio (RR): 2.58; 95% CI: 1.09, 6.08] and preterm birth (PTB) (RR: 3.30; 95% CI: 1.47, 7.40). At 36 weeks of gestation, higher SBP was associated with lower birth weight, length, and head circumference and shorter gestation; higher DBP was associated with lower birth weight and length; and women with high DBP had greater risk of LBW (RR: 3.39; 95% CI: 1.32, 8.69). Neither high SBP nor hypertension were associated with birth outcomes at either time point.ConclusionsDaily provision of LNSs does not affect maternal hypertension, compared with IFA and MMN. Higher SBP and DBP are associated with a shorter gestation and smaller birth size; however, only high DBP is associated with LBW and PTB. The new BP cutoffs may help identify pregnancies at risk of adverse birth outcomes.This trial was registered at clinicaltrials.gov as NCT00970866.

Malaria and iron deficiency (ID) are common and interrelated public health problems in African children. Observational data suggest that interrupting malaria transmission reduces the prevalence of ID1. To test the hypothesis that malaria might cause ID, we used sickle cell trait (HbAS, rs334 ), a genetic variant that confers specific protection against malaria2, as an instrumental variable in Mendelian randomization analyses. HbAS was associated with a 30% reduction in ID among children living in malaria-endemic countries in Africa (n = 7,453), but not among individuals living in malaria-free areas (n = 3,818). Genetically predicted malaria risk was associated with an odds ratio of 2.65 for ID per unit increase in the log incidence rate of malaria. This suggests that an intervention that halves the risk of malaria episodes would reduce the prevalence of ID in African children by 49%.

ABSTRACT Background Meta-analyses have demonstrated that small-quantity lipid-based nutrient supplements (SQ-LNS) reduce stunting and wasting prevalence among infants and young children. Identification of subgroups who benefit most from SQ-LNS may facilitate program design. Objective Our objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child growth outcomes. Methods We conducted a two-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n=37,066). We generated study-specific and subgroup estimates of SQ-LNS vs. control and pooled the estimates using fixed-effects models, with random-effects models as sensitivity analyses. We used random effects meta-regression to examine study-level effect modifiers. Heterogeneity was assessed using I 2 and Tau 2 statistics. Sensitivity analyses were conducted to examine whether results differed depending on inclusion criteria for arms within trials 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 mid-upper arm circumference (MUAC < 125 mm or MUACZ < −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 z-score < −2) by 9%. Effects of SQ-LNS on growth outcomes 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 reported compliance with SQ-LNS. Effects of SQ-LNS 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 (vs. first-born) children; and effects on wasting and acute malnutrition were greater among children in households with improved (vs. unimproved) sanitation. Results were similar across sensitivity analyses. Conclusions The positive impact of SQ-LNS on growth is apparent across a wide variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNS in the mix of interventions to prevent both stunting and wasting. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

ABSTRACT Background Small-quantity lipid-based nutrient supplements (SQ-LNS) have been shown to reduce the prevalence of anemia and iron deficiency among infants and young children, but effects on other micronutrients are less well known. Identifying subgroups who may experience greater benefits from SQ-LNS, or who are more likely to respond to the intervention, may facilitate the development of public health policies and programs. Objective Our objective was to identify study-level and individual-level modifiers of the effect of SQ-LNS on child hematological and micronutrient status outcomes. Methods We conducted a two-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNS provided to children 6 to 24 months of age in low- and middle-income countries (n = 15,946). Outcomes were hemoglobin (Hb), inflammation-adjusted plasma ferritin, soluble transferrin receptor, zinc, retinol and retinol binding protein (RBP), and erythrocyte zinc protoporphyrin, and respective dichotomous outcomes indicative of anemia and micronutrient deficiency. We generated study-specific estimates of SQ-LNS vs. control, including main effects and subgroup estimates for individual-level effect modifiers, and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers. Results Provision of SQ-LNS 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-LNS on hematological and iron status outcomes within all subgroups of the study-level and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNS on anemia and iron status were greater in trials that provided SQ-LNS for > 12 months and provided 9 mg/d vs. < 9 mg iron/d, and among later-born (vs. first-born) children. There was no effect of SQ-LNS on plasma zinc or retinol, but there was a 7% increase in plasma 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-LNS provided to infants and young children 6-24 months of age can substantially reduce the prevalence of anemia, iron deficiency, and IDA across a range of individual, population and study design characteristics. Policy-makers and program planners should consider SQ-LNS within intervention packages to prevent anemia and iron deficiency. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663.

