Search

Background: Undernutrition during pregnancy increases the risk of giving birth to a small vulnerable newborn. Small-quantity lipid-based nutrient supplements (SQ-LNS) contain both macro- and micronutrients and can help prevent multiple nutritional deficiencies., Objectives: We examined effects of SQ-LNS provided during pregnancy, compared to a) iron and folic acid or standard of care (IFA/SOC) or b) multiple micronutrient supplements (MMS), and identified characteristics that modified the estimates of effects of SQ-LNS on birth outcomes., Methods: We conducted a 2-stage meta-analysis of individual participant data from 4 randomized controlled trials of SQ-LNS provided during pregnancy (n = 5,273). We generated study-specific and subgroup estimates of SQ-LNS compared with IFA/SOC or MMS and pooled the estimates. In sensitivity analyses, we examined whether results differed depending on methods for gestational age dating, birth anthropometry, or study design., Results: SQ-LNS (vs IFA/SOC) increased birth weight (mean difference: +49g; 95% CI: 26, 71g) and all birth anthropometric z-scores (+0.10-0.13 SD); it reduced risk of low birthweight by 11%, newborn stunting by 17%, newborn wasting by 11%, and small head size by 15%. Only 2 trials compared SQ-LNS and MMS; p-values for birth outcomes were >0.10 except for head circumference (e.g., z-score for gestational age +0.11; 95% CI: -0.01, 0.23). Effect estimates for SQ-LNS vs IFA/SOC were greater among female infants and, for certain outcomes, among mothers with body mass index < 20 kg/m 2 , inflammation, malaria, or household food insecurity. Effect estimates for SQ-LNS vs MMS were greater for certain outcomes among female infants, first-born infants, and mothers < 25 y., Conclusions: SQ-LNS had positive impacts on multiple outcomes compared to IFA/SOC, but further research directly comparing SQ-LNS and MMS is needed. Targeting SQ-LNS to vulnerable subgroups may be worth considering. Analysis registered at www.crd.york.ac.uk/PROSPERO (CRD42021283391). REGISTRY AND REGISTRY NUMBER FOR SYSTEMATIC REVIEWS OR META-ANALYSES: Registered at www.crd.york.ac.uk/PROSPERO as CRD42021283391 on 11 April 2021., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: There is limited research on whether nutritional supplementation in the first 1000 d affects long-term child outcomes. We previously demonstrated that pre- and postnatal small-quantity lipid-based nutrient supplements (SQ-LNS) increased birth weight and child length at 18 mo of age in Ghana., Objectives: We aimed to investigate the effect of pre- and postnatal SQ-LNS on child growth and blood pressure at 9-11 y., Methods: In the International Lipid-Based Nutrient Supplements (iLiNS)-DYAD-Ghana trial, 1320 females ≤20 weeks of gestation were randomly assigned to receive daily: iron and folic acid (IFA) during pregnancy and placebo during 6 mo postpartum or multiple micronutrients (MMNs) during pregnancy and 6 mo postpartum, or SQ-LNS during pregnancy and 6 mo postpartum and for their children aged from 6 to 18 mo. We re-enrolled 966 children aged 9-11 y and assessed child blood pressure, height-for-age z-score (HAZ), body mass index (BMI)-for-age z-score, waist-to-height ratio, triceps skinfold, and midupper arm circumference. We compared SQ-LNS with control (IFA + MMN) groups adjusting for child's age., Results: Mean (standard deviation [SD]) HAZ in SQ-LNS and control group was -0.04 (0.96) and -0.16 (0.99); P = 0.060. There were no indications of group differences in the other outcomes (P > 0.10). Effects on HAZ varied by child sex (P-interaction = 0.075) and maternal prepregnancy BMI (kg/m 2 ; P-interaction = 0.007). Among females, HAZ was higher in the SQ-LNS [0.08 (1.04)] than in the control group [-0.16 (1.01)] (P = 0.010); among males, SQ-LNS [-0.16 (0.85)] and control groups [-0.16 (0.96)] did not differ (P = 0.974). Among children of females with BMI of <25, HAZ was higher in the SQ-LNS [-0.04 (1.00)] than in the control group [-0.29 (0.94)] (P = 0.004); among females with BMI of ≥25, SQ-LNS [-0.04 (0.91)] and control groups [0.07 (1.00)] did not differ (P = 0.281)., Conclusions: There is a sustained impact of prenatal and postnatal SQ-LNS on linear growth among female children and children whose mothers were not overweight. This trial was registered at clinicaltrials.gov as NCT00970866 (https://clinicaltrials.gov/ct2/show/record/NCT00970866)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

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&#95;record.php?ID=CRD42022382448., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Racial and ethnic disparities in infant-feeding practices may negatively influence diet quality and health., Objectives: This study investigated the racial, ethnic, and language (English or Spanish) differences in infant diet quality, later diet quality, and weight status at 2-5 y, and whether these differences were explained through infant diet quality among participants in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC)., Methods: Using the WIC Infant and Toddler Feeding Practices Study-2 (unweighted n = 2663; weighted n = 362,712), relationships between the Infant Dietary Quality Index (IDQI; range 0-1) and Healthy Eating Index-2020 (HEI-2020; range 0-100) and BMI z-score (BMIz) at 2-5 y were analyzed by race, ethnicity, and language preference [Hispanic Spanish-speaking, Hispanic English-speaking, non-Hispanic (NH) White, and NH Black participants]. Statistical interaction between IDQI and each group was evaluated in multivariable models. The mediation of each group through the IDQI was assessed using causal mediation methods., Results: Differences in IDQI [mean (standard deviation)] were observed between Hispanic Spanish-speaking participants [0.41 (0.10)], Hispanic English-speaking participants [0.37 (0.10)], NH White participants [0.36 (0.10)], and NH Black participants [0.35 (0.09)], P < 0.001. Differences in HEI-2020 occurred at 2-5 y, with the Hispanic Spanish-speaking participants having consistently higher HEI-2020 scores. Differences in BMIz were observed at 5 y, with higher scores among Hispanic Spanish-speaking participants. Interaction between race, ethnicity, and IDQI was observed for all outcomes except for BMIz at 3 y. Through mediation, IDQI explained 13%-20% of the difference in HEI-2020 scores between Hispanic Spanish-speaking and NH White participants at 2-5 y. IDQI explained 22%-25% of the difference in HEI-2020 scores between the Hispanic Spanish-speaking and NH Black participants at 4 y and 5 y., Conclusions: Higher infant diet quality scores observed in Hispanic Spanish-speaking participants explain some of the racial and ethnic differences observed in later diet quality, suggesting that improving infant diet quality may help reduce diet disparities during early childhood., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

