The Effects of Iodized Salt on Cognitive Development in Ethiopia
Condition: Iodine Deficiency; Goiter; Cretinism
MeSH terms: Congenital Hypothyroidism; Goiter
Study type: Interventional

Summary: 
      Many school children in Ethiopia and their mothers are known to be iodine deficient.
      Prevalence in the Amhara region is around 29%. Micronutrient Initiative, a development
      organization based in Ottawa, plans to help iodize the salt by providing iodization machines
      and iodine to the salt producers in Lake Afdira where salt is produced and distributed to the
      population of Ethiopia. Although it is generally assumed that iodine is important for
      cognitive development, very few studies examining the effects of iodized salt have been
      conducted. Studies using a single dose of iodine capsules with children 6 to 12 years showed
      mixed outcomes with approximately 25% yielding positive outcomes for the intervention
      children. Sixty districts in Amhara will be randomly selected and randomly assigned so that
      half receive early delivery of iodized salt. Approximately 6200 mothers and their children
      6-, 18-, or 60-months old will be recruited from 1-2 villages in each of the 60 districts,
      with the help of government-paid Health Extension Workers, for a 12-mo longitudinal study
      starting in May 2011, prior to the introduction of iodized salt. These same mothers and
      children will be visited 12 months later for repeated measures. Measures include nutritional
      status such as height and hemoglobin, along with iodine sufficiency (e.g., goitre, urinary
      iodine, thyroglobulin), and child development (Bayley Scales of Infant and Toddler
      Development III, Wechsler Preschool and Primary School Intelligence test for older children).
      Comparisons will be made within and between groups to determine whether iodized salt has an
      effect on children's mental development.
    

Detailed description: 
      MATERIALS AND METHODS Sample size was estimated on the basis of the Bayley Scales of Infant
      and Toddler Development III (Bayley) where the mean is 100 and the standard deviation is 15.
      Using an effect size of 0.20 standard deviation, a beta of .05 and power of .80, and
      accommodating for clustering within villages and attrition, the investigators require a
      sample size of 800 for each group (intervention and control). Severely anemic children (< 8
      mg/L) will be referred for treatment and not included in the study.

      In this longitudinal study the investigators will recruit 3200 6-mo old infants and 1600
      children from each of two other age groups: 18-, and 60-months (inclusion criteria) and their
      mothers. The exclusion criteria: severe anemia (hemoglobin < 8g/dL). If children are too
      disabled to take a cognitive test, this will be noted but no cognitive testing administered.

      From six zones around Bahir Dar, the investigators will randomly select 60 districts. Half
      will be assigned randomly to start receiving iodized salt in July 2011; the other half will
      receive iodized salt as it becomes available in the market. From each district, 1-2 villages
      will be randomly selected for recruiting 30 children from each age group. It is assumed that
      with a pregnancy rate of 3.7%, approximately 166 children are born every year in a village of
      4500, and 13 are born every month. So within 3 months, starting in May 2011, 30 children of
      each age could be recruited.

      With the help of Health Extension Workers, trained field workers will identify the
      participants : children of eligible age. Mothers will provide written consent for themselves
      and their children to participate.

      Mothers will be interviewed at baseline and endline concerning the family's economic and
      demographic information, child's health and diet, and opportunities for stimulation of
      children (Home Observation for Measurement of the Environment Inventory; Center for
      Epidemiologic Studies Depression Scale symptom scores). Children's nutritional status will be
      measured with a food frequency questionnaire, length/height, weight, blood indicators for
      thyroid function (thyroglobulin, thyroxin, triiodothyronine) and iron status (hemoglobin,
      ferritin, soluble transferrin receptor), and inflammation (C-reactive protein), goiter, and
      urinary iodine. A maximum of 10 mL will be collected for blood by venipuncture. Finally,
      trained assistants will administer the Bayley Scales of Infant and Toddler Development III
      (cognitive, language, and fine motor scales) to children under-3 years and two Wechsler
      Preschool and Primary School Intelligence test subscales and School Readiness test for
      60-month olds. Salt will be collected at various places of purchase and in households to test
      for iodine content (first qualitatively, then quantitatively if iodized) at baseline and at
      the end of the study. All data collection will be done at home or a convenient site in the
      village.

      Conversion of diet into iodine content will be done based on food composition table.
      Anthropometric data will be converted to standardized scores using the new World Health
      Organization reference curves, using World Health Organization's software Anthro v. 2 for
      children up to 60 months of age.

      Analyses will compare the nutritional and developmental outcomes of two groups who differ in
      iodized salt exposure, covarying confounders such as mother's education, family assets,
      child's sex, and adjusting for clustering. Developmental scores will be derived for the
      Bayley subtests, and the Wechsler Preschool and Primary School Intelligence test. These tests
      typically assign 1 point for every correct answer and 0 points for incorrect answers; the
      summed continuous scores are then used for analysis. Potential confounds include the Home
      Observation for Measurement of the Environment Inventory and Center for Epidemiologic Studies
      Depression Scale symptom scores, which also are calculated as the sum of individual item
      points. Laboratory analyses will be conducted to determine hemoglobin, ferritin, soluble
      transferrin receptor, thyroglobulin, thyroxin, and triiodothyronine from blood samples, and
      iodine excretion from urine samples. Analyses of salt will also indicate whether salt
      consumed by participants in the intervention districts has the required ppm of iodine and
      more than salt consumed in control districts. If households in the control sites have higher
      than expected levels of iodine, this will be recorded and included in the analyses.
    

Intervention name(s): Iodized salt
Intervention type(s): Other
Intervention description(s): salt for human consumption is fortified at the national level with iodine. The experimental group will receive iodized salt early. the comparison group will receive it by market forces. presently there is only enough iodized salt to meet 10% of the countries needs, and is targeted mainly to urban areas.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: iodine; goiter; cretinism; child nutrition; cognition