Background Small-quantity lipid-based nutrient supplements (SQ-LNS) reduce child stunting and provide many of the fatty acids and micronutrients that are necessary for rapid brain development that occurs during infancy and early childhood. Positive effects of SQ-LNS on developmental outcomes have been found in some trials, but not others. Objectives Our objectives were to generate pooled estimates of the effect of SQ-LNS, compared to control groups that received no intervention or an intervention without any nutritional supplement, 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 two-stage meta-analysis of individual participant data from 14 intervention versus control group comparisons in 13 randomized trials of SQ-LNS provided to infants and young children age 6 to 24 months in 9 low- or middle-income countries (total n=30,024). We generated study-specific estimates of SQ-LNS vs. control groups (including main effects and subgroup estimates for individual-level effect modifiers) and pooled the estimates using fixed-effects models. We used random effects meta-regression to examine potential study-level effect modifiers. Results In 11-13 intervention versus control group comparisons (n=23,588-24,561), SQ-LNS increased mean language (mean difference: 0.07 standard deviations; 95% CI: 0.04, 0.10), social-emotional (0.08; 0.05, 0.11), and motor scores (0.08; 0.05, 0.11) and reduced the prevalence of children in the lowest decile of these scores by 17% (prevalence ratio: 0.83, 95% CI 0.76, 0.91), 19% (0.81; 0.74, 0.90), and 16% (0.84; 0.77, 0.92), respectively. SQ-LNS also increased the prevalence of children walking without support at 12 months by 9% (1.09; 1.05, 1.14). Effects of SQ-LNS on language, social-emotional, and motor outcomes were larger among study populations with a higher burden (≥ 35%) of child stunting at 18 months (mean difference 0.11-0.13 SD; 8-9 comparisons) than in populations with lower stunting burden (estimates near zero). At the individual level, greater effects of SQ-LNS 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 socio-economic 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 SQ-LNS provided daily to children in the range of 6-24 months of age can be expected to result in modest, but potentially important, developmental gains, particularly in populations with high child stunting burden. Certain groups of children who experience higher risk environments, such as those from poor households or with poor baseline nutritional status, have greater potential to benefit from SQ-LNS in developmental outcomes. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971.

Dysregulation of the stress response can occur early in life and may be affected by nutrition. Our objective was to evaluate the long-term effect of nutritional supplementation during gestation and early childhood on child cortisol and buccal telomere length (a marker of cellular aging) at 4-6 years of age. We conducted a follow-up study of children born to women who participated in a nutritional supplementation trial in Ghana. In one group, a lipid-based nutrient supplement (LNS) was provided to women during gestation and the first 6 months postpartum and to their infants from age 6 to 18 months. The control groups received either iron and folic acid (IFA) during gestation or multiple micronutrients during gestation and the first 6 months postpartum, with no infant supplementation. At age 4-6 years, we measured hair cortisol, buccal telomere length, and salivary cortisol before and after a stressor. Salivary cortisol was available for 364 children across all three trial arms and hair cortisol and telomere length were available for a subset of children (n = 275 and 278, respectively) from the LNS and IFA groups. Telomere length, salivary cortisol, and hair cortisol did not differ by supplementation group. Overall, these findings suggest that nutritional supplementation given during gestation and early childhood does not have an effect on child stress response or chronic stress in children at 4-6 years. Trial registration: ClinicalTrials.gov Identifier NCT00970866.Lay SummaryThis study addressed a research gap about whether improved nutrition during pregnancy and early childhood impacts telomere length and cortisol in preschool children. There was no difference in child telomere length or cortisol between two trial arms of a nutritional supplementation trial that began during pregnancy. The research outcomes indicate lipid-based nutrient supplements, a relatively new form of supplementation, do not have an effect on markers of stress or cellular aging measured in later childhood.

Prenatal micronutrient deficiencies are associated with negative maternal and birth outcomes. Multiple micronutrient supplementation (MMS) during pregnancy is a cost-effective intervention to reduce these adverse outcomes. However, important knowledge gaps remain in the implementation of MMS interventions. The Child Health and Nutrition Research Initiative (CHNRI) methodology was applied to inform the direction of research and investments needed to support the implementation of MMS interventions for pregnant women in low- and middle-income countries (LMIC). Following CHNRI methodology guidelines, a group of international experts in nutrition and maternal health provided and ranked the research questions that most urgently need to be resolved for prenatal MMS interventions to be successfully implemented. Seventy-three research questions were received, analyzed, and reorganized, resulting in 35 consolidated research questions. These were scored against four criteria, yielding a priority ranking where the top 10 research options focused on strategies to increase antenatal care attendance and MMS adherence, methods needed to identify populations more likely to benefit from MMS interventions and some discovery issues (e.g., potential benefit of extending MMS through lactation). This exercise prioritized 35 discrete research questions that merit serious consideration for the potential of MMS during pregnancy to be optimized in LMIC.

Pregnancy and breastfeeding make demands on maternal nutrient stores. The extent of depletion and the degree to which nutrient stores are replenished between pregnancies has implications for a mother's nutritional status at conception of the subsequent child and therefore that child's birth outcomes and growth. Using follow-up data collected several years after a randomized effectiveness trial conducted in rural Bangladesh and a randomized efficacy trial conducted in semiurban Ghana, we evaluated the impact of maternal supplementation with small-quantity lipid-based nutrient supplements (LNS) or multiple micronutrients (MMN) through pregnancy (the index pregnancy) and 6 months postpartum on the growth status of the next living younger sibling conceived and born after the index pregnancy. In both Bangladesh (n = 472 younger siblings) and Ghana (n = 327 younger siblings), there were no overall differences in the growth status or the prevalence of undernutrition among younger siblings whose mothers had received LNS (or MMN, Ghana only) during and after the index pregnancy compared with the younger siblings of mothers who had received iron plus folic acid (IFA) during the index pregnancy (Ghana) or during and for 3 months after the index pregnancy (Bangladesh). These findings do not indicate that preconception nutrition interventions do not improve child growth. Rather, they suggest that any benefits of maternal LNS or MMN supplementation during one pregnancy and for 6 months postpartum are unlikely to extend to the growth of her next child beyond any effects due to IFA alone.