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 children's 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 children's 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 (<2%) experienced high parent-reported social-emotional difficulties at 9-11 y, in contrast to the high prevalence at age 5 in this cohort (25%). Among children in less-enriched early childhood home environments, the SQ-LNS group had 0.37 SD (-0.04 to 0.82) lower self-reported conduct problems than the control group (P-interaction = 0.047)., Conclusions: Overall positive effects of SQ-LNS on social-emotional development previously found at age 5 y are not sustained to age 9-11 y; however, there is some evidence of positive effects among children in less-enriched environments. The lack of effects may be owing to low prevalence of social-emotional problems at preadolescence, resulting in little potential to benefit from early nutritional intervention at this age in this outcome domain. Follow-up during adolescence, when social-emotional problems more typically onset, may yield further insights. This trial was registered at clinicaltrials.gov as NCT00970866. https://clinicaltrials.gov/ct2/show/record/NCT00970866., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Healthy nutrition during the first year of life is critical for optimal growth and development. Limited techniques are available to assess diet quality in infancy, and few have been shown to be predictive of dietary and adiposity outcomes in low-income children., Objective: The objectives of this study were to construct an Infant Diet Quality Index (IDQI) to assess the diet quality from birth to 12 mo and to determine whether the IDQI exhibits predictive validity by estimating the longitudinal associations of IDQI scores with diet quality and weight status at 2 to 4 y., Design: Data were analyzed from the longitudinal Women, Infants, and Children Infant and Toddler Feeding Practices Study-2 (unweighted, n = 2858; weighted. N = 392,439) using one 24-h dietary recall and survey responses during infancy. The newly constructed IDQI consists of 16 equally-weighted components: 1) breastfeeding duration; 2) exclusive breastfeeding; age of first introduction of: 3) solids, 4) iron-rich cereals, 5) cow milk, 6) sugar-sweetened beverages, 7) salty/sweet snacks, 8) other drinks/liquids, and 9) textured foods; frequency of consuming 10) fruit or 11) vegetables; frequency of consuming different 12) fruit or 13) vegetables; 14) nonrecommended bottle-feeding practices; 15) use of commercial baby foods; and 16) number of meals and snacks. Regression analysis was used to estimate associations between the total IDQI score (range, 0-1) and Healthy Eating Index-2015 (HEI-2015) scores and body mass index z-scores (BMIz) at 2 to 4 y of age, adjusted for covariates (e.g., child age, sex and race/ethnicity; maternal education level, etc.) RESULTS: The total IDQI score was positively associated with HEI-2015 at the age of 2 y (β = 16.7; 95% CI: 12.6, 20.9; P < 0.001), 3 y (β = 14.5; 95% CI: 8.1, 21.0; P < 0.001), and 4 y (β = 15.4; 95% CI: 8.4, 22.4; P < 0.001); and negatively associated with BMIz at the age of 2 y (β = -1.24; 95% CI: -2.01, -0.47; P = 0.002) and 4 y (β = -0.92; 95% CI: -1.53, -0.30; P = 0.003)., Conclusions: The IDQI has predictive validity for diet quality and weight status in low-income US children., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: The National Cancer Institute (NCI) method has been used widely by researchers to make inferences about usual dietary intake distributions of foods and nutrients based on a limited number of 24-h dietary recalls (24-HRs). Although the NCI method does not provide individual estimates of usual intake, it can be used to address many research questions, including modeling effects of nutrition interventions on population distributions of usual intake. Software for implementing the NCI method, and corresponding code examples, is publicly available in the form of SAS macros but little formal guidance exists for conducting advanced analyses., Objectives: We aim to present advanced techniques for working with NCI macros to conduct both basic and advanced dietary analyses and modeling., Method: We first present the 3 basic building blocks of analyses using the NCI method: 1) data set preparation, 2) application of the MIXTRAN macro to estimate parameters of the usual intake distribution, including effects of covariates, after transformation of 24-HRs to approximate normality, and 3) application of the DISTRIB macro to estimate the distribution of usual nutrient intake. Then, we illustrate how researchers can employ these building blocks to answer questions beyond typical descriptive analyses., Results: Researchers can adapt the building blocks to: 1) account for factors such as demographic changes or nutrition interventions such as food fortification, 2) estimate the prevalence of dietary inadequacy via the full probability method, 3) incorporate nutrient intake from sources not always captured by 24-HRs, such as dietary supplements and human milk, and 4) carry out multiple subgroup analyses. This article describes the theoretical basis and operational guidance for these techniques., Conclusion: With this article as a detailed resource, researchers can leverage the basic NCI building blocks to investigate a wide range of questions about usual dietary intake distribution., (Copyright © 2022 American Society for Nutrition.)

Background: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child wasting and stunting. There is little information regarding effects on severe wasting or stunting., Objectives: We aimed to identify the effect of SQ-LNSs on prevalence of severe wasting (weight-for-length z score < -3) and severe stunting (length-for-age z score < -3)., Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age. We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons., Results: SQ-LNS provision led to a relative reduction of 31% in severe wasting [prevalence ratio (PR): 0.69; 95% CI: 0.55, 0.86; n = 34,373] and 17% in severe stunting (PR: 0.83; 95% CI: 0.78, 0.90; n = 36,795) at endline. Results were similar in most of the sensitivity analyses but somewhat attenuated when comparisons using passive control arms were excluded (PR: 0.74; 95% CI: 0.57, 0.96; n = 26,327 for severe wasting and PR: 0.88; 95% CI: 0.81, 0.95; n = 28,742 for severe stunting). Study-level characteristics generally did not significantly modify the effects of SQ-LNSs, but results suggested greater effects of SQ-LNSs in sites with greater burdens of wasting or stunting, or with poorer water quality or sanitation., Conclusions: Including SQ-LNSs in preventive interventions to promote healthy child growth and development is likely to reduce rates of severe wasting and stunting. This meta-analysis was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592., (Copyright © 2022 American Society for Nutrition.)

