Importance of vitamin D in critically ill children with subgroup analyses of sepsis and respiratory tract infections: a systematic review and meta-analysis
File(s)e027666.full.pdf (4 MB)
Published version
Author(s)
Cariolou, Margarita
Cupp, Meghan
Evangelou, Evangelos
Tzoulaki, Ioanna
Berlanga-Taylor, Antonio
Type
Journal Article
Abstract
Background: Critical care and sepsis remain high priority concerns in children. Observational studies report high prevalence of vitamin D deficiency and present mixed results regarding the correlation between vitamin D status and adverse outcomes. Associations between deficiency and mortality, particularly in children with sepsis, remain unclear. We performed a systematic review and meta-analysis to address this uncertainty. Methods: PubMed, OVID and Google Scholar were searched for observational studies in critically ill children. We obtained pooled prevalence estimates for vitamin D deficiency and odds ratios for the association of mortality in critically ill children treated in intensive care units, with subgroup analysis for those with sepsis and those with respiratory tract infections. Meta-regression and sensitivity analyses were used to investigate heterogeneity. Findings: Forty-eight studies were included. The total sample size was 7,199, with 1,679 (23%) children acting as controls in case-control studies. Of 5,520 critically ill children, 2,664 (48%) were vitamin D deficient (< 50 nmol/L). Results of the random effects model demonstrated a pooled prevalence of vitamin D deficiency of 54.9% (95% CI 48.0-61.6, I 2 =95.0%, 95% CI 94.0-95.8, p < 0.0001). In subgroup analysis of children with sepsis (16 studies, 788 total individuals) we observed higher prevalence of deficiency (63.8%, 95% CI 49.9-75.7, I 2 =90.5%, 95% CI 86.2-93.5%, p < 0.0001). In patients admitted for respiratory tract infections (24 studies, 1,683 total individuals), prevalence was 49.9% (95% CI 37.6-62.2; I 2 = 93.9%, 95% CI 92.1-95.3, p < 0.0001). Only one identified study assessed vitamin D levels in sepsis and mortality. The meta-regression model with all available variables (year of publication, total study sample size, quality score, study design, country group and clinical setting) explained 37.52% of I 2 (F = 5.1119, p = 0.0005) with clinical setting and country groups being significant predictors for prevalence. Meta-analysis of mortality (18 studies, 2,463 total individuals) showed an increased risk of death in vitamin D deficient critically ill children both with the random (OR 1.81, 95% CI 1.24-2.64, p-value = 0.002) and fixed effects (OR 1.72, 95% CI 1.27-2.33, p= 0.0005) models with low heterogeneity (I 2 = 25.7%, 95% CI 0.0-58.0, p = 0.153) and low evidence of publication bias (p = 0.084, Eggers test). There were insufficient studies to perform meta-analyses for sepsis and respiratory tract infections related mortality. Interpretation: Circulating vitamin D deficiency is common amongst critically ill children, particularly in those with sepsis. Our results suggest that vitamin D deficiency in critically ill children is associated with increased mortality. Clinical trials, studies with larger sample sizes and standardized approaches are needed to further assess associations between circulating levels of vitamin D and mortality or other outcomes in the pediatric population.
Date Issued
2019-05-22
Date Acceptance
2019-04-10
Citation
BMJ Open, 2019, 9
ISSN
2044-6055
Publisher
BMJ Journals
Journal / Book Title
BMJ Open
Volume
9
Copyright Statement
© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council
Grant Number
MR/L01632X/1
MR/L01632X/1
MEDBIO UK
Subjects
intensive care
meta-analysis
mortality
paediatric
prevalence
respiratory tract infections
sepsis
systematic review
vitamin D
Publication Status
Published
Article Number
e027666
Date Publish Online
2019-05-22