ObjectiveWe aimed to identify factors (child diet, physical activity; maternal BMI) associated with body composition of Ghanaian pre-school children.DesignLongitudinal analysis of the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD-Ghana randomized trial, which enrolled 1320 pregnant women at ≤20 weeks' gestation and followed them and their infants until 6 and 18 months postpartum, respectively. At follow-up, child age 4-6 years, we collected data on body composition (by 2H dilution), physical activity and diet, extracted dietary patterns using factor analysis, and examined the association of children's percentage body fat with maternal and child factors by regression analysis.SettingEastern Region, Ghana.ParticipantsChildren 4-6 years of age.ResultsThe analysis included 889 children with percentage body fat and dietary data at follow-up. We identified two major dietary patterns, a snacking and a cooked foods pattern. Percentage body fat was positively associated (standardized β (se)) with maternal BMI at follow-up (0·10 (0·03); P = 0·003) and negatively associated with physical activity (-0·15 (0·05); P = 0·003, unadjusted for child gender), but not associated with the snacking (0·06 (0·03); P = 0·103) or cooked foods (-0·05 (0·07); P = 0·474) pattern. Boys were more active than girls (1470 v. 1314 mean vector magnitude counts/min; P < 0·0001) and had lower percentage body fat (13·8 v. 16·9 %; P < 0·0001).ConclusionsIn this population, maternal overweight and child physical activity, especially among girls, may be key factors for addressing child overweight/obesity. We did not demonstrate a relationship between the dietary patterns and body fatness, which may be related to limitations of the dietary data available.

BackgroundAdequate knowledge about the safety of consumption of small-quantity lipid-based nutrient supplements (SQ-LNSs) is needed.ObjectiveWe aimed to test the hypothesis that SQ-LNS consumption is noninferior to control with respect to child morbidity.MethodsWomen (n = 1320) ≤20 wk pregnant were assigned to iron and folic acid until delivery with no supplementation for offspring; or multiple micronutrient supplements until 6 mo postpartum with no supplementation for offspring; or SQ-LNSs until 6 mo postpartum, and SQ-LNSs for offspring (6 mg Fe/d) from 6 to 18 mo of age [the lipid-based nutrient supplement (LNS) group]. We assessed noninferiority (margin ≤20%) between any 2 groups during 0-6 mo of age, and between the non-LNS and LNS groups during 6-18 mo of age for caregiver-reported acute respiratory infection, diarrhea, gastroenteritis, fever/suspected malaria, poor appetite, and "other illnesses."ResultsDuring 0-6 mo of age, 1197 infants contributed 190,503 infant-days. For all morbidity combined, overall mean incidence (per 100 infant-days) was 3.3 episodes, overall mean prevalence (percentage of infant-days) was 19.3%, and the 95% CIs of the incidence rate ratio (IRR) and longitudinal prevalence rate ratio (LPRR) between any 2 groups were ≤1.20. During 6-18 mo, there were 240,097 infant-days for the non-LNS group and 118,698 for the LNS group. For all morbidity combined, group mean incidences were 4.3 and 4.3, respectively (IRR: 1.0; 95% CI: 1.0, 1.1), and mean prevalences were 28.2% and 29.3%, respectively (LPRR: 1.0; 95% CI: 1.0, 1.1). Noninferiority was inconclusive for diarrhea, fever/suspected malaria, and poor appetite.ConclusionsSQ-LNS consumption does not increase reported overall child morbidity in this population compared with the 2 other treatments.This trial was registered at clinicaltrials.gov as NCT00970866.

Evidence on whether nutritional supplementation affects physical activity (PA) during early childhood is limited. We examined the long-term effects of lipid-based nutrient supplements (LNS) on total PA, moderate-to-vigorous PA (MVPA) and sedentary behaviour (SB) of children at 4-6 years using an accelerometer for 1 week. Their mothers were enrolled in the International Lipid-based Nutrient Supplement-DYAD randomised controlled trial in Ghana, assigned to daily LNS or multiple micronutrients (MMN) during pregnancy through 6 months postpartum or Fe and folic acid (IFA) during pregnancy and placebo for 6 months postpartum. From 6 to 18 months, children in the LNS group received LNS; the other two groups received no supplements. Analysis was done with intention to treat comparing two groups: LNS v. non-LNS (MMN+ IFA). Of the sub-sample of 375 children fitted with accelerometers, 353 provided sufficient data. Median vector magnitude (VM) count was 1374 (interquartile range (IQR) 309), and percentages of time in MVPA and SB were 4·8 (IQR 2) and 31 (IQR 8) %, respectively. The LNS group (n 129) had lower VM (difference in mean -73 (95 % CI -20, -126), P = 0·007) and spent more time in SB (LNS v. non-LNS: 32·3 v. 30·5 %, P = 0·020) than the non-LNS group (n 224) but did not differ in MVPA (4·4 v. 4·7 %, P = 0·198). Contrary to expectations, provision of LNS in early life slightly reduced the total PA and increased the time in SB but did not affect time in MVPA. Given reduced social-emotional difficulties in the LNS group previously reported, including hyperactivity, one possible explanation is less restless movement in the LNS group.

