Preventive lipid‐based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes

Jai K Das; Rehana A Salam; Yousaf Bashir Hadi; Sana Sadiq Sheikh; Afsah Z Bhutta; Zita Weise Prinzo; Zulfiqar A Bhutta

doi:10.1002/14651858.CD012611.pub3

Cochrane Database of Systematic Reviews

Preventive lipid‐based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes

Información

DOI:

https://doi.org/10.1002/14651858.CD012611.pub3 Copiar DOI

Base de datos:

Cochrane Database of Systematic Reviews

Versión publicada:

02 mayo 2019see what's new

Tipo:

Intervention

Etapa:

Review

Grupo Editorial Cochrane:

Grupo Cochrane de Problemas de desarrollo, psicosociales y de aprendizaje

Copyright:

Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Contraer

Autores

Jai K Das

Division of Women and Child Health, Aga Khan University Hospital, Karachi, Pakistan
Rehana A Salam

Division of Women and Child Health, Aga Khan University Hospital, Karachi, Pakistan
Yousaf Bashir Hadi

Department of Internal Medicine, West Virginia University, Morgantown, USA
Sana Sadiq Sheikh

Division of Women and Child Health, Aga Khan University Hospital, Karachi, Pakistan
Afsah Z Bhutta

Dow University of Health Sciences, Karachi, Pakistan
Zita Weise Prinzo

Department of Nutrition for Health and Development, World Health Organization, Geneva, Switzerland
Zulfiqar A Bhutta

Correspondencia a: Centre for Global Child Health, The Hospital for Sick Children, Toronto, Canada

[email protected]

[email protected]

Center for Excellence in Women and Child Health, Aga Khan University Hospital, Karachi, Pakistan

Contributions of authors

All review authors contributed to the development of the review.

Rehana A Salam (RAS), Yousaf Bashir, Sana Sadiq Sheikh and Afsah Zulfiqar Bhutta selected which studies to include, obtained copies of the studies and extracted data from the studies.
Jai K Das (JKD) and RAS entered data into RevMan, carried out the analysis and interpreted the results.
JKD, RAS, Zita Weise Prinzo and Zulfiqar A Bhutta (ZAB) drafted the final review.

As the contact author, ZAB has overall responsibility for the review.

Sources of support

Internal sources

Evidence and Programme Guidance, Department of Nutrition for Health and Development, World Health Organization (WHO), Switzerland.

Zita Weise Prinzo is a full‐time member of staff at the WHO
Aga Khan University, Karachi, Pakistan.

Jai K Das, Rehana A Salam, Sana Sadiq Sheikh and Zulfiqar A Bhutta are full‐time employees of Aga Khan University, Karachi

External sources

The Bill & Melinda Gates Foundation, USA.

WHO thanks the Bill & Melinda Gates Foundation for supporting the preparation of systematic reviews of the evidence of the effects and harms of nutrition and nutrition‐sensitive interventions.
Evidence and Programme Guidance, Department of Nutrition for Health and Development, WHO, Switzerland.

WHO provided financial support for this work.
Nutrition International, Canada.

WHO thank Nutrition International for supporting the Evidence and Programme Guidance Unit, Department of Nutrition for Health and Development, for the preparation of systematic reviews of the evidence of the effects and harms of nutrition and nutrition‐sensitive interventions.

Declarations of interest

We certify that we have no affiliations with, or involvement in, any organisation or entity with a direct financial interest in the subject matter of the review (e.g. employment, consultancy, stock ownership, honoraria, expert testimony).

Jai K Das ‐ none known.
Rehana A Salam ‐ none known.
Yousaf Bashir Hadi ‐ none known.
Sana Sadiq Sheikh ‐ none known.
Afsah Zulfiqar Bhutta ‐ none known.
Zita Weise Prinzo is a full‐time member of staff of the WHO.
Zulfiqar A Bhutta's institution was awarded a grant from the WHO to undertake this review.

The review authors alone are responsible for the views expressed in this publication; the views do not necessarily represent the official position, decisions, policy or views of the WHO.

Acknowledgements

We are grateful to the Cochrane Developmental, Psychosocial and Learning Problems editorial team for their support in the preparation of this review. We are also thankful to the four peers (a content editor, a statistical editor, and two reviewers who are external to the editorial team) who commented on the review.

The review was partially developed during the World Health Organization/Cochrane/Cornell University Summer Institute for Systematic Reviews in Nutrition Global Policy Making, hosted at the Division of Nutritional Sciences, Cornell University, Ithaca, USA, from 25 July to 5 August 2016.

We would like to acknowledge Nida Ashraf for assisting with the preliminary data extraction and analysis.

We acknowledge Kathryn Dewey (KD) who reviewed the draft meticulously and provided critical input, especially on the technical aspects of the intervention and methodological aspects of the studies of which she was Principal Investigator. KD had no role in finalising the findings and conclusions of the review.

Version history

Published

Title

Stage

Authors

Version

2019 May 02

Preventive lipid‐based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes

Review

Jai K Das, Rehana A Salam, Yousaf Bashir Hadi, Sana Sadiq Sheikh, Afsah Z Bhutta, Zita Weise Prinzo, Zulfiqar A Bhutta

https://doi.org/10.1002/14651858.CD012611.pub3

2019 Mar 29

Provision of preventive lipid‐based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes

Protocol

Jai K Das, Rehana A Salam, Zita Weise Prinzo, Sana Sadiq Sheikh, Zulfiqar A Bhutta

https://doi.org/10.1002/14651858.CD012611.pub2

2017 Mar 29

Provision of preventive lipid‐based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes

Protocol

Jai K Das, Rehana A Salam, Zita Weise Prinzo, Sana Sadiq Sheikh, Zulfiqar A Bhutta

https://doi.org/10.1002/14651858.CD012611

Differences between protocol and review

Subgroup analysis and investigation of heterogeneity

In our protocol (Das 2017), we had planned to conduct an analysis by 'duration of intervention' according to the following subgroups: 'less than three months versus three to six months versus six months or more'. However, in the review, we changed these subgroups to 'up to 6 months versus 6‐12 months versus more than 12 months', according to the findings of the included studies and to be more clinically relevant.

We had also planned to conduct an analysis by 'age at follow‐up' according to '6 to 11 months versus 12 to 23 months versus other' (Das 2017), but changed these in the review to the following subgroups: 'at 12 months versus at 18 months versus at 24 months versus at 36 months'. Again, this was done according to the findings of the included studies identified at the review stage, and to be more clinically relevant.

We could not conduct the following, preplanned subgroup analyses (Das 2017), since the included studies did not report this information.

Breastfeeding practices (breastfed versus not breastfed)
Frequency of intervention (daily versus weekly versus flexible)
Living in an emergency‐affected country (Wisner 2002) or in a refugee or internally displaced persons' camp (yes versus no)
Anaemic status of participants at start of intervention (anaemic (defined as haemoglobin values < 110 g/L) versus non anaemic or unknown status)

These exploratory analyses have been archived in Table 1 for use in future updates of this review.

Search methods

We searched the Database of Abstracts of Reviews of Effects (DARE) to find other reviews.

Inclusion criteria: Type of study

In our protocol, we had specified that we would be including randomised controlled trials (RCTs), quasi‐RCTs, controlled before‐and‐after studies (CBAs), and interrupted time series (ITS); however since almost all the included studies in the review were RCTs, we decided to restrict our inclusion to RCTs and quasi‐RCTs only, to strengthen the quality of the evidence.

Keywords

MeSH

Medical Subject Headings (MeSH) Keywords

Medical Subject Headings Check Words

Child, Preschool; Humans; Infant;

PICO

Population

Intervention

Comparison

Outcome

El uso y la enseñanza del modelo PICO están muy extendidos en el ámbito de la atención sanitaria basada en la evidencia para formular preguntas y estrategias de búsqueda y para caracterizar estudios o metanálisis clínicos. PICO son las siglas en inglés de cuatro posibles componentes de una pregunta de investigación: paciente, población o problema; intervención; comparación; desenlace (outcome).

