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Study flow diagram
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Figure 1

Study flow diagram

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 2

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

Risk of bias summary: review authors' judgements about each risk of bias item for each included study
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Figure 3

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

Funnel plot of comparison zinc versus placebo. Outcome 1.1 ‐ Mental Development Index
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Figure 4

Funnel plot of comparison zinc versus placebo. Outcome 1.1 ‐ Mental Development Index

Funnel plot of comparison zinc versus placebo. Outcome 1.2 ‐ Psychomotor Development Index
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Figure 5

Funnel plot of comparison zinc versus placebo. Outcome 1.2 ‐ Psychomotor Development Index

Comparison 1 Zinc versus placebo, Outcome 1 Mental Development Index.
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Analysis 1.1

Comparison 1 Zinc versus placebo, Outcome 1 Mental Development Index.

Comparison 1 Zinc versus placebo, Outcome 2 Psychomotor Development Index.
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Analysis 1.2

Comparison 1 Zinc versus placebo, Outcome 2 Psychomotor Development Index.

Summary of findings for the main comparison. Zinc compared to placebo for mental and motor development in children

Zinc compared to placebo for mental and motor development in children

Patient or population: infants and children
Settings: populations at risk of zinc deficiency
Intervention: zinc
Comparison: placebo

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

Placebo

Zinc

Mental Development Index
BSID II. Scale from: 0 to 100
Follow‐up: median 6 months

The mean MDI ranged across control groups from
86.4 to 113 points

The mean MDI in the intervention groups was
0.50 lower
(2.06 lower to 1.06 higher)

2134
(8 studies)

⊕⊕⊕⊝
moderate1

Psychomotor Development Index

BSID II. Scale from: 0 to 100
Follow‐up: median 6 months

The mean PDI ranged across control groups from
87.6 to 104.5 points

The mean PDI in the intervention groups was
1.54 higher
(2.26 lower to 5.34 higher)

2134
(8 studies)

⊕⊕⊕⊝
moderate1

Cognition scores

Data not available

Intelligence quotient

Data not available

Adverse effects

Data not available

*The basis for the assumed risk (for example, the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
BSID: Bayley Scales of Infant Development; CI: confidence interval; MDI: Mental Development Index; PDI: Psychomotor Development Index.

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.

1 Heterogeneity was marked in the included trials with I2 statistic being 67% to 92% and not explicable by the differences in study design, participants, form of intervention (included in subgroup analyses).

Figures and Tables -
Summary of findings for the main comparison. Zinc compared to placebo for mental and motor development in children
Table 1. Sensitivity analyses

Variable

MDI

RR (95% CI)

PDI

RR (95% CI)

Attrition

Less than 10%

More than 10%

0.17 (‐0.9 to 1.24)

‐1.09 (‐3.25 to 1.07)

‐0.36 (‐1.87 to 1.15)

2.08 (‐2.96 to 7.13)

Allocation concealment

Adequate

Inadequate

‐0.35 (‐2.09 to 1.40)

‐0.94 (‐5.64 to 3.76)

1.63 (‐2.86 to 6.12)

1.21 (‐6.07 to 8.49)

CI: confidence interval; MDI: Mental Development Index; PDI: Psychomotor Development Index; RR: risk ratio

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Table 1. Sensitivity analyses
Comparison 1. Zinc versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Mental Development Index Show forest plot

8

Mean Difference (IV, Random, 95% CI)

Subtotals only

1.1 Primary analysis

8

2134

Mean Difference (IV, Random, 95% CI)

‐0.50 [‐2.06, 1.06]

1.2 Neonatal zinc supplementation

4

560

Mean Difference (IV, Random, 95% CI)

‐2.30 [‐5.30, 0.70]

1.3 Post‐neonatal zinc supplementation

4

1574

Mean Difference (IV, Random, 95% CI)

0.60 [‐0.28, 1.48]

1.4 Zinc supplementation for 6 months or less

5

1700

Mean Difference (IV, Random, 95% CI)

0.00 [‐1.70, 1.71]

1.5 Zinc supplementation for more than 6 months

3

434

Mean Difference (IV, Random, 95% CI)

‐1.15 [‐4.74, 2.44]

1.6 Zinc sulphate supplementation

5

1179

Mean Difference (IV, Random, 95% CI)

‐0.84 [‐2.89, 1.22]

1.7 Zinc acetate supplementation

2

384

Mean Difference (IV, Random, 95% CI)

‐0.94 [‐5.64, 3.76]

1.8 Zinc supplementation with other salts

1

571

Mean Difference (IV, Random, 95% CI)

1.5 [‐0.28, 3.28]

1.9 Zinc supplementation in low birthweight babies

3

415

Mean Difference (IV, Random, 95% CI)

‐2.35 [‐5.82, 1.12]

1.10 Zinc supplementation in low HDI countries

5

1772

Mean Difference (IV, Random, 95% CI)

0.15 [‐1.18, 1.48]

1.11 Zinc supplementation in high HDI countries

3

362

Mean Difference (IV, Random, 95% CI)

‐1.82 [‐6.37, 2.72]

2 Psychomotor Development Index Show forest plot

8

Mean Difference (IV, Random, 95% CI)

Subtotals only

2.1 Primary analysis

8

2134

Mean Difference (IV, Random, 95% CI)

1.54 [‐2.26, 5.34]

2.2 Neonatal zinc supplementation

4

560

Mean Difference (IV, Random, 95% CI)

1.38 [‐7.10, 9.86]

2.3 Post‐neonatal zinc supplementation

4

1574

Mean Difference (IV, Random, 95% CI)

1.01 [‐0.84, 2.86]

2.4 Zinc supplementation for 6 months or less

5

1700

Mean Difference (IV, Random, 95% CI)

0.64 [‐1.22, 2.50]

2.5 Zinc supplementation for more than 6 months

3

434

Mean Difference (IV, Random, 95% CI)

2.82 [‐6.64, 12.28]

2.6 Zinc sulphate supplementation

5

1179

Mean Difference (IV, Random, 95% CI)

1.56 [‐4.41, 7.53]

2.7 Zinc acetate supplementation

2

384

Mean Difference (IV, Random, 95% CI)

1.21 [‐6.07, 8.49]

2.8 Zinc supplementation with other salts

1

571

Mean Difference (IV, Random, 95% CI)

1.70 [‐0.20, 3.60]

2.9 Zinc supplementation in low birthweight babies

3

415

Mean Difference (IV, Random, 95% CI)

3.77 [‐4.67, 12.21]

2.10 Zinc supplementation in low HDI countries

5

1772

Mean Difference (IV, Random, 95% CI)

0.68 [‐1.09, 2.46]

2.11 Zinc supplementation in high HDI countries

3

362

Mean Difference (IV, Random, 95% CI)

2.64 [‐7.36, 12.64]

Figures and Tables -
Comparison 1. Zinc versus placebo