Introduction: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) may influence infants' plasma fatty acid (FA) profiles, which could be associated with short- and long-term outcomes., Objectives: We aimed to determine the impact of SQ-LNS consumption on infants' plasma FA profiles in Ghana and Malawi., Methods: Ghanaian (n = 1320) and Malawian (n = 1391) women ≤20 weeks pregnant were assigned to consume 60 mg iron and 400 μg folic acid daily until delivery [iron and folic acid (IFA) group], multiple-micronutrient supplements (MMNs) until 6 months postpartum (MMN group), or SQ-LNSs (∼7.8 linoleic acid:α-linolenic acid ratio) until 6 months postpartum (LNS group). LNS group infants received SQ-LNS from 6 to 18 months of age. We compared infant plasma FAs by intervention group in subsamples (n = 379 in Ghana; n = 442 in Malawi) at 6 and 18 months using ANOVA and Poisson regression models. Main outcomes were mean percentage compositions (%Cs; percentage of FAs by weight) of α-linolenic acid (ALA), linoleic acid (LA), EPA, DHA, and arachidonic acid (AA)., Results: At 6 months, LNS infants had greater mean ± SD ALA %Cs in Ghana (0.23 ± 0.08; IFA, 0.21 ± 0.06; MMN, 0.21 ± 0.07; P = 0.034) and Malawi (0.42 ± 0.16; IFA, 0.38 ± 0.15; MMN, 0.38 ± 0.14; P = 0.034) and greater AA values in Ghana (6.25 ± 1.24; IFA, 6.12 ± 1.13; MMN, 5.89 ± 1.24; P = 0.049). At 18 months, LNS infants had a tendency towards greater ALA (0.32 ± 0.16; IFA, 0.24 ± 0.08; MMN, 0.24 ± 0.10; P = 0.06) and LA (27.8 ± 3.6; IFA, 26.9 ± 2.9; MMN, 27.0 ± 3.1; P = 0.06) in Ghana, and greater ALA (0.45 ± 0.18; IFA, 0.39 ± 0.18; MMN, 0.39 ± 0.18; P < 0.001) and LA (29.7 ± 3.5; IFA, 28.7 ± 3.3; MMN, 28.6 ± 3.4; P = 0.011) in Malawi. The prevalence of ALA below the population-specific 10th percentile was lower in the LNS group compared to the MMN group, but not the IFA group. Groups did not differ significantly in plasma EPA or DHA levels., Conclusions: SQ-LNS increased infants' plasma essential FA levels in Ghana and Malawi, which may have implications for health and developmental outcomes. These trials were registered at clinicaltrials.gov as NCT00970866 and NCT01239693., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Small-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development., Objectives: We aimed to generate pooled estimates of the effect of SQ-LNSs on developmental outcomes (language, social-emotional, motor, and executive function), and to identify study-level and individual-level modifiers of these effects., Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 intervention against control group comparisons in 13 randomized trials of SQ-LNSs provided to children age 6-24 mo (total n = 30,024)., Results: In 11-13 intervention against control group comparisons (n = 23,588-24,561), SQ-LNSs increased mean language (mean difference: 0.07 SD; 95% CI: 0.04, 0.10 SD), social-emotional (0.08; 0.05, 0.11 SD), and motor scores (0.08; 95% CI: 0.05, 0.11 SD) and reduced the prevalence of children in the lowest decile of these scores by 16% (prevalence ratio: 0.84; 95% CI: 0.76, 0.92), 19% (0.81; 95% CI: 0.74, 0.89), and 16% (0.84; 95% CI: 0.76, 0.92), respectively. SQ-LNSs also increased the prevalence of children walking without support at 12 mo by 9% (1.09; 95% CI: 1.05, 1.14). Effects of SQ-LNSs on language, social-emotional, and motor outcomes were larger among study populations with a higher stunting burden (≥35%) (mean difference: 0.11-0.13 SD; 8-9 comparisons). At the individual level, greater effects of SQ-LNSs were found on language among children who were acutely malnourished (mean difference: 0.31) at baseline; on language (0.12), motor (0.11), and executive function (0.06) among children in households with lower socioeconomic status; and on motor development among later-born children (0.11), children of older mothers (0.10), and children of mothers with lower education (0.11)., Conclusions: Child SQ-LNSs can be expected to result in modest developmental gains, which would be analogous to 1-1.5 IQ points on an IQ test, particularly in populations with a high child stunting burden. Certain groups of children who experience higher-risk environments have greater potential to benefit from SQ-LNSs in developmental outcomes.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020159971., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Small-quantity lipid-based nutrient supplements (SQ-LNSs) were designed to provide multiple micronutrients within a food base that also provides energy, protein, and essential fatty acids, targeted towards preventing malnutrition in vulnerable populations. Previous meta-analyses demonstrated beneficial effects of SQ-LNSs on child growth, anemia, and mortality. To further examine the efficacy and effectiveness of SQ-LNSs, and explore study-level and individual-level effect modifiers, we conducted an individual participant data meta-analysis of 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n > 37,000). We examined growth, development, anemia, and micronutrient status outcomes. Children who received SQ-LNSs had a 12-14% lower prevalence of stunting, wasting, and underweight; were 16-19% less likely to score in the lowest decile for language, social-emotional, and motor development; had a 16% lower prevalence of anemia; and had a 64% lower prevalence of iron-deficiency anemia compared with control group children. For most outcomes, beneficial effects of SQ-LNSs were evident regardless of study-level characteristics, including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average reported compliance with SQ-LNSs. For development, the benefits of SQ-LNSs were greater in populations with higher stunting burden, in households with lower socioeconomic status, and among acutely malnourished children. For hemoglobin and iron status, benefits were greater in populations with higher anemia prevalence and among acutely malnourished children, respectively. Thus, targeting based on potential to benefit may be worthwhile for those outcomes. Overall, co-packaging SQ-LNSs with interventions that reduce constraints on response, such as the prevention and control of prenatal and child infections, improving health care access, and promotion of early child development, may lead to greater impact. Policymakers and program planners should consider including SQ-LNSs in strategies to reduce child mortality, stunting, wasting, anemia, iron deficiency, and delayed development. This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592, CRD42020159971, and CRD42020156663., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design., Objectives: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes., Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria and types of comparisons., Results: SQ-LNS provision decreased stunting (length-for-age z score < -2) by 12% (relative reduction), wasting [weight-for-length (WLZ) z score < -2] by 14%, low midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -2) by 18%, acute malnutrition (WLZ < -2 or MUAC < 125 mm) by 14%, underweight (weight-for-age z score < -2) by 13%, and small head size (head circumference-for-age z score < -2) by 9%. Effects of SQ-LNSs generally did not differ by study-level characteristics including region, stunting burden, malaria prevalence, sanitation, water quality, duration of supplementation, frequency of contact, or average compliance with SQ-LNS. Effects of SQ-LNSs on stunting, wasting, low MUAC, and small head size were greater among girls than among boys; effects on stunting, underweight, and low MUAC were greater among later-born (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation., Conclusions: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Small-quantity lipid-based nutrient supplements (SQ-LNSs) have been shown to reduce the prevalence of child anemia and iron deficiency, but effects on other micronutrients are less well known. Identifying subgroups who benefit most from SQ-LNSs could support improved program design., Objectives: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child hemoglobin (Hb), anemia, and inflammation-adjusted micronutrient status outcomes., Methods: We conducted a 2-stage meta-analysis of individual participant data from 13 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 15,946). We generated study-specific and subgroup estimates of SQ-LNSs compared with control, and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine potential study-level effect modifiers., Results: SQ-LNS provision decreased the prevalence of anemia (Hb < 110 g/L) by 16% (relative reduction), iron deficiency (plasma ferritin < 12 µg/L) by 56%, and iron deficiency anemia (IDA; Hb < 110 g/L and plasma ferritin <12 µg/L) by 64%. We observed positive effects of SQ-LNSs on hematological and iron status outcomes within all subgroups of the study- and individual-level effect modifiers, but effects were larger in certain subgroups. For example, effects of SQ-LNSs on anemia and iron status were greater in trials that provided SQ-LNSs for >12 mo and provided 9 (as opposed to <9) mg Fe/d, and among later-born (than among first-born) children. There was no effect of SQ-LNSs on plasma zinc or retinol, but there was a 7% increase in plasma retinol-binding protein (RBP) and a 56% reduction in vitamin A deficiency (RBP < 0.70 µmol/L), with little evidence of effect modification by individual-level characteristics., Conclusions: SQ-LNSs can substantially reduce the prevalence of anemia, iron deficiency, and IDA among children across a range of individual, population, and study design characteristics. Policy-makers and program planners should consider SQ-LNSs within intervention packages to prevent anemia and iron deficiency.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42020156663., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Information on long-term dietary intake is often required for research or program planning, but surveys routinely use short-term assessments such as 24-h recalls (24HRs). Methods to reduce the impact of within-person variation in 24HRs, such as the National Cancer Institute (NCI) method, typically require extensive training and skill., Objectives: We introduce the Simulating Intake of Micronutrients for Policy Learning and Engagement (SIMPLE) macro, a new tool to increase the accessibility of 24HR analysis. We explain the underlying theory behind the tool and provide examples of potential applications., Methods: The SIMPLE macro connects the core NCI statistical code to estimate usual intake distributions and includes additional code to enable advanced analyses such as predictive modeling. The related SIMPLE-Iron macro applies the full probability method to estimate inadequate iron intake, and the SIMPLE-1D macro is used for descriptive or modeling analyses of data with a single 24HR per person. The macros and associated documentations are freely available. We analyzed data from the US National Health and Nutrition Examination Survey (NHANES) and the Cameroon National Micronutrient Survey to compare the SIMPLE macro to 1) the core NCI code using the Estimated Average Requirement cut point method, and 2) the IMAPP software for iron only, and to demonstrate the applications of the SIMPLE macro for estimating usual intake and predictive modeling., Results: The SIMPLE macro generates identical results to the core NCI code. The SIMPLE-Iron macro also produces estimates of inadequate iron intake comparable to the IMAPP software. The examples demonstrate application of the SIMPLE macro to 1) descriptive analyses of nutrient intake from food and supplements (NHANES), and 2) analyses accounting for breast-milk nutrient intake and modeling fortification and supplementation programs (Cameroon)., Conclusions: The SIMPLE macros may facilitate the analysis and modeling of dietary data to inform nutrition research, programs, and policy., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Vitamin A (VA) deficiency is prevalent in preschool-aged children in sub-Saharan Africa., Objectives: We assessed the effect of small-quantity lipid-based nutrient supplements (SQ-LNS) given to women during pregnancy and lactation and their children from 6 to 18 mo of age on women's plasma and milk retinol concentrations in Malawi, and children's plasma retinol concentration in Malawi and Ghana., Methods: Pregnant women (≤20 wk of gestation) were randomized to receive daily: 1) iron and folic acid (IFA) during pregnancy only; 2) multiple micronutrients (MMN; 800 μg retinol equivalent (RE)/capsule), or 3) SQ-LNS (800 μg RE/20g) during pregnancy and the first 6 mo postpartum. Children of mothers in the SQ-LNS group received SQ-LNS (400 μg RE/20 g) from 6 to 18 mo of age; children of mothers in the IFA and MMN groups received no supplement. Plasma retinol was measured in mothers at ≤20 and 36 wk of gestation and 6 mo postpartum, and in children at 6 and 18 mo of age. Milk retinol was measured at 6 mo postpartum. VA status indicators were compared by group., Results: Among Malawian mothers, geometric mean (95% CI) plasma retinol concentrations at 36 wk of gestation and 6 mo postpartum were 0.97 μmol/L (0.94, 1.01 μmol/L) and 1.35 μmol/L (1.31, 1.39 μmol/L), respectively; geometric mean (95% CI) milk retinol concentration at 6 mo postpartum was 1.04 μmol/L (0.97, 1.13 μmol/L); results did not differ by intervention group. Geometric mean (95% CI) plasma retinol concentrations for Malawian children at 6 and 18 mo of age were 0.78 μmol/L (0.75, 0.81 μmol/L) and 0.81 μmol/L (0.78, 0.85 μmol/L), respectively, and for Ghanaian children they were 0.85 μmol/L (0.82, 0.88 μmol/L) and 0.88 μmol/L (0.85, 0.91 μmol/L), respectively; results did not differ by intervention group in either setting., Conclusions: SQ-LNS had no effect on VA status of mothers or children, possibly because of low responsiveness of the VA status indicators., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Determining the proportion of a population at risk of inadequate or excessive nutrient intake is a crucial step in planning and managing nutrition intervention programs. Multiple days of 24-h dietary intake data per subject allow for adjustment of modeled usual nutrient intake distributions for the proportion of total variance in intake attributable to within-individual variation (WIV:total). When only single-day dietary data are available, an external adjustment factor can be used; however, WIV:total may vary by population, and use of incorrect WIV:total ratios may influence the accuracy of prevalence estimates and subsequent program impacts. WIV:total values were compiled from publications and from reanalyses of existing datasets to describe variation in WIV:total across populations and settings. The potential impact of variation in external WIV:total on estimates of prevalence of inadequacy was assessed through simulation analyses using the National Cancer Institute 1-d method. WIV:total values were extracted from 40 publications from 24 countries, and additional values were calculated from 15 datasets from 12 nations. Wide variation in WIV:total (from 0.02 to 1.00) was observed in publications and reanalyses. Few patterns by population characteristics were apparent, but WIV:total varied by age in children (< vs. >1 y) and between rural and urban settings. Simulation analyses indicated that estimates of the prevalence of inadequate intake are sensitive to the selected ratio in some cases. Selection of an external WIV:total estimate should consider comparability between the reference and primary studies with regard to population characteristics, study design, and statistical methods. Given wide variation in observed ratios with few discernible patterns, the collection of ≥2 days of intake data in at least a representative subsample in population dietary studies is strongly encouraged. In the case of single-day dietary studies, sensitivity analyses are recommended to determine the robustness of prevalence estimates to changes in the variance ratio., (© The Author(s) 2020. Published by Oxford University Press on behalf of American Society for Nutrition.)