Para saber más sobre el uso del modelo PICO, puede consultar el Manual Cochrane.

Figure 1

Study flow diagram.

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Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

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Figure 4

Forest plot of comparison: 1 LNS versus no intervention, outcome: 1.1 Moderate stunting.

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Figure 5

Forest plot of comparison: 1 LNS versus no intervention, outcome: 1.5 Moderate wasting.

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Analysis 1.1

Comparison 1 LNS versus no intervention, Outcome 1 Moderate stunting.

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Analysis 1.2

Comparison 1 LNS versus no intervention, Outcome 2 Severe stunting.

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Analysis 1.3

Comparison 1 LNS versus no intervention, Outcome 3 Moderate stunting: Sensitivity analysis.

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Analysis 1.4

Comparison 1 LNS versus no intervention, Outcome 4 Severe stunting: Sensitivity analysis.

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Analysis 1.5

Comparison 1 LNS versus no intervention, Outcome 5 Moderate wasting.

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Analysis 1.6

Comparison 1 LNS versus no intervention, Outcome 6 Severe wasting.

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Analysis 1.7

Comparison 1 LNS versus no intervention, Outcome 7 Moderate wasting: Sensitivity analysis.

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Analysis 1.8

Comparison 1 LNS versus no intervention, Outcome 8 Severe wasting: Sensitivity analysis.

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Analysis 1.9

Comparison 1 LNS versus no intervention, Outcome 9 Moderate underweight.

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Analysis 1.10

Comparison 1 LNS versus no intervention, Outcome 10 Severe underweight.

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Analysis 1.11

Comparison 1 LNS versus no intervention, Outcome 11 Moderate underweight: Sensitivity analysis.

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Analysis 1.12

Comparison 1 LNS versus no intervention, Outcome 12 Severe underweight: Sensitivity analysis.

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Analysis 1.13

Comparison 1 LNS versus no intervention, Outcome 13 Anaemia.

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Analysis 1.14

Comparison 1 LNS versus no intervention, Outcome 14 Adverse effects.

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Analysis 1.15

Comparison 1 LNS versus no intervention, Outcome 15 Adverse effects: Sensitivity analysis.

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Analysis 1.16

Comparison 1 LNS versus no intervention, Outcome 16 Mid‐upper arm circumference (MUAC).

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Analysis 1.17

Comparison 1 LNS versus no intervention, Outcome 17 Serum haemoglobin (g/L).

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Analysis 1.18

Comparison 1 LNS versus no intervention, Outcome 18 Mortality.

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Analysis 1.19

Comparison 1 LNS versus no intervention, Outcome 19 HAZ.

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Analysis 1.20

Comparison 1 LNS versus no intervention, Outcome 20 WAZ.

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Analysis 1.21

Comparison 1 LNS versus no intervention, Outcome 21 WHZ.

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Analysis 2.1

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 1 Severe stunting.

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Analysis 2.2

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 2 Moderate stunting.

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Analysis 2.3

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 3 Moderate wasting.

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Analysis 2.4

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 4 Severe wasting.

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Analysis 2.5

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 5 Moderate underweight.

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Analysis 2.6

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 6 Severe underweight.

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Analysis 2.7

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 7 Anaemia.

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Analysis 2.8

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 8 Adverse effects.

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Analysis 2.9

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 9 Mid‐upper arm circumference (MUAC).

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Analysis 2.10

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 10 Serum haemoglobin (g/L).

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Analysis 2.11

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 11 Mortality.

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Analysis 2.12

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 12 HAZ.

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Analysis 2.13

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 13 WHZ.

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Analysis 2.14

Comparison 2 LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided, Outcome 14 WAZ.

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Analysis 3.1

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 1 Moderate stunting.

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Analysis 3.2

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 2 Severe stunting.

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Analysis 3.3

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 3 Moderate wasting.

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Analysis 3.4

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 4 Severe wasting: 6 to 12 months.

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Analysis 3.5

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 5 Moderate underweight.

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Analysis 3.6

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 6 Severe underweight: 6 to 12 months.

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Analysis 3.7

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 7 Anaemia.

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Analysis 3.8

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 8 Adverse effects.

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Analysis 3.9

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 9 Mid‐upper arm circumference (MUAC).

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Analysis 3.10

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 10 Serum haemoglobin (g/L).

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Analysis 3.11

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 11 Mortality.

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Analysis 3.12

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 12 HAZ.

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Analysis 3.13

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 13 WAZ.

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Analysis 3.14

Comparison 3 LNS versus no intervention: Subgroup analysis by duration of intervention, Outcome 14 WHZ.

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Analysis 4.1

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 1 Moderate stunting.

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Analysis 4.2

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 2 Severe stunting.

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Analysis 4.3

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 3 Moderate wasting.

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Analysis 4.4

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 4 Severe wasting.

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Analysis 4.5

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 5 Moderate underweight.

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Analysis 4.6

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 6 Severe underweight: at 18 months.

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Analysis 4.7

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 7 Anaemia.

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Analysis 4.8

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 8 Adverse effects: At 18 months.

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Analysis 4.9

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 9 Mid‐upper arm circumference (MUAC).

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Analysis 4.10

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 10 Serum haemoglobin (g/L).

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Analysis 4.11

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 11 Mortality.

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Analysis 4.12

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 12 HAZ.

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Analysis 4.13

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 13 WAZ.

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Analysis 4.14

Comparison 4 LNS versus no intervention: Subgroup analysis by age at follow‐up, Outcome 14 WHZ.

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Analysis 5.1

Comparison 5 LNS versus fortified blended food (FBF), Outcome 1 Moderate stunting.

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Analysis 5.2

Comparison 5 LNS versus fortified blended food (FBF), Outcome 2 Severe stunting.

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Analysis 5.3

Comparison 5 LNS versus fortified blended food (FBF), Outcome 3 Moderate wasting.

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Analysis 5.4

Comparison 5 LNS versus fortified blended food (FBF), Outcome 4 Severe wasting.

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Analysis 5.5

Comparison 5 LNS versus fortified blended food (FBF), Outcome 5 Moderate underweight.

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Analysis 5.6

Comparison 5 LNS versus fortified blended food (FBF), Outcome 6 Severe underweight.

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Analysis 5.7

Comparison 5 LNS versus fortified blended food (FBF), Outcome 7 MUAC.

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Analysis 5.8

Comparison 5 LNS versus fortified blended food (FBF), Outcome 8 Haemoglobin (g/L).

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Analysis 5.9

Comparison 5 LNS versus fortified blended food (FBF), Outcome 9 HAZ.

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Analysis 5.10

Comparison 5 LNS versus fortified blended food (FBF), Outcome 10 WAZ.

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Analysis 5.11

Comparison 5 LNS versus fortified blended food (FBF), Outcome 11 WHZ.

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Analysis 6.1

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 1 Moderate stunting.

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Analysis 6.2

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 2 Moderate wasting.

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Analysis 6.3

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 3 Moderate underweight.

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Analysis 6.4

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 4 Anaemia.

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Analysis 6.5

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 5 Anaemia: Sensitivity analysis.

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Analysis 6.6

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 6 Serum haemoglobin (g/L).

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Analysis 6.7

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 7 Serum haemoglobin (g/L): Sensitivity analysis.

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Analysis 6.8

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 8 HAZ.

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Analysis 6.9

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 9 HAZ: Sensitivity analysis.

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Analysis 6.10

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 10 WAZ.

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Analysis 6.11

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 11 WAZ: Sensitivity analysis.

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Analysis 6.12

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 12 WHZ.

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Analysis 6.13

Comparison 6 LNS versus micronutrient powders (MNP), Outcome 13 WHZ: Sensitivity analysis.

