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Meta-Analysis
. 2020 Apr 8;4(4):CD010205.
doi: 10.1002/14651858.CD010205.pub2.

Zinc supplementation for the promotion of growth and prevention of infections in infants less than six months of age

Zohra S Lassi  1 , Jaameeta Kurji  2 , Cristieli Sérgio de Oliveira  3 , Anoosh Moin  4 , Zulfiqar A Bhutta  5
Affiliations
Meta-Analysis

Zinc supplementation for the promotion of growth and prevention of infections in infants less than six months of age

Zohra S Lassi et al. Cochrane Database Syst Rev. .

Abstract

Background: Zinc is a vital micronutrient for humans and is essential for protein synthesis, cell growth, and differentiation. Severe zinc deficiency can lead to slower physical, cognitive and sexual growth, cause skin disorders, decrease immunity, increase incidence of acute illnesses in infants and children and contribute to childhood stunting. By estimation, 17.3% of the world population is at risk of inadequate zinc intake. Such nutritional impairment increases the risk of diarrhoea and pneumonia by 20%, as well as leads to a global loss of more than 16 million disability-adjusted life years in children less than five years of age. Not only does zinc deficiency affect lives, it adds to the considerable financial burden on depleted resources in countries that are most affected. By preventing or curing this deficiency, we can improve childhood mortality, morbidity and growth.

Objectives: To assess the effectiveness of zinc supplementation for the promotion of growth, reduction in mortality, and the prevention of infections in infants less than six months of age.

Search methods: We used the standard search strategy of the Cochrane Neonatal Group to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 4), MEDLINE via PubMed (1966 to 18 May 2018), Embase (1980 to 18 May 2018), and CINAHL (1982 to 18 May 2018). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. An updated search from 1 January 2018 to 29 January 2020 was run in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost.

Selection criteria: All randomised controlled (individual and cluster randomised) and quasi-randomised trials of zinc supplementation in healthy, term infants, less than six months of age comparing infant mortality, incidence of diarrhoea or respiratory illnesses, growth and/or serum zinc levels were eligible.

Data collection and analysis: Two review authors screened search results (title and abstracts) and relevant full texts. Studies fulfilling prespecified inclusion criteria were included with any disagreements resolved by consensus. Extraction and analysis were then conducted. We used the GRADE approach to assess the quality of evidence as indicated by certainty in effect estimates.

Main results: Eight studies (with 85,629 infants) were included and five studies were meta-analysed, out of which four studies compared zinc with placebo, and one compared zinc plus riboflavin versus riboflavin. Certain growth outcomes after six months of intervention (Weight for Age Z-scores (WAZ) (standardised mean difference) (SMD) 0.16, 95% CI 0.03 to 0.29; three studies, n = 955; fixed-effect; heterogeneity Chi² P = 0.96); I² = 0%); change in WAZ (SMD 0.16, 95% CI 0.07 to 0.25; one study, n = 386; fixed-effect); (Weight-for-Length Z-score (WLZ) (SMD 0.15, 95% CI 0.02 to 0.28; three studies, n = 955; fixed-effect; heterogeneity: Chi² P = 0.81); I² = 0%); (change in WLZ (SMD 0.17, 95% CI 0.06 to 0.28; one study, n = 386; fixed-effect)) were positively affected by zinc supplementation compared to placebo. A single study reported no difference in the incidence of diarrhoea and lower respiratory tract infection with zinc supplementation. Zinc had no effect on mortality in children younger than 12 months. When zinc plus riboflavin was compared to riboflavin only, significant improvement was observed in the incidence of wasting at 24 months (risk ratio (RR) 0.59, 95% CI 0.37 to 0.96; one study, n = 296; fixed-effect), but significant worsening of incidence of stunting was present at 21 months (RR 1.53, 95% CI 1.09 to 2.16; one study, n = 298; fixed-effect).

