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
K. Ryan Wessells, Charles D. Arnold, Christine P. Stewart, Elizabeth L. Prado, Souheila Abbeddou, Seth Adu‐Afarwuah, Benjamin F. Arnold, Per Ashorn, Ulla Ashorn, Elodie Becquey, Kenneth H. Brown, Kendra Byrd, Rebecca K. Campbell, Parul Christian, Lia C. H. Fernald, Yue‐Mei Fan, Emanuela Galasso, Sonja Y. Hess, Lieven Huybregts, Josh M Jorgensen, Marion Kiprotich, Emma Kortekangas, Anna Lartey, Agnès Le Port, Jef L Leroy, Audrie Lin, Kenneth Maleta, Susana L Matias, Mduduzi N. N. Mbuya, Malay Kanti Mridha, Kuda Mutasa, Abu Mohd Naser, Rina Rani Paul, Harriet Okronipa, Jean‐Bosco Ouédraogo, Amy J. Pickering, Mahbubur Rahman, Kerry Schulze, Laura E. Smith, Ann M. Weber, Amanda Zongrone, Kathryn G. Dewey
Abstract
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.