Iron Treatment for Young Children With Non-anemic Iron Deficiency

Study Overview
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Brief Summary
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The pre-school years are critical years for children to acquire early learning skills such as language, fine motor and social skills; this is termed early child development. Primary care doctors (family doctors and pediatricians) are in a unique position to identify children with health or developmental problems. Screening is the process of testing healthy people for the earliest signs of health problems, followed by treatment, with the expectation that screening will improve the health of those screened. The focus of this research is screening young children for the earliest signs of iron deficiency (low blood iron levels) followed by treatment with oral iron. Previous research has shown that children with later stages of iron deficiency have serious delays in their development. Some research has shown that these delays may persist into young adulthood often with a significant reduction in intelligence. Early stages of iron deficiency may be difficult for parents or doctors to detect, and a blood test is usually needed. However, Canadian guidelines do not recommend screening all children for iron deficiency, because there is not enough good quality research to prove that screening is effective. In this study, the investigators will ask parents to allow their child between the ages of 1 to 3 years to have a blood test for iron levels. If the blood level is low, the child will be randomly assigned to receive either oral iron liquid for 4 months plus diet counseling, or a placebo liquid plus diet counseling. A psychologist will measure each child's early learning ability before and after the treatment. If this approach to screening children's blood iron levels followed by treatment improves children's development, parents and doctors may consider that routine blood screening tests are justified. Overall, this research is an important step to improving the ways in which primary care doctors can ensure that children have the best start to life-long health and achievement.

Official Title
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Optimizing Early Child Development in the Primary Care Practice Setting: Pragmatic Randomized Trial of Iron Treatment for Young Children With Non-anemic Iron Deficiency (OptEC)

Conditions
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Non-anemic Iron Deficiency

Intervention / Treatment
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* Dietary Supplement: Ferrous Sulfate
* Dietary Supplement: Placebo
* Behavioral: Dietary counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 36 months attending any well child visit Informed parental consent Exclusion Criteria: Previously diagnosed: developmental disorder, genetic, chromosomal or syndromic condition, chronic medical condition, (with the exception of asthma and allergies), including chronic anemia, iron deficiency or recent oral iron supplementation or treatment Prematurity with a gestational age less than 35 weeks; low birth weight less than 2500 grams Attending the office for an acute illness, such as a viral illness, or other health concern other than well-child assessment Any contraindications to receiving elemental iron (i.e. NHP [natural health product], comparator or placebo) The use of any Natural Health Product containing the same medicinal ingredient(s) as the investigational product English not spoken to the child in the home or in a child care setting

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 40 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iron plus dietary counseling (Non-anemic iron deficiency)<br> | Dietary Supplement: Ferrous Sulfate<br>* 6 mg elemental iron/kg/day (0.4 ml/kg/day) in 2 or 3 divided doses (at the discretion of prescribing study doctor) for four months plus dietary counseling<br>* Other names: NPN #: 00762954;Behavioral: Dietary counseling<br>* Dietary counseling will include written recommendations regarding maximum daily cow's milk intake, varied solid food intake including high iron containing foods, and avoidance of foods which reduce iron absorption.<br>|
| Placebo Comparator: Placebo plus dietary counseling (Non-anemic iron deficiency)<br> | Dietary Supplement: Placebo<br>* 0.4 ml/kg/day in 2 or 3 divided doses (at the discretion of prescribing study doctor) for four months plus dietary counseling<br>Behavioral: Dietary counseling<br>* Dietary counseling will include written recommendations regarding maximum daily cow's milk intake, varied solid food intake including high iron containing foods, and avoidance of foods which reduce iron absorption.<br>|
| No Intervention: Iron sufficient<br>From the screening cohort of it is anticipated that 25 children will have iron deficiency anemia and an equal number of randomly selected children with iron sufficiency (n=25) will be sampled. These children will be compared to the children with non-anemic iron deficiency. | |
| Active Comparator: Iron deficiency anemia<br>From the screening cohort of it is anticipated that 25 children will have iron deficiency anemia and an equal number of randomly selected children with iron sufficiency (n=25) will be sampled. These children will be compared to the children with non-anemic iron deficiency. | Dietary Supplement: Ferrous Sulfate<br>* 6 mg elemental iron/kg/day (0.4 ml/kg/day) in 2 or 3 divided doses (at the discretion of prescribing study doctor) for four months plus dietary counseling<br>* Other names: NPN #: 00762954;Behavioral: Dietary counseling<br>* Dietary counseling will include written recommendations regarding maximum daily cow's milk intake, varied solid food intake including high iron containing foods, and avoidance of foods which reduce iron absorption.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mullen Scales of Early Learning | The Mullen Scales of Early Learning assess the cognitive functioning of young children from birth to 68 months. The assessment is based on the child's responses to activities prepared by the trained examiner. Five skill areas are measured: Gross Motor and four cognitive skills (summarized into an Early Learning Composite score) - Fine Motor, Visual Reception, Receptive Language, and Expressive Language. The raw scores for each scale can be converted into age-adjusted normalized scores. | Baseline | 
| Mullen Scales of Early Learning | The Mullen Scales of Early Learning assess the cognitive functioning of young children from birth to 68 months. The assessment is based on the child's responses to activities prepared by the trained examiner. Five skill areas are measured: Gross Motor and four cognitive skills (summarized into an Early Learning Composite score) - Fine Motor, Visual Reception, Receptive Language, and Expressive Language. The raw scores for each scale can be converted into age-adjusted normalized scores. | 4 months and 12 months post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Laboratory measures | The current study focuses on laboratory measures of iron status, including hemoglobin, mean corpuscular volume, and serum ferritin. Standardized reference ranges will be used to determine if the result is normal or abnormal. | Baseline and 4 months post-treatment | 
| Child temperament | The Early Childhood Behavior Questionnaire (ECBQ) assesses the following dimensions in children 18-36 months: Activity level/Energy, Attentional Focusing, Attentional Shifting, Cuddliness, Discomfort, Fear, Frustration, High-intensity Pleasure, Impulsivity, Inhibitory Control, Low-intensity Pleasure, Motor Activation, Perceptual Sensitivity, Positive Anticipation, Sadness, Shyness, Sociability, Soothability. | Baseline and 4 months post-treatment | 
| Child growth | Growth will be measured as children's weight and height/length and then converted to age and sex adjusted z-scores using the WHO growth standards. Growth indicators will include - z-scores for weight for height (WHZ), weight for age (WAZ), height for age (HAZ) and BMI for age (BMI-AZ). BMI will be calculated as weight in kilograms divided by height in meters squared. | Baseline and 4 and 12 months post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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child development, screening, Non-anemic iron deficiency, primary care pediatrics, prevention and health promotion