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LNS plus complementary feeding compared with no intervention
Patient or population: children aged 6 to 23 months Settings: community Intervention: LNS plus complementary feeding Comparison: no intervention
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	No intervention	LNS plus complementary feeding
*Stunting*
Moderate stunting Measured as height‐for‐age z score < −2 SD Measured at 12, 18 and 24 months of age	2618/7137	2353/7060	RR 0.93 (0.88 to 0.98)	13,372 (9 studies)	⊕⊕⊕⊝ Moderate^a	2 studies, Kumwenda 2014 and Mangani 2015, contributed data to multiple comparisons; total number of comparisons = 13
Severe stunting Measured as height‐for‐age z score < −3 SD Measured at 12, 18 and 24 months of age	471/4188	290/2868	RR 0.85 (0.74 to 0.98)	6151 (5 studies)	⊕⊕⊕⊝ Moderate^a	2 studies, Kumwenda 2014 and Mangani 2015, contributed data to multiple comparisons; total number of comparisons = 9
*Wasting*
Moderate wasting Measured as weight‐for‐height z score < −2 SD Measured at 12, 18 and 24 months of age	695/6213	624/6959	RR 0.82 (0.74 to 0.91)	13,172 (8 studies)	⊕⊕⊕⊝ Moderate^a	1 study, Kumwenda 2014, contributed data to 2 comparisons; total number of comparisons = 11
Severe wasting Measured as weight‐for‐height z score < −3 SD Measured at 12 and 18 months of age	18/1636	21/1663	RR 1.27 (0.66 to 2.46)	2329 (3 studies)	⊕⊕⊕⊕ Moderate^b	1 study, Kumwenda 2014, contributed data to 4 comparisons; total number of comparisons = 6
Underweight
Moderate underweight Measured as weight‐for‐age z score < −2 SD Measured at 12, 18 and 24 months of age	1723/7013	1525/6861	RR 0.85 (0.80 to 0.91)	13,073 (8 studies)	⊕⊕⊕⊝ Moderate^a	1 study, Kumwenda 2014, contributed data to 4 comparisons; total number of comparisons = 11
Severe underweight Measured as weight‐for‐age z score < −3 SD Measured at 12 and 18 months of age	62/1224	50/1258	RR 0.78 (0.54 to 1.13)	1729 (2 studies)	⊕⊕⊕⊕ Moderate^b	1 study, Kumwenda 2014, contributed data to 4 comparisons; total number of comparisons = 5
Anaemia Measured as haemoglobin < 10 g/dL Measured at 12, 18 and 24 months of age	697/1359	558/973	RR 0.79 (0.69 to 0.90)	2332 (5 studies)	⊕⊕⊝⊝ Low^a,c	‐
Adverse effects Defined as deaths, hospitalisations, congenital abnormalities and life‐threatening conditions requiring an immediate hospital visit Assessed at 12 and 18 months of age	314/1369	401/2333	RR 0.86 (0.74 to 1.01)	3382 (3 studies)	⊕⊕⊕⊝ Moderate^a	1 study, Kumwenda 2014, contributed data to 2 comparisons; total number of comparisons = 4
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; LNS: lipid‐based nutrient supplement; RR: risk ratio; SD: standard deviation
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.
^aDowngraded one level due to study limitations: high risk of selection bias (inadequate sequence generation process) in one study (Adu‐Afarwuah 2007); high risk of performance bias in seven studies (Adu‐Afarwuah 2016; Ashorn 2015; Christian 2015; Dewey 2017; Hess 2015; Luby 2018; Null 2018); and high risk of detection bias in one study (Christian 2015). ^bDowngraded one level due to inconsistency (I² = 88%). ^cDowngraded one level due to imprecision.

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LNS plus complementary feeding compared with fortified blended food (FBF)
Patient or population: children aged 6 to 23 months Settings: community Intervention: LNS plus complementary feeding Comparison: FBF
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	FBF	LNS plus complementary feeding
*Stunting*
Moderate stunting Measured as height‐for‐age z score < −2 SD Measured at 12 months and 18 months of age	461/1048	735/1829	RR 0.89 (0.82 to 0.97)	2828 (3 studies)	⊕⊕⊕⊝ Moderate^a	1 study, Phuka 2008, contributed data to 2 comparisons; total number of comparisons = 4
Severe stunting Measured as height‐for‐age z score < −3 SD Measured at 12 months and 18 months of age	43/292	53/493	RR 0.41 (0.12 to 1.42)	729 (2 studies)	⊕⊕⊕⊝ Low^a,b	1 study, Phuka 2008, contributed data to 2 comparisons; total number of comparisons = 3
*Wasting*
Moderate wasting Measured as weight‐for‐height z score < −2 SD Measured at 12 months and 18 months of age	145/886	195/1462	RR 0.79 (0.65 to 0.97)	2290 (2 studies)	⊕⊕⊕⊝ Moderate^a	1 study, Phuka 2008, contributed data to 2 comparisons; total number of comparisons = 3
Severe wasting Measured as weight‐for‐height z score < −3 SD Measured at 12 months and 18 months of age	5/296	5/497	RR 0.64 (0.19 to 2.18)	735 (2 studies)	⊕⊕⊕⊝ Moderate^a	1 study, Phuka 2008, contributed data to 2 comparisons; total number of comparisons = 3
*Underweight*
Moderate underweight Measured as weight‐for‐age z score < −2 SD Measured at 12 months and 18 months of age	355/876	478/1457	RR 0.81 (0.73 to 0.91)	2280 (2 studies)	⊕⊕⊕⊝ Moderate^a	1 study, Phuka 2008, contributed data to 2 comparisons; total number of comparisons = 3
Severe underweight Measured as weight‐for‐age z score < −3 SD Measured at 12 months of age	34/722	60/1505	RR 1.23 (0.67 to 2.25)	173 (1 study)	⊕⊕⊝⊝ Low^a,c	1 study, Phuka 2008, contributed data to 2 arms to this analysis; total number of comparisons = 2
Anaemia						None of the included studies reported this outcome
Adverse effects						None of the included studies reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; LNS: lipid‐based nutrient supplements; RR: Risk Ratio; SD: Standard deviation.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate
^aDowngraded one level due to study limitations: high risk of performance bias in two studies (Christian 2015; Phuka 2008). ^bDowngraded one level due to imprecision (high heterogeneity; I² = 57%). ^cDowngraded one level due to small sample size.

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LNS plus complementary feeding compared with micronutrient powders (MNP)
Patient or population: children aged 6 to 23 months Settings: community Intervention: LNS plus complementary feeding Comparison: MNP
Outcomes	*Illustrative comparative risks (95% CI)**		Relative effect (95% CI)	Number of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	MNP	LNS plus complementary feeding
Moderate stunting Measured as height‐for‐age z score < −2 SD Measured at 12 months and 24 months of age	421/1059	336/945	RR 0.92 (0.82 to 1.02)	2365 (3 studies)	⊕⊕⊕⊝ Moderate^a	‐
Moderate wasting Measured as weight‐for‐height z score < −2 SD Measured at 12 months and 24 months of age	133/1059	115/945	RR 0.97 (0.77 to 1.23)	2004 (2 studies)	⊕⊕⊕⊝ Moderate^a	‐
Moderate underweight Measured as weight‐for‐age z score < −2 SD Measured at 12 months and 24 months of age	376/1059	292/945	RR 0.88 (0.78 to 0.99)	2004 (2 studies)	⊕⊕⊕⊝ Moderate^a	‐
Anaemia Measured as haemoglobin < 10 g/dL Measured at 12 months of age	18/98	10/98	RR 0.38 (0.21 to 0.68)	557 (2 studies)	⊕⊕⊝⊝ Low^a,b	‐
Adverse effects						None of the included studies reported this outcome
The basis for the assumed risk* (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; LNS: Lipid‐based nutrient supplements; RR: Risk ratio; SD: Standard deviation.
GRADE Working Group grades of evidence High quality: further research is very unlikely to change our confidence in the estimate of effect Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate Very low quality: we are very uncertain about the estimate
^aDowngraded one level due to study limitations: high risk of performance bias in two studies (Adu‐Afarwuah 2016; Dewey 2017). ^bDowngraded one level due to small sample size.

