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

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

doi:10.1093/ajcn/nqab277

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

Am J Clin Nutr. 2021 Nov 2;114(Suppl 1):43S-67S. doi: 10.1093/ajcn/nqab277.

Authors

Elizabeth L Prado¹, Charles D Arnold¹, K Ryan Wessells¹, Christine P Stewart¹, Souheila Abbeddou², Seth Adu-Afarwuah³, Benjamin F Arnold⁴, Ulla Ashorn⁵, Per Ashorn^{5

6}, Elodie Becquey⁷, Kenneth H Brown^{1

8}, Jaya Chandna⁹, Parul Christian¹⁰, Holly N Dentz¹, Sherlie J L Dulience¹¹, Lia C H Fernald¹², Emanuela Galasso¹³, Lotta Hallamaa⁵, Sonja Y Hess¹, Lieven Huybregts⁷, Lora L Iannotti¹¹, Elizabeth Y Jimenez¹⁴, Patricia Kohl¹¹, Anna Lartey³, Agnes Le Port¹⁵, Stephen P Luby¹⁶, Kenneth Maleta¹⁷, Andrew Matchado¹⁸, Susana L Matias¹⁹, Malay K Mridha²⁰, Robert Ntozini²¹, Clair Null²², Maku E Ocansey²³, Sarker M Parvez²⁴, John Phuka¹⁷, Amy J Pickering²⁵, Andrew J Prendergast²⁶, Abu A Shamim²⁰, Zakia Siddiqui²⁷, Fahmida Tofail²⁸, Ann M Weber²⁹, Lee S F Wu¹⁰, Kathryn G Dewey¹

Affiliations

¹ Institute for Global Nutrition & Department of Nutrition, University of California Davis, Davis, CA, USA.
² Public Health Nutrition, Department of Public Health and Primary Care, University of Ghent, Ghent, Belgium.
³ Department of Nutrition and Food Science, University of Ghana, Legon, Accra, Ghana.
⁴ Francis I Proctor Foundation, University of California, San Francisco, San Francisco, CA, USA.
⁵ Center for Child Health Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
⁶ Department of Paediatrics, Tampere University Hospital, Tampere, Finland.
⁷ Poverty, Health, and Nutrition Division, International Food Policy Research Institute, Washington, DC, USA.
⁸ Helen Keller International, New York, NY, USA.
⁹ Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, United Kingdom.
¹⁰ Program in Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹¹ Brown School, Washington University in St. Louis, St Louis, MO, USA.
¹² School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
¹³ Development Research Group, World Bank, Washington, DC, USA.
¹⁴ Departments of Pediatrics and Internal Medicine and College of Population Health, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
¹⁵ Independent consultant, Dakar, Senegal.
¹⁶ Division of Infectious Diseases and Geographic Medicine, Stanford University, Stanford, CA, USA.
¹⁷ Department of Public Health, School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.
¹⁸ Malawi Epidemiology and Intervention Research Unit, Karonga, Malawi.
¹⁹ Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA, USA.
²⁰ Center for Non-communicable Diseases and Nutrition, BRAC James P Grant School of Public Health, Dhaka, Bangladesh.
²¹ Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
²² Mathematica, Washington, DC, USA.
²³ CDC Foundation, Atlanta, GA, USA.
²⁴ Infectious Diseases Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
²⁵ School of Engineering, Tufts University, Medford, MA, USA.
²⁶ Blizard Institute, Queen Mary University of London, London, United Kingdom.
²⁷ Healthy Systems and Population Studies Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
²⁸ Nutrition and Clinical Sciences Division, International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
²⁹ Division of Epidemiology, School of Community Health Sciences, University of Nevada, Reno, Reno, NV, USA.

Abstract

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.

Keywords: child undernutrition; complementary feeding; executive function; language development; motor development; nutrient supplements; social-emotional development.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

MeSH terms

Africa South of the Sahara / epidemiology
Bangladesh / epidemiology
Child Development / drug effects*
Child, Preschool
Dietary Supplements*
Effect Modifier, Epidemiologic
Female
Haiti / epidemiology
Humans
Infant
Infant Nutritional Physiological Phenomena*
Language Development
Lipids / administration & dosage*
Male
Motor Skills
Randomized Controlled Trials as Topic
Socioeconomic Factors

Substances

Lipids

Grants and funding

P30 DK092950/DK/NIDDK NIH HHS/United States