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
Authors: Prado Elizabeth L. , Arnold Charles D. , Wessells K. Ryan , Stewart Christine P. , Abbeddou Souheila , Adu-Afarwuah Seth , Arnold Benjamin F. , Ashorn Ulla , Ashorn Per , Becquey Elodie , Brown Kenneth H. , Chandna Jaya , Christian Parul , Dentz Holly N. , Dulience Sherlie J. L. , Fernald Lia C. H. , Galasso Emanuela , Hallamaa Lotta , Hess Sonja Y. , Huybregts Lieven , Iannotti Lora L. , Jimenez Elizabeth Yakes , Kohl Patricia , Lartey Anna , Port Agnes Le , Luby Stephen P. , Maleta Kenneth , Matchado Andrew , Matias Susana L. , Mridha Malay K. , Ntozini Robert , Null Clair , Ocansey Maku E. , Parvez Sarker Masud , Phuka John , Pickering Amy J. , Prendergast Andrew J. , Shamim Abu Ahmed , Siddiqui Zakia , Tofail Fahmida , Weber Ann M. , Wu Lee S. F. , Dewey Kathryn G. 
Published: February 2021

AbstractBackgroundSmall-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.ObjectivesOur 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.MethodsWe 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.ResultsIn 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).ConclusionsSQ-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 atwww.crd.york.ac.uk/PROSPEROas CRD42020159971.