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Table 1. Unused methods

Method	Approach
Measures of treatment effects	Rates If rates represent events that could occur more than once per participant, we will report the rate difference using the methodologies described in Deeks 2011.
Unit of analysis issues	Cluster‐randomised trials We will follow the methods described in theCochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b), and adjust the sample sizes or standard errors of cluster‐randomised trials by using an estimate of the intra‐cluster correlation co‐efficient (ICC) derived from the study (if possible), from a similar trial or from a study of a similar population. If we use ICCs from other sources, we will report this in the results section, and conduct sensitivity analyses to investigate the effect of variation in the ICC. We will acknowledge heterogeneity in the randomisation unit and perform a sensitivity analysis to investigate the effects of the randomisation unit in the future updates of the review, if applicable.
Dealing with missing data	If we find studies with high levels of missing data, we will explore the effect in the overall assessment of treatment effect by removing such studies and conducting a sensitivity analysis.
Assessment of reporting bias	If we include 10 or more studies in a meta‐analysis, we will investigate reporting biases (such as publication bias) using funnel plots. We will assess funnel plot asymmetry visually, and use formal tests for funnel plot asymmetry. For continuous outcomes, we will use the test proposed by Egger 1997. For dichotomous outcomes, we will use the test proposed by Harbord 2006. If asymmetry is detected in any of these tests or is suggested by a visual assessment, we will perform exploratory analyses to investigate it.
Subgroup analysis and investigation of heterogeneity	We will conduct exploratory subgroup analyses on the primary outcomes, irrespective of heterogeneity, when there are more than three studies contributing data. We will conduct the following analyses. Breastfeeding practices (breastfed versus not breastfed) Frequency of intervention (daily versus weekly versus flexible) Living in an emergency‐affected country (Wisner 2002), or in a refugee or internally displaced persons' camp (yes verus no) Anaemic status of participants at start of intervention (anaemic (defined as haemoglobin values < 110 g/L) versus non‐anaemic or unknown status).
Sensitivity analysis	We will carry out a sensitivity analysis to examine: the effect of removing non‐randomised studies from the analysis; and the effects of different ICCs, and the randomisation unit, for cluster trials (if these are included).
ICC: Intra‐class correlation coefficient; WHO: World Health Organization.

