title: 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.
abstract: BACKGROUND
  Three decades of research suggests that prevention of iron deficiency anemia (IDA) in the primary care setting may be an unrealized and unique opportunity to prevent poor developmental outcomes in children. A longitudinal study of infants with IDA showed that the developmental disadvantage persists long term despite iron therapy. Early stages of iron deficiency, termed non-anemic iron deficiency (NAID), provide an opportunity for early detection and treatment before progression to IDA. There is little research regarding NAID, which may be associated with delayed development in young children. The aim of this study is to compare the effectiveness of four months of oral iron treatment plus dietary advice, with placebo plus dietary advice, in improving developmental outcomes in children with NAID and to conduct an internal pilot study.
  
  
  METHODS
  From a screening cohort, those identified with NAID (hemoglobin ≥110 g/L and serum ferritin <14 μg/L) are invited to participate in a pragmatic, multi-site, placebo controlled, blinded, parallel group, superiority randomized trial. Participating physicians are part of a primary healthcare research network called TARGet Kids! Children between 12 and 40 months of age and identified with NAID are randomized to receive four months of oral iron treatment at 6 mg/kg/day plus dietary advice, or placebo plus dietary advice (75 per group). The primary outcome, child developmental score, is assessed using the Mullen Scales of Early Learning at baseline and at four months after randomization. Secondary outcomes include an age appropriate behavior measure (Children's Behavior Questionnaire) and two laboratory measures (hemoglobin and serum ferritin levels). Change in developmental and laboratory measures from baseline to the end of the four-month follow-up period will be analyzed using linear regression (analysis of covariance method).
  
  
  CONCLUSIONS
  This trial will provide evidence regarding the association between child development and NAID, and the effectiveness of oral iron to improve developmental outcomes in children with NAID. The sample size of the trial will be recalculated using estimates taken from an internal pilot study.
  
  
  BACKGROUND
  This trial was registered with Clinicaltrials.gov (identifier: NCT01481766 ) on 22 November 2011.
authors: Pediatric Outcomes Research Team, Division of Pediatric Medicine, Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Canada. kawsari.abdullah@sickkids.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3 M6, Toronto, Canada. kawsari.abdullah@sickkids.ca.
authors: Kawsari
authors: K
authors: Abdullah
authors: Li Ka Shing Knowledge Institute of St Michael's Hospital, 30 Bond Street, M5B 1 W8, Toronto, Canada. kevin.thorpe@utoronto.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3 M7, Toronto, Canada. kevin.thorpe@utoronto.ca.
authors: Kevin E
authors: KE
authors: Thorpe
authors: Department of Psychology, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Canada. eva.mamak@sickkids.ca.
authors: Eva
authors: E
authors: Mamak
authors: Pediatric Outcomes Research Team, Division of Pediatric Medicine, Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Canada. jonathon.maguire@utoronto.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3 M6, Toronto, Canada. jonathon.maguire@utoronto.ca.|Li Ka Shing Knowledge Institute of St Michael's Hospital, 30 Bond Street, M5B 1 W8, Toronto, Canada. jonathon.maguire@utoronto.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3 M7, Toronto, Canada. jonathon.maguire@utoronto.ca.|Department of Pediatrics, St Michael's Hospital, University of Toronto, 30 Bond Street, M5B 1 W8, Toronto, Canada. jonathon.maguire@utoronto.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. jonathon.maguire@utoronto.ca.
authors: Jonathon L
authors: JL
authors: Maguire
authors: Pediatric Outcomes Research Team, Division of Pediatric Medicine, Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Canada. catherine.birken@sickkids.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3 M6, Toronto, Canada. catherine.birken@sickkids.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3 M7, Toronto, Canada. catherine.birken@sickkids.ca.|Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay Street, M5G 0A4, Toronto, Canada. catherine.birken@sickkids.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. catherine.birken@sickkids.ca.
authors: Catherine S
authors: CS
authors: Birken
authors: Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3 M6, Toronto, Canada. dfehlings@hollandbloorview.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3 M7, Toronto, Canada. dfehlings@hollandbloorview.ca.|Division of Developmental Pediatrics, Holland Bloorview Kids Rehabilitation Hospital, and Bloorview Research Institute, 150 Kilgour Road, M4G 1R8, Toronto, Canada. dfehlings@hollandbloorview.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. dfehlings@hollandbloorview.ca.
authors: Darcy
authors: D
authors: Fehlings
authors: Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3 M7, Toronto, Canada. anthony.hanley@utoronto.ca.|Department of Nutritional Sciences, University of Toronto, FitzGerald Building, 150 College Street, Room 316, M5S 3E2, Toronto, Canada. anthony.hanley@utoronto.ca.|Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. anthony.hanley@utoronto.ca.
authors: Anthony J
authors: AJ
authors: Hanley
authors: Pediatric Outcomes Research Team, Division of Pediatric Medicine, Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Canada. colin.macarthur@sickkids.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3 M6, Toronto, Canada. colin.macarthur@sickkids.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3 M7, Toronto, Canada. colin.macarthur@sickkids.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. colin.macarthur@sickkids.ca.|Research Institute, The Hospital for Sick Children, Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay Street, M5G 0A4, Toronto, Canada. colin.macarthur@sickkids.ca.
authors: Colin
authors: C
authors: Macarthur
authors: Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3 M7, Toronto, Canada. Stanley.zlotkin@sickkids.ca.|Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay Street, M5G 0A4, Toronto, Canada. Stanley.zlotkin@sickkids.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. Stanley.zlotkin@sickkids.ca.|Department of Nutritional Sciences, University of Toronto, FitzGerald Building, 150 College Street, Room 316, M5S 3E2, Toronto, Canada. Stanley.zlotkin@sickkids.ca.|Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children and University of Toronto, 555 University Avenue, M5G 1X8, Toronto, Canada. Stanley.zlotkin@sickkids.ca.
authors: Stanley H
authors: SH
authors: Zlotkin
authors: Pediatric Outcomes Research Team, Division of Pediatric Medicine, Department of Pediatrics, The Hospital for Sick Children, 555 University Avenue, M5G 1X8, Toronto, Canada. patricia.parkin@sickkids.ca.|Institute of Health Policy, Management and Evaluation, University of Toronto, 155 College Street Suite 425, M5T 3 M6, Toronto, Canada. patricia.parkin@sickkids.ca.|Dalla Lana School of Public Health, University of Toronto, 155 College Street 6th floor, M5T 3 M7, Toronto, Canada. patricia.parkin@sickkids.ca.|Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Peter Gilgan Centre for Research and Learning (PGCRL), 686 Bay Street, M5G 0A4, Toronto, Canada. patricia.parkin@sickkids.ca.|Department of Pediatrics, Faculty of Medicine, University of Toronto, 1 King's College Circle, Medical Sciences Building, Room 2109, M5S 1A8, Toronto, Canada. patricia.parkin@sickkids.ca.
authors: Patricia C
authors: PC
authors: Parkin
mesh_terms: D000284:Administration, Oral; D018798:Anemia, Iron-Deficiency / Q000453:epidemiology; D002657:Child Development / Q000502:physiology*; D002675:Child, Preschool; D002985:Clinical Protocols; D005296:Ferrous Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007223:Infant; D007501:Iron / Q000008:administration & dosage; D000090463:Iron Deficiencies; D011320:Primary Health Care
chemical_list: D005296:Ferrous Compounds; C020748:ferrous sulfate; D007501:Iron