A systematic review and meta-analysis of Vitamin D status and clinical outcomes in critically ill neonates.

INTRODUCTION

Vitamin D is key in immunoregulation and impacts critical care outcomes. With a high prevalence of neonatal Vitamin D deficiency (VDD), we aim to evaluate its association with clinical outcomes in the neonatal intensive care unit (NICU).

METHODS

Systematic search of PubMed, EMBASE, Web of Science and Scopus was conducted. Primary outcomes included mortality and incidence of sepsis, while secondary outcomes were length of stay (LOS), incidence of bronchopulmonary dysplasia (BPD), and need for mechanical ventilation (MV). Eligible studies included preterm and term NICU neonates with 25-hydroxyvitamin D levels reported on admission. Definition of VDD was based on individual studies due to significant inter-study heterogeneity, however further sub-analyses with VDD definitions of ≤ 30 ng/mL and Vitamin D sufficient (VDS) > 30 ng/mL were performed to evaluate possible dose-response relationships. Pooled estimates were calculated with random-effects model due to study heterogeneity.

RESULTS

Among 2,735 articles, 18 studies met predefined inclusion criteria (n = 1981 patients). VDD was associated with increased incidence of sepsis [odds ratio (OR) 2.31, 95%CI 1.50-3.57], length of hospital stay (mean difference 4.52 days, 95% CI 1.66-7.37) and need for MV (OR 1.67, 95%CI 1.09-2.55), in comparison to VDS neonates. Further subgroup analyses for preterm (OR 2.05, 95%CI 1.04-4.04) and term neonates (OR 3.96, 95%CI 1.68-9.35) continued to show significant association between VDD and sepsis. No differences were observed between both groups for mortality and incidence of BPD. Further subgroup analyses based on Vitamin D levels found that those ≤ 30 ng/mL had no significant difference (mean difference 0 days, 95%CI -1.89 - 1.89) in terms of length of hospital stay.

CONCLUSION

VDD in critically ill neonates is significantly associated with increased odds of sepsis, need for MV, and longer LOS. However, these findings are limited by significant heterogeneity across studies. This warrants further interventional studies, involving both term and preterm neonates, to examine the potential of optimization of Vitamin D levels to improve critical care outcomes in NICU.