Dataset Information

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.

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.

SUBMITTER: Dewey KG

PROVIDER: S-EPMC8560308 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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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.

Dewey Kathryn G KG Wessells K Ryan KR Arnold Charles D CD Prado Elizabeth L EL Abbeddou Souheila S Adu-Afarwuah Seth S Ali Hasmot H Arnold Benjamin F BF Ashorn Per P Ashorn Ulla U Ashraf Sania S Becquey Elodie E Bendabenda Jaden J Brown Kenneth H KH Christian Parul P Colford John M JM Dulience Sherlie J L SJL Fernald Lia C H LCH Galasso Emanuela E Hallamaa Lotta L Hess Sonja Y SY Humphrey Jean H JH Huybregts Lieven L Iannotti Lora L LL Jannat Kaniz K Lartey Anna A Le Port Agnes A Leroy Jef L JL Luby Stephen P SP Maleta Kenneth K Matias Susana L SL Mbuya Mduduzi N N MNN Mridha Malay K MK Nkhoma Minyanga M Null Clair C Paul Rina R RR Okronipa Harriet H Ouédraogo Jean-Bosco JB Pickering Amy J AJ Prendergast Andrew J AJ Ruel Marie M Shaikh Saijuddin S Weber Ann M AM Wolff Patricia P Zongrone Amanda A Stewart Christine P CP

The American journal of clinical nutrition 20211101 Suppl 1

<h4>Background</h4>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.<h4>Objectives</h4>We aimed to identify study-level and individual-level modifiers of the effect of SQ-LNSs on child growth outcomes.<h4>Methods</h4>We conducted a 2-stage meta-analysis of individual participant data from 14 randomized controlled trials of SQ-LNSs provided to ...[more]

PMID: 34590672

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Project description:BackgroundSmall-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.ObjectivesWe 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.MethodsWe 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.ResultsSQ-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.ConclusionsSQ-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.

Project description:BackgroundSmall vulnerable newborn types, defined by combinations of being born too soon or too small, have distinct determinants and health consequences. We aimed to assess the effects of prenatal multiple micronutrient supplementation (MMS) and small-quantity lipid-based nutrient supplementation (SQ-LNS) on small vulnerable newborn types, which are currently unknown.MethodsIn this meta-analysis, individual participant data from randomised controlled trials of MMS and randomised controlled trials of SQ-LNS in low-income and middle-income countries were used. We systematically searched the literature using PubMed, Embase, and Web of Science to identify randomised controlled trials of prenatal nutritional supplementation using MMS or SQ-LNS among pregnant people published between Jan 1, 2000, and Dec 31, 2021. Studies were excluded if they were conducted exclusively among participants selected by pre-existing health conditions, such as anaemia status, HIV infection, or diabetes. We contacted the corresponding authors of all identified studies to seek data contribution. As individual participant data became available, we mapped relevant variables and harmonised the data across studies. Iron and folic acid supplementation was the control group in most studies. Newborns were classified into ten groups through the combinations of preterm or term birth, small, appropriate, and large for gestational age, and low birthweight (LBW) or non-LBW. Newborns were also analysed using a four-group categorisation of preterm or term and LBW or non-LBW. Log-binomial models were used to estimate study-specific risk ratios (RRs), which were pooled using meta-analyses.Findings14 randomised controlled trials of MMS (n=42 618; the mean maternal age at study enrolment was 24·3 years [SD 5.6]; 22 086 [51·8%] male neonates and 20 532 [48·2%] female neonates) and four randomised controlled trials of SQ-LNS (n=6246; the mean maternal age at study enrolment was 23·3 years [SD 5·3]; 3137 [50·2%] male neonates and 3109 [49·8%] female neonates) were used. In the ten-group categorisation of small vulnerable newborns, prenatal MMS reduced the risk of preterm-small for gestational age (SGA)-LBW (RR 0·73, 95% CI 0·64-0·84; p=0·0003); preterm-appropriate for gestational age (AGA)-LBW (0·82, 0·74-0·91; p=0·0010); preterm-AGA-non-LBW (0·89, 0·80-0·98; p=0·019); term-SGA-LBW (0·91, 0·85-0·96; p=0·0046); and term-SGA-non-LBW (0·95, 0·90-1·00; p=0·050). In the four-group categorisation, prenatal MMS reduced the risk of preterm-SGA (0·71, 0·62-0·82; p=0·0002) and term-SGA (0·93, 0·89-0·98; p=0·0066). Prenatal SQ-LNS had no significant effects on the risk of giving birth to small vulnerable newborns except for preterm-large for gestational age-non-LBW in the ten-group categorisation (0·78, 0·65-0·94; p=0·023).InterpretationPrenatal MMS and SQ-LNS reduce the risk of giving birth to small vulnerable newborns to varying extents, with the greatest magnitude of effects observed for small vulnerable newborn types that confer the greatest neonatal mortality risk. This study underscores the importance of nutritional supplements in prenatal care.FundingBill & Melinda Gates Foundation.