Objective: To investigate the impact of food skills on food security and dietary diversity among asylum seekers living in Norwegian reception centers., Design: Cross-sectional study., Setting: Eight asylum reception centers., Participants: A total of 205 asylum seekers (131 men and 74 women) recruited through convenience sampling., Main Outcome Measures: Food skills were measured using questions from the Canadian Rapid Response on Food Skills and divided into cooking skills and shopping skills. Food security was measured with the 10-item version of the Radimer/Cornell Scale. The dietary diversity score was based on a 24-h recall., Analysis: Bivariate and multivariable logistic regression., Results: Cooking skills were associated with adequate dietary diversity (adjusted odds ratio, 2.12; 95% confidence interval, 1.04-4.31), but not with adult food insecurity (adjusted odds ratio. 0.63; 95% confidence interval, 0.26-1.53). Shopping skills were not associated with either measure of dietary diversity or adult food insecurity. Women had higher cooking skills than men, but there were no gender differences in shopping skills., Conclusions and Implications: Food skills had a limited association with food security and dietary diversity. Further research is needed to identify food skills beneficial for asylum seekers and to address the multiple causes of food insecurity., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Eggs are a rich source of nutrients important for brain development, including choline, riboflavin, vitamins B-6 and B-12, folate, zinc, protein, and DHA., Objective: Our objective was to evaluate the effect of the consumption of 1 egg per day over a 6-mo period on child development., Methods: In the Mazira Project randomized controlled trial, 660 children aged 6-9 mo were randomly allocated into an intervention or control group. Eggs were provided to intervention households during twice-weekly home visits for 6 mo. Control households were visited at the same frequency. At enrollment, blinded assessors administered the Malawi Developmental Assessment Tool (MDAT), and 2 eye-tracking tasks using a Tobii-Pro X2-60 eye tracker: a visual paired comparison memory task and an Infant Orienting with Attention task. At endline, 6-mo later, blinded assessors administered the MDAT and eye-tracking tasks plus an additional elicited imitation memory task., Results: At endline, intervention and control groups did not significantly differ in any developmental score, with the exception that a smaller percentage of children were delayed in fine motor development in the intervention group (10.6%) compared with the control group (16.5%; prevalence ratio: 0.59, 95% CI: 0.38-0.91). Among 10 prespecified effect modifiers for the 8 primary developmental outcomes, we found 7 significant interactions demonstrating a consistent pattern that children who were less vulnerable, for example, those with higher household wealth and maternal education, showed positive effects of the intervention. Given multiple hypothesis testing, some findings may have been due to chance., Conclusion: The provision of 1 egg per day had no overall effect on child development in this population of children, however, some benefits may be seen among children in less vulnerable circumstances. This trial was registered at clinicaltrials.gov as NCT03385252., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Diet may alter the configuration of gut microbiota, but the impact of prenatal and postnatal nutritional interventions on infant gut microbiota has not been investigated., Objective: We evaluated whether providing lipid-based nutrient supplements (LNSs) to mother-infant dyads promotes a more diverse and mature infant gut microbiota, compared to maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA)., Methods: We enrolled 869 pregnant women in a randomized trial in Malawi. There were 3 study groups, with women receiving 1 MMN capsule daily during pregnancy and 6 mo postpartum, or 1 LNS sachet (20 g) daily during pregnancy and 6 mo postpartum, or 1 IFA capsule daily (during pregnancy) then a placebo daily (postpartum). Infants in the LNS group received LNS from 6 to 18 mo; infants in the other groups did not receive supplements. The infants' fecal microbiota were characterized by PCR amplification and sequencing of the bacterial 16S rRNA gene (variable region 4). The primary outcomes were microbiota α diversity and maturation [as microbiota-for-age z score (MAZ)]. Specific associations of taxa with intervention were established with indicator species analysis (ISA)., Results: Primary outcomes did not differ between IFA and MMN groups, so these groups were combined (IFA + MMN). Mean ± SD α diversity was higher in the LNS group at 18 mo for Shannon index [3.01 ± 0.57 (LNS) compared with 2.91 ± 0.60 (IFA + MMN), P = 0.032] and Pielou's evenness index [0.61 ± 0.08 (LNS) compared with 0.60 ± 0.09 (IFA + MMN), P = 0.043]; no significant differences were observed at 1, 6, 12, or 30 mo. MAZ and β diversity did not differ at any age. We found 10 and 3 operational taxonomic units (OTUs) positively associated with LNS and IFA + MMN, respectively; however, these associations became nonsignificant following false discovery rate correction at 10%., Conclusions: Prenatal and postnatal LNS intake promoted infant gut microbiota diversity at 18 mo, after 12 mo of child supplementation, but did not alter microbiota maturation. This trial was registered at clinicaltrials.gov as NCT01239693., (Copyright © The Author(s) 2020.)

