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Meta-Analysis
. 2021 Nov 2;114(Suppl 1):15S-42S.
doi: 10.1093/ajcn/nqab278.

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

Kathryn G Dewey  1 , K Ryan Wessells  1 , Charles D Arnold  1 , Elizabeth L Prado  1 , Souheila Abbeddou  2 , Seth Adu-Afarwuah  3 , Hasmot Ali  4 , Benjamin F Arnold  5 , Per Ashorn  6   7 , Ulla Ashorn  6 , Sania Ashraf  8 , Elodie Becquey  9 , Jaden Bendabenda  10 , Kenneth H Brown  1   11 , Parul Christian  12 , John M Colford  13 , Sherlie J L Dulience  14 , Lia C H Fernald  13 , Emanuela Galasso  15 , Lotta Hallamaa  6 , Sonja Y Hess  1 , Jean H Humphrey  12   16 , Lieven Huybregts  9 , Lora L Iannotti  14 , Kaniz Jannat  17 , Anna Lartey  3 , Agnes Le Port  18 , Jef L Leroy  9 , Stephen P Luby  19 , Kenneth Maleta  20 , Susana L Matias  21 , Mduduzi N N Mbuya  16   22 , Malay K Mridha  23 , Minyanga Nkhoma  20 , Clair Null  24 , Rina R Paul  23 , Harriet Okronipa  25 , Jean-Bosco Ouédraogo  26 , Amy J Pickering  27 , Andrew J Prendergast  16   28 , Marie Ruel  9 , Saijuddin Shaikh  4 , Ann M Weber  29 , Patricia Wolff  30 , Amanda Zongrone  31 , Christine P Stewart  1
Affiliations
Meta-Analysis

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

Kathryn G Dewey et al. Am J Clin Nutr. .

Abstract

Background: Meta-analyses show that small-quantity lipid-based nutrient supplements (SQ-LNSs) reduce child stunting and wasting. Identification of subgroups who benefit most from SQ-LNSs may facilitate program design.

Objectives: We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes.

Methods: We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to children 6-24 mo of age (n = 37,066). We generated study-specific and subgroup estimates of SQ-LNS compared with control and pooled the estimates using fixed-effects models. We used random-effects meta-regression to examine study-level effect modifiers. In sensitivity analyses, we examined whether results differed depending on study arm inclusion criteria 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 midupper arm circumference (MUAC) (<125 mm or MUAC-for-age z score < -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-for-age z score < -2) by 9%. Effects of SQ-LNSs 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 compliance with SQ-LNS. Effects of SQ-LNSs 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 (than among firstborn) children; and effects on wasting and acute malnutrition were greater among children in households with improved (as opposed to unimproved) sanitation.

Conclusions: The positive impact of SQ-LNSs on growth is apparent across a variety of study-level contexts. Policy-makers and program planners should consider including SQ-LNSs in packages of interventions to prevent both stunting and wasting.This trial was registered at www.crd.york.ac.uk/PROSPERO as CRD42019146592.

Keywords: child undernutrition; complementary feeding; home fortification; nutrient supplements; stunting; wasting.