Table 1. Unused methods

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Table 2. Composition of LNS

Study	Total energy	Lipid content	Protein Content	Micronutrients
Adu‐Afarwuah 2007	108 kcal (20 g/day)	linoleic acid (1.29 g); linolenic acid (0.29 g)	Not specified	Carotene (400 μg RE); vitamin C (30 mg); folic acid (80 g); thiamine (0.3 mg); riboflavin (0.4 mg); vitamin B3 (4 mg); pantothenic acid (1.8 mg); vitamin B6 (0.3 mg); vitamin B12 (0.5 g); iron sulphate (9 mg); zinc sulphate (4 mg); calcium phosphate (100 mg); potassium (152 mg); copper sulphate (0.2 mg); sodium selenite (10 ug); potassium iodate (90 ug); phosphate (82 mg); magnesium (16 mg); manganese (0.08 mg); phytate (82 mg)
Adu‐Afarwuah 2016	118 kcal (20 g/day)	9.6 g	2.6 g	Linoleic acid (4.46 g); α‐linolenic acid (0.58 g); vitamin A (400 mg retinol equivalents); thiamine (0.3 mg); riboflavin (0.4 mg); niacin (4 mg); vitamin B6 (0.3 mg); vitamin B12 (0.5 mg); vitamin C (30 mg); vitamin D (5 mg); vitamin E (6 mg); vitamin K (30 mg); folic acid (80 mg); pantothenic acid (1.8 mg); iron (6 mg); zinc (8 mg); copper (0.34 mg); calcium (280 mg); phosphorus (190 mg); potassium (200 mg); magnesium (40 mg); selenium (20 mg); iodine (90 mg); manganese (1.2 mg)
Ashorn 2015	118 kcal (20 g/day)	9.6 g	2.6 g	Linoleic acid (4.46 g); a‐linolenic acid (0.58 g); vitamin A (400 mg RE); vitamin C (30 mg); vitamin B1 (0.3 mg); vitamin B2 (0.4 mg); niacin (4 mg); folic acid (80 mg); pantothenic acid (1.8 mg); vitamin B6 (0.3 mg); vitamin B12 (0.5 mg); vitamin D (5 mg); vitamin E (6 mg); vitamin K (30 mg); iron (6 mg); zinc (8 mg); copper (0.34 mg); calcium (280 mg); phosphorus (190 mg); potassium (200 mg); magnesium (40 mg); selenium (20 mg); iodine (90 mg); manganese (1.2 mg)
Bisimwa 2012	275 kcal (50 g/day)	Not specified	Not specified	Vitamin A (412 IU); vitamin D (307 IU); vitamin C (75 mg); thiamine (0.7 mg); riboflavin (1.0 mg); vitamin B12 (1.0 μg); pyridoxine (0.24 mg); niacin (10.3 mg); pantothenic acid (3.8 mg); folic acid (0.07 mg); vitamin K (0.01 mg); calcium (514 mg); phosphorus (265 mg); iron (9.5 mg); zinc (8.3 mg); copper (0.3 mg); iodine (0.07 mg); selenium (0.003 mg); magnesium (23.4 mg); phytic acid (0.425 mg²); phytic acid:iron molar ratio² (2.1); phytic acid:zinc molar ratio² (1.9)
Christian 2015	250 kcal (46 g/day)	Not specified	Not specified	Not specified
Dewey 2017	118 kcal (20 g/day)	9.6 g	2.6 g	Linoleic acid (4.46 g); α‐linolenic acid (0.58 g); vitamin A (400 mg RE); thiamine (0.5 mg); riboflavin (0.5 mg); niacin (6 mg); folic acid (150 mg); pantothenic acid (2 mg); vitamin B6 (0.5 mg); vitamin B12 (0.9 mg); vitamin C (30 mg); vitamin D (5 mg); vitamin E (6 mg); vitamin K (30 mg); calcium (280 mg); copper (0.34 mg); iodine (90 mg); iron (9 mg); magnesium (40 mg); manganese (1.2 mg); phosphorus (190 mg); potassium (200 mg); selenium (20 mg); zinc (8 mg)
Hess 2015	118 kcal (20 g/day)	9.6 g	2.6 g	Linoleic acid (4.46 g); α‐Linolenic acid (0.58 g); vitamin A (400 mg); thiamine (0.3 mg); riboflavin (0.4 mg); niacin (4 mg); pantothenic acid (1.8 mg); vitamin B6 (0.3 mg); vitamin B12 (0.5 mg); folic acid (80 mg); vitamin C (30 mg); vitamin D (5 mg); vitamin E (6 mg); vitamin K (30 mg); calcium (280 mg); copper (0.34 mg); iodine (90 mg); iron (6 mg); magnesium (40 mg); manganese (1.2 mg); phosphorus (190 mg); potassium (200 mg); selenium (20 μg); zinc (0 mg)
Huybregts 2012	247 kcal (46 g/day)	16 g	5.9 g	Linoleic acid (2 g); α‐linolenic acid (0.3 g); vitamin A (400 mg); vitamin E (6 mg); thiamine (0.5 mg); niacin (6 mg); pantothenic acid (2 mg); vitamin B6 (0.5 mg); folic acid (160 mg); vitamin B12 (0.9 mg); vitamin C (30 mg); magnesium (60 mg); zinc (4 mg); iron (9 mg); copper (0.3 mg); potassium (310 mg); calcium (387 mg); phosphorus (275 mg); selenium (17 mg); manganese (0.17 mg); iodine (90 mg)
Iannotti 2014	108 kcal (20 g/day)	7.08 g	2.56 g	Linoleic acid (1.29 g); α‐linoleic acid (0.29 g); vitamin A (400 mg); thiamine (0.3 mg); riboflavin (0.4 mg); niacin (4 mg); pantothenic acid (1.8 mg); vitamin B6 (0.3 mg); vitamin B12 (0.5 mg); folic acid (80 mg); vitamin C (30 mg); calcium (100 mg); copper (0.2 mg); iodine (90 mg); iron (9 mg); magnesium (16 mg); manganese (0.08 mg); phosphorus (82.2 mg); potassium (152 mg); selenium (10 mg); zinc (4 mg)
Kumwenda 2014	55 kcal (10 g/day)	4.7 g	1.3 g	Linoleic acid (2.22 g); α‐linolenic acid (0.29 g); vitamin A (400 μg RE); vitamin C (30 mg); vitamin B1 (0.3 mg); vitamin B2 (0.4 mg); niacin (4 mg); folic acid (80 μg); pantothenic acid (1.8 mg); vitamin B6 (0.3 mg); vitamin B12 (0.5 μg); vitamin D (200 IU); vitamin E (6 6 mg); vitamin K (30 μg); iron (6 mg); zinc (8 mg); copper (0.34 mg); calcium (240 mg); phosphorus (208 mg); potassium (265 mg); magnesium (50 mg); selenium (20 μg); iodine (90 μg); manganese (1.2 mg); phytate (28 mg)
	17 kcal (20 g/day)	9.5 g	2.5 g	Linoleic acid (4.44 g); α‐linolenic acid (0.58 g); vitamin A (400 μg RE); vitamin C (30 mg); vitamin B1 (0.3 mg); vitamin B2 (0.4 mg); niacin (4 mg); folic acid (80 μg); pantothenic acid (1.8 mg); vitamin B6 (0.3 mg); vitamin B12 (0.5 μg); vitamin D (200 IU); vitamin E (6 6 mg); vitamin K (30 μg); iron (6 mg); zinc (8 mg); copper (0.34 mg); calcium (240 mg); phosphorus (208 mg); potassium (265 mg); magnesium (50 mg); selenium (20 μg); iodine (90 μg); manganese (1.2 mg); phytate (56 mg)
	241 kcal (40 g/day)	18.9 g	5 g	Linoleic acid (8.88 g); α‐linolenic acid (1.16 g); vitamin A (400 μg RE); vitamin C (30 mg); vitamin B1 (0.3 mg); vitamin B2 (0.4 mg); niacin (4 mg); folic acid (80 μg); pantothenic acid (1.8 mg); vitamin B6 (0.3 mg); vitamin B12 (0.5 μg); vitamin D (200 IU); vitamin E (6 6 mg); vitamin K (30 μg); iron (6 mg); zinc (8 mg); copper (0.34 mg); calcium (240 mg); phosphorus (208 mg); potassium (265 mg); magnesium (50 mg); selenium (20 μg); iodine (90 μg); manganese (1.2 mg); phytate (112 mg)
Luby 2018	118 kcal (20 g/day)	9.6 g	2.6 g	Linoleic acid (4.46 g); Alpha‐linolenic acid (0.58 g); Vitamin A (400 μg); Vitamin D (5 μg); Vitamin E (6 mg); Vitamin K (30 μg); Vitamin C (30 mg) Folic acid (150 μg); Thiamine (B1) (0.5 mg); Riboflavin (B2) (0.5 mg); Niacin (6 mg); Pantothenic acid (B5) (2 mg); Vitamin B6 (0.5 mg); Vitamin B12 (0.9 μg); Calcium (280 mg); Copper (0.34 mg); Iodine (90 μg); Iron (9 mg); Magnesium (40 mg); Manganese (1.2 mg); Phosphorous (190 mg); Potassium (200 mg); Selenium (20 μg); Zinc (8 mg)
Mangani 2015	Milk‐LNS 284.8 kcal (54 g/day)	17.9 g	8.2 g	Retinol (400 μg RE); folate (160 μg); niacin (6 mg); pantothenic acid (2 mg); riboflavin (0.5 mg); thiamine (0.5 mg); vitamin B6 (0.5 mg); vitamin B12 (0.9 μg); vitamin C (30 mg); vitamin D (5 μg); calcium (366 mg); copper (0.4 mg); iodine (90 μg); iron (6 mg); magnesium (78.5 mg); selenium (20 μg); zinc (6.0 mg); phosphorus (185.6 mg); potassium (318.6 mg); manganese (0.60 mg)
Mangani 2015	Soy‐LNS 276.1 kcal (54 g/day)	18.5 g	7.5 g	Retinol (400 μg RE); folate (160 μg); niacin (6 mg); pantothenic acid (2 mg); riboflavin (0.5 mg); thiamine (0.5 mg); vitamin B6 (0.5 mg); vitamin B12 (0.9 μg); vitamin C (30 mg); vitamin D (5 μg); calcium (366 mg); copper (0.4 mg); iodine (90 μg); iron (6 mg); magnesium (78.5 mg); selenium (20 μg); zinc (6.0 mg); phosphorus (185.6 mg); potassium (307.3 mg); manganese (0.60 mg)
Matias 2017	110 kcal (20 g/day)	7 g	2.6 g	Linoleic acid (1.29 g); α‐linolenic acid (0.29 g); folic acid (80 μg); niacin (4 mg); pantothenic acid (1.8 mg); riboflavin (0.4 mg); thiamine (0.3 mg); vitamin A (400 μg); vitamin B12 (0.5 μg); vitamin B6 (0.3 mg); vitamin C (30 mg); calcium (100 mg); copper (0.2 mg); iodine (90 μg); iron (9 mg); magnesium (16 mg); manganese (0,08 mg); phosphorous (82 mg); potassium (152 mg); selenium (10 μg); zinc (4 mg)
Null 2018	118 kcal (20 g/day)	9.6 g	2.6 g	Linoleic acid (4.46 g); Alpha‐linolenic acid (0.58 g); Vitamin A (400 μg); Vitamin D (5 μg); Vitamin E (6 mg); Vitamin K (30 μg); Vitamin C (30 mg) Folic acid (150 μg); Thiamine (B1) (0.5 mg); Riboflavin (B2) (0.5 mg); Niacin (6 mg); Pantothenic acid (B5) (2 mg); Vitamin B6 (0.5 mg); Vitamin B12 (0.9 μg); Calcium (280 mg); Copper (0.34 mg); Iodine (90 μg); Iron (9 mg); Magnesium (40 mg); Manganese (1.2 mg); Phosphorous (190 mg); Potassium (200 mg); Selenium (20 μg); Zinc (8 mg)
Olney 2018	118 kcal (20 g/day)	9.6 g	2.6 g	Linoleic acid (4.5 g); α‐linolenic acid (0.6 g); vitamin A (400 μg); vitamin C (30 mg); vitamin D (5 mg); vitamin E (6 mg); vitamin K (30 mg); thiamine (0.5 mg); riboflavin (0.5 mg); niacin (6 mg); pantothenic acid (2 mg); vitamin B6 (0.5 mg); folic acid (150 μg); vitamin B12 (0.9 μg); iron (9 mg); zinc (8 mg); copper (0.3 mg); selenium (20 μg); iodine (90 μg); calcium (280 mg); magnesium (40 mg); manganese (1.2 mg); phosphorus (190 mg); potassium (200 mg)
Phuka 2008	130 kcal (25 g/day)	8.3 g	3.8 g	Retinol (400 mg RE); folate (160 mg); niacin (6 mg); pantothenic acid (2 mg); riboflavin (0.5 mg); thiamine (0.5 mg); vitamin B 6 (0.5 mg); vitamin B12 (0.9 mg); vitamin C (30 mg); vitamin D (5 mg); calcium (283 mg); copper (0.5 mg); iodine (90 mg); iron (8 mg); magnesium (60 mg); selenium (17 mg); zinc (8.4 mg)
Phuka 2008	264 kcal (50 g/day)	16.5 g	7.6 g	Retinol (400 mg RE); folate (160 mg); niacin (6 mg); pantothenic acid (2 mg); riboflavin (0.5 mg); thiamine (0.5 mg); vitamin B6 (0.5 mg); vitamin B12 (0.9 mg); vitamin C (30 mg); vitamin D (5 mg); calcium (366 mg); copper (0.4 mg); iodine (90 mg); iron (8 mg); magnesium (60 mg); selenium (17 mg); zinc (8.4 mg)
Siega‐Riz 2014	247 kcal (46.4 g/day)	16 g	5.9 g	Vitamin A (400 μg); vitamin B12 (0.9 μg); iron (9 mg); zinc (9 mg)
g: gram; LNS: lipid‐based nutrient supplements mg: milligram

