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
BMJ Open 2019;9:e027666. doi:10.1136/ bmjopen-2018-027666
Margarita Cariolou,1 Meghan A Cupp, 1 Evangelos Evangelou,1,2 Ioanna Tzoulaki, 1,2 Antonio J Berlanga-Taylor1 a.berlanga at imperial.ac.uk
- Vitamin D reduces sepsis
- Treatment of neonate sepsis greatly aided by Vitamin D – RCT June 2019
- Neonatal Sepsis 4.8 X more likely if poor Vitamin D receptor – June 2018
- Sadly, the word RECEPTOR did not occur once in the meta-analysis on this page
Objectives To estimate the prevalence of 25-hydroxyvitamin D (25(OH)D) deficiency and investigate its association with mortality in children with acute or critical conditions.
Design Systematic review and meta-analysis of observational studies.
Data sources PubMed, OVID, Google Scholar and the Cochrane Library searched until 21 December 2018.
Eligibility criteria Studies of children hospitalised with acute or critical conditions who had blood 25(OH)D levels measured.
Data extraction and synthesis We 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.
Results Fifty-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.
Conclusions Our 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.
Strengths and limitations of this study
- We comprehensively assessed the magnitude and relevance of vitamin D (25(OH)D) circulating levels in paediatric patients with acute and critical illness using a large number of studies with large total sample size with prespecified subgroup and sensitivity analyses.
- We used the currently recommended cut-off of less than 50 nmol/L for vitamin D deficiency.
- We did not find enough studies to perform meta-analyses for mortality from sepsis or respiratory tract infection in relation to vitamin D status.
- We did not identify longitudinal studies with multiple time point, preadmission or predisease vitamin D measurements.
- Most studies were single centre with heterogeneous patient groups and few controlled for important con- founders that influence vitamin D levels such as age, body mass index, gender, season of measurements, vitamin D supplementation and comorbidities.