Background: Undernutrition is associated with an elevated risk of mortality among children in low- and middle-income countries. Small-quantity lipid-based nutrient supplements (LNS) have been evaluated as a method to prevent undernutrition and improve infant development, but the effects on mortality are unknown., Objective: Our objective was to evaluate the effect of LNS on all-cause mortality among children 6-24 mo old., Methods: We conducted a systematic review and meta-analysis of randomized controlled trials of LNS designed to prevent undernutrition, with or without other interventions. Literature was searched in May 2019 and trials were included if they enrolled children between 6 and 24 mo old and the period of supplementation lasted ≥6 mo. We extracted data from participant flow diagrams and contacted study investigators to request data. We conducted a meta-analysis to produce summary RR estimates., Results: We identified 18 trials conducted in 11 countries that enrolled 41,280 children and reported 586 deaths. The risk of mortality was lower in the LNS arms than in the non-LNS comparison arms (RR: 0.73; 95% CI: 0.59, 0.89; 13 trials). Estimates were similar when trials with maternal LNS intervention arms were added or when alternative formulations of LNS were excluded. The results appeared stronger in trials in which LNS were compared with passive control arms. Excluding these contrasts and only comparing multicomponent arms with LNS groups and comparison groups that contained all the same components without LNS attenuated the effect estimate (RR: 0.82; 95% CI: 0.61, 1.10)., Conclusions: LNS provided for the prevention of undernutrition may reduce the risk of mortality, but more trials with appropriate comparison groups allowing isolation of the effect of LNS alone are needed.This study was registered at www.crd.york.ac.uk/PROSPERO as CRD42019128718., (Copyright © The Author(s) 2019.)

