Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. The Study Protocol and Search Strategy
2.2. Selection Criteria
- (1)
- Randomized controlled trials (RCTs);
- (2)
- Children and adolescents within the age range of 5–19 years;
- (3)
- From LMICs classified by the World Bank according to the year of the study;
- (4)
- Oral iron supplementation where iron was the only micronutrient provided;
- (5)
- The control group could be a placebo or no intervention.
- (1)
- Interventional studies without appropriate control groups;
- (2)
- Observational studies;
- (3)
- Editorials, reviews, opinions, or review articles were ineligible; however, these articles were reviewed to determine eligible research;
- (4)
- Participants with pregnancy or HIV/AIDS, or lactating.
2.3. Data Extraction
2.4. Outcome
2.5. Quality Assessment
2.6. Statistical Analysis
3. Results
3.1. Document Retrieval Results
3.2. Basic Features Included in The Study
3.3. Outcomes
3.4. Subgroup Comparisons
3.5. Methodological Quality, Publication Bias, and Sensitivity Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Author | Country | Age at Intervention, Years | Intervention Group | Control Group | Duration of Intervention | Outcomes |
---|---|---|---|---|---|---|
Baumgartner [26], 2012 | South Africa | 6–11 | 50 mg*4/wk FeSO4 (n = 81) | Placebo (n = 80) | 8.5 months | KABC sequential processing: Triangles, Hand movement, Atlantis Delayed |
Devaki [20], 2009 | India | 15–18 | 100 mg*6/wk EFe (n = 30) | Control placebo (n = 30) | 8 months | WAIS, Short term memory, long term memory, Scholastic performance test |
Pollitt [27], 1989 | Thailand | 9–11 | FeSO4 50 mg/d for 2 weeks and FeSO4 100 mg/d for 14 weeks (n = 5) | Placebo (n = 4) | 4 months | IQ, Mathematics |
Rezaeian [28], 2014 | Iran | 14–18 | 50 mg*2/wk FeSO4 (n = 100) | Control group (n = 100) | 16 weeks | Attention score |
Seshadri (C) [29], 1989 | India | 8–15 | (1) 40 mg/d EFe (n = 16) (2) 30 mg/d EFe (n = 16) | Placebo (n = 16) | 4 months | Mazes, Digit span, Visual recall |
Seshadri (D) [29], 1989 | India | 8–15 | 60 mg/d EFe (n = 65) | Placebo (n = 65) | 8 months | Mazes, Digit span, Visual recall |
Soemantri (A) [30], 1985 | Indonesia | Average 9.5 | (1) anemia: 10 mg/kg/d FeSO4 (n = 43) (2) Non-anemia: 10 mg/kg/d FeSO4 (n = 16) | (1) anemia placebo (n = 35) (2) non-anemia placebo (n = 25) | 3 mouths | IQ |
Soemantri (B) [31], 1989 | India | 8.1–11.6 | 2 mg/kg/d EFe (n = 37) | Placebo (n = 35) | 3 months | IQ, math scores |
Sungthong [32], 2004 | Thailand | 6–13 | (1) 300 mg/d FeSO4 (n = 140); (2) 300 mg/wk. FeSO4 (n = 134) | Placebo (n = 123) | 16 weeks | IQ, mathematics |
Subgroup Analyses | Heterogeneity Test | Pooled SMD Values (95% CI) | Pooled SMD Values’ Tests Statistic | |||
---|---|---|---|---|---|---|
q | d.f. | I2 | Z | p | ||
Sex | ||||||
Whole population | 116.61 | 8 | 93.1% | 0.67 (0.12, 1.22) | 2.38 | 0.017 |
Male | 2.83 | 2 | 29.3% | 0.64 (0.14, 1.13) | 2.53 | 0.011 |
Female | 1.64 | 1 | 39.1% | 0.50 (−0.11, 1.11) | 1.62 | 0.106 |
Age, year | ||||||
≤11 | 47.32 | 6 | 87.3% | 0.29 (−0.03, 0.61) | 1.75 | 0.08 |
>11 | 56.39 | 6 | 89.4% | 1.18 (0.33, 2.04) | 2.7 | 0.007 |
Dose, mg/day | ||||||
<60 | 23.98 | 6 | 75.0% | 0.38 (−0.06, 0.81) | 1.71 | 0.088 |
≥60 | 97.44 | 6 | 93.8% | 0.91 (0.38, 1.45) | 3.37 | 0.001 |
Duration, month | ||||||
<4 | 12.24 | 3 | 75.5% | 0.34 (−0.19, 0.86) | 1.26 | 0.208 |
≥4 | 112.71 | 9 | 92.0% | 0.81 (0.38, 1.25) | 3.66 | <0.001 |
Iron status | ||||||
Anemia | 43.98 | 5 | 88.6% | 1.01 (0.34, 1.68) | 2.97 | 0.003 |
Non-anemia | 28.26 | 5 | 82.3% | 0.68 (0.17, 1.18) | 2.63 | 0.009 |
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Chen, Z.; Yang, H.; Wang, D.; Sudfeld, C.R.; Zhao, A.; Xin, Y.; Chen, J.C.; Fawzi, W.W.; Xing, Y.; Li, Z. Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis. Nutrients 2022, 14, 5332. https://doi.org/10.3390/nu14245332
Chen Z, Yang H, Wang D, Sudfeld CR, Zhao A, Xin Y, Chen JC, Fawzi WW, Xing Y, Li Z. Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis. Nutrients. 2022; 14(24):5332. https://doi.org/10.3390/nu14245332
Chicago/Turabian StyleChen, Zekun, Huanhuan Yang, Dongqing Wang, Christopher R. Sudfeld, Ai Zhao, Yiqian Xin, Jiawen Carmen Chen, Wafaie W. Fawzi, Yan Xing, and Zhihui Li. 2022. "Effect of Oral Iron Supplementation on Cognitive Function among Children and Adolescents in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis" Nutrients 14, no. 24: 5332. https://doi.org/10.3390/nu14245332