Prevention of Post-Cardiac Surgery Vitamin D Deficiency in Children With Congenital Heart Disease: A Pilot Dose Evaluation Randomized Controlled Trial

1 - INTRODUCTION 1.1 Summary of problem CHD is a common condition with an estimated prevalence of 1 per 100 in the general population. A significant proportion of these pediatric patients require one or more corrective surgeries over their lifetime, leading to 15000 procedures per year in North America. Post-operatively, these patients suffer significant morbidities which may include a pronounced systemic inflammatory response, coagulopathy, respiratory failure, electrolyte disturbances, arrhythmia, myocardial dysfunction, kidney failure, infection and endocrine imbalances. Interventions that prevent or modulate post-operative pathophysiology may prevent illness, speed recovery and decrease chronic morbidity in this high risk pediatric population. Vitamin D is recognized as a pleiotropic hormone important for the functioning of multiple organ systems, including those central to critical illness pathophysiology. Recent research by our group and others has documented not only that 4 out of every 5 CHD patients have inadequate blood levels of vitamin D following surgery, but an association between immediate post-operative hormone levels and clinical course. Altogether, these findings and similar results in adult critical care and cardiac surgery populations, suggest that optimization of vitamin D status following CHD repair could lessen inflammation, reduce nosocomial infection and improve cardiac function. As an inexpensive medication (~$15/month) that is generally regarded as safe, vitamin D has the potential to be an ideal intervention for improving outcomes following CHD repair. Clinical trials will be required to determine whether elevation of pre-operative 25-hydroxyvitamin D (25OHD) and prevention of post-operative vitamin D deficiency improves the health of patients with CHD who require cardiac surgery.

1.2 - Gaps in current knowledge regarding vitamin D supplementation in CHD

The current body of knowledge suggests that optimization of vitamin D status prior to and following CHD repair could improve outcomes through reduced inflammation, fewer nosocomial infections and improved cardiac function. However, before these findings can be translated into clinical practice a number of unknowns must be addressed:

1. Evidence of benefit from interventional studies - As a unique and under-appreciated problem, there have been no interventional studies establishing that prevention of post-operative vitamin D deficiency improves clinical outcomes in CHD patients.
2. Lack of studies evaluating vitamin D dosing in the CHD population - Attempts to perform a large randomized control trial (RCT) would be premature as a dosing regimen that prevents post-operative vitamin D deficiency has not yet been identified. Moreover, there have been no vitamin D dosing studies or guidelines developed specific to the CHD population; presently children with CHD receive the same advice regarding supplementation as healthy children.
3. The safety of vitamin D doses above usual care has not been studied in the CHD population - Although it is tempting to extrapolate recent safety data from high dose vitamin D studies on healthy children to the CHD population, this may be inappropriate. CHD patients have unique metabolic demands, organ dysfunctions, and known and unknown genetic abnormalities that potentially make them more or less susceptible to vitamin D.

To begin addressing these knowledge gaps we will complete a pilot dose evaluation trial with the goal of identifying a supplementation regimen that safely prevents post-operative vitamin D deficiency.