Project description:BackgroundIt is estimated that over 250 million children under 5 years of age in low- and middle-income countries (LMICs) do not reach their full developmental potential. Poor maternal diet, anemia, and micronutrient deficiencies during pregnancy are associated with suboptimal neurodevelopmental outcomes in children. However, the effect of prenatal macronutrient and micronutrient supplementation on child development in LMIC settings remains unclear due to limited evidence from randomized trials.Methods and findingsWe conducted a 3-arm cluster-randomized trial (n = 53 clusters) that evaluated the efficacy of (1) prenatal multiple micronutrient supplementation (MMS; n = 18 clusters) and (2) lipid-based nutrient supplementation (LNS; n = 18 clusters) as compared to (3) routine iron-folic acid (IFA) supplementation (n = 17 clusters) among pregnant women in the rural district of Madarounfa, Niger, from March 2015 to August 2019 (ClinicalTrials.gov identifier NCT02145000). Children were followed until 2 years of age, and the Bayley Scales of Infant and Toddler Development III (BSID-III) were administered to children every 3 months from 6 to 24 months of age. Maternal report of WHO gross motor milestone achievement was assessed monthly from 3 to 24 months of age. An intention-to-treat analysis was followed. Child BSID-III data were available for 559, 492, and 581 singleton children in the MMS, LNS, and IFA groups, respectively. Child WHO motor milestone data were available for 691, 781, and 753 singleton children in the MMS, LNS, and IFA groups, respectively. Prenatal MMS had no effect on child BSID-III cognitive (standardized mean difference [SMD]: 0.21; 95% CI: -0.20, 0.62; p = 0.32), language (SMD: 0.16; 95% CI: -0.30, 0.61; p = 0.50) or motor scores (SMD: 0.18; 95% CI: -0.39, 0.74; p = 0.54) or on time to achievement of the WHO gross motor milestones as compared to IFA. Prenatal LNS had no effect on child BSID-III cognitive (SMD: 0.17; 95% CI: -0.15, 0.49; p = 0.29), language (SMD: 0.11; 95% CI: -0.22, 0.44; p = 0.53) or motor scores (SMD: -0.04; 95% CI: -0.46, 0.37; p = 0.85) at the 24-month endline visit as compared to IFA. However, the trajectory of BSID-III cognitive scores during the first 2 years of life differed between the groups with children in the LNS group having higher cognitive scores at 18 and 21 months (approximately 0.35 SD) as compared to the IFA group (p-value for difference in trajectory <0.001). Children whose mothers received LNS also had earlier achievement of sitting alone (hazard ratio [HR]: 1.57; 95% CI: 1.10 to 2.24; p = 0.01) and walking alone (1.52; 95% CI: 1.14 to 2.03; p = 0.004) as compared to IFA, but there was no effect on time to achievement of other motor milestones. A limitation of our study is that we assessed child development up to 2 years of age, and, therefore, we may have not captured effects that are easier to detect or emerge at older ages.ConclusionsThere was no benefit of prenatal MMS on child development outcomes up to 2 years of age as compared to IFA. There was evidence of an apparent positive effect of prenatal LNS on cognitive development trajectory and time to achievement of selected gross motor milestones.Trial registrationClinicalTrials.gov NCT02145000.

