Exploration of Effects of Excessive Iodine on Children and Tolerable Upper Intake Level of Iodine for Children
Condition: Iodine Disorders
Study type: Observational

Summary: 
      With the implementation of Universal Salt Iodization (USI) in 1995, China has successfully
      combated Iodine Deficiency Diseases (IDD). However, China is a country with a complicated
      iodine geographical environment with wide natural variation in the iodine content of drinking
      water. It has been reported that the water iodine of at least 11 provinces and cities in
      China is high, with nearly 31 million people exposed to the risks of excessive iodine intake.
      This has raised a new public health concern that a safe upper level of iodine intake should
      be established to ensure that people avoid ingesting excessive iodine intake while continuing
      to implement USI to control IDD. The investigators have successfully explored the tolerable
      upper intake level (UL) of iodine for Chinese adults by conducting a randomized
      double-blinded trial in 256 euthyroid volunteers. However, due to limited data on the safe
      upper intake level of iodine for children worldwide, current ULs of iodine for children are
      extrapolated from those for adults based on body weight or body surface area. As it is
      impossible to ethically conduct a randomized clinical trial regarding excessive iodine intake
      in children, the investigators plan an observational study to investigate children who have
      been living with different drinking water iodine levels for over 5 years, observing the
      changes of thyroid function in response to each iodine exposure level. Subtle changes in
      thyroid function and thyroid volume of children corresponding to different iodine intake
      levels will be determined, which will contribute to the establishment of UL of iodine for
      children.

      The aim was:

        1. To establish the tolerable upper intake level (UL) of iodine for children of China.

        2. To define the adverse effects of excess iodine on children.

        3. To monitor the iodine status of children living in high water iodine areas in China.
    

Detailed description: 
      The project is designed as a cross-sectional comparative epidemiological study, to be
      conducted in areas with high water iodine and adequate iodine intake, respectively. The
      research will include the following three stages.

      First stage: In an initial contact phase of the study, workshops on the subject matter will
      be held in Shandong province. Regions will be sampled according to the monitoring data on
      water iodine collected by the Shandong Institute for Endemic Disease Control and Research,
      which will be a collaborative department for this study, as well as the pre-investigation.
      Areas in Shandong with water iodine ranging from 150μg/L to 800μg/L iodine, corresponding to
      urinary iodine excretion (UIE) of 300-800μg/L, will be investigated as high iodine intake
      areas (HI); regions with varying water iodine levels within this range will be included.
      Matching areas in Shandong with 10-100μg/L iodine in water, corresponding to UIE of
      100-299μg/L, will be selected as the comparison areas of adequate iodine intake (AI).
      Refresher courses will be given to investigators and the capacity of laboratory staff will be
      updated. All relevant local authorities will be properly contacted. Pre-investigations will
      be conducted to determine the water iodine level and the former iodine status of residents,
      which will help the investigators to select suitable study areas. A pilot study will be
      conducted in a small number of subjects, including 24h urine collection and 3d dietary record
      to ensure that these methods are appropriate and feasible.

      Second stage: A cross-sectional study of iodine intake and thyroid function in 7-14-yr-old
      children will be carried out. This stage mainly includes two parts.

      In Part 1, 24-h and spot urinary samples (2 times) from all children will be collected to
      precisely evaluate the daily iodine intake of subjects. Spot urinary samples will be taken
      before collection of the 24-h urine samples. Teachers and parents will be trained to help
      children in performing the collection. 3d dietary records will be used to collect information
      on food and nutrient intake of participants. The parents (or guardian) and children will be
      trained on how to record food intake. The dietary record may be started any day of a week and
      correspond to the day of urine collection. The record will comprise all home food and water
      intake as well as out-of-home food consumption. Food frequency questionnaires (FFQ) will be
      used in combination with the dietary records to evaluate long-term habitual iodine intake.
      Simultaneously, food samples, including locally-consumed foods with relatively high iodine
      content and those which local residents generally consume frequently, will be sampled to
      determine iodine content, as will salt and water.

      In Part 2, Blood samples will be collected to evaluate thyroid function and thyroid
      auto-antibodies, and thyroid volume of children will be detected by ultrasonography which
      will be conducted by professional technicians

      Third stage: Iodine intake of all children will be calculated precisely and comprehensively
      through both 24-h UIE and dietary iodine intake (as described in Part 1). Adverse effects
      will be defined by parameters detected in Part 2.
    

Intervention name(s): Natural exposure of high iodine
Intervention type(s): Other
Intervention description(s): Natural exposure of high iodine intake from drinking water
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        High water iodine areas in Shandong are far-ranging. An investigation in 2005 showed that
        water iodine content exceeded 150μg/L in 17 of the 20 counties, while water iodine in the
        other 3 exceeded 300μg/L. Regions with water iodine content in the range of 150-800µg/L
        were chosen as, with a corresponding UIE range of 300-800µg/L, were selected as high iodine
        intake (HI) areas for the study. Regions with water iodine content in the range of
        10-100µg/L with a corresponding UIE range of 100-299µg/L were selected as adequate iodine
        intake (AI) study areas. Areas with high fluorine will be excluded. One to six primary
        schools were selected from each city by randomly sampling. Children were selected from
        these schools.
      
Biospecimen description: 
      -  whole blood

        -  24-h urine samples

        -  spot urine samples
    
Keywords: iodine excess; thyroid disease; children; tolerable upper intake level