Table 2. Composition of LNS

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Comparison 1. LNS versus no intervention

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Moderate stunting Show forest plot	9	13372	Risk Ratio (Random, 95% CI)	0.93 [0.88, 0.98]

2 Severe stunting Show forest plot	5	6151	Risk Ratio (Random, 95% CI)	0.85 [0.74, 0.98]

3 Moderate stunting: Sensitivity analysis Show forest plot	7		Risk Ratio (Random, 95% CI)	0.92 [0.88, 0.96]

4 Severe stunting: Sensitivity analysis Show forest plot	4		Risk Ratio (Random, 95% CI)	0.84 [0.73, 0.97]

5 Moderate wasting Show forest plot	8	13172	Risk Ratio (Random, 95% CI)	0.82 [0.74, 0.91]

6 Severe wasting Show forest plot	3	2329	Risk Ratio (Random, 95% CI)	1.27 [0.66, 2.46]

7 Moderate wasting: Sensitivity analysis Show forest plot	6		Risk Ratio (Random, 95% CI)	0.81 [0.73, 0.90]

8 Severe wasting: Sensitivity analysis Show forest plot	2		Risk Ratio (Random, 95% CI)	1.24 [0.61, 2.51]

9 Moderate underweight Show forest plot	8	13073	Risk Ratio (Random, 95% CI)	0.85 [0.80, 0.91]

10 Severe underweight Show forest plot	2	1729	Risk Ratio (Random, 95% CI)	0.78 [0.54, 1.13]

11 Moderate underweight: Sensitivity analysis Show forest plot	6		Risk Ratio (Random, 95% CI)	0.85 [0.80, 0.90]

12 Severe underweight: Sensitivity analysis Show forest plot	1		Risk Ratio (Random, 95% CI)	0.79 [0.54, 1.16]

13 Anaemia Show forest plot	5	2332	Risk Ratio (Random, 95% CI)	0.79 [0.69, 0.90]

14 Adverse effects Show forest plot	3	3382	Risk Ratio (Random, 95% CI)	0.86 [0.74, 1.01]

15 Adverse effects: Sensitivity analysis Show forest plot	1	1932	Risk Ratio (Random, 95% CI)	0.76 [0.60, 0.95]

16 Mid‐upper arm circumference (MUAC) Show forest plot	6	8187	Std. Mean Difference (Random, 95% CI)	0.13 [0.05, 0.22]

17 Serum haemoglobin (g/L) Show forest plot	4	4518	Mean Difference (Random, 95% CI)	5.78 [2.27, 9.30]

18 Mortality Show forest plot	3	3321	Risk Ratio (Random, 95% CI)	0.93 [0.63, 1.37]

19 HAZ Show forest plot	12	15795	Std. Mean Difference (Random, 95% CI)	0.11 [0.05, 0.16]

20 WAZ Show forest plot	10	12188	Std. Mean Difference (Random, 95% CI)	0.09 [0.02, 0.16]

21 WHZ Show forest plot	10	12894	Std. Mean Difference (Random, 95% CI)	0.08 [0.04, 0.13]

Comparison 1. LNS versus no intervention

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Comparison 2. LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Severe stunting Show forest plot	5	6151	Risk Ratio (Random, 95% CI)	0.85 [0.74, 0.98]

1.1 SQ LNS	4	4956	Risk Ratio (Random, 95% CI)	0.83 [0.70, 0.99]
1.2 MQ LNS	2	1195	Risk Ratio (Random, 95% CI)	0.88 [0.69, 1.12]
2 Moderate stunting Show forest plot	9	13372	Risk Ratio (Random, 95% CI)	0.93 [0.88, 0.98]

2.1 SQ LNS	7	9710	Risk Ratio (Random, 95% CI)	0.92 [0.84, 1.00]
2.2 MQ LNS	3	3662	Risk Ratio (Random, 95% CI)	0.94 [0.88, 1.02]
3 Moderate wasting Show forest plot	8	13172	Risk Ratio (Random, 95% CI)	0.82 [0.74, 0.91]

3.1 SQ LNS	7	9903	Risk Ratio (Random, 95% CI)	0.83 [0.73, 0.95]
3.2 MQ LNS	2	3269	Risk Ratio (Random, 95% CI)	0.78 [0.63, 0.96]
4 Severe wasting Show forest plot	3	2329	Risk Ratio (Random, 95% CI)	1.27 [0.66, 2.46]

4.1 SQ LNS	2	1106	Risk Ratio (Random, 95% CI)	1.74 [0.73, 4.15]
4.2 MQ LNS	2	1223	Risk Ratio (Random, 95% CI)	0.84 [0.31, 2.30]
5 Moderate underweight Show forest plot	8	13073	Risk Ratio (Random, 95% CI)	0.85 [0.80, 0.91]

5.1 SQ LNS	7	9880	Risk Ratio (Random, 95% CI)	0.88 [0.80, 0.96]
5.2 MQ LNS	2	3193	Risk Ratio (Random, 95% CI)	0.83 [0.76, 0.92]
6 Severe underweight Show forest plot	2	1729	Risk Ratio (Random, 95% CI)	0.78 [0.54, 1.13]

6.1 SQ LNS	2	1083	Risk Ratio (Random, 95% CI)	0.84 [0.52, 1.37]
6.2 MQ LNS	1	646	Risk Ratio (Random, 95% CI)	0.71 [0.41, 1.24]
7 Anaemia Show forest plot	5	2332	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.69, 0.90]

7.1 SQ LNS	3	1107	Risk Ratio (M‐H, Random, 95% CI)	0.63 [0.43, 0.93]
7.2 MQ LNS	2	1225	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.78, 0.94]
8 Adverse effects Show forest plot	3	3382	Risk Ratio (Random, 95% CI)	0.86 [0.74, 1.01]

8.1 SQ LNS	3	2576	Risk Ratio (Random, 95% CI)	0.86 [0.69, 1.06]
8.2 MQ LNS	1	806	Risk Ratio (Random, 95% CI)	0.85 [0.63, 1.15]
9 Mid‐upper arm circumference (MUAC) Show forest plot	6	8187	Std. Mean Difference (Random, 95% CI)	0.13 [0.05, 0.22]

9.1 SQ LNS	5	6546	Std. Mean Difference (Random, 95% CI)	0.12 [‐0.00, 0.24]
9.2 MQ LNS	2	1641	Std. Mean Difference (Random, 95% CI)	0.17 [0.08, 0.26]
10 Serum haemoglobin (g/L) Show forest plot	4	4518	Mean Difference (IV, Random, 95% CI)	5.78 [2.27, 9.30]

10.1 SQ LNS	2	3293	Mean Difference (IV, Random, 95% CI)	8.95 [7.66, 10.23]
10.2 MQ LNS	2	1225	Mean Difference (IV, Random, 95% CI)	3.01 [2.73, 3.28]
11 Mortality Show forest plot	3	3321	Risk Ratio (Random, 95% CI)	0.93 [0.63, 1.37]

11.1 SQ LNS	3	2195	Risk Ratio (Random, 95% CI)	0.88 [0.49, 1.60]
11.2 MQ LNS	1	1126	Risk Ratio (Random, 95% CI)	1.06 [0.58, 1.92]
12 HAZ Show forest plot	12	15795	Std. Mean Difference (Random, 95% CI)	0.11 [0.05, 0.16]

12.1 SQ LNS	9	10919	Std. Mean Difference (Random, 95% CI)	0.12 [0.04, 0.20]
12.2 MQ LNS	4	4876	Std. Mean Difference (Random, 95% CI)	0.08 [0.01, 0.15]
13 WHZ Show forest plot	10	12894	Std. Mean Difference (Random, 95% CI)	0.08 [0.04, 0.13]