Authors' conclusions: There was a significant positive impact of zinc supplementation on WAZ and WLZ after six months of intervention in infants compared to placebo. When a combined supplement of zinc and riboflavin was compared to riboflavin, there was a significant reduction in wasting at 24 months, but stunting at 21 months was negatively affected. Although included trials were of good-to-moderate quality, evidence that could be meta-analysed was based on a few studies which affected the overall quality of results. Regardless, there is a need for strong trials conducted in infants younger than six months before a strong recommendation can be made supporting zinc supplementation in this age group.

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Conflict of interest statement

ZS has no interest to declare.

AM has no interest to declare.

JK has no interest to declare.

CO has no interest to declare.

ZB has no interest to declare.

Figures

1
1
Study flow diagram.
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
4
4
Forest plot of comparison: 1 Zinc supplementation vs placebo/ no treatment, outcome: 1.8 Weight for age Z‐score after 6 months.
5
5
Forest plot of comparison: 1 Zinc supplementation vs placebo/ no treatment, outcome: 1.11 Length for age Z‐score after 6 months.
6
6
Forest plot of comparison: 1 Zinc supplementation vs placebo/ no treatment, outcome: 1.14 Weight for length Z‐score after 6 months.
1.1
1.1. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 1 Change in length (cm) after 6 months.
1.2
1.2. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 2 Length after 6 months.
1.3
1.3. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 3 Change in weight (g) after 6 months.
1.4
1.4. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 4 Weight after 6 months; country.
1.5
1.5. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 5 Change in head circumference (cm) after 6 months.
1.6
1.6. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 6 Head circumference (cm) at 6 months.
1.7
1.7. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 7 Change in WAZ at 6 months.
1.8
1.8. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 8 Weight for age Z score after 6 months.
1.9
1.9. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 9 Weight for age Z score after 12 months.
1.10
1.10. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 10 Change in LAZ after 6 months.
1.11
1.11. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 11 Length for age Z score after 6 months.
1.12
1.12. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 12 Length for age Z score after 12 months.
1.13
1.13. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 13 Change in WLZ after 6 months.
1.14
1.14. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 14 Weight for length Z score after 6 months.
1.15
1.15. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 15 Weight for length Z score after 12 months.
1.16
1.16. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 16 Stunted after 6 months.
1.17
1.17. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 17 Stunted after 12 months.
1.18
1.18. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 18 Wasted after 6 months.
1.19
1.19. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 19 Wasted at 12 months.
1.20
1.20. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 20 Underweight after 6 months.
1.21
1.21. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 21 Underweight after 12 months.
1.22
1.22. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 22 Incidence of diarrhoea.
1.23
1.23. Analysis
Comparison 1 Zinc supplementation vs placebo/ no treatment, Outcome 23 Incidence of lower respiratory tract infection.
2.1
2.1. Analysis
Comparison 2 Zinc plus riboflavin vs riboflavin, Outcome 1 Length (cm).
2.2
2.2. Analysis
Comparison 2 Zinc plus riboflavin vs riboflavin, Outcome 2 Weight (g).
2.3
2.3. Analysis
Comparison 2 Zinc plus riboflavin vs riboflavin, Outcome 3 Stunted.
2.4
2.4. Analysis
Comparison 2 Zinc plus riboflavin vs riboflavin, Outcome 4 Wasted.
2.5
2.5. Analysis
Comparison 2 Zinc plus riboflavin vs riboflavin, Outcome 5 Underweight.
2.6
2.6. Analysis
Comparison 2 Zinc plus riboflavin vs riboflavin, Outcome 6 Serum Zinc (ug/dL).
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Berger 2006 {published data only}
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Mallard 2014 {published data only}
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Ninh 1996 {published data only}
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Olney 2006 {published data only}
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Osendarp 2002 {published data only}
    1. Osendarp SJ, Santosham M, Black RE, Wahed MA, Raaij JM, Fuchs GJ. Effect of zinc supplementation between 1 and 6 mo of life on growth and morbidity of Bangladeshi infants in urban slums. American Journal of Clinical Nutrition 2002;76(6):1401‐8. [DOI: 10.1093/ajcn/76.6.1401; PUBMED: 12450909] - DOI - PubMed
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Roy 2007 {published data only}
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References to studies awaiting assessment

Castillo Durán 2001 {published data only}
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NCT02319499 {published data only}
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