It is important to identify the periods during childhood when exposure to environmental risk factors results in long-term neurodevelopmental deficits. Stunting and anaemia may be sensitive indicators of exposure to such risks. In a prospective cohort enrolled before birth, we investigated the association of developmental scores at 4-6 years with (a) birth length and linear growth during three postnatal periods and (2) haemoglobin (Hb) concentration at three time points. Children were participants in a follow-up study of a randomized controlled trial of nutritional supplementation in Ghana. At 4-6 years, cognitive, motor, and social-emotional developments were assessed using standard tests adapted for this population. We estimated the associations of length-for-age z-score (LAZ) at birth and postnatal linear growth (n = 710) and Hb (n = 617) with developmental scores in regression models, using multistage least squares analysis to calculate uncorrelated residuals for postnatal growth. Cognitive development at 4-6 years was significantly associated with LAZ at birth (β = 0.12, 95% CI = 0.05, 0.19), ΔLAZ from 6 to 18 months (β = 0.16, 95% CI = 0.04, 0.28), and Hb at 18 months (β = 0.13, 95% CI = 0.06, 0.20), but not with ΔLAZ during 0-6 months, ΔLAZ from 18 months to 4-6 years, Hb at 6 months, or Hb at 4-6 years. No evidence of associations with motor or social-emotional development were found. These results suggest that in similar contexts, the earlier periods prior to birth and up to 18 months are more sensitive to risk factors for long-term cognitive development associated with LAZ and Hb compared with later childhood. This may inform the optimal timing of interventions targeting improved cognitive development.

Inadequate micronutrient intakes are relatively common in low- and middle-income countries (LMICs), especially among pregnant women, who have increased micronutrient requirements. This can lead to an increase in adverse pregnancy and birth outcomes. This review presents the conclusions of a task force that set out to assess the prevalence of inadequate micronutrient intakes and adverse birth outcomes in LMICs; the data from trials comparing multiple micronutrient supplements (MMS) that contain iron and folic acid (IFA) with IFA supplements alone; the risks of reaching the upper intake levels with MMS; and the cost-effectiveness of MMS compared with IFA. Recent meta-analyses demonstrate that MMS can reduce the risks of preterm birth, low birth weight, and small for gestational age in comparison with IFA alone. An individual-participant data meta-analysis also revealed even greater benefits for anemic and underweight women and female infants. Importantly, there was no increased risk of harm for the pregnant women or their infants with MMS. These data suggest that countries with inadequate micronutrient intakes should consider supplementing pregnant women with MMS as a cost-effective method to reduce the risk of adverse birth outcomes.

BackgroundFew studies have evaluated the long-term effects of nutritional supplementation during the first 1000 d of life. We previously reported that maternal and child lipid-based nutrient supplements (LNS) increased child length by 18 mo.ObjectiveThe aim of this study was to examine the effects of LNS on later growth and body composition at 4-6 y of age.DesignThis was a follow-up of children in the International Lipid-based Nutrient Supplements (iLiNS)-DYAD trial in Ghana. Women (n = 1320) at ≤20 weeks of gestation were randomly assigned to: 1) iron and folic acid during pregnancy and 200 mg calcium/d for 6 mo postpartum, 2) multiple micronutrients (1-2 RDA of 18 vitamins and minerals) during both periods, or 3) maternal LNS during both periods plus child LNS from 6 to 18 mo. At 4-6 y, we compared height, height-for-age z score (HAZ), and % body fat (deuterium dilution method) between the LNS group and the 2 non-LNS groups combined.ResultsData were available for 961 children (76.5% of live births). There were no significant differences between LNS compared with non-LNS groups in height [106.7 compared with 106.3 cm (mean difference, MD, 0.36; P = 0.226)], HAZ [-0.49 compared with -0.57 (MD = 0.08; P = 0.226)], stunting (< -2 SD) [6.5 compared with 6.3% (OR = 1.00; P = 0.993)], or % body fat [15.5 compared with 15.3% (MD = 0.16; P = 0.630)]. However, there was an interaction with maternal prepregnancy BMI (kg/m2) (P-interaction = 0.046 before correction for multiple testing): among children of women with BMI

BackgroundThe impact of feeding a slightly sweet nutrient supplement early in life on later sweet taste preference is unknown.ObjectiveWe tested the hypothesis that the level of sucrose most preferred by 4-6-y-old children exposed to a slightly sweet lipid-based nutrient supplement (LNS) early in life would not be higher than that of children never exposed to LNS.DesignWe followed up children born to women (n = 1,320) who participated in a randomized trial in Ghana. In one group, LNS was provided to women on a daily basis during pregnancy and the first 6 mo postpartum and to their infants from age 6 to 18 mo (LNS group). The control groups received daily iron and folic acid or multiple micronutrients during pregnancy and the first 6 mo postpartum, with no infant supplementation (non-LNS group). At age 4-6 y, we randomly selected a subsample of children (n = 775) to assess the concentration of sucrose most preferred using the Monell 2-series, forced-choice, paired-comparison tracking procedure. We compared LNS with non-LNS group differences using a noninferiority margin of 5% weight/volume (wt/vol).ResultsOf the 624 children tested, most (61%) provided reliable responses. Among all children, the mean ± SD sucrose solution most preferred (% wt/vol) was 14.6 ± 8.6 (LNS group 14.9 ± 8.7; non-LNS group 14.2 ± 8.4). However, among children with reliable responses, it was 17.0 ± 10.2 (LNS group 17.5 ± 10.4; non-LNS group 16.5 ± 10.0). The upper level of the 95% CI of the difference between groups did not exceed the noninferiority margin in either the full sample or those with reliable responses, indicating that the LNS group did not have a higher sweet preference than the non-LNS group.ConclusionExposure to a slightly sweet nutrient supplement early in life did not increase the level of sweet taste most preferred during childhood. This trial was registered at clinicaltrials.gov as NCT00970866.

