Impact of nutritional supplements on cognitive development of children in developing countries: A meta-analysis

Nutritional supplements may be important on cognition but the evidence is heterogeneous. This meta-analysis aimed (1) to determine whether nutritional supplements provided to pregnant women or young children could improve cognitive development of children in developing countries, and (2) to explore how supplementation characteristics could improve children’s cognitive outcomes. This meta-analysis examined nutritional supplementation studies in 9 electronic databases and 13 specialist websites. Experimental studies were included if they were published from 1992 to 2016, were conducted in developing countries, had nutritional supplementation for pregnant women or children aged ≤8, and reported effect sizes on cognitive outcomes. Interventions with confounded components, such as stimulation and parenting, were excluded. 67 interventions (48 studies) for 29814 children from 20 developing countries were evaluated. Childhood nutritional supplementation could improve children’s cognitive development (d 0.08, 95% CI 0.03–0.13) and those with ≥5 nutrients was particularly beneficial (0.15, 0.08–0.22). Antenatal supplementation did not improve cognitive development (0.02, -0.01 to 0.06) except for those implemented in the first trimester (0.15, 0.03–0.28). In conclusion, childhood nutritional supplementation was beneficial to cognitive development but could be optimised by providing multiple nutrients; antenatal supplementation should target pregnancy women in the first trimester for better cognitive benefits.


Keywords for electronic database search in DFID Rigorous Literature Review
The following keywords were used for the electronic database search in the original rigorous literature review for articles published in 1992-2013, from which we extracted studies on nutritional supplementation for our meta-analysis. The keywords for searching used the intersection (AND operator) of keyword groups: 1. Union (OR operator) of these keywords for developing countries

Detailed inclusion and exclusion criteria in DFID Rigorous Literature Review
The inclusion and exclusion criteria of the original rigorous literature review, from which we extracted studies on nutritional supplementation for our meta-analysis.
1. The interventions must have begun during early childhood; that is, before the children were 8 years of age.
2. The interventions must contain at least one of the following components: (a) parentfocused education and support; (b) child-focused education and stimulation; (c) nutrition and health; and (d) income supplementation including cash transfers.
3. The interventions could be home-, centre-, and/or community-based. Centre-based approaches involved several kinds of institutions offering early years provision such as preschools, childcare centres, crèches, playgroups, day care nurseries, and nursery schools, which served as alternative physical and social environments for care, development, and education.
4. The interventions must have explicitly documented cognitive and/or schooling outcomes.
5. The evidence assessed linkages between participation in the interventions and cognitive outcomes.
6. The studies were published after 1 st January 1992 and before 31 st December 2012.
7. The studies provided information from a primary study which was not a literature review.
8. Research methods, statistical analyses, and findings were sufficiently detailed to provide a basis for judgment about the robustness of the conclusions; that is, the research procedures and characteristics of the sample were specified in detail, so that the validity of the results could be evaluated.
9. Comparisons (concurrent between groups or before-and-after within groups) among groups of people exposed to the intervention and those who were not exposed or less exposed to the intervention were available.
10. Studies involving special populations such as Down's syndrome, cerebral palsy, autism or any specific form of disability (sensory, physical, intellectual, or psychological), and extreme malnutrition were not included.

Rigor of study: Level of rigor in study design
Code Meaning 1 Other, lowest level of rigor 2 Single group before and after 3 Retrospective controlled/secondary data analysis/construction of comparison groups 4 Other prospective quasi-experimental design 5 Quasi-experimental design with the use of an econometric model 6 Randomized controlled trial Soundness of study: Level of validity and reliability of the study Code Meaning 1 Low (major and or numerous deficiencies in sampling, data collection, or data analysis) 2 Medium (some deficiencies in sampling, data collection, or data analysis, but the methods and interpretations were generally valid and reliable) 3 High (demonstrates adherence to appropriate sampling and data collection methods and reliable data analysis)

Overall quality of study: Code of Rigor + Code of Soundness
Studies with overall quality <6 were excluded from this study.
6  Altogether 3431 candidate studies were identified using the four search strategies. After screening the abstracts and full articles, 111 studies fulfilled the criteria and with good quality received in-depth review and 41 studies without information for effect size calculation were excluded. Among the remaining 70 studies, 43 without nutritional supplementations and two with combination of educational and nutritional interventions were further excluded. As a result, 25 studies published from 1993 to 2012 were included in the final meta-analysis (see Figure 1 for the identification procedure).

Figure 2. Funnel plot for childhood supplementations
Egger's regression test reported no significant asymmetry in the funnel plot (z 0.64, p=0.52).