Leila M Larson

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, Cohens 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.

Adjusting soluble transferrin receptor concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: Iron deficiency is thought to be one of the most prevalent micronutrient deficiencies globally, but an accurate assessment in populations who are frequently exposed to infections is impeded by the inflammatory response, which causes iron-biomarker alterations. Objectives: We assessed the relation between soluble transferrin receptor (sTfR) concentrations and inflammation and malaria in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y) and investigated adjustment algorithms to account for these effects. Design: Cross-sectional data from the Biomarkers Reflecting the Inflammation and Nutritional Determinants of Anemia (BRINDA) project from 11,913 PSC in 11 surveys and from 11,173 WRA in 7 surveys were analyzed individually and combined with the use of a meta-analysis. The following 3 adjustment approaches were compared with estimated iron-deficient erythropoiesis (sTfR concentration >8.3 mg/L): 1) the exclusion of individuals with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2) the application of arithmetic correction factors, and 3) the use of regression approaches. Results: The prevalence of elevated sTfR concentrations incrementally decreased as CRP and AGP deciles decreased for PSC and WRA, but the effect was more pronounced for AGP than for CRP. Depending on the approach used to adjust for inflammation, the estimated prevalence of iron-deficient erythropoiesis decreased by 4.4–14.6 and 0.3–9.5 percentage points in PSC and WRA, respectively, compared with unadjusted values. The correction-factor approach yielded a more modest reduction in the estimated prevalence of iron-deficient erythropoiesis than did the regression approach. Mostly, adjustment for malaria in addition to AGP did not significantly change the estimated prevalence of iron-deficient erythropoiesis. Conclusions: sTfR may be useful to assess iron-deficient erythropoiesis, but inflammation influences its interpretation, and adjustment of sTfR for inflammation and malaria should be considered. More research is warranted to evaluate the proposed approaches in different settings, but this study contributes to the evidence on how and when to adjust sTfR for inflammation and malaria.

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

Abstract 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 &mgr;mol/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 individuals RBP by an internal correction factor; (4) by an external correction factor; and (5) using regression (corrected RBP = exp(InRBP – &bgr;1(lnCRPobs‐lnCRPref) – &bgr;2(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 &mgr;mol/L (95% CI: 0.76, 0.82) vs. 0.95 &mgr;mol/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.

Adjusting retinol-binding protein concentrations for inflammation: Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project

Background: The accurate estimation of the prevalence of vitamin A deficiency (VAD) is important in planning and implementing interventions. Retinol-binding protein (RBP) is often used in population surveys to measure vitamin A status, but its interpretation is challenging in settings where inflammation is common because RBP concentrations decrease during the acute-phase response. Objectives: We aimed to assess the relation between RBP concentrations and inflammation and malaria in preschool children (PSC) (age range: 6–59 mo) and women of reproductive age (WRA) (age range: 15–49 y) and to investigate adjustment algorithms to account for these effects. Design: Cross-sectional data from 8 surveys for PSC (n = 8803) and 4 surveys for WRA (n = 4191) from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project were analyzed individually and combined with the use of a meta-analysis. Several approaches were explored to adjust RBP concentrations in PSC in inflammation and malaria settings as follows: 1) the exclusion of subjects with C-reactive protein (CRP) concentrations >5 mg/L or α-1-acid glycoprotein (AGP) concentrations >1 g/L, 2) the application of arithmetic correction factors, and 3) the use of a regression correction approach. The impact of adjustment on the estimated prevalence of VAD (defined as <0.7 μmol/L) was examined in PSC. Results: The relation between estimated VAD and CRP and AGP deciles followed a linear pattern in PSC. In women, the correlations between RBP and CRP and AGP were too weak to justify adjustments for inflammation. Depending on the approach used to adjust for inflammation (CRP+AGP), the estimated prevalence of VAD decreased by a median of 11–18 percentage points in PSC compared with unadjusted values. There was no added effect of adjusting for malaria on the estimated VAD after adjusting for CRP and AGP. Conclusions: The use of regression correction (derived from internal data), which accounts for the severity of inflammation, to estimate the prevalence of VAD in PSC in regions with inflammation and malaria is supported by the analysis of the BRINDA data. These findings contribute to the evidence on adjusting for inflammation when estimating VAD with the use of RBP.