BackgroundPrevious literature suggests a U-shaped relation between hemoglobin concentration and adverse birth outcomes. There is less evidence on associations between iron status and birth outcomes.ObjectiveOur objective was to determine the associations of maternal hemoglobin concentration and iron status with birth outcomes.MethodsWe conducted a secondary data analysis of data from 2 cohorts of pregnant women receiving iron-containing nutritional supplements (20-60 mg ferrous sulfate) in Ghana (n = 1137) and Malawi (n = 1243). Hemoglobin concentration and 2 markers of iron status [zinc protoporphyrin and soluble transferrin receptor (sTfR)] were measured at ≤20 weeks and 36 weeks of gestation. We used linear and Poisson regression models and birth outcomes included preterm birth (PTB), newborn stunting, low birth weight (LBW), and small-for-gestational-age.ResultsPrevalence of iron deficiency (sTfR >6.0 mg/L) at enrollment was 9% in Ghana and 20% in Malawi. In early pregnancy, iron deficiency was associated with PTB (9% compared with 17%, adjusted RR: 1.63; 95% CI: 1.14, 2.33) and stunting (15% compared with 23%, adjusted RR: 1.44; 95% CI: 1.09, 1.94) in Malawi but not Ghana, and was not associated with LBW in either country; replete iron status (sTfR

BackgroundWhether consuming sweet foods early in life affects sweet food preferences and consumption later in childhood is unknown.ObjectiveWe tested the hypothesis that exposure to a slightly sweet lipid-based nutrient supplement (LNS) early in life would not increase preference for or consumption of sweet items at preschool age.MethodsWe followed up children who had participated in a randomized trial in Ghana in which LNS was provided to 1 group of women during pregnancy and 6 mo postpartum and to their infants from ages 6-18 mo (LNS group). The control group (non-LNS group) received iron and folic acid during pregnancy or multiple micronutrients during pregnancy and 6 mo postpartum, with no infant supplementation. At 4-6 y, we obtained data from caregivers on children's food and beverage preferences and consumption (n = 985). For a randomly selected subsample (n = 624), we assessed preference for sweet items using a photo game (range in potential scores, 0-15). For the photo game and reported consumption of sweet items, we examined group differences using predetermined noninferiority margins equivalent to an effect size of 0.2.ResultsMedian (quartile 1, quartile 3) reported consumption of sweet items (times in previous week) was 14 (8, 23) in the LNS group and 16 (9, 22) in the non-LNS group; in the photo game, the number of sweet items selected was 15 (11, 15) and 15 (11, 15), respectively. The upper level of the 95% CI of the mean difference between LNS and non-LNS groups did not exceed the noninferiority margins for these outcomes. Caregiver-reported preferences for sweet items also did not differ between groups (P = 0.9).ConclusionIn this setting, where child consumption of sweet foods was common, exposure to a slightly sweet LNS early in life did not increase preference for or consumption of sweet foods and beverages at preschool age. This trial was registered at clinicaltrials.gov as NCT00970866.

BackgroundIn the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD-Ghana trial, prenatal small-quantity lipid-based nutrient supplements (LNSs) had a positive effect on birth weight. Birth weight may be inversely related to blood pressure (BP) later in life.ObjectivesWe examined the effect of the intervention on BP at 4-6 y of age, and maternal and child factors related to BP.MethodsThe iLiNS-DYAD-Ghana study was a partially double-blind, randomized controlled trial which assigned women (n = 1320) ≤20 weeks of gestation to daily supplementation with: 1) iron and folic acid during pregnancy and 200 mg Ca for 6 mo postpartum , 2) multiple micronutrients during pregnancy and postpartum, or 3) LNSs during pregnancy and postpartum plus LNSs for infants from 6 to 18 mo of age. At 4-6 y of age (n = 858, 70% of live births), we compared BP, a secondary outcome, between non-LNS and LNS groups and examined whether BP was related to several factors including maternal BP, child weight-for-age z score (WAZ), and physical activity.ResultsNon-LNS and LNS groups did not differ in systolic (99.2 ± 0.4 compared with 98.5 ± 0.6 mm Hg; P = 0.317) or diastolic (60.1 ± 0.3 compared with 60.0 ± 0.4 mm Hg; P = 0.805) BP, or prevalence of high BP (systolic or diastolic BP ≥90th percentile of the US National Heart, Lung, and Blood Institute reference: 31% compared with 28%; P = 0.251). BP at 4-6 y of age was positively related to birth weight; this relation was largely mediated through concurrent WAZ in a path model. Concurrent WAZ and maternal BP were the factors most strongly related to child BP.ConclusionsDespite greater birth weight in the LNS group, there was no intervention group difference in BP at 4-6 y. In this preschool population at high risk of adult hypertension based on BP at 4-6 y, high maternal BP and child WAZ were key factors related to BP. This trial was registered at clinicaltrials.gov as NCT00970866.

