The role of zinc and iron-folic acid supplementation on early child temperament and eating behaviors in rural Nepal: a randomized controlled trial.

UNLABELLED: Child eating behaviors play an important role in nutrient intake, ultimately affecting child growth and later outcomes in adulthood. The study assessed the effects of iron-folic acid and zinc supplementation on child temperament and child eating behaviors in rural Nepal. Children (N = 569) aged 4-17 months in Sarlahi district, southern Nepal were randomized to receive daily supplements of placebo, iron-folic acid, zinc, or zinc plus iron-folic acid and followed for approximately 1 year. At baseline and four follow-up visits mothers completed questionnaires including information on demographic characteristics and child temperament and eating behaviors. The main effects of zinc and iron-folic acid supplementation on temperament and eating behaviors were assessed through crude and adjusted differences in mean cumulative score changes between visits 1 and 5. The adjusted rate-of-change for these outcomes was modeled using generalized estimating equations. Mean changes in temperament scores and in eating behavior scores between visits 1 and 5 were not significant in either the zinc or non-zinc group. Children in the iron-folic acid group increased temperament scores by 0.37 points over 5 visits (95% CI 0.02, 0.7), which was not significant after adjustment. Neither the adjusted rate-of-change in temperament scores between zinc and non-zinc (ß = -0.03, 95% CI -0.3, 0.2) or iron-folic acid and non-iron-folic acid (ß = 0.08, 95% CI -0.2, 0.3) were significantly different. Adjusted rate of change analysis showed no significant difference between zinc and non-zinc (ß = -0.14, 95% CI -0.3, 0.04) or between iron and non-iron eating behavior scores (ß = -0.11, 95% CI -0.3, 0.1). Only among children with iron-deficiency anemia at baseline was there a significant decrease in eating behavior score, indicating better eating behaviors, when supplemented with zinc (ß = -0.3, 95% CI -0.6, -0.01), Ultimately, this effect of zinc on eating behaviors was the only effect we observed after approximately one year of micronutrient supplementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00109551.

Effects of zinc and iron supplementation fail to improve motor and language milestone scores of infants and toddlers.

OBJECTIVE: To assess the effects of zinc and iron-folic acid supplementation on motor and language milestones in Nepali children. METHODS: Five hundred forty-four children 4 to 17 mo old residing in Ishwarpur, Nepal were randomized to receive placebo, iron-folic acid, zinc, or zinc plus iron-folic acid daily. Data were collected at baseline and at 3-mo intervals for 1 y. The main effects of zinc and iron folic-acid supplementation were estimated for motor and language milestones. Crude and adjusted mean cumulative changes in scores from visits 1 to 5 and adjusted rates of change were modeled. RESULTS: Adjusted differences in motor milestone scores from visits 1 to 5 and rates of change were not significantly different for the zinc and non-zinc groups (adjusted ß = -0.7, 95% confidence interval [CI] -1.4 to 0.01; adjusted ß = -0.1, 95% CI -0.5 to 0.3, respectively). Motor milestones in children receiving and not receiving iron supplements were not significantly different (adjusted ß = 0.1, 95% CI -0.7 to 0.8, from visits 1 to 5; adjusted ß = 0.1, 95% CI -0.3 to 0.5, for rate of change). Children receiving zinc had a 0.8 lower mean crude change in language score from visits 1 to 5 compared with children not receiving zinc (95% CI -1.3 to -0.3), but the significance was lost after adjustment (adjusted ß = -0.2, 95% CI -0.6 to 0.2, for visits 1 to 5; ß = -0.1, 95% CI -0.3 to 0.2, for rate of change). No significant difference in motor or language milestone scores from iron supplementation was observed. CONCLUSION: After 1 y, neither zinc nor iron-folic acid supplementation in Nepali children improved the attainment of motor or language milestones.

Inconsistent effects of iron-folic acid and/or zinc supplementation on the cognitive development of infants.

Despite concerns over the neurocognitive effects of micronutrient deficiencies in infancy, few studies have examined the effects of micronutrient supplementation on specific cognitive indicators. This study investigated, in 2002, the effects of iron-folic acid and/or zinc supplementation on the results of Fagan Test of Infant Intelligence (FTII) and the A-not-B Task of executive functioning among 367 Nepali infants living in Sarlahi district. Infants were enrolled in a cluster-randomized, placebo-controlled clinical trial of daily supplementation with 5 mg of zinc, 6.25 mg of iron with 25 microg of folic acid, or zinc-iron-folic acid, or placebo. These were tested on both the tasks using five indicators of information processing: preference for novelty (FTII), fixation duration (FTII), accelerated performance (> or = 85% correct; A-not-B), deteriorated performance (< 75% correct and > 1 error on repeat-following-correct trails; A-not-B), and the A-not-B error (A-not-B). At 39 and 52 weeks, 247 and 333 infants respectively attempted the cognitive tests; 213 made an attempt to solve both the tests. The likelihood of females completing the A-not-B Task was lower compared to males when cluster randomization was controlled [odds ratio = 0.67; 95% confidence interval 0.46-0.97; p < 0.05]. All of the five cognitive outcomes were modelled in linear and logistic regression. The results were not consistent across either the testing sessions or the information-processing indicators. Neither the combined nor the individual micronutrient supplements improved the performance on the FTII or the A-not-B Task (p > 0.05). These findings suggest that broader interventions (both in terms of scope and duration) are needed for infants who face many biological and social stressors.