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Figures

FIGURE 1
FIGURE 1
Study flow diagram. IPD, individual participant data; LNS, lipid-based nutrient supplement; SQ, small-quantity; RCT, randomized controlled trial.
FIGURE 2
FIGURE 2
Forest plot of effect of small-quantity LNSs on stunting prevalence. Individual study estimates were generated from log-binomial regression controlling for baseline measure when available and with clustered observations using robust SEs for cluster-randomized trials. Pooled estimates were generated using inverse-variance weighting with both fixed and random effects. LNS, lipid-based nutrient supplement; PR, prevalence ratio.
FIGURE 3
FIGURE 3
Forest plot of effect of small-quantity LNSs on wasting prevalence. Individual study estimates were generated from log-binomial regression controlling for baseline measure when available and with clustered observations using robust SEs for cluster-randomized trials. Pooled estimates were generated using inverse-variance weighting with both fixed and random effects. LNS, lipid-based nutrient supplement; PR, prevalence ratio.
FIGURE 4
FIGURE 4
Pooled effect of small-quantity LNSs on stunting stratified by study-level characteristics. P value for the difference was estimated using random-effects meta-regression with the indicated effect modifier as the predictor of intervention effect size; stratified pooled estimates are presented for each stratum. AFR, African Region; LNS, lipid-based nutrient supplement; P-diff, P value for the difference in effects of small-quantity lipid-based nutrient supplements between the 2 levels of the effect modifier; PR, prevalence ratio; SEAR, South-East Asia Region.
FIGURE 5
FIGURE 5
Pooled effect of small-quantity LNSs on wasting stratified by study-level effect characteristics. P value for the difference was estimated using random-effects meta-regression with the indicated effect modifier as the predictor of intervention effect size; stratified pooled estimates are presented for each stratum. AFR, African Region; LNS, lipid-based nutrient supplement; P-diff, P value for the difference in effects of small-quantity lipid-based nutrient supplements between the 2 levels of the effect modifier; PR, prevalence ratio; SEAR, South-East Asia Region.
FIGURE 6
FIGURE 6
Pooled effect of small-quantity LNSs on stunting stratified by individual-level maternal and child characteristics. Individual study estimates for interaction effect were generated from log-binomial regression controlling for baseline measure when available and with clustered observations using robust SEs for cluster-randomized trials. Pooled subgroup estimates and statistical testing of the pooled interaction term were generated using inverse-variance weighting fixed effects. LNS, lipid-based nutrient supplement; P-interaction, P value for the interaction indicating the difference in effects of small-quantity lipid-based nutrient supplements between the 2 levels of the effect modifier; PR, prevalence ratio.
FIGURE 7
FIGURE 7
Pooled effect of small-quantity LNSs on stunting stratified by individual-level household characteristics. Individual study estimates for interaction effect were generated from log-binomial regression controlling for baseline measure when available and with clustered observations using robust SEs for cluster-randomized trials. Pooled subgroup estimates and statistical testing of the pooled interaction term were generated using inverse-variance weighting fixed effects. LNS, lipid-based nutrient supplement; P-interaction, P value for the interaction indicating the difference in effects of small-quantity lipid-based nutrient supplements between the 2 levels of the effect modifier; PR, prevalence ratio; SES, socioeconomic status.
FIGURE 8
FIGURE 8
Pooled effect of small-quantity LNSs on wasting stratified by individual-level maternal and child characteristics. Individual study estimates for interaction effect were generated from log-binomial regression controlling for baseline measure when available and with clustered observations using robust SEs for cluster-randomized trials. Pooled subgroup estimates and statistical testing of the pooled interaction term were generated using inverse-variance weighting fixed effects. LNS, lipid-based nutrient supplement; P-interaction, P value for the interaction indicating the difference in effects of small-quantity lipid-based nutrient supplements between the 2 levels of the effect modifier; PR, prevalence ratio.
FIGURE 9
FIGURE 9
Pooled effect of small-quantity LNSs on wasting stratified by individual-level household characteristics. Individual study estimates for interaction effect were generated from log-binomial regression controlling for baseline measure when available and with clustered observations using robust SEs for cluster-randomized trials. Pooled subgroup estimates and statistical testing of the pooled interaction term were generated using inverse-variance weighting fixed effects. LNS, lipid-based nutrient supplement; P-interaction, P value for the interaction indicating the difference in effects of small-quantity lipid-based nutrient supplements between the 2 levels of the effect modifier; PR, prevalence ratio; SES, socioeconomic status.
FIGURE 10
FIGURE 10
Overview of individual-level effect modification. The reference subgroup is the group expected to have the greatest potential to benefit. Green indicates a stronger effect in the reference subgroup, whereas blue indicates a stronger effect in the opposite subgroup. Box 1 provides subgroup definitions. Dark color indicates P-interaction < 0.05; light color indicates 0.05 < P < 0.1. The letter “C” indicates that the apparent effect modification is due to the cutoff effect; when “C” is in parentheses, it is partially explained by the cutoff effect. HCZ, head circumference-for-age z score; LAZ, length-for-age z score; MD, mean difference; MUAC, midupper arm circumference; MUACZ, midupper arm circumference-for-age z score; PD, prevalence difference; PR, prevalence ratio; SES, socioeconomic status; WAZ, weight-for-age z score; WLZ, weight-for-length z score.
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