Background: Stunted growth is a significant public health problem in many low-income countries., Objective: The aim of this study was to evaluate the impact of 1 egg per day on child growth in rural Malawi., Design: We conducted an individually randomized controlled trial in which 660 children aged 6-9 mo were equally allocated into an intervention (1 egg/d) or control group. Eggs were provided during twice-weekly home visits for 6 mo. Control households were visited at the same frequency. Assessors blinded to intervention group measured length, weight, head circumference, and midupper arm circumference at baseline and the 6-mo follow-up visit. To assess adherence, multipass 24-h dietary recalls were administered at baseline, 3-mo, and 6-mo visits., Results: Between February and July 2018, 660 children were randomly assigned into the intervention (n = 331) and control (n = 329) groups. Losses to follow-up totaled 10%. In the intervention group, egg consumption increased from 3.9% at baseline to 84.5% and 70.3% at the 3-mo and 6-mo visits, whereas in the control group, it remained below 8% at all study visits. The baseline prevalence of stunting was 14%, underweight was 8%, and wasting was 1% and did not differ by group. There was no intervention effect on length-for-age, weight-for-age, or weight-for-length z scores. There was a significantly higher head circumference for age z score of 0.18 (95% CI: 0.01, 0.34) in the egg group compared with the control group. There was a significant interaction with maternal education (P = 0.024), with an effect on length-for-age z score only among children whose mothers had higher education., Conclusions: The provision of 1 egg per day to children in rural Malawi had no overall effect on linear growth. A background diet rich in animal source foods and low prevalence of stunting at baseline may have limited the potential impact. This trial was registered at clinicaltrials.gov as NCT03385252., (Copyright © American Society for Nutrition 2019.)

Background: To estimate usual intake distributions of dietary components, collection of nonconsecutive repeated 24-h dietary recalls is recommended, but resource limitations sometimes restrict data collection to single-day dietary data per person., Objectives: We developed a new statistical method, the NCI 1-d method, which uses single-day dietary data and an external within-person to between-person variance ratio to estimate population distributions of usual intake of nearly-daily consumed foods and nutrients., Methods: We used NHANES 2011-2014 data for men (n = 4938 and n = 4293 for the first and second 24-h recalls) to compare nutrient intake distributions of vitamin A, magnesium, folate, and vitamin E generated by the 1-d method (with use of only the first recall per person) with those from the NCI amount-only method (with use of all days of dietary intake per person). The within-person to between-person variance ratio from the amount-only model was used as the unbiased "external" estimate for the 1-d method. We also examined the effect of mis-specification of variance ratios on usual intake distributions., Results: The amount-only and 1-d methods estimated statistically equivalent median (25p, 75p): 647 (459, 890) compared with 648 (461, 886) µg retinol activity equivalents/d, 338 (268, 420) compared with 334 (266, 417) mg magnesium/d, 595 (458, 762) compared with 589 (456, 758) µg dietary folate equivalents/d, and 9.7 (7.3, 12.6) compared with 9.6 (7.3, 12.7) mg vitamin E/d. As the external variance ratios increased from 25% to 200% of the unbiased ratios, the prevalence of inadequate intake ranged from 53% to 43% for vitamin A, 57% to 55% for magnesium, 16% to 2% for folate, and 70% to 73% for vitamin E., Conclusions: The 1-d method is a viable statistical method for estimating usual intakes of nearly-daily consumed dietary components when the variance ratio is unbiased. Results are sensitive to variance ratio selection, so researchers should still collect replicate data where possible., (Copyright © American Society for Nutrition 2019.)

Background: Nutritional interventions may affect child morbidity., Objective: The aim of this study was to examine whether providing lipid-based nutrient supplements (LNSs) to pregnant and lactating women or LNS or micronutrient powder (MNP) to their infants influences child morbidity., Methods: In a 4-arm cluster-randomized effectiveness trial, participants enrolled at ≤20 weeks of gestation (n = 4011) received: 1) maternal LNSs until 6 mo postpartum and child LNSs from 6-24 mo of age (LNS-LNS); 2) iron and folic acid (IFA) until 3 mo postpartum and child LNSs at 6-24 mo (IFA-LNS); 3) IFA (as above) and child MNP at 6-24 mo (IFA-MNP); or 4) IFA and no child supplement (IFA-Control). At 6, 12, 18, and 24 mo of age, we collected information on acute lower and upper respiratory infection (ALRI/AURI), diarrhea, and fever in the previous 14 d, and on episodes of illness in the previous 6 mo., Results: At 6 mo, prevalence of ALRI, fever, or diarrhea in the previous 14 d (17.6%, 18.9% and 6.8%, respectively) did not differ between infants of women who received LNS and infants of women who received IFA, but prevalence of AURI was lower in the LNS-LNS group than in all other groups combined (27.7% compared with 31.7%; OR: 0.83; 95% CI: 0.70, 0.99). At 12, 18, and 24 mo, the 4 arms did not differ in prevalence of fever (∼18.3%) or ALRI (≤15%) in the previous 14 d, but prevalence of AURI at 12 mo was lower in IFA-LNS than in IFA-Control infants (27.6% compared with 33.9%, OR: 0.74; 95% CI: 0.56, 0.99). The mean ± SD number of diarrhea episodes in the previous 6 mo was significantly higher among IFA-LNS than among IFA-Control infants at 6-12 (0.46 ± 0.04 compared with 0.33 ± 0.03) and 12-18 (0.45 ± 0.03 compared with 0.33 ± 0.02) mo. No other pairwise group differences were significant., Conclusion: Providing LNSs to women or LNSs or MNP to children generally did not increase or decrease childhood illnesses. This trial was registered at clinicaltrials.gov as NCT01715038., (Copyright © American Society for Nutrition 2019.)

Background: The impact of feeding a slightly sweet nutrient supplement early in life on later sweet taste preference is unknown., Objective: We 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., Design: We 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)., Results: Of 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., Conclusion: Exposure 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., (Copyright © American Society for Nutrition 2019.)

Background: Whether consuming sweet foods early in life affects sweet food preferences and consumption later in childhood is unknown., Objective: We 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., Methods: We 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., Results: Median (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)., Conclusion: In 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., (© 2019 American Society for Nutrition.)