BackgroundAdequate nutrition is necessary for brain development during pregnancy and infancy. Few randomized controlled trials of supplementation during these periods have measured later developmental outcomes.ObjectiveOur objective was to investigate the effects of provision of prenatal and postnatal lipid-based nutrient supplements (LNS) on child development at preschool age.MethodsWe conducted a follow-up study of 966 children aged 4-6 y in 2016, born to women who participated in the International Lipid-Based Nutrient Supplements-DYAD trial conducted in Ghana in 2009-2014, representing 79% of eligible children. Women ≤20 weeks of gestation were randomized to daily LNS or multiple micronutrient (MMN) capsules during pregnancy through 6 mo postpartum or iron and folic acid (IFA) capsules during pregnancy and calcium placebo capsules during 6 mo postpartum. Children in the LNS group received LNS from 6 to 18 mo. Primary outcomes of this follow-up study were (1) a cognitive factor score based on a test battery adapted from several standard tests, 2) fine motor score (9-hole pegboard test), and (3) social-emotional difficulties (Strengths and Difficulties Questionnaire; SDQ). Eight secondary outcomes were calculated in specific domains (e.g., language, SDQ prosocial). Analysis was by a complete case intention to treat in a 2-group comparison: LNS compared with non-LNS (MMN + IFA).ResultsChildren in the LNS group had significantly lower social-emotional difficulties z-scores than children in the non-LNS group (adjusted for child age β = -0.12, 95% CI: -0.25, 0.02, P = 0.087; fully adjusted β = -0.16, 95% CI: -0.29, -0.03, P = 0.013). The effect of LNS on social-emotional difficulties score was larger among children living in households with lower home environment scores (P-interaction = 0.081). No other outcomes differed between the 2 intervention groups.ConclusionsProvision of LNS during the first 1000 d of development improved behavioral function, particularly for children from low nurturing and stimulation households, but did not affect cognition at preschool age in this setting. Trial Registration: clinicaltrials.gov, Identifier NCT00970866.

Stunting prevalence is an indicator of a country's progress towards United Nations' Sustainable Development Goal 2, which is to end hunger and achieve improved nutrition. Accelerating progress towards reducing stunting requires a deeper understanding of the factors that contribute to linear growth faltering. We conducted path analyses of factors associated with 18-month length-for-age z-score (LAZ) in four prospective cohorts of children who participated in trials conducted as part of the International Lipid-Based Nutrient Supplements Project in Ghana (n=1039), Malawi (n=684 and 1504) and Burkina Faso (n=2619). In two cohorts, women were enrolled during pregnancy. In two other cohorts, infants were enrolled at 6 or 9 months. We examined the association of 42 indicators of environmental, maternal, caregiving and child factors with 18-month LAZ. Using structural equation modelling, we examined direct and indirect associations through hypothesised mediators in each cohort. Out of 42 indicators, 2 were associated with 18-month LAZ in three or four cohorts: maternal height and body mass index (BMI). Six factors were associated with 18-month LAZ in two cohorts: length for gestational age z-score (LGAZ) at birth, pregnancy duration, improved household water, child dietary diversity, diarrhoea incidence and 6-month or 9-month haemoglobin concentration. Direct associations were more prevalent than indirect associations, but 30%-62% of the associations of maternal height and BMI with 18-month LAZ were mediated by LGAZ at birth. Factors that were not associated with LAZ were maternal iron status, illness and inflammation during pregnancy, maternal stress and depression, exclusive breast feeding during 6 months post partum, feeding frequency and child fever, malaria and acute respiratory infections. These findings may help in identifying interventions to accelerate progress towards reducing stunting; however, much of the variance in linear growth status remained unaccounted for by these 42 individual-level factors, suggesting that community-level changes may be needed to achieve substantial progress.

BackgroundInterventions are needed to address iron deficiency in low-income settings.ObjectiveThis secondary outcome analysis aimed to compare the hemoglobin (Hb) and iron status [zinc protoporphyrin (ZPP)] of children born to women enrolled in the iLiNS-DYAD trial in Ghana.MethodsWomen ≤20 wk pregnant (n = 1320) were assigned to receive 60 mg Fe/d and 400 µg folic acid/d until delivery and placebo thereafter, and no supplementation for infants (IFA group); or multiple micronutrients containing 20 mg Fe/d until 6 mo postpartum and no supplementation for infants (MMN); or small-quantity lipid-based nutrient supplements (SQ-LNSs) containing 20 mg Fe/d until 6 mo postpartum, and SQ-LNSs for infants from 6 to 18 mo of age (LNS). We compared infants' Hb (g/L) and ZPP (µmol/mol heme) at 6 and 18 mo of age.ResultsAt 6 mo of age, groups did not differ in mean ± SD Hb (overall: 113 ± 9.9 g/L) or geometric mean (95% CI) ZPP [overall: 62.6 (60.6, 64.7)]. At 18 mo of age, mean ± SD Hb (overall: 112 ± 10.4 g/L) did not differ significantly between groups, whereas geometric mean (95% CI) ZPP was lower (P = 0.031) in the LNS group [53.9 (50.7, 57.3)] than the IFA [60.4 (56.7, 64.3)] but not the MMN [58.8 (55.6, 62.2)] group. Further, the LNS group, compared with the IFA and MMN groups combined, had a lower prevalence of elevated (>70) ZPP (27.5% compared with 35%; P = 0.02) and a marginally lower prevalence of anemia (38.7% compared with 44.9%; P = 0.06). These results generally remained unchanged when controlling for prespecified covariates or correcting for inflammation.ConclusionsIn this setting, providing SQ-LNSs or multiple micronutrients with 20 mg Fe/d, compared with iron (60 mg/d) and folic acid, to pregnant women does not affect their infants' Hb or iron status at 6 mo of age, but maternal and infant supplementation with SQ-LNSs increases infants' iron status at 18 mo of age. This trial was registered at clinicaltrials.gov as NCT00970866.