13.1 SQ LNS	8	10631	Std. Mean Difference (Random, 95% CI)	0.08 [0.02, 0.15]
13.2 MQ LNS	3	2263	Std. Mean Difference (Random, 95% CI)	0.07 [0.00, 0.14]
14 WAZ Show forest plot	10	12188	Std. Mean Difference (Random, 95% CI)	0.09 [0.02, 0.16]

14.1 SQ LNS	9	10959	Std. Mean Difference (Random, 95% CI)	0.11 [0.02, 0.19]
14.2 MQ LNS	2	1229	Std. Mean Difference (Random, 95% CI)	0.05 [‐0.04, 0.14]

Comparison 2. LNS versus no intervention: Subgroup analysis by energy content/formulation of product provided

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Comparison 3. LNS versus no intervention: Subgroup analysis by duration of intervention

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Moderate stunting Show forest plot	9	13372	Risk Ratio (Random, 95% CI)	0.93 [0.88, 0.98]

1.1 6 to 12 months	6	7871	Risk Ratio (Random, 95% CI)	0.96 [0.89, 1.03]
1.2 More than 12 months	3	5501	Risk Ratio (Random, 95% CI)	0.89 [0.81, 0.97]
2 Severe stunting Show forest plot	5	6151	Risk Ratio (Random, 95% CI)	0.85 [0.74, 0.98]

2.1 6 to 12 months	3	2251	Risk Ratio (Random, 95% CI)	0.89 [0.74, 1.07]
2.2 More than 12 months	2	3900	Risk Ratio (Random, 95% CI)	0.80 [0.64, 0.99]
3 Moderate wasting Show forest plot	8	13172	Risk Ratio (Random, 95% CI)	0.82 [0.74, 0.91]

3.1 6 to 12 months	5	7669	Risk Ratio (Random, 95% CI)	0.81 [0.72, 0.92]
3.2 More than 12 months	3	5503	Risk Ratio (Random, 95% CI)	0.83 [0.69, 0.99]
4 Severe wasting: 6 to 12 months Show forest plot	3	2329	Risk Ratio (Random, 95% CI)	1.27 [0.66, 2.46]

5 Moderate underweight Show forest plot	8	13073	Risk Ratio (Random, 95% CI)	0.85 [0.80, 0.91]

5.1 6 to 12 months	5	7532	Risk Ratio (Random, 95% CI)	0.87 [0.78, 0.97]
5.2 More than 12 months	3	5541	Risk Ratio (Random, 95% CI)	0.87 [0.79, 0.95]
6 Severe underweight: 6 to 12 months Show forest plot	2	1729	Risk Ratio (Random, 95% CI)	0.78 [0.54, 1.13]

7 Anaemia Show forest plot	5	2332	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.69, 0.90]

7.1 Upto 6 months	2	1176	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.20, 1.47]
7.2 6 to 12 months	2	627	Risk Ratio (M‐H, Random, 95% CI)	0.84 [0.71, 1.00]
7.3 More than 12 months	1	529	Risk Ratio (M‐H, Random, 95% CI)	0.70 [0.55, 0.88]
8 Adverse effects Show forest plot	3	3382	Risk Ratio (Random, 95% CI)	0.86 [0.74, 1.01]

9 Mid‐upper arm circumference (MUAC) Show forest plot	6	8187	Std. Mean Difference (Random, 95% CI)	0.13 [0.05, 0.22]

9.1 Upto 6 months	2	1472	Std. Mean Difference (Random, 95% CI)	0.06 [‐0.23, 0.35]
9.2 6 to 12 months	3	5114	Std. Mean Difference (Random, 95% CI)	0.18 [0.10, 0.26]
9.3 More than 12 months	1	1601	Std. Mean Difference (Random, 95% CI)	0.04 [‐0.04, 0.12]
10 Serum haemoglobin (g/L) Show forest plot	4	4518	Mean Difference (IV, Random, 95% CI)	5.78 [2.27, 9.30]

10.1 Upto 6 months	2	1176	Mean Difference (IV, Random, 95% CI)	5.58 [0.52, 10.64]
10.2 6 to 12 months	2	3342	Mean Difference (IV, Random, 95% CI)	5.96 [0.08, 11.84]
11 Mortality Show forest plot	3	3321	Risk Ratio (Random, 95% CI)	0.93 [0.63, 1.37]

11.1 6 to 12 months	3	3321	Risk Ratio (Random, 95% CI)	0.93 [0.63, 1.37]
12 HAZ Show forest plot	12	15795	Std. Mean Difference (Random, 95% CI)	0.11 [0.05, 0.16]

12.1 Upto 6 months	3	1510	Std. Mean Difference (Random, 95% CI)	0.19 [0.01, 0.36]
12.2 6 to 12 months	6	8784	Std. Mean Difference (Random, 95% CI)	0.08 [0.00, 0.15]
12.3 More than 12 months	3	5501	Std. Mean Difference (Random, 95% CI)	0.14 [0.03, 0.25]
13 WAZ Show forest plot	10	12188	Std. Mean Difference (Random, 95% CI)	0.09 [0.02, 0.16]

13.1 Upto 6 months	3	1103	Std. Mean Difference (Random, 95% CI)	0.09 [‐0.00, 0.19]
13.2 6 to 12 months	4	5544	Std. Mean Difference (Random, 95% CI)	0.03 [‐0.12, 0.18]
13.3 More than 12 months	3	5541	Std. Mean Difference (Random, 95% CI)	0.13 [0.03, 0.24]
14 WHZ Show forest plot	10	12894	Std. Mean Difference (Random, 95% CI)	0.08 [0.04, 0.13]

14.1 Upto 6 months	2	1216	Std. Mean Difference (Random, 95% CI)	0.13 [‐0.12, 0.38]
14.2 6 to 12 months	5	6175	Std. Mean Difference (Random, 95% CI)	0.07 [0.00, 0.14]
14.3 More than 12 months	3	5503	Std. Mean Difference (Random, 95% CI)	0.09 [0.01, 0.17]

Comparison 3. LNS versus no intervention: Subgroup analysis by duration of intervention

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Comparison 4. LNS versus no intervention: Subgroup analysis by age at follow‐up

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Moderate stunting Show forest plot	9	13492	Risk Ratio (Random, 95% CI)	0.93 [0.88, 0.98]

1.1 At 12 months	1	564	Risk Ratio (Random, 95% CI)	1.01 [0.86, 1.19]
1.2 At 18 months	6	7427	Risk Ratio (Random, 95% CI)	0.95 [0.88, 1.02]
1.3 At 24 months	3	5501	Risk Ratio (Random, 95% CI)	0.89 [0.81, 0.97]
2 Severe stunting Show forest plot	5	6151	Risk Ratio (Random, 95% CI)	0.85 [0.74, 0.98]

2.1 At 12 months	1	564	Risk Ratio (Random, 95% CI)	0.96 [0.67, 1.38]
2.2 At 18 months	2	1687	Risk Ratio (Random, 95% CI)	0.86 [0.70, 1.07]
2.3 At 24 months	2	3900	Risk Ratio (Random, 95% CI)	0.80 [0.64, 0.99]
3 Moderate wasting Show forest plot	8	13172	Risk Ratio (Random, 95% CI)	0.80 [0.73, 0.88]

3.1 At 18 months	6	7669	Risk Ratio (Random, 95% CI)	0.79 [0.71, 0.89]
3.2 At 24 months	3	5503	Risk Ratio (Random, 95% CI)	0.83 [0.69, 0.99]
4 Severe wasting Show forest plot	3	2329	Risk Ratio (Random, 95% CI)	1.27 [0.66, 2.46]

4.1 At 12 months	1	563	Risk Ratio (Random, 95% CI)	0.78 [0.12, 4.93]
4.2 At 18 months	2	1766	Risk Ratio (Random, 95% CI)	1.39 [0.67, 2.87]
5 Moderate underweight Show forest plot	8	13073	Risk Ratio (Random, 95% CI)	0.85 [0.81, 0.90]

