Abstract
BackgroundVitamin D deficiency (VDD) has been hypothesized not only to be common but also to represent a potentially modifiable risk factor for greater illness severity and clinical outcome during critical illness. The objective of this systematic review was to determine the frequency of VDD in pediatric critical illness and its association with clinical outcomes.MethodsMEDLINE, Embase, and CENTRAL were searched through December 12, 2016, with no date or language restrictions. The primary objective was to estimate the prevalence of VDD in the pediatric intensive care unit (PICU) and compare vitamin D status with healthy control populations. Secondary objectives were to evaluate whether VDD is associated with mortality, increased illness severity, PICU interventions, and patient clinical course. Random effects meta-analysis was used to calculate pooled VDD event rate, compare levels with those of control subjects, and evaluate for associations between VDD and clinical outcome.ResultsAmong 2700 citations, 17 studies meeting study eligibility were identified. The studies reported a total of 2783 critically ill children and had a median sample size of 120 (range 12–511). The majority of studies used a 25-hydroxyvitamin D [25(OH)D] level less than 50 nmol/L to define VDD, and the pooled VDD prevalence was 54.8 (95% CI 45.4–63.9). Average 25(OH)D levels were significantly lower in PICU patients than in healthy control subjects (pooled difference −17.3 nmol/L, 95% CI −14.0 to −20.6). In a meta-analysis calculation, we found that VDD was associated with increased mortality (OR 1.62, 95% CI 1.11–2.36), illness severity, and need for PICU interventions.ConclusionsApproximately 50% of critically ill children have VDD at the time of PICU admission, defined as a blood total 25(OH)D concentration under 50 nmol/L. VDD was further determined to be associated with greater illness severity, multiple organ dysfunction, and mortality in the PICU setting. Clinical trials are required to determine if optimization of vitamin D status improves patient outcome.Trial registrationPROSPERO, CRD42016026617. Registered on 11 January 2016.
Highlights
Vitamin D deficiency (VDD) has been hypothesized to be common and to represent a potentially modifiable risk factor for greater illness severity and clinical outcome during critical illness
Eligibility criteria Studies were included if the following eligibility criteria were met: (1) observational cohort or case-control study; (2) described a hospitalized pediatric population; (3) study participants were admitted to the pediatric intensive care unit (PICU); (4) reported on vitamin D status, determined by total 25(OH)D; and (5) reported at least one of the following outcomes: mortality, mechanical ventilation, use of vasoactive agents, or PICU illness severity score
The worldwide prevalence of VDD was calculated as 54% at the time of PICU admission, with deficiency associated with greater illness severity, use of intensive care unit (ICU) interventions, and mortality
Summary
Vitamin D deficiency (VDD) has been hypothesized to be common and to represent a potentially modifiable risk factor for greater illness severity and clinical outcome during critical illness. 25(OH)D concentration below 50 nmol/L, with severe deficiency developing at 25–30 nmol/L [10,11,12,13,14] These thresholds are based on both biochemical indicators of axis stress and values below which symptoms and disease predisposition rise. As 25(OH)D falls into the 30 nmol/L range, production of active hormone begins to fall, and healthy individuals can develop electrolyte disturbances and clinically evident disease related to inadequate blood and body calcium (rickets, seizures, myocardial disease) [16,17,18]. As a consequence of these mechanisms and others including potential roles in skeletal myopathy and kidney disease [25,26,27,28], critical care physicians and researchers have hypothesized that VDD could lead to poorer outcome in the ICU setting
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