A child's endowment is a reflection of his/her genetic makeup and the conditions faced in early life. Parents build on their child's endowment by investing resources in their child, and together, a child's endowment and subsequent investments act as input into important later-life outcomes. A positive or negative shock to a child's endowment can have a direct biological effect on a child's long-term outcomes but may also affect parents' decisions about investments in the health and human capital of their children. Using follow-up data collected several years after a randomized trial in Ghana, we explored whether maternal and child supplementation with small-quantity lipid-based nutrient supplements (SQ-LNS) throughout much of the first 1,000 days influenced parental investments in the health and human capital of their children. Across the domains of family planning, breastfeeding, health, education, and paternal financial support, we found that, in general, the intervention did not affect investments in the treated child nor his/her untreated siblings. These results suggest that given production technologies, constraints, and preferences, the intervention either did not change parents' optimal investment strategies or that the effects of the intervention, namely increased birth size and attained length at 18 months of age, were too small for parents to perceive or to have any meaningful impact on parents' expectations about the returns to investments in their children.

Small-quantity lipid-based nutrient supplements (SQ-LNS) have been studied in efficacy and effectiveness trials, but little is known about how parents perceive the products and their effects. In a randomised trial in Ghana, efficacy of SQ-LNS provided to women during pregnancy and the first 6 months postpartum and to their children from 6 to 18 months of age was assessed by comparison with iron-folic acid (IFA) capsules and multiple micronutrient (MMN) capsules provided to women. In a follow-up study conducted when the index children from the original trial were between 4 and 6 years of age, we used survey-based methods to assess retrospective and current parental perceptions of nutrient supplements generally and of SQ-LNS and their effects compared with perceptions IFA and MMN capsules. Most parents perceived that the assigned supplements (SQ-LNS, IFA, or MMN) positively impacted the mother during pregnancy (approximately 89% of both mothers and fathers) and during lactation (84% of mothers and 86% of fathers). Almost all (≥90%) of mothers and fathers perceived that the assigned supplement positively impacted the index child and expected continued positive impacts on the child's health and human capital into the future. A smaller percentage of parents perceived negative impacts of the supplements (7%-17% of mothers and 4%-12% of fathers). Perceptions of positive impacts and of negative impacts did not differ by intervention group. The results suggest that similar populations would likely be receptive to programs to deliver SQ-LNS or micronutrient capsules.

In Ghana, breastfeeding and complementary feeding counselling have been used as a nutritional intervention to promote optimal Infant and Young Child Feeding (IYCF) and nutrition. This study examined IYCF practices in four geographically and ethnically diverse districts (Ho West, Tain, Talensi and Tolon). A qualitative study involving key informant interviews (KIIs) and focus group discussions (FGDs) was conducted between November and December 2019 among women who participated in a pilot micronutrient powder intervention for children 6–23 months of age. The KIIs and FGDs were audio-taped, transcribed verbatim, and analyzed thematically using NVivo 10. Three themes emerging from the KIIs and FGDs were: level of adherence to IYCF recommendations among mothers and caregivers; IYCF recommendations perceived as the hardest to follow; and perceived motivators, facilitators, and barriers to IYCF practices. Mothers in the four districts generally followed the eight IYCF recommendations. Mothers in the Tolon district demonstrated adherence to IYCF practices, often citing the need for early initiation of breastfeeding, timely introduction of complementary feeding, and feeding children aged 9–23 months 3 times daily in addition to breastfeeding. In contrast, mothers in other districts faced challenges that hindered adherence. Giving children 4 or more food groups and timely introduction of complementary feeding were perceived as the hardest practices to follow. The main facilitators of IYCF practices include midwives and frontline nurses teaching mothers how to breastfeed, and midwives ensuring mothers initiate breastfeeding immediately after delivery. The main barriers to IYCF practices identified were insufficient breastmilk; mothers-in-law giving water to children before six months; resumption of work; and lack of financial means. Mothers in the Ho West district reported more barriers to IYCF practices, followed by mothers in the Tain, Talensi, and Tolon districts. Health practitioners, stakeholders, and policymakers should design targeted interventions that address the contextual barriers to improve IYCF practices in the various districts. [ABSTRACT FROM AUTHOR]

It is common for health and nutrition interventions to target specific household members and for evaluations of their effects to focus exclusively on those members. However, if a targeted intervention changes a household's utility maximization problem or influences decision-making, households might respond to the intervention in unintended ways with the potential to affect the wellbeing of non-targeted members. Using panel data from a randomized controlled nutrition trial in Ghana, we evaluate household behavioral responses to the provision of small-quantity lipid-based nutrient supplements (SQ-LNS) to mothers and their infants to prevent undernutrition. We find that targeted supplementation with SQ-LNS had a positive effect on household expenditures on food, including some nutrient-rich food groups, as well as on non-food goods and services. We also find a positive impact on labor income, particularly among fathers. We then explore intrahousehold spillover effects on the nutritional status of non-targeted young children in the household. We find evidence that the targeted provision of SQ-LNS led to higher height-for-age z-scores among non-targeted children in the LNS group compared to the non-LNS group, though only among those with relatively taller mothers, which is an indicator of a child's growth potential. These findings support existing evidence and suggest that unintended behavioral responses and spillover are a real possibility in the context of nutrition interventions targeting nutritionally-vulnerable household members. Thoughtfully considering this possibility in the design, analyses, and evaluation of targeted nutrition interventions may provide a more complete picture of overall effects.

