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Background: Children's development is affected by the interplay of internal and external factors and changes in one factor can precipitate changes in multiple developmental domains., Aims: The aim of this study was to test a theoretical model of children's development using structural equation modeling., Study Design: This was designed as a substudy of a randomized, placebo-controlled, 2 × 2 factorial trial of the effects of daily supplementation with iron (12.5 mg) + folic acid (50 μg) (FeFA) with or without zinc (10 mg) (Zn) on child mortality., Subjects: Zanzibari children aged 5-9 mo (n = 106) and 10-14 mo (n = 141) at baseline were included in this sub study., Outcome Measures: Longitudinal data on children's hemoglobin, growth, malaria infection, motor development, motor activity, and language development and caregiver behavior were used to test the fit of the theoretical model for two age groups and to examine the direct and indirect relationships among the variables in the model., Results: The theoretical models were a good fit to the data for both age groups and revealed that FeFA with or without Zn had positive effects on motor development. FeFA alone had negative effects on language development in both age groups and Zn alone had negative effects on language development in children aged 10-14 mo. The incidence of malaria had negative effects on the majority of health and development outcomes in children aged 5-9 mo, and on motor development and hemoglobin in children aged 10-14 mo., Conclusions: These findings illustrate how nutrition and health factors can affect different domains of development and how these changes can precipitate changes in other domains. More work is needed to better understand the multiple impacts of internal and external factors on children's development and how changes in developmental domains interact with each other over time to determine children's overall developmental trajectory. The randomized, placebo-controlled study was registered as an International Standard Randomized Controlled Trial, number ISRCTN59549825., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Nutritionally at-risk children suffer delays in physical growth and motor and language development. Infectious diseases such as malaria pose an additional risk. We examined the cross-sectional relationships among malaria infection, hemoglobin (Hb) concentration, length-for-age Z-scores (LAZ), motor activity, behavior, and motor and language development in 841 Zanzibari children 5-19 mo old. We used structural equation modeling to test the fit of the data to a theoretical model and to examine the relationships among the variables in 3 age groups (5-9, 10-14, and 15-19 mo). The model fit the data for all age groups. In the youngest and oldest groups, children with higher malaria parasite densities had significantly lower Hb and LAZ. Higher LAZ significantly predicted higher total motor activity, and motor and language development scores in all age groups. In the oldest group, children who had higher Hb had higher motor development and activity scores. Malaria was directly and indirectly related to motor activity in the 10- to 14-mo-old group [standardized total effects, -0.14; direct, -0.10 (P = 0.015); and indirect, -0.038]. The significant fit of the models to the data and the statistical significance of many of the specific pathways highlight the complexities of the relationships between health and nutrition and child development outcomes in this population. In addition, the results suggest that multiple interventions are likely necessary to improve child development outcomes in this population of nutritionally at-risk children and that the potential effectiveness of interventions may differ according to age (i.e. prevention and treatment of anemia, stunting, and malaria).

Motor activity improves cognitive and social-emotional development through a child's exploration of his or her physical and social environment. This study assessed anemia, iron deficiency, hemoglobin (Hb), length-for-age Z-score (LAZ), and malaria infection as predictors of motor activity in 771 children aged 5-19 mo. Trained observers conducted 2- to 4-h observations of children's motor activity in and around their homes. Binary logistic regression assessed the predictors of any locomotion. Children who did not locomote during the observation (nonmovers) were excluded from further analyses. Linear regression evaluated the predictors of total motor activity (TMA) and time spent in locomotion for all children who locomoted during the observation combined (movers) and then separately for crawlers and walkers. Iron deficiency (77.0%), anemia (58.9%), malaria infection (33.9%), and stunting (34.6%) were prevalent. Iron deficiency with and without anemia, Hb, LAZ, and malaria infection significantly predicted TMA and locomotion in all movers. Malaria infection significantly predicted less TMA and locomotion in crawlers. In walkers, iron deficiency anemia predicted less activity and locomotion, whereas higher Hb and LAZ significantly predicted more activity and locomotion, even after controlling for attained milestone. Improvements in iron status and growth and prevention or effective treatment of malaria may improve children's motor, cognitive, and social-emotional development either directly or through improvements in motor activity. However, the relative importance of these factors is dependent on motor development, with malaria being important for the younger, less developmentally advanced children and Hb and LAZ becoming important as children begin to attain walking skills.

