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), withanadjustedmeandifference 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.