Preschool micronutrient supplementation effects on intellectual and motor function in school-aged Nepalese children.

OBJECTIVE: To examine intellectual and motor functioning of children who received micronutrient supplementation from 12 to 35 months of age. DESIGN: Cohort follow-up of children 7 to 9 years of age who participated in a 2 × 2 factorial, placebo-controlled, randomized trial from October 2001 through January 2006. SETTING: Rural Nepal. PARTICIPANTS: A total of 734 children 12 to 35 months of age at supplementation and 7 to 9 years of age at testing. INTERVENTIONS: Children received iron plus folic acid (12.5 mg of iron and 50 µg of folic acid); zinc (10 mg); iron plus folic acid and zinc; or placebo. MAIN OUTCOME MEASURES: Intellectual, motor, and executive function. RESULTS: In both the unadjusted and adjusted analyses, iron plus folic acid supplementation had no effect overall or on any individual outcome measures being tested. In the unadjusted analysis, zinc supplementation had an overall effect, although none of the individual test score differences were significant. In the adjusted analysis, the overall difference was not significant. CONCLUSION: In rural Nepal, we found that iron plus folic acid or zinc supplementation during the preschool years had no effect on aspects of intellectual, executive, and motor function at 7 to 9 years of age, suggesting no long-term developmental benefit of iron or zinc supplementation during 12 to 35 months of age.

Prenatal micronutrient supplementation and intellectual and motor function in early school-aged children in Nepal.

CONTEXT: Iron and zinc are important for the development of both intellectual and motor skills. Few studies have examined whether iron and zinc supplementation during gestation, a critical period of central nervous system development, affects children's later functioning. OBJECTIVE: To examine intellectual and motor functioning of children whose mothers received micronutrient supplementation during pregnancy. DESIGN, SETTING, AND PARTICIPANTS: Cohort follow-up of 676 children aged 7 to 9 years in June 2007-April 2009 who had been born to women in 4 of 5 groups of a community-based, double-blind, randomized controlled trial of prenatal micronutrient supplementation between 1999 and 2001 in rural Nepal. Study children were also in the placebo group of a subsequent preschool iron and zinc supplementation trial. INTERVENTIONS: Women whose children were followed up had been randomly assigned to receive daily iron/folic acid, iron/folic acid/zinc, or multiple micronutrients containing these plus 11 other micronutrients, all with vitamin A, vs a control group of vitamin A alone from early pregnancy through 3 months postpartum. These children did not receive additional micronutrient supplementation other than biannual vitamin A supplementation. MAIN OUTCOME MEASURES: Children's intellectual functioning, assessed using the Universal Nonverbal Intelligence Test (UNIT); tests of executive function, including go/no-go, the Stroop test, and backward digit span; and motor function, assessed using the Movement Assessment Battery for Children (MABC) and finger-tapping test. RESULTS: The difference across outcomes was significant (Bonferroni-adjusted P < .001) for iron/folic acid vs control but not for other supplement groups. The mean UNIT T score in the iron/folic acid group was 51.7 (SD, 8.5) and in the control group was 48.2 (SD, 10.2), with an adjusted mean difference of 2.38 (95% confidence interval [CI], 0.06-4.70; P = .04). Differences were not significant between the control group and either the iron/folic acid/zinc (0.73; 95% CI, -0.95 to 2.42) or multiple micronutrient (1.00; 95% CI, -0.55 to 2.56) groups. In tests of executive function, scores were better in the iron/folic acid group relative to the control group for the Stroop test (adjusted mean difference in proportion who failed, -0.14; 95% CI, -0.23 to -0.04) and backward digit span (adjusted mean difference, 0.36; 95% CI, 0.01-0.71) but not for the go/no-go test. The MABC score was lower (better) in the iron/folic acid group compared with the control group but not after adjustment for confounders (mean difference, -1.47; 95% CI, -3.06 to 0.12; P = .07). Finger-tapping test scores were higher (mean difference, 2.05; 95% CI, 0.87-3.24; P = .001) in the iron/folic acid group. CONCLUSION: Aspects of intellectual functioning including working memory, inhibitory control, and fine motor functioning among offspring were positively associated with prenatal iron/folic acid supplementation in an area where iron deficiency is prevalent. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00115271.