Abstract

Growing evidence suggests an association between the vitamin D levels and respiratory outcomes of preterm infants. The objective of this systematic review and meta-analysis was to explore whether premature neonates with a vitamin D deficiency have an increased risk of respiratory distress syndrome (RDS). We searched PubMed, EMBASE, and the Cochrane Library up through July 20, 2021. The search terms were 'premature infant', 'vitamin D', and 'respiratory distress syndrome'. We retrieved randomized controlled trials and cohort and case-control studies. For statistical analysis, we employed the random-effects model in Comprehensive Meta-Analysis Software ver. 3.3. We employed the Newcastle-Ottawa Scales for quality assessment of the included studies. A total of 121 potentially relevant studies were found, of which 15 (12 cohort studies and 3 case-control studies) met the inclusion criteria; the studies included 2,051 preterm infants. We found significant associations between RDS development in such infants and vitamin D deficiency within 24 h of birth based on various criteria, thus vitamin D levels < 30 ng/mL (OR 3.478; 95% CI 1.817-6.659; p < 0.001), < 20 ng/mL (OR 4.549; 95% CI 3.007-6.881; p < 0.001), < 15 ng/mL (OR 17.267; 95% CI 1.084-275.112; p = 0.044), and < 10 ng/ml (OR 1.732; 95% CI 1.031-2.910; p = 0.038), and an even lower level of vitamin D (SMD = -0.656; 95% CI -1.029 to -0.283; p = 0.001). Although the vitamin D deficiency definitions varied and different methods were used to measure vitamin D levels, vitamin D deficiency or lower levels of vitamin D within 24 h of birth were always associated with RDS development. Monitoring of neonatal vitamin D levels or the maintenance of adequate levels may reduce the risk of RDS.

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