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

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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.

Section: Discussionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Wessells

Arnold

Stewart

et al. 2021

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“…For this article, our objectives were to generate pooled estimates of the effect of SQ-LNSs on each growth outcome and identify study-level and individual-level modifiers of the effect of SQ-LNSs on these outcomes. Two companion articles report results for other outcome domains: anemia and micronutrient status ( 17 ) and development ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

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

Dewey

Wessells

Prado

et al. 2021

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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.

“…Recent systematic reviews have demonstrated a 16%–21% reduction in anemia ( 25 , 33 ), a 56% reduction in iron deficiency ( 33 ), and a 64% reduction in iron deficiency anemia ( 33 ) when SQ-LNSs are provided, similar to the efficacy of MNPs. SQ-LNSs also reduce the risk of impaired growth ( 34 ) and development ( 35 ), as well as mortality ( 36 ). Neither MNPs nor SQ-LNSs were developed to replace a varied age-appropriate diet for young children, but each plays a role in improving diets that may be inadequate in some essential nutrients.…”

Section: Evidence-based Solutions Availablementioning

confidence: 99%

Perspective: Putting the youngest among us into the nutrition “call for action” for food fortification strategies

Zlotkin

Dewey

2021

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Adequate iron intake is essential for optimal child development, but iron deficiency and anemia among infants and young children are widespread in low- and middle-income countries. Large-scale food fortification strategies hold great promise for reducing micronutrient deficiencies; however, for children <2 y of age, the impact of such strategies is limited because their intake of staple foods is relatively low and fortification levels are targeted at the adult population. Iron supplementation, iron fortification of foods targeted to infants, and point-of-use fortification with iron-containing products such as multiple micronutrient powders (MNPs) and small-quantity lipid-based nutrient supplements are evidence-based approaches recommended to reduce anemia among infants and young children when used in the right context. Since 2003, the WHO, with support from UNICEF, has recommended the use of MNPs to control iron deficiency. However, the percentage of children with anemia has changed very little over the past 10 y. Five years ago the UN declared a decade of action on nutrition, including World Health Assembly (WHA) targets for maternal, infant, and young child nutrition, yet the WHA set no anemia targets for children. In July 2020 the leaders of 4 UN agencies issued a call for action to protect children's right to nutrition in the face of the COVID-19 pandemic and beyond. Given persistently high rates of anemia among young children, the negative developmental impact, the challenge of meeting iron needs from typical complementary food diets, and the availability of successful evidence-based fortification strategies for this age group, we encourage planners, speakers, and donors at this year's UN Food Systems Summit and the Tokyo Nutrition for Growth Summit to 1) call for the WHA to set anemia targets for infants and young children and 2) promote investment in evidence-based interventions to improve the iron status of young children.