Project description:BackgroundUndernutrition during pregnancy increases the risk of giving birth to a small vulnerable newborn. Small-quantity lipid-based nutrient supplements (SQ-LNSs) contain both macro- and micronutrients and can help prevent multiple nutritional deficiencies.ObjectivesWe examined the effects of SQ-LNSs provided during pregnancy compared with 1) iron and folic acid or standard of care (IFA/SOC) or 2) multiple micronutrient supplements (MMSs) and identified characteristics that modified the estimates of effects of SQ-LNSs on birth outcomes.MethodsWe conducted a 2-stage meta-analysis of individual participant data from 4 randomized controlled trials of SQ-LNSs provided during pregnancy (n = 5273). We generated study-specific and subgroup estimates of SQ-LNS compared with IFA/SOC or MMS and pooled the estimates. In sensitivity analyses, we examined whether the results differed depending on methods for gestational age dating, birth anthropometry, or study design.ResultsSQ-LNSs (compared with IFA/SOC) increased birth weight [mean difference: +49 g; 95% confidence interval (CI): 26, 71 g] and all birth anthropometric z-scores (+0.10-0.13 standard deviation); they reduced risk of low birth weight by 11%, newborn stunting by 17%, newborn wasting by 11%, and small head size by 15%. Only 2 trials compared SQ-LNSs and MMSs; P values for birth outcomes were >0.10 except for head circumference (e.g., z-score for gestational age: +0.11; 95% CI: -0.01, 0.23). Effect estimates for SQ-LNSs compared with IFA/SOC were greater among female infants and, for certain outcomes, among mothers with body mass index <20 kg/m2, inflammation, malaria, or household food insecurity. Effect estimates for SQ-LNSs compared with MMSs were greater for certain outcomes among female infants, first-born infants, and mothers <25 y.ConclusionsSQ-LNSs had positive impacts on multiple outcomes compared to IFA/SOC, but further research directly comparing SQ-LNSs and MMSs is needed. Targeting SQ-LNSs to vulnerable subgroups may be worth considering.Clinical trial registryThis study was registered at PROSPERO as CRD42021283391.

Project description:BackgroundSmall-quantity (SQ) lipid-based nutrient supplements (LNSs) provide many nutrients needed for brain development.ObjectivesWe 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.MethodsWe 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).ResultsIn 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).ConclusionsChild 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.

Project description:Background: It is unknown whether self-reported measures of household food insecurity change in response to food-based nutrient supplementation.Objective: We assessed the impacts of providing lipid-based nutrient supplements (LNSs) to women during pregnancy and postpartum and/or to their children on self-reported household food insecurity in Malawi [DOSE and DYAD trial in Malawi (DYAD-M)], Ghana [DYAD trial in Ghana (DYAD-G)], and Bangladesh [Rang-Din Nutrition Study (RDNS) trial].Methods: Longitudinal household food-insecurity data were collected during 3 individually randomized trials and 1 cluster-randomized trial testing the efficacy or effectiveness of LNSs (generally 118 kcal/d). Seasonally adjusted Household Food Insecurity Access Scale (HFIAS) scores were constructed for 1127 DOSE households, 732 DYAD-M households, 1109 DYAD-G households, and 3671 RDNS households. The impact of providing LNSs to women during pregnancy and the first 6 mo postpartum and/or to their children from 6 to 18-24 mo on seasonally adjusted HFIAS scores was assessed by using negative binomial models (DOSE, DYAD-M, and DYAD-G trials) and mixed-effect negative binomial models (RDNS trial).Results: In the DOSE and DYAD-G trials, seasonally adjusted HFIAS scores were not different between the LNS and non-LNS groups. In the DYAD-M trial, the average household food-insecurity scores were 14% lower (P = 0.01) in LNS households than in non-LNS households. In the RDNS trial, compared with non-LNS households, food-insecurity scores were 17% lower (P = 0.02) during pregnancy and the first 6 mo postpartum and 15% lower (P = 0.02) at 6-24 mo postpartum in LNS households.Conclusions: The daily provision of LNSs to mothers and their children throughout much of the "first 1000 d" may improve household food security in some settings, which could be viewed as an additional benefit that may accrue in households should policy makers choose to invest in LNSs to promote child growth and development. These trials were registered at clinicaltrials.gov as NCT00945698 (DOSE) NCT01239693 (DYAD-M), NCT00970866 (DYAD-G) and NCT01715038 (RDNS).

Dataset Information

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

Objectives

Methods

Results

Conclusions

Publications

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.

Similar Datasets

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