Importance of vitamin D in acute and critically ill children with subgroup analyses of sepsis and respiratory tract infections: a systematic review and meta-analysis

Abstract

ObjectivesTo estimate the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency and investigate its association with mortality in children with acute or critical conditions.DesignSystematic review and meta-analysis of observational studies.Data sourcesPubMed, OVID, Google Scholar and the Cochrane Library searched until 21 December 2018.Eligibility criteriaStudies of children hospitalised with acute or critical conditions who had blood 25(OH)D levels measured.Data extraction and synthesisWe obtained pooled prevalence estimates of 25(OH)D deficiency and ORs for mortality. We calculated 95% CI and prediction intervals and investigated heterogeneity and evidence of small-study effects.ResultsFifty-two studies were included. Of 7434 children, 3473 (47.0%) were 25(OH)D deficient (<50 nmol/L). The pooled prevalence estimate of 25(OH)D deficiency was 54.6% (95% CI 48.5% to 60.6%, I2=95.3%, p<0.0001). Prevalence was similar after excluding smaller studies (51.5%). In children with sepsis (18 studies, 889 total individuals) prevalence was 64.0% (95% CI 52.0% to 74.4%, I2=89.3%, p<0.0001) and 48.7% (95% CI 38.2% to 59.3%; I2=94.3%, p<0.0001) in those with respiratory tract infections (RTI) (25 studies, 2699 total individuals). Overall, meta-analysis of mortality (18 cohort studies, 2463 total individuals) showed increased risk of death in 25(OH)D deficient children (OR 1.81, 95% CI 1.24 to 2.64, p=0.002, I2=25.7%, p=0.153). Four (22.0%) of the 18 studies statistically adjusted for confounders. There were insufficient studies to meta-analyse sepsis and RTI-related mortality.ConclusionsOur results suggest that 25(OH)D deficiency in acute and critically ill children is high and associated with increased mortality. Small-study effects, reverse causation and other biases may have confounded results. Larger, carefully designed studies in homogeneous populations with confounder adjustment are needed to clarify the association between 25(OH)D levels with mortality and other outcomes.Prospero registration number CRD42016050638.

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“…As of March 06, 94 patients were discharged from hospital, median hospital stay was 15 (IQR, [11][12][13][14][15][16][17][18] days. MODS developed in 17 (7.1%) patients, septic shock in 6 (2.5%) patients.…”

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“…Similarly, critically ill patients have a very high prevalence of vitamin D deficiency, and low vitamin D levels are clearly associated with greater illness severity, morbidity, and mortality in both adult and pediatric intensive care unit (ICU) patients, as well as medical and surgical ICUs [23]. However, as in most other populations, the most important question remains unanswered: whether low vitamin D is an innocent bystander, simply reflecting greater disease severity, or represents an independent and modifiable risk factor amenable to rapid normalization through loading dose supplementation [24,25].…”

Systematic reviews and meta-analysis in nutrition research

“…In addition, it has been suggested that because PI are calculated based on trials that are generally homogeneous, that is, patient populations and comparator treatments are interchangeable, the overall effect estimates may not be accurate if they do not meet this criterion (99) . As an example of PI use in nutrition, Cariolou et al recently conducted an AD meta-analysis on the association between 25-hydroxyvitamin D deficiency and mortality in children with acute or critical conditions (100) . Based on a random-effects model, the pooled OR and 95 % CI of the risk of mortality in vitamin D deficient v. vitamin D non-deficient acute and critically ill children was 1•81 (95 % CI 1•24, 2•64).…”

“…Based on a random-effects model, the pooled OR and 95 % CI of the risk of mortality in vitamin D deficient v. vitamin D non-deficient acute and critically ill children was 1•81 (95 % CI 1•24, 2•64). However, based on 95 % PI (0 •71, 4•20), there was much less certainty, that is, wider intervals that also included 1, regarding this association (100) .…”