Daily supplementation with iron plus folic acid, zinc, and their combination is not associated with younger age at first walking unassisted in malnourished preschool children from a deficient population in rural Nepal.

A community-based, cluster-randomized, placebo-controlled trial of daily zinc and/or iron+folic acid supplementation was conducted in rural southern Nepal to examine motor milestone attainment among 3264 children 1-36 mo of age between 2001 and 2006. Treatment groups included placebo, zinc (10 mg), iron+folic acid (12.5 mg iron + 50 microg folic acid), and zinc+iron+folic acid (10 mg zinc + 12.5 mg iron + 50 microg folic acid). Infants received half of these doses. The iron arms were stopped November 2003 by recommendation of the Data Safety and Monitoring Board; zinc and placebo continued until January 2006. A total of 2457 children had not walked at the time of entry into the trial and 1775 were followed through 36 mo. Mean age at first walking unassisted did not differ among groups and was 444 +/- 81 d (mean +/- SD) in the placebo group, 444 +/- 81 d in the zinc group, 464 +/- 85 d in the iron+folic acid group, and 446 +/- 87 d in the iron+folic acid+zinc group. Results were similar after adjustment for age at enrollment, asset ownership, maternal literacy, and prior child deaths in the household and in children who consumed at least 60 tablets. Compared with placebo, iron+folic acid was associated with an adjusted mean delay of 28.0 d (95% CI: 11.3, 44.7) in time to walking among infants and the delay was more pronounced with mid-upper arm circumference (MUAC) < 9.5 cm [60.6 d, (95% CI: 28.5, 92.6)]. Risks and benefits of universal iron+folic acid supplementation of infants beyond improved hematologic status deserve further consideration.

The effects of iron and/or zinc supplementation on maternal reports of sleep in infants from Nepal and Zanzibar.

BACKGROUND: There is some evidence that sleep patterns may be affected by iron deficiency anemia but the role of iron in sleep has not been tested in a randomized iron supplementation trial. OBJECTIVE: We investigated the effect of iron supplementation on maternal reports of sleep in infants in 2 randomized, placebo-controlled trials from Pemba Island, Zanzibar, and Nepal. DESIGN: In both studies, which had parallel designs and were carried out in years 2002 to 2003, infants received iron-folic acid with or without zinc daily for 12 months, and assessments of development were made every 3 months for the duration of the study. Eight hundred seventy-seven Pemban (12.5 +/- 4.0 months old) and 567 Nepali (10.8 +/- 4.0 months) infants participated. Maternal reports of sleep patterns (napping frequency and duration, nighttime sleep duration, frequency of night waking) were collected. RESULTS: Mean Hb concentration was 9.2 +/- 1.1 for Pemban and 10.1 +/- 1.2 g/dL for Nepali infants. Approximately, one-third of the children were stunted. Supplemental iron was consistently associated with longer night and total sleep duration. The effects of zinc supplementation also included longer sleep duration. CONCLUSIONS: Micronutrient supplementation in infants at high risk for iron deficiency and iron deficiency anemia was related to increased night sleep duration and less night waking.

Maternal reports of sleep in 6-18 month-old infants from Nepal and Zanzibar: association with iron deficiency anemia and stunting.

BACKGROUND: Infants with iron deficiency anemia (IDA) and stunting explore and interact less with their environment. They may also be fatigued more often, suggesting their sleep may be affected. It is unclear whether fatigue in these infants is due to poor nighttime sleep or if it is compensated for with frequent naps or longer sleep. AIMS: In 2 studies from Pemba Island, Zanzibar and 1 from Nepal we investigated the relationship between IDA, stunting, and maternal reports of sleep in 6-18 mo old infants. METHODS: Parents reported on the number and duration of naps, hours of nighttime sleep, and frequency of night waking. Anemia was defined as Hb<10 g/dL, iron deficiency as zinc protoporphyrin (ZPP > or = 90 micromol/mol heme), stunting as HAZ<-2 SD, and IDA as Hb<10 g/dL and ZPP > or = 90 micromol/mol heme. RESULTS: The prevalence of IDA and stunting was 34-84% and 22-37%, respectively. Most infants napped during the day and took approximately 1.5 naps (mean nap duration 1.4-1.7 h). Mean nighttime sleep duration was 8.3-9.7 h and infants awoke 2.1-2.5 times per night. Both IDA and stunting were associated with differences in reported sleep characterized by shorter night sleep duration and higher frequency of night waking; stunting was also related to shorter nap duration. CONCLUSIONS: We found reduced sleep duration and increased night waking among infants with IDA and stunting. Because sleep plays an essential role in infant development, our findings indicate a clear need for further research into these relationships.

Growth indices, anemia, and diet independently predict motor milestone acquisition of infants in south central Nepal.

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.