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 A 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; Agnes Le Port; Jef L Leroy; Audrie Lin; Kenneth Maleta; Susana L Matias; Mduduzi N N Mbuya; Malay K Mridha; Kuda Mutasa; Abu M Naser; Rina R Paul; Harriet Okronipa; Jean-Bosco Ouédraogo; Amy J Pickering; Mahbubur Rahman; Kerry Schulze; Laura E Smith; Ann M Weber; Amanda Zongrone; Kathryn G Dewey

doi:10.1093/ajcn/nqab276

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

Am J Clin Nutr. 2021 Nov 2;114(Suppl 1):68S-94S. doi: 10.1093/ajcn/nqab276.

Authors

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

6}, Ulla Ashorn⁵, Elodie Becquey⁷, Kenneth H Brown^{1

8}, Kendra A Byrd⁹, Rebecca K Campbell¹⁰, Parul Christian¹¹, Lia C H Fernald¹², Yue-Mei Fan⁵, Emanuela Galasso¹³, Sonja Y Hess¹, Lieven Huybregts⁷, Josh M Jorgensen¹⁴, Marion Kiprotich¹⁵, Emma Kortekangas⁵, Anna Lartey³, Agnes Le Port¹⁶, Jef L Leroy⁷, Audrie Lin¹², Kenneth Maleta¹⁷, Susana L Matias¹⁸, Mduduzi N N Mbuya^{19

20}, Malay K Mridha²¹, Kuda Mutasa¹⁹, Abu M Naser^{22

23}, Rina R Paul²¹, Harriet Okronipa²⁴, Jean-Bosco Ouédraogo²⁵, Amy J Pickering²⁶, Mahbubur Rahman²², Kerry Schulze¹¹, Laura E Smith²⁷, Ann M Weber²⁸, Amanda Zongrone²⁹, Kathryn G Dewey¹

Affiliations

¹ Institute for Global Nutrition and 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 WorldFish, Bayan Lepas, Penang, Malaysia.
¹⁰ Division of Epidemiology and Biostatistics, University of Illinois at Chicago School of Public Health, Chicago, IL, USA.
¹¹ Program in Human Nutrition, Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
¹² School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
¹³ Development Research Group, World Bank, Washington, DC, USA.
¹⁴ Nutrition Program, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA.
¹⁵ One Acre Fund, Nairobi, Kenya.
¹⁶ Independent consultant, Dakar, Senegal.
¹⁷ Department of Public Health, School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.
¹⁸ Department of Nutritional Sciences and Toxicology, University of California, Berkeley, Berkeley, CA, USA.
¹⁹ Zvitambo Institute for Maternal and Child Health Research, Harare, Zimbabwe.
²⁰ Global Alliance for Improved Nutrition, Washington, DC, USA.
²¹ Center for Non-communicable Diseases and Nutrition, BRAC James P Grant School of Public Health, Dhaka, Bangladesh.
²² International Center for Diarrheal Diseases Research (icddr,b), Dhaka, Bangladesh.
²³ Gangarosa Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
²⁴ Department of Population Medicine and Diagnostic Sciences, Cornell University, Ithaca, NY, USA.
²⁵ Health Sciences Research Institute (IRSS), Bobo-Dioulasso, Burkina Faso.
²⁶ School of Engineering, Tufts University, Medford, MA, USA.
²⁷ Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York at Buffalo, Buffalo, NY, USA.
²⁸ Division of Epidemiology, School of Community Health Sciences, University of Nevada, Reno, Reno, NV, USA.
²⁹ Independent consultant, Washington, DC, USA.

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.

Keywords: anemia; child undernutrition; complementary feeding; home fortification; iron deficiency; micronutrient status; nutrient supplements.

Publication types

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

MeSH terms

Africa South of the Sahara / epidemiology
Anemia / epidemiology*
Anemia, Iron-Deficiency / epidemiology*
Bangladesh / epidemiology
Child, Preschool
Dietary Supplements*
Effect Modifier, Epidemiologic
Female
Humans
Infant
Infant Nutritional Physiological Phenomena*
Lipids / administration & dosage*
Male
Micronutrients / blood
Micronutrients / deficiency
Nutritional Status*
Randomized Controlled Trials as Topic

Substances

Lipids
Micronutrients