![]() Funnel plot for motor development based on standard mean difference (SMD).įigure S3. Funnel plot for end line hemoglobin based on standard mean difference (SMD).įigure S2. Effect sizes of iron supplementation interventions with or without other nutrients on hemoglobin, growth, and development.įigure S1. Metaregression coefficients for the associations between standardized hemoglobin effect sizes and growth and child development effect sizes from iron supplementation without other nutrients, unadjusted and adjusted. Metaregression coefficients for the associations between baseline characteristics and effect sizes from iron supplementation without other nutrients on growth and child development. Pooled effect sizes (95% CI) for studies of iron supplementation with or without other nutrients on hemoglobin, growth, and development, stratified by anemia prevalence, iron deficiency prevalence, type of supplementation, mean age of children, malaria transmission, study quality, and study duration (including outliers). Observational studies examining associations between continuous hemoglobin concentration in children under 5 years and growth and development. Iron supplementation interventions in children under 5 years of age examining effects on growth, development and brain functions. Future research is needed to examine associations of Hb with growth and development in populations with varying levels of Hb, inflammation, and in different ages and settings. Available evidence was not able to establish an inflection point at which decreasing Hb begins to be associated with negative functional outcomes. Heterogeneity among observational studies precluded calculation of pooled associations between Hb and functional outcomes. Iron supplementation trials among children with lower Hb concentrations at baseline showed stronger associations between their effects on Hb and their effects on mental development ( P-interaction = 0.008). For each 1 standard deviation (SD) increase in Hb, motor scores increased by 0.28 SD and mental scores increased by 0.24 SD. Among iron supplementation trials, a metaregression indicated significant associations between intervention effects on Hb and their effects on motor and mental development. A literature search returned 5049 studies of these, 56 intervention and 20 observational studies fit the inclusion criteria. This systematic review and meta-analysis of iron intervention and observational studies aimed to clarify the consequences of low Hb concentration in children under age 5 years on growth, development, and chronic disease (functional outcomes) across the full range of Hb values. In children under 5, a hemoglobin (Hb) cutoff of 11 g/dL is recommended by the World Health Organization to define anemia, yet few studies have examined whether this cut point accurately coincides with negative functional consequences.
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