5.1 At 18 months	6	7532	Risk Ratio (Random, 95% CI)	0.85 [0.78, 0.92]
5.2 At 24 months	3	5541	Risk Ratio (Random, 95% CI)	0.87 [0.79, 0.95]
6 Severe underweight: at 18 months Show forest plot	2	1729	Risk Ratio (Random, 95% CI)	0.78 [0.54, 1.13]

7 Anaemia Show forest plot	5	2332	Risk Ratio (M‐H, Random, 95% CI)	0.79 [0.69, 0.90]

7.1 At 12 months	2	1176	Risk Ratio (M‐H, Random, 95% CI)	0.55 [0.20, 1.47]
7.2 At 18 months	3	1156	Risk Ratio (M‐H, Random, 95% CI)	0.80 [0.71, 0.91]
7.3 At 36 months	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8 Adverse effects: At 18 months Show forest plot	3	3382	Risk Ratio (Random, 95% CI)	0.86 [0.74, 1.01]

9 Mid‐upper arm circumference (MUAC) Show forest plot	6	8187	Std. Mean Difference (Random, 95% CI)	0.13 [0.05, 0.22]

9.1 At 12 months	1	1193	Std. Mean Difference (Random, 95% CI)	0.15 [0.06, 0.24]
9.2 At 18 months	3	4355	Std. Mean Difference (Random, 95% CI)	0.12 [‐0.11, 0.34]
9.3 At 24 months	1	1601	Std. Mean Difference (Random, 95% CI)	0.04 [‐0.04, 0.12]
9.4 At 36 months	1	1038	Std. Mean Difference (Random, 95% CI)	0.2 [0.06, 0.34]
10 Serum haemoglobin (g/L) Show forest plot	4	4518	Mean Difference (IV, Random, 95% CI)	5.78 [2.27, 9.30]

10.1 At 12 months	1	194	Mean Difference (IV, Random, 95% CI)	8.5 [4.46, 12.54]
10.2 At 18 months	2	3342	Mean Difference (IV, Random, 95% CI)	5.96 [0.08, 11.84]
10.3 At 36 months	1	982	Mean Difference (IV, Random, 95% CI)	3.30 [1.42, 5.18]
11 Mortality Show forest plot	3	3321	Risk Ratio (Random, 95% CI)	0.93 [0.63, 1.37]

11.1 At 12 months	1	1932	Risk Ratio (Random, 95% CI)	0.85 [0.56, 1.30]
11.2 At 18 months	2	1389	Risk Ratio (Random, 95% CI)	1.10 [0.42, 2.89]
12 HAZ Show forest plot	12	15795	Std. Mean Difference (Random, 95% CI)	0.10 [0.05, 0.15]

12.1 At 12 to 15 months	3	1103	Std. Mean Difference (Random, 95% CI)	0.07 [‐0.02, 0.15]
12.2 At 18 months	6	8153	Std. Mean Difference (Random, 95% CI)	0.08 [0.00, 0.16]
12.3 At 24 months	3	5501	Std. Mean Difference (Random, 95% CI)	0.14 [0.03, 0.25]
12.4 At 36 months	1	1038	Std. Mean Difference (Random, 95% CI)	0.27 [0.10, 0.44]
13 WAZ Show forest plot	10	12188	Std. Mean Difference (Random, 95% CI)	0.10 [0.04, 0.16]

13.1 At 12 to 15 months	3	1103	Std. Mean Difference (Random, 95% CI)	0.09 [‐0.00, 0.19]
13.2 At 18 months	5	5544	Std. Mean Difference (Random, 95% CI)	0.05 [‐0.06, 0.17]
13.3 At 24 months	3	5541	Std. Mean Difference (Random, 95% CI)	0.13 [0.03, 0.23]
14 WHZ Show forest plot	10	12894	Std. Mean Difference (Random, 95% CI)	0.12 [0.02, 0.22]

14.1 At 12 to 15 months	2	809	Std. Mean Difference (Random, 95% CI)	0.10 [‐0.02, 0.22]
14.2 At 18 months	5	5544	Std. Mean Difference (Random, 95% CI)	0.13 [‐0.05, 0.31]
14.3 At 24 months	3	5503	Std. Mean Difference (Random, 95% CI)	0.09 [0.01, 0.17]
14.4 At 36 months	1	1038	Std. Mean Difference (Random, 95% CI)	0.04 [‐0.08, 0.16]

Comparison 4. LNS versus no intervention: Subgroup analysis by age at follow‐up

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Comparison 5. LNS versus fortified blended food (FBF)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Moderate stunting Show forest plot	3	2828	Risk Ratio (Random, 95% CI)	0.89 [0.82, 0.97]

2 Severe stunting Show forest plot	2	729	Risk Ratio (Random, 95% CI)	0.41 [0.12, 1.42]

3 Moderate wasting Show forest plot	2	2290	Risk Ratio (Random, 95% CI)	0.79 [0.65, 0.97]

4 Severe wasting Show forest plot	2	735	Risk Ratio (Random, 95% CI)	0.64 [0.19, 2.18]

5 Moderate underweight Show forest plot	2	2280	Risk Ratio (Random, 95% CI)	0.81 [0.73, 0.91]

6 Severe underweight Show forest plot	1		Risk Ratio (Random, 95% CI)	Totals not selected

7 MUAC Show forest plot	2	1512	Std. Mean Difference (IV, Random, 95% CI)	0.02 [‐0.08, 0.12]

8 Haemoglobin (g/L) Show forest plot	1	182	Mean Difference (IV, Random, 95% CI)	0.29 [‐6.00, 6.59]

9 HAZ Show forest plot	4	4047	Std. Mean Difference (IV, Random, 95% CI)	0.06 [0.00, 0.13]

10 WAZ Show forest plot	3	1933	Mean Difference (IV, Random, 95% CI)	0.05 [‐0.04, 0.14]

11 WHZ Show forest plot	3	1933	Std. Mean Difference (IV, Random, 95% CI)	0.07 [‐0.02, 0.16]

Comparison 5. LNS versus fortified blended food (FBF)

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Comparison 6. LNS versus micronutrient powders (MNP)

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Moderate stunting Show forest plot	3	2365	Risk Ratio (Random, 95% CI)	0.92 [0.82, 1.02]

2 Moderate wasting Show forest plot	2	2004	Risk Ratio (Random, 95% CI)	0.97 [0.77, 1.23]

3 Moderate underweight Show forest plot	2	2004	Risk Ratio (Random, 95% CI)	0.88 [0.78, 0.99]

4 Anaemia Show forest plot	2	557	Risk Ratio (Random, 95% CI)	0.38 [0.21, 0.68]

5 Anaemia: Sensitivity analysis Show forest plot	1		Risk Ratio (Random, 95% CI)	0.56 [0.27, 1.14]

6 Serum haemoglobin (g/L) Show forest plot	2	557	Mean Difference (Random, 95% CI)	5.13 [2.00, 8.26]

7 Serum haemoglobin (g/L): Sensitivity analysis Show forest plot	1		Mean Difference (Random, 95% CI)	3.6 [‐0.13, 7.33]

8 HAZ Show forest plot	3	2362	Std. Mean Difference (IV, Random, 95% CI)	0.10 [‐0.08, 0.27]

9 HAZ: Sensitivity analysis Show forest plot	2	2001	Std. Mean Difference (IV, Random, 95% CI)	0.16 [0.03, 0.28]

10 WAZ Show forest plot	3	2362	Std. Mean Difference (IV, Random, 95% CI)	0.12 [0.02, 0.21]

11 WAZ: Sensitivity analysis Show forest plot	2	2001	Std. Mean Difference (IV, Random, 95% CI)	0.14 [0.05, 0.23]

12 WHZ Show forest plot	3	2362	Std. Mean Difference (IV, Random, 95% CI)	0.05 [‐0.06, 0.17]

13 WHZ: Sensitivity analysis Show forest plot	2	2001	Std. Mean Difference (IV, Random, 95% CI)	0.10 [0.01, 0.18]

Comparison 6. LNS versus micronutrient powders (MNP)

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Preventive lipid‐based nutrient supplements given with complementary foods to infants and young children 6 to 23 months of age for health, nutrition, and developmental outcomes

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