Significant association between vitamin D deficiency and sepsis: a systematic review and meta-analysis

Background: A number of observational studies have found an association between low vitamin D levels and risk of sepsis. We conducted a systematic review and meta-analysis to determine the overall estimate of risk. Methods: This was a systematic review and meta-analysis conducted by online searches (CENTRAL, PubMed/MEDLINE, and EMBASE) was registered in PROSPERO (CRD42014014767). Primary outcome was incidence, prevalence, relative risk or odds ratio of having sepsis or bloodstream infection between patients with vitamin D deficiency and controls. Results: The initial search yielded 647 articles. Twenty-one articles underwent full-length review and data were extracted from 10 observational studies. Pooled odds ratio of sepsis in participants with vitamin D deficiency was 1.78 (95 % confidence interval [CI] = 1.55 to 2.03, p < 0.01) compared with controls in studies that reported participant numbers and was 1.45 (95 % CI = 1.26 to 1.66, p < 0.01) in studies that reported an adjusted odds ratio of vitamin D deficiency for developing sepsis. Statistical between-study heterogeneity was low (I-2 = 0 % and 5 %, respectively). Standardized mean difference of 25-hydroxyvitamin D levels in patients with sepsis and controls was -0.24 (95 % CI = -0.49 to 0.00, p = 0.05) and lower in the sepsis group compared with non-sepsis or control participants. The statistical between-study heterogeneity (I-2) was 0 %. Conclusion: Vitamin D deficiency were associated with an increased susceptibility of sepsis.