| Background: Approximately two-thirds of sub-Saharan Africans are at risk of low zinc intake. Evidence is mounting that zinc plays a critical role in the mental and psychomotor development of children. The molecular and physiological mechanisms that might explain the deleterious effects of zinc deficiency on brain development and functioning are poorly understood. Evidence from epidemiological studies and animal studies suggests that mental and psychomotor impairment due to zinc deficiency can be reversed or prevented to some degree by supplementation, but results from randomised controlled trials have so far been inconsistent and inconclusive. Objectives: The study proposed aims to show the existence of zinc deficiency and to determine the potential role of improved zinc nutrition on mental and psychomotor development in Kenyan children. Innovative aspects: 1) Inconsistency of trial results that have been obtained so far may have been due to limitations of the tests employed to assess mental functioning. This problem is much reduced in the present project because multiple measures will be used. 2) The health benefits of increasing the dietary supply of zinc, particularly on mental and psychomotor development, largely remain to be confirmed in Africa. 3) Conventionally, population burden of micronutrient deficiencies is assessed by comparing response to supplementation with single nutrients in placebo-controlled trials. Because of suspicions that other nutrient deficiencies may limit the response to zinc, we propose a factorial design whereby children allocated to supplements with zinc or its placebo are both divided into groups also receiving supplements with either multinutrients without zinc, or a placebo for these multinutrients. This improved design and analysis may help in understanding of the underlying factors that determine the response to interventions, thus allowing policy makers to make better informed decisions about intervention efficacy. Methods: In a community-based survey among rural Kenyan children (n=300), micronutrient and infection status will be determined, and instruments to measure mental and psychomotor development will be adapted for use in the Kenyan context. In a subsequent randomised controlled trial, children aged 6-60 months (n=672) will receive for a period of 26 weeks a daily oral supplement with either zinc or its placebo, and additionally a daily oral supplement with either multiple micronutrients other than zinc or its placebo. Group differences will be measured and reported in mental and psychomotor development assessed at the end of the intervention period by the Bayley Scales of Infant Development, the Kaufman Assessment Battery for Children and a range of other tests to measure attention and information processing, activity, psychomotor development and neurological indicators. Effects of interventions will be analysed on an intention-to-treat basis relative to the placebo group, using multivariate and non-parametric methods as appropriate. Integration with complementary projects: This project is one of three complementary PhD research projects to assess the benefits and the underlying mechanisms of improved zinc nutrition on the health, development and well-being of African children. The other two projects will assess effects on incidence and severity of infectious diseases, child growth and nutritional status, and cellular and serological indicators of immunocompetence. |
