Prevention of vitamin D deficiency in children following cardiac surgery: study protocol for a randomized controlled trial.
BACKGROUND
Vitamin D is a pleiotropic hormone important for the recovery of organ systems after critical illness. Recent observational studies have suggested that three out of every four children are vitamin D deficient following cardiac surgery, with inadequate preoperative intake and surgical losses playing important contributory roles. Observed associations between postoperative levels, cardiovascular dysfunction and clinical course suggest that perioperative optimization of vitamin D status could improve outcome. With this two-arm, parallel, double blind, randomized controlled trial (RCT), we aim to compare immediate postoperative vitamin D status in children requiring cardiopulmonary bypass for congenital heart disease who receive preoperative daily high dose vitamin D supplementation (high-dose arm) with those who receive usual intake (low-dose arm).


METHODS
Eligibility requirements include age (>36 weeks, <18 years) and a congenital heart defect requiring cardiopulmonary bypass surgical correction. Enrollment of 62 participants will take place at a single Canadian tertiary care center over a period of 2 years. Children randomized to the high-dose group will receive age-based dosing that was informed by the Institute of Medicine (IOM) daily tolerable upper intake level (<1 year old = 1,600 IU/day, >1 year old = 2,400 IU/day). Children in the low-dose arm will receive usual care based on IOM recommendations (<1 year old = 400 IU, >1 year old = 600 IU). The primary outcome measure is immediate postoperative vitamin D status, using blood 25(OH)D.


CONCLUSIONS
Maintaining adequate postoperative vitamin D levels following surgery could represent an effective therapy to speed recovery following CHD surgery. The proposed research project will determine whether preoperative supplementation with a dosing regimen based on the IOM recommended daily upper tolerable intake will prevent postoperative vitamin-D deficiency in the majority of children. The results will then be used to inform the design of a large international RCT exploring whether preoperative optimization of vitamin D status might improve short and long-term outcomes in this vulnerable population.


BACKGROUND
Clinicaltrials.gov Identifier--NCT01838447 Date of registration: 11 April 2013.
Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada. dayre.mcnally@gmail.com.|Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada. dayre.mcnally@gmail.com.
J Dayre
JD
McNally
Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada. kohearn@cheo.on.ca.
Katie
K
O'Hearn
Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada. Lawson@cheo.on.ca.|Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada. Lawson@cheo.on.ca.
Margaret L
ML
Lawson
Division of Cardiovascular Surgery, University of Ottawa, Ottawa, Canada. Gmaharajh@cheo.on.ca.
Gyaandeo
G
Maharajh
Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada. pgeier@cheo.on.ca.|Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada. pgeier@cheo.on.ca.
Pavel
P
Geier
School of Dietetics and Human Nutrition, McGill University, Montreal, QC, Canada. hope.weiler@mcgill.ca.
Hope
H
Weiler
Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada. sredpath@cheo.on.ca.
Stephanie
S
Redpath
Department of Medicine (Division of Critical Care), Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, ON, Canada. lmcintyre@ottawahospital.on.ca.
Lauralyn
L
McIntyre
Department of Epidemiology and Community Medicine, Ottawa Hospital Research Institute (OHRI), University of Ottawa, Ottawa, ON, Canada. dafergusson@ohri.ca.
Dean
D
Fergusson
Department of Pediatrics, Faculty of Medicine, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada. menon@cheo.on.ca.|Research Institute, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, K1H 8L1, Canada. menon@cheo.on.ca.
Kusum
K
Menon
D000293:Adolescent; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000009:adverse effects*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D019587:Dietary Supplements; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000601:surgery*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009864:Ontario; D010865:Pilot Projects; D012107:Research Design; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*
D015415:Biomarkers; D014807:Vitamin D; C104450:25-hydroxyvitamin D