Approaches to assess vitamin a status in settings of inflammation: Biomarkers reflecting inflammation and nutritional determinants of anemia (BRINDA) project

The accurate estimation of vitamin A deficiency (VAD) is critical to informing programmatic and policy decisions that could have important public health implications. However, serum retinol and retinol binding protein (RBP) concentrations, two biomarkers often used to estimate VAD, are temporarily altered during the acute phase response, potentially overestimating the prevalence of VAD in populations with high levels of inflammation. In 22 nationally-representative surveys, we examined (1) the association between C-reactive protein (CRP) or α1-acid glycoprotein (AGP) and retinol or RBP, and (2) how different adjustment approaches for correcting for inflammation compare with one another. In preschool age children (PSC) and school age children (SAC), the association between inflammation and retinol and RBP was largely statistically significant; using the regression approach, adjustments for inflammation decreased the estimated prevalence of VAD compared to unadjusted VAD (range: −22.1 to −6.0 percentage points). In non-pregnant women of reproductive age (WRA), the association between inflammation and vitamin A biomarkers was inconsistent, precluding adjustments for inflammation. The burden of VAD can be overestimated if inflammation is not accounted for, and the regression approach provides a method for adjusting retinol and RBP for inflammation across the full range of concentrations in PSC and SAC.

A Cross-Sectional Survey in Rural Bihar, India, Indicates That Nutritional Status, Diet, and Stimulation Are Associated with Motor and Mental Development in Young Children

Background: Many malnourished children in resource-poor settings fail to fulfill their developmental potential. Objective: The objectives of this analysis were to examine the nutritional, psychosocial, environmental, and household correlates of child development in Bihar, India, and identify mediators between dietary diversity and mental development. Methods: Using 2-stage cluster randomized sampling, we surveyed 4360 households with children 6–18 mo of age in the West Champaran district of Bihar. We measured motor and mental development with the use of the Developmental Milestones Checklist II. In a random subsample (n = 2838), we measured anthropometric characteristics and hemoglobin. Cluster-adjusted multiple linear regression analysis was used to examine the associations between nutrition indicators and development scores. Sobel’s test was used to assess significant mediators in the association between diet diversity and development scores. Analyses were stratified by children 6–11 and 12–18 mo of age. Results: In all children, length-for-age z score (LAZ), dietary diversity, and psychosocial stimulation were significant (P < 0.05) correlates of motor development scores [(β coefficient ± SE) in children 6–11 mo: LAZ = 0.46 ± 0.08, dietary diversity = 0.43 ± 0.09, and stimulation = 0.15 ± 0.04; in children 12–18 mo: LAZ = 0.73 ± 0.07, dietary diversity = 0.30 ± 0.09, and stimulation = 0.31 ± 0.05] and mental development scores [(β coefficient ± SE) in children 6–11 mo: LAZ = 0.57 ± 0.10, dietary diversity = 0.84 ± 0.13, and stimulation = 0.54 ± 0.07; in children 12–18 mo: LAZ = 0.54 ± 0.11, dietary diversity = 0.40 ± 0.16, and stimulation = 0.62 ± 0.09]. Stimulation, gross motor development, and fine motor development were significant mediators in the relation between dietary diversity and mental development. Conclusion: Strategies to improve dietary diversity and psychosocial stimulation could have important implications for child development of young North Indian children. This trial was registered at clinicaltrials.gov as NCT02593136.

A Path Analysis of Nutrition, Stimulation, and Child Development Among Young Children in Bihar, India

Nutrition plays an important role in the development of a child, particularly in low‐ and middle‐income countries where malnutrition is often widespread. The relation between diet, hemoglobin, nutritional status, motor development, stimulation and mental development was examined in a cross‐sectional sample of 1,079 children 12–18 months of age living in rural Bihar, India. Path analysis revealed associations between (a) length‐for‐age z‐scores and motor development, standardized β (β) = .285, p < .001, and (b) motor and all mental development outcomes (language: β = .422; personal‐social: β = .490; memory: β = .139; and executive function: β = .072, all p < .001). Additionally, stimulation was significantly associated with language scores and hemoglobin concentration with memory. These findings inform interventions aimed at improving child development in Northern India.