Iron and zinc deficiencies have been associated with delayed motor development in nutritionally at-risk children, albeit inconsistently. In this community-based, randomized double-blind trial, iron+folic acid (FeFA) (12.5 mg Fe + 50 mug folic acid), zinc (Zn) (10 mg), and iron+folic acid+zinc (FeFA+Zn) supplements or a placebo were given daily for 1 y to nutritionally at-risk children in Pemba, Zanzibar. The effects of these treatments on attaining unassisted walking were evaluated using survival analysis for 354 children aged 5-11 mo at the start of supplementation. Treatment effects on changes in hemoglobin (Hb) and zinc protoporphyrin (ZPP) and height-for-age (HAZ) and weight-for-age (WAZ) Z scores were evaluated using linear regression. Attained motor milestone was recorded every 2 wk for 1 y. Hb, ZPP, HAZ, and WAZ were measured at baseline and after 6 mo of treatment. FeFA with or without Zn reduced the time it took for children to walk assisted. Children who received any iron walked unassisted sooner than those who received no iron [median difference approximately 15 d, P = 0.035, risk ratio (RR) = 1.28, 95% CI = 1.02, 1.61] and this effect was stronger in those who had iron deficiency anemia (IDA) at baseline (median difference was approximately 30 d; P = 0.002; RR = 1.68; 95% CI = 1.21, 2.32). FeFA alone and Zn alone improved Hb and ZPP compared with placebo. There were no significant treatment effects on changes in HAZ or WAZ. The effects of treatment on time to walking may have been mediated by improvements in iron status or hemoglobin, but were not mediated through improvements in growth.

The acquisition of bipedal locomotion is an important aspect of gross motor development that ultimately affects the cognition of young children. Evidence for associations between nutrition-related variables and walking acquisition exist; however, questions remain about the importance of weight-for-length and dietary factors and the independent contribution of anemia and growth to walking. We examined the effect of nutritional factors on the acquisition of walking in a cross-sectional cohort of 4- to 17-mo old Nepali children (n = 485) adjusting for age, sex, caste, and socioeconomic status (SES). Participants were identified from census data collected in 1 village development committee in Sarlahi District and enrolled in a cross-sectional, community-based study between January and March 2002. Hemoglobin and erythrocyte protoporphyrin (EP) were measured at baseline using a heel-prick technique. The mean hemoglobin concentration was 101 +/- 12.5 g/L; 58% were anemic (hemoglobin < 105 g/L), 2.1% were severely anemic (hemoglobin < 70 g/L), and 43% of the children had iron-deficiency anemia (hemoglobin < 105 g/L; EP > or = 90 micromol/mol heme). Growth was delayed, i.e., 33.7% were stunted and 20.6% were wasted. Multivariate logistic models that controlled for age, sex, caste, and SES revealed that children with higher length-for-age and weight-for-length Z-scores, no anemia, and meat consumption walked at an earlier age than children with lower scores, anemia, and no meat consumption. We conclude that growth, anemia, and diet are independently associated with delays in the onset of bipedal locomotion among young Nepali children.

Locomotion allows infants to explore their environment, promoting development in other domains. Motor progression involves biological systems and experiential factors. Nutritional deficiencies could interfere with systems involved in locomotion. This study examined the associations between height-for-age (HAZ), weight-for-height (WHZ) Z-scores and anemia-iron status on locomotion in 646 Zanzibari infants. Motor milestones were assessed by trained observers using a 14-item scale. Two mutually exclusive samples were created. The crawling sample (n = 167, 6-18 mo old) included infants that crawled only or did not crawl; the walking sample (n = 479, 9-18 mo old) included children that walked alone or did not walk alone. Of the crawling and walking samples, 82.6 and 83.9% respectively, were iron deficient and/or anemic (hemoglobin < 100 g/L; zinc protoporphyrin > or = 90 micromol/mol heme). Stunting (HAZ less than -2) occurred in 30.5% of the crawling sample and 38.4% of the walking sample. Logistic regression models estimated the influence of factors on crawling vs. not crawling or walking vs. not walking. Two models were tested: 1) included sex, age, SES, HAZ and WHZ; 2) added anemia-iron status category to Model 1. HAZ improved the odds of crawling by 30%, but was not significant in either model. Model 2 fit the walking sample data best (P < 0.0001); an increase in HAZ doubled the odds of walking and nonanemic, noniron deficient children were 66% more likely to walk than those with anemia and/or iron deficiency. In this sample of poorly nourished infants, growth and anemia-iron status are significant predictors of walking, but not crawling.