Iron Treatment for Young Children With Non-anemic Iron Deficiency

NCT01481766 | Completed Results

• 1 other identifier: 1000027782
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Non-anemic Iron Deficiency

Keywords

child development; screening; Non-anemic iron deficiency; primary care pediatrics; prevention and health promotion

Outcome Measures

Primary Outcomes (1)

• Early Learning Composite (ELC) From the Mullen Scales of Early Learning

  ELC is a measure of infant cognition (similar to IQ). In populations, infants have a mean score of 100 points and standard deviation of 15 points. A higher score indicates higher cognitive ability. Four cognitive skills are summarized into an Early Learning Composite score - Fine Motor, Visual Reception, Receptive Language, and Expressive Language.

  Baseline and 4 months after enrollment

Secondary Outcomes (1)

• Serum Ferritin

  4 months after enrollment

Study Arms (4)

Iron plus dietary counseling (Non-anemic iron deficiency)

EXPERIMENTAL

Dietary Supplement: Ferrous Sulfate; Behavioral: Dietary counseling

Placebo plus dietary counseling (Non-anemic iron deficiency)

PLACEBO COMPARATOR

Dietary Supplement: Placebo; Behavioral: Dietary counseling

Iron sufficient

NO INTERVENTION

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.

Iron deficiency anemia

ACTIVE COMPARATOR

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; Behavioral: Dietary counseling

Interventions

Ferrous Sulfate DIETARY_SUPPLEMENT

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

Also known as: Brand name: Fer-In-Sol by Mead Johnson Nutrition, NPN #: 00762954

Iron deficiency anemia; Iron plus dietary counseling (Non-anemic iron deficiency)

Placebo DIETARY_SUPPLEMENT

0.4 ml/kg/day in 2 or 3 divided doses (at the discretion of prescribing study doctor) for four months plus dietary counseling

Placebo plus dietary counseling (Non-anemic iron deficiency)

Dietary counseling BEHAVIORAL

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.

Iron deficiency anemia; Iron plus dietary counseling (Non-anemic iron deficiency); Placebo plus dietary counseling (Non-anemic iron deficiency)

Eligibility Criteria

• Age: 12 Months - 40 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age between 12 and 40 months attending any well child visit
• Informed parental consent

You may not qualify if:

• developmental disorder
• genetic, chromosomal or syndromic condition
• chronic medical condition (with the exception of asthma and allergies)
• chronic anemia, iron deficiency, or recent oral iron supplementation or treatment
• prematurity, with a gestational age of less than 35 weeks
• low birth weight less than 2,500 g;
• attending the office for an acute illness, such as a viral illness, or other health concern other than for a well-child assessment
• any contraindications to receiving elemental iron
• the use of any natural health product containing the same medicinal ingredient(s) as the investigational product
• English is not spoken to the child in the home or in a child care setting
• CRP level ≥10 mg/L

Sponsors & Collaborators

• The Hospital for Sick Children: lead
• Canadian Institutes of Health Research (CIHR): collaborator
• Mead Johnson Nutrition: collaborator
• Mount Sinai Hospital, Canada: collaborator
• Unity Health Toronto: collaborator

Study Sites (2)

St. Michael's Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

The Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Related Publications (5)

• Parkin PC, Borkhoff CM, Macarthur C, Abdullah K, Birken CS, Fehlings D, Koroshegyi C, Maguire JL, Mamak E, Mamdani M, Thorpe KE, Zlotkin SH, Zuo F; TARGet Kids! Collaboration. Randomized Trial of Oral Iron and Diet Advice versus Diet Advice Alone in Young Children with Nonanemic Iron Deficiency. J Pediatr. 2021 Jun;233:233-240.e1. doi: 10.1016/j.jpeds.2021.01.073. Epub 2021 Feb 4.

  PMID: 33548262 RESULT

• Gingoyon A, Borkhoff CM, Koroshegyi C, Mamak E, Birken CS, Maguire JL, Fehlings D, Macarthur C, Parkin PC. Chronic Iron Deficiency and Cognitive Function in Early Childhood. Pediatrics. 2022 Dec 1;150(6):e2021055926. doi: 10.1542/peds.2021-055926.

  PMID: 36412051 RESULT

• Parkin PC, Koroshegyi C, Mamak E, Borkhoff CM, Birken CS, Maguire JL, Thorpe KE; TARGet Kids! Collaboration. Association between Serum Ferritin and Cognitive Function in Early Childhood. J Pediatr. 2020 Feb;217:189-191.e2. doi: 10.1016/j.jpeds.2019.09.051. Epub 2019 Nov 2.

  PMID: 31685227 DERIVED

• Abdullah K, Thorpe KE, Mamak E, Maguire JL, Birken CS, Fehlings D, Hanley AJ, Macarthur C, Zlotkin SH, Parkin PC. An internal pilot study for a randomized trial aimed at evaluating the effectiveness of iron interventions in children with non-anemic iron deficiency: the OptEC trial. Trials. 2015 Jul 14;16:303. doi: 10.1186/s13063-015-0829-4.

  PMID: 26170014 DERIVED

• Abdullah K, Thorpe KE, Mamak E, Maguire JL, Birken CS, Fehlings D, Hanley AJ, Macarthur C, Zlotkin SH, Parkin PC. Optimizing early child development for young children with non-anemic iron deficiency in the primary care practice setting (OptEC): study protocol for a randomized controlled trial. Trials. 2015 Apr 2;16:132. doi: 10.1186/s13063-015-0635-z.

  PMID: 25873050 DERIVED

MeSH Terms

Conditions

Iron Deficiencies

Interventions

ferrous sulfate; Nutrition Assessment

Condition Hierarchy (Ancestors)

Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Epidemiologic Measurements; Public Health; Environment and Public Health

Limitations and Caveats

For children with NAID enrolled in the RCT, limitations include: our study population with high maternal education; our end points may not have been long enough; we were not able to measure chronicity of iron deficiency; the effect estimate for our primary outcome was based on findings from previous iron studies, but there is uncertainty regarding what is considered a meaningful treatment effect

Results Point of Contact

• Title: Dr. Patricia Parkin
• Organization: Hospital for Sick Children, Toronto, Canada

patricia.parkin@sickkids.ca

416-81307654

Study Officials

• Parkin C Parkin, MD

  The Hospital for Sick Children

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The research pharmacy prepared ferrous sulfate and placebo in bottles of similar appearance and weight. The placebo was developed by the research pharmacy, was similar in color and consistency to the active agent, and had a distinctive taste. Individuals masked to group allocation throughout the study included parents, attending physicians, research assistants, study personnel conducting outcome assessments, data analysts, and investigators. The biostatistician was unmasked after completion of data collection and locking of the database. The principal investigator was unmasked after the analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2011
• First Posted: November 30, 2011
• Study Start: June 1, 2012
• Primary Completion: October 1, 2018
• Study Completion: December 1, 2018
• Last Updated: October 30, 2025
• Results First Posted: October 30, 2025

Record last verified: 2025-10

Locations

CA (2)