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

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 I2 and Tau2 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][1] as CRD42019146592. ### Competing Interest Statement All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: KGD, KRW and CDA had financial support from the Bill & Melinda Gates Foundation for the submitted work; KRW and SYH have received research grants from Nutriset, SAS, outside the submitted work; all other co-authors report financial support for the original trials that contributed data to this paper, but not for the work directly related to this analysis; no other relationships or activities that could appear to have influenced the submitted work. ### Clinical Protocols ### Funding Statement This work was funded by a grant from the Bill & Melinda Gates Foundation (OPP49817). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The analyses were approved by the institutional review board of the University of California Davis (1463609-1). All individual trial protocols were approved by the relevant institutional ethics committees. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data described in the manuscript, code book, and analytic code will not be made available because they are compiled from 14 different trials, and access is under the control of the investigators of each of those trials. [1]: http://www.crd.york.ac.uk/PROSPERO