Background: Anemia in young children is a global health problem. Risk factors include poor nutrient intake and poor water quality, sanitation, or hygiene., Objective: We evaluated the effects of water quality, sanitation, handwashing, and nutrition interventions on micronutrient status and anemia among children in rural Kenya and Bangladesh., Design: We nested substudies within 2 cluster-randomized controlled trials enrolling pregnant women and following their children for 2 y. These substudies included 4 groups: water, sanitation, and handwashing (WSH); nutrition (N), including lipid-based nutrient supplements (LNSs; ages 6-24 mo) and infant and young child feeding (IYCF) counseling; WSH+N; and control. Hemoglobin and micronutrient biomarkers were measured after 2 y of intervention and compared between groups using generalized linear models with robust SEs., Results: In Kenya, 699 children were assessed at a mean ± SD age of 22.1 ± 1.8 mo, and in Bangladesh 1470 participants were measured at a mean ± SD age of 28.0 ± 1.9 mo. The control group anemia prevalences were 48.8% in Kenya and 17.4% in Bangladesh. There was a lower prevalence of anemia in the 2 N intervention groups in both Kenya [N: 36.2%; prevalence ratio (PR): 0.74; 95% CI: 0.58, 0.94; WSH+N: 27.3%; PR: 0.56; 95% CI: 0.42, 0.75] and Bangladesh (N: 8.7%; PR: 0.50; 95% CI: 0.32, 0.78; WSH+N: 7.9%, PR: 0.46; 95% CI: 0.29, 0.73). In both trials, the 2 N groups also had significantly lower prevalences of iron deficiency, iron deficiency anemia, and low vitamin B-12 and, in Kenya, a lower prevalence of folate and vitamin A deficiencies. In Bangladesh, the WSH group had a lower prevalence of anemia (12.8%; PR: 0.74; 95% CI: 0.54, 1.00) than the control group, whereas in Kenya, the WSH+N group had a lower prevalence of anemia than did the N group (PR: 0.75; 95% CI: 0.53, 1.07), but this was not significant (P = 0.102)., Conclusions: IYCF counseling with LNSs reduced the risks of anemia, iron deficiency, and low vitamin B-12. Effects on folate and vitamin A varied between studies. Improvements in WSH also reduced the risk of anemia in Bangladesh but did not provide added benefit over the nutrition-specific intervention. These trials were registered at clinicaltrials.gov as NCT01590095 (Bangladesh) and NCT01704105 (Kenya).

Background: The relation between subclinical hemoglobinopathies and concentrations of the iron-regulatory hormone hepcidin is not well characterized., Objective: We investigated the relation of hepcidin concentration with hemoglobinopathies among young children in Kenya., Methods: We quantified serum hepcidin and ferritin in 435 Kenyan children aged 14-20 mo in a subsample of the Water, Sanitation, and Handwashing (WASH) Benefits Trial. Blood samples were genotyped for α+-thalassemia and for sickle cell disorder. Hepcidin was compared across sickle cell and α+-thalassemia genotypes separately by using generalized linear models, and children who were normozygous for both conditions were also compared with those who had either of these conditions. In the association between hepcidin and ferritin, we assessed effect modification by genotype., Results: In this population, we found that 16.2% had sickle cell trait and 0.2% had sickle cell disorder, whereas 40.0% were heterozygous for α+-thalassemia and 8.2% were homozygous. Hepcidin concentration did not differ by genotype, but effect modification was found by genotype in the association between hepcidin and ferritin (P < 0.1). Among normozygous sickle cell children (HbAA), there was an association between hepcidin and ferritin (β = 0.92; 95% CI: 0.72, 1.10). However, among those with sickle cell trait (HbAS), the association was no longer significant (β = 0.31; 95% CI: -0.04, 0.66). Similarly, among children who were normozygous (αα/αα) or heterozygous (-α/αα) for α+-thalassemia, hepcidin and ferritin were significantly associated [β = 0.94 (95% CI: 0.68, 1.20) and β = 0.77 (95% CI: 0.51, 1.03), respectively]; however, in children who were homozygous for α+-thalassemia (-α/-α), there was no longer a significant association (β = 0.45; 95% CI: -0.10, 1.00)., Conclusion: Hepcidin was not associated with hemoglobin genotype, but there may be a difference in the way hepcidin responds to iron status among those with either sickle cell trait or homozygous α+-thalassemia in young Kenyan children. This trial was registered at clinicaltrials.gov as NCT01704105.

Background: It is unknown whether self-reported measures of household food insecurity change in response to food-based nutrient supplementation. Objective: We assessed the impacts of providing lipid-based nutrient supplements (LNSs) to women during pregnancy and postpartum and/or to their children on self-reported household food insecurity in Malawi [DOSE and DYAD trial in Malawi (DYAD-M)], Ghana [DYAD trial in Ghana (DYAD-G)], and Bangladesh [Rang-Din Nutrition Study (RDNS) trial]. Methods: Longitudinal household food-insecurity data were collected during 3 individually randomized trials and 1 cluster-randomized trial testing the efficacy or effectiveness of LNSs (generally 118 kcal/d). Seasonally adjusted Household Food Insecurity Access Scale (HFIAS) scores were constructed for 1127 DOSE households, 732 DYAD-M households, 1109 DYAD-G households, and 3671 RDNS households. The impact of providing LNSs to women during pregnancy and the first 6 mo postpartum and/or to their children from 6 to 18-24 mo on seasonally adjusted HFIAS scores was assessed by using negative binomial models (DOSE, DYAD-M, and DYAD-G trials) and mixed-effect negative binomial models (RDNS trial). Results: In the DOSE and DYAD-G trials, seasonally adjusted HFIAS scores were not different between the LNS and non-LNS groups. In the DYAD-M trial, the average household food-insecurity scores were 14% lower ( P = 0.01) in LNS households than in non-LNS households. In the RDNS trial, compared with non-LNS households, food-insecurity scores were 17% lower ( P = 0.02) during pregnancy and the first 6 mo postpartum and 15% lower ( P = 0.02) at 6-24 mo postpartum in LNS households. Conclusions: The daily provision of LNSs to mothers and their children throughout much of the "first 1000 d" may improve household food security in some settings, which could be viewed as an additional benefit that may accrue in households should policy makers choose to invest in LNSs to promote child growth and development. These trials were registered at clinicaltrials.gov as NCT00945698 (DOSE) NCT01239693 (DYAD-M), NCT00970866 (DYAD-G) and NCT01715038 (RDNS)., Competing Interests: Author disclosures: KPA, EA, TEP, MKM, SA-A, MA, CDA, JC, SH, CK, SLM, UA, AL, KMM, SAV, and KGD, no conflicts of interest.

Background: Maternal iodine deficiency during pregnancy and lactation is common in Bangladesh. Objective: We evaluated the effect of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on urinary iodine concentration (UIC). Methods: We conducted a cluster-randomized controlled effectiveness trial in which we enrolled 4011 pregnant women at ≤20 gestational weeks. Women in 48 clusters received iron and folic acid (IFA; 60 mg Fe/d + 400 μg folic acid/d) and women in 16 clusters received LNS-PL (20 g/d, 118 kcal) containing 22 vitamins and minerals (including 250 μg I). We randomly selected a subsample of 1159 women for repeated urine sample collection, i.e., at enrollment, at 36 wk of gestation, and at 6 mo postpartum, for UIC analysis, a secondary outcome of the trial. Results: The geometric mean UIC at 36 wk of gestation and at 6 mo postpartum did not differ significantly between the IFA and LNS-PL groups. The median (quartile 1, quartile 3) UIC at 36 wk was 27.4 μg/L (16.9, 52.7 μg/L) in the IFA group and 30.2 μg/L (17.7, 56.6 μg/L) in the LNS-PL group; at 6 mo, these were 23.0 μg/L (10.0, 45.9 μg/L) in the IFA group and 22.2 μg/L (9.1, 50.4 μg/L) in the LNS-PL group. Conclusion: Daily consumption of LNS-PL containing 250 μg I did not increase the UICs of pregnant and lactating women in Bangladesh. Iodine from lipid-based nutrient supplements may have been stored in the thyroid gland or secreted in breast milk instead of being excreted in urine. Additional research that uses other biomarkers of iodine status is needed to determine how to meet the iodine requirements of pregnant and lactating women in Bangladesh and similar settings. This trial was registered at clinicaltrials.gov as NCT01715038., Competing Interests: Author disclosures: MKM, SLM, RRP, SH, MSAK, ZS, BU, MS, MH, RTY, CDA, and KGD, no conflicts of interest., (© 2017 American Society for Nutrition.)

