A meta-analysis of nutrition interventions on mental development of children under-two in low- and middle-income countries.

Interventions to improve nutritional status of young children in low- and middle-income countries (LMIC) may have the added benefit of improving their mental and motor development. This meta-analysis updates and goes beyond previous ones by answering two important questions: (1) do prenatal and postnatal nutritional inputs improve mental development, and (2) are effects on mental development associated with two theoretically interesting mediators namely physical growth and motor development? The meta-analysis of articles on Medline, PsycINFO, Global Health and Embase was limited to randomized trials in LMICs, with mental development of children from birth to age two years as an outcome. The initial yield of 2689 studies was reduced to 33; 12 received a global quality rating of strong. Of the 10 prenatal and 23 postnatal nutrition interventions, the majority used zinc, iron/folic acid, vitamin A or multiple micronutrients, with a few evaluating macronutrients. The weighted mean effect size, Cohen's d (95% CI) for prenatal and postnatal nutrition interventions on mental development was 0.042 (-0.0084, 0.092) and 0.076 (0.019, 0.13), respectively. Postnatal supplements consisting of macronutrients yielded an effect size d (95% CI) of 0.14 (0.0067, 0.27), multiple micronutrients 0.082 (-0.012, 0.18) and single micronutrients 0.058 (-0.0015, 0.12). Motor development, but not growth status, effect sizes were significantly associated with mental development in postnatal interventions. In summary, nutrition interventions had small effects on mental development. Future studies might have greater effect if they addressed macronutrient deficiencies combined with child stimulation and hygiene and sanitation interventions.

Accounting for the influence of inflammation on retinol-binding protein in a population survey of Liberian preschool-age children.

Vitamin A deficiency (VAD) is an important contributor to child morbidity and mortality. The prevalence of VAD, measured by retinol-binding protein (RBP) or retinol, is overestimated in populations with a high prevalence of inflammation. We aimed to quantify and adjust for the effect of inflammation on VAD prevalence in a nationally representative survey of Liberian children 6 to 35 months of age. We compared five approaches to adjust RBP for inflammation and estimate VAD prevalence (defined as RBP < 0.7 µmol/L): (1) ignoring inflammation; (2) excluding individuals with inflammation (C-reactive protein (CRP) >5 mg/L or alpha1-acid glycoprotein (AGP) >1 g/)L; (3) multiplying each individual's RBP by an internal correction factor; (4) by an external correction factor; and (5) using regression (corrected RBP = exp(InRBP - ß1 (lnCRPobs -lnCRPref ) - ß2 (lnAGPobs -lnAGPref )). Corrected RBP was based on a regression model where reference lnCRP and lnAGP were set to the maximum of the lowest decile. The unadjusted prevalence of VAD was 24.7%. Children with elevated CRP and/or AGP had significantly lower RBP concentrations than their apparently healthy peers (geometric mean RBP 0.79 µmol/L (95% CI: 0.76, 0.82) vs. 0.95 µmol/L (95% CI: 0.92, 0.97), P < 0.001). Using approaches 2-5 resulted in a prevalence of VAD of 11.6%, 14.3%, 13.5% and 7.3%, respectively. Depending on the approach, the VAD prevalence is reduced 10-17 percentage points when inflammation is taken into account. Further quantification of the influence of inflammation on biomarkers of vitamin A status from other national surveys is needed to compare and recommend the preferred adjustment approach across populations.

Effects of increased hemoglobin on child growth, development, and disease: a systematic review and meta-analysis.

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. 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. A literature search returned 5049 studies; of these, 56 intervention and 20 observational studies fit the inclusion criteria. Among iron supplementation trials, a metaregression indicated significant associations between intervention effects on Hb and their effects on motor and mental development. For each 1 standard deviation (SD) increase in Hb, motor scores increased by 0.28 SD and mental scores increased by 0.24 SD. 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). Heterogeneity among observational studies precluded calculation of pooled associations between Hb and functional outcomes. Available evidence was not able to establish an inflection point at which decreasing Hb begins to be associated with negative functional outcomes. 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.