BackgroundSince the adoption of United Nations' Sustainable Goal 4.2 to ensure that all children have access to quality early child development (ECD) so that they are ready for primary education, the demand for valid ECD assessments has increased in contexts where they do not yet exist. The development of early language ability is important for school readiness. Our objective was to evaluate the validity of a method to develop vocabulary checklists in new languages to assess early language development, based on the MacArthur-Bates Communicative Development Inventories.MethodsThrough asking mothers of young children what words their children say and through pilot testing, we developed 100-word vocabulary checklists in multilingual contexts in Malawi and Ghana. In Malawi, we evaluated the validity of the vocabulary checklist among 29 children age 17-25 months compared to three language measures assessed concurrently: Developmental Milestones Checklist-II (DMC-II) language scale, Malawi Developmental Assessment Tool (MDAT) language scale, and the number of different words (NDW) in 30-min recordings of spontaneous speech. In Ghana, we assessed the predictive validity of the vocabulary checklist at age 18 months to forecast language, pre-academic, and other skills at age 4-6 years among 869 children. We also compared the predictive validity of the vocabulary checklist scores to that of other developmental assessments administered at age 18 months.ResultsIn Malawi, the Spearman's correlation of the vocabulary checklist score with DMC-II language was 0.46 (p = 0.049), with MDAT language was 0.66 (p = 0.016) and with NDW was 0.50 (p = 0.033). In Ghana, the 18-month vocabulary checklist score showed the strongest (rho = 0.12-0.26) and most consistent (8/12) associations with preschool scores, compared to the other 18-month assessments. The largest coefficients were the correlations of the 18-month vocabulary score with the preschool cognitive factor score (rho = 0.26), language score (0.25), and pre-academic score (0.24).ConclusionsWe have demonstrated the validity of a method to develop vocabulary checklists in new languages, which can be used in multilingual contexts, using a feasible adaptation process requiring about 2 weeks. This is a promising method to assess early language development, which is associated with later preschool language, cognitive, and pre-academic skills.

Small-quantity lipid-based nutrient supplements (SQ-LNS) are designed to enrich maternal and child diets with the objective of preventing undernutrition during the first 1,000 days. Scaling up the delivery of supplements such as SQ-LNS hinges on understanding private demand and creatively leveraging policy-relevant factors that might influence demand. We used longitudinal stated willingness-to-pay (WTP) data from contingent valuation studies that were integrated into randomized controlled nutrition trials in Ghana and Malawi to estimate private valuation of SQ-LNS during pregnancy, postpartum, and early childhood. We found that average stated WTP for a day's supply of SQ-LNS was more than twice as high in Ghana than Malawi, indicating that demand for SQ-LNS (and by extension, the options for effective delivery of SQ-LNS) may be very context specific. We also examined factors associated with WTP, including intervention group, household socioeconomic status, birth outcomes, child growth, and maternal and child morbidity. In both sites, WTP was consistently negatively associated with household food insecurity, indicating that subsidization might be needed to permit food insecure households to acquire SQ-LNS if it is made available for purchase. In Ghana, WTP was higher among heads of household than among mothers, which may be related to control over household resources. Personal experience using SQ-LNS was not associated with WTP in either site.

There is little information on whether prenatal multiple micronutrient (MMN) supplements containing iodine affect women's iodine status. In the International Lipid-based Nutrient Supplements DYAD-Ghana trial, we aimed to assess women's urinary iodine concentration (UIC, μg/L) during pregnancy, as one of the planned secondary outcomes. Women (n = 1,320)

We examined the impact on depression at 6 months postpartum of maternal supplementation with small-quantity lipid-based nutrient supplement (SQ-LNS) compared to supplementation with iron and folic acid (IFA) or multiple micronutrients (MMN). In this partially double-blinded randomized controlled trial, pregnant women ≤20 weeks gestation (n = 1320) were recruited from antenatal clinics and randomly assigned to receive either (1) SQ-LNS during pregnancy and for 6 months postpartum, or (2) IFA during pregnancy only, or (3) MMN during pregnancy and for 6 months postpartum. Maternal depressive symptoms were measured at 6 months postpartum using the Edinburgh Postnatal Depression Scale (EPDS). Women who scored 12 or more on the EPDS were considered to show symptoms of depression. One thousand one hundred fifty-one women were included in this analysis (LNS = 382, IFA = 387 and MMN = 382). Characteristics of the three groups were similar at baseline, and there were no significant differences between women who were included in the analysis (n = 1151) and those who were not (n = 169). At 6 months postpartum, 13% of the women overall showed symptoms of depression, and this did not differ by group (LNS = 13.1%, IFA = 11.2% and MMN = 14.7%. P = 0.36). The median (25, 75 percentile) EPDS score did not differ by group (LNS 4.0 (1.0, 8.0), IFA 4.0 (1.0, 8.0), MMN 5.0 (2.0, 9.0), P transformed = 0.13). Adjustment for covariates did not alter these findings. Maternal supplementation with SQ-LNS compared to MMN or IFA did not affect postnatal depressive symptoms in this sample of Ghanaian women.