Background: Stunting in linear growth occurs mainly during the first 1000 d, from conception through 24 mo of age. Despite the recognition of this critical period, there have been few evaluations of the growth impact of interventions that cover most of this window. Objective: We evaluated home fortification approaches for preventing maternal and child undernutrition within a community-based health program. We hypothesized that small-quantity lipid-based nutrient supplements (LNSs) provided to women during pregnancy and the first 6 mo postpartum, LNSs provided to their offspring from 6 to 24 mo of age, or both would result in greater child length-for-age z score (LAZ) at 24 mo than iron and folic acid (IFA) provided to women during pregnancy and postpartum plus micronutrient powder (MNP) or no supplementation for their offspring from 6 to 24 mo. Design: We conducted a cluster-randomized effectiveness trial with 4 arms: 1 ) women and children both received LNSs (LNS-LNS group), 2 ) women received IFA and children received LNSs (IFA-LNS group), 3 ) women received IFA and children received MNP (IFA-MNP group), and 4 ) women received IFA and children received no supplements (IFA-Control group). We enrolled 4011 women at ≤20 wk of gestation within 64 clusters, each comprising the supervision area of a community health worker. Analyses were primarily performed by using ANCOVA F tests and Tukey-Kramer-corrected pairwise comparisons. Results: At 24 mo, the LNS-LNS group had significantly higher LAZ (+0.13 compared with the IFA-MNP group) and head circumference (+0.15 z score compared with the IFA-Control group); these outcomes did not differ between the other groups. Stunting prevalence (LAZ <-2) was lower in the LNS-LNS group at 18 mo than in the IFA-MNP group (OR: 0.70; 95% CI: 0.53, 0.92), but the difference diminished by 24 mo (OR: 0.81; 95% CI: 0.63, 1.04). Conclusion: Home fortification with small-quantity LNSs, but not MNP, during the first 1000 d improved child linear growth and head size in rural Bangladesh. This trial was registered at clinicaltrials.gov as NCT01715038., (© 2017 American Society for Nutrition.)

Background: Nutrition during the first 1000 d is critical for brain development. Objective: We evaluated the effects on child development of home fortification with lipid-based nutrient supplements (LNSs) for mothers and/or children or micronutrient powder (MNP) for children. Design: We conducted a cluster-randomized effectiveness trial with 4 arms: 1 ) LNSs during pregnancy and the first 6 mo postpartum and LNSs for the offspring from 6 to 24 mo (LNS-LNS), 2 ) iron and folic acid (IFA) during pregnancy and the first 3 mo postpartum and LNSs for the children from 6 to 24 mo (IFA-LNS), 3 ) IFA (as above) and MNP for the offspring from 6 to 24 mo (IFA-MNP), and 4 ) IFA (as above) and no child supplement (IFA-Control). Women were enrolled at ≤20 wk of gestation; children were assessed at 12 ( n = 3331), 18 ( n = 3364), and 24 ( n = 3379) mo. Results: Compared with the IFA-Control group, motor development scores were higher in the LNS-LNS ( P = 0.016) and IFA-LNS groups ( P = 0.006) at 18 mo and in the IFA-MNP group ( P = 0.048) at 24 mo. Receptive language scores were higher for the LNS-LNS group ( P = 0.028) at 18 mo and for all 3 groups at 24 mo ( P = 0.008 for LNS-LNS, P = 0.022 for IFA-LNS, and P = 0.009 for IFA-MNP compared with IFA-Control). Expressive language scores did not differ at 18 mo ( P = 0.236) but were higher in the LNS-LNS ( P = 0.035) and IFA-MNP ( P = 0.002) groups than in the IFA-Control group at 24 mo. Groups did not differ in personal-social scores at 18 ( P = 0.233) or 24 ( P = 0.146) mo or in executive function score at 24 mo ( P = 0.467). Conclusion: Prenatal LNSs, postnatal LNSs, or both, or postnatal MNP had a positive effect on motor and language development in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT01715038., (© 2017 American Society for Nutrition.)

Background: Maternal undernutrition and low macro- and micronutrient intake and weight gain during pregnancy have been reported in Bangladesh., Objective: We aimed to determine the effects of lipid-based nutrient supplements for pregnant and lactating women (LNS-PL) on weight gain and midupper arm circumference (MUAC) during pregnancy., Methods: The Rang-Din Nutrition Study, a cluster-randomized effectiveness trial conducted in Bangladesh, enrolled 4011 pregnant women at ≤20 wk gestation who received either 60 mg Fe + 400 μg folic acid/d or 20 g LNS-PL/d (118 kcal) containing essential fatty acids and vitamins and minerals until delivery. At 36 wk gestation, women were interviewed at home and then attended a follow-up examination at local clinics (n = 2877), where anthropometric measurements were taken., Results: No significant differences between intervention groups in maternal weight gain per week, low weight gain per week, or MUAC at 36 wk gestation were observed in the full sample. However, among multiparous women aged ≥25 y, those in the LNS-PL group gained 34 g/wk more than their counterparts in the iron and folic acid (IFA) group (P = 0.001), whereas no differences were seen in the other parity/age subgroups. Women aged ≥25 y in the LNS-PL group had a 0.4-cm greater MUAC than their counterparts in the IFA group (P = 0.003); no significant differences were observed in the other age groups. Among women whose height at baseline was in the lowest quartile of the distribution, those in the LNS-PL group had a 0.1-0.3-cm greater MUAC at 36 wk gestation than those in the IFA group (P = 0.004-0.014)., Conclusions: Lipid-based nutrient supplements provided during pregnancy did not affect maternal anthropometric indicators in the overall sample but increased MUAC among women aged ≥25 y and those with lower stature and weight gain among multiparous women aged ≥25 y. This trial was registered at clinicaltrials.gov as NCT01715038., (© 2016 American Society for Nutrition.)