Cord Blood Vitamin D Deficiency Is Associated With Respiratory Syncytial Virus Bronchiolitis

Department of Pediatrics, University Medical Center Utrecht, Utrecht.
PEDIATRICS (Impact Factor: 5.47). 06/2011; 127(6):e1513-20. DOI: 10.1542/peds.2010-3054
Source: PubMed


Respiratory syncytial virus (RSV) is the most important pathogen causing severe lower respiratory tract infection (LRTI) in infants. Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI.
To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI.
A prospective birth cohort study was performed in healthy term neonates. Concentrations of 25-hydroxyvitamin D (25-OHD) in cord blood plasma were related to RSV LRTI in the first year of life, defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen.
The study population included 156 neonates. Eighteen (12%) developed RSV LRTI. The mean plasma 25-OHD concentration was 82 nmol/L. Overall, 27% of neonates had 25-OHD concentrations < 50 nmol/L, 27% had 50-74 nmol/L and only 46% had 25-OHD 75 nmol/L. Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy. Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not (65 nmol/L versus 84 nmol/L, P = .009). Neonates born with 25-OHD concentrations <50 nmol/L had a sixfold (95% confidence interval: 1.6-24.9; P = .01) increased risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥ 75 nmol/L.
Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life. Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy.

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    • "In addition to the persuasive cellular, molecular, and biochemical data to support the relationship between 25(OH)D levels and immune function, associations of vitamin D status with the risk of various community-acquired and nosocomial infections are also evident. Indeed, 25(OH)D levels appear to influence the risk of URIs [28,29], bronchiolitis [30,31], and chronic sinusitis [32,33] in community dwelling adults and children. Moreover, emerging evidence suggests that vitamin D status may be associated with the risk of surgical site infections in post-operative patients [34] and with the risk of blood stream infections in hospitalized patients [35]. "
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    ABSTRACT: To investigate the association between serum 25-hydroxyvitamin D [25(OH)D] level and history of community-acquired pneumonia (CAP). We identified 16,975 individuals (≥17 years) from the third National Health and Nutrition Examination Survey (NHANES III) with documented 25(OH)D levels. To investigate the association of 25(OH)D with history of CAP in these participants, we developed a multivariable logistic regression model, adjusting for demographic factors (age, sex, race, poverty-to-income ratio, and geographic location), clinical data (body mass index, smoking status, asthma, chronic obstructive pulmonary disease, congestive heart failure, diabetes mellitus, stroke, chronic kidney disease, neutropenia, and alcohol consumption), and season. Locally weighted scatterplot smoothing (LOWESS) was used to depict the relationship between increasing 25(OH)D levels and the cumulative frequency of CAP in the study cohort. The median [interquartile range (IQR)] serum 25(OH)D level was 24 (IQR 18-32) ng/mL. 2.1% [95% confidence interval (CI): 1.9-2.3] of participants reported experiencing a CAP within one year of their participation in the national survey. After adjusting for demographic factors, clinical data, and season, 25(OH)D levels <30 ng/mL were associated with 56% higher odds of CAP [odds ratio 1.56; 95% confidence interval: 1.17-2.07] compared to levels ≥30 ng/mL. LOWESS analysis revealed a near linear relationship between vitamin D status and the cumulative frequency of CAP up to 25(OH)D levels around 30 ng/mL. Among 16,975 participants in NHANES III, 25(OH)D levels were inversely associated with history of CAP. Randomized controlled trials are warranted to determine the effect of optimizing vitamin D status on the risk of CAP.
    Full-text · Article · Nov 2013 · PLoS ONE
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    • "Low serum 25(OH) VitD3 levels, and the decrease in levels observed during winter [37], are associated with the risk of respiratory infections, with a 7% reduction in adult respiratory infection reported for every 10 nM/l increase in serum 25(OH) VitD3 reported [38]. In addition, newborns with low cord blood 25(OH) VitD3 levels were found to have a significantly greater risk of developing RSV-associated lower respiratory tract infections [39]. Expression of hCAP-18/LL-37 can be regulated by vitamin D [12], [30], [31] and further upregulated by exposure to RSV in the presence of vitamin D [11]. "
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    ABSTRACT: Respiratory syncytial virus is a leading cause of lower respiratory tract illness among infants, the elderly and immunocompromised individuals. Currently, there is no effective vaccine or disease modifying treatment available and novel interventions are urgently required. Cathelicidins are cationic host defence peptides expressed in the inflamed lung, with key roles in innate host defence against infection. We demonstrate that the human cathelicidin LL-37 has effective antiviral activity against RSV in vitro, retained by a truncated central peptide fragment. LL-37 prevented virus-induced cell death in epithelial cultures, significantly inhibited the production of new infectious particles and diminished the spread of infection, with antiviral effects directed both against the viral particles and the epithelial cells. LL-37 may represent an important targetable component of innate host defence against RSV infection. Prophylactic modulation of LL-37 expression and/or use of synthetic analogues post-infection may represent future novel strategies against RSV infection.
    Full-text · Article · Aug 2013 · PLoS ONE
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    • "However, children can be diagnosed with clinical rickets at higher 25[OH]D levels. Levels of 25[OH]D above the 25 nmol/L cut-off may be associated with other poor health outcomes [39], such as upper respiratory tract infections [40] and bronchiolitis [41]. A recent paper in the British Medical Journal summarises current opinion regarding adult vitamin D endocrine levels (Table 1) [37]. "
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    ABSTRACT: A potential role for vitamin D as a therapeutic immunomodulator in tuberculosis (TB) has been recognised for over 150 years, but has only recently returned to the centre of the research arena due to the increasing awareness of the global vitamin D deficiency epidemic. As early as birth a child is often deficient in vitamin D, which may not only affect their bone metabolism but also modulate their immune function, contributing to the increased susceptibility to many infections seen early in life. Recent studies have begun to explain the mechanisms by which vitamin D affects immunity. Antimicrobial peptides are induced in conjunction with stimulation of innate pattern recognition receptors enhancing immunity to particular infections. In contrast the role of vitamin D within the adaptive immune response appears to be more regulatory in function, perhaps as a mechanism to reduce unwanted inflammation. In this paper we focus on the effect of vitamin D on immunity to TB. Where much of the attention has been paid by past reviews to the role of vitamin D in adult TB patients, this paper, where possible, focuses on research in paediatric populations.
    Full-text · Article · Jul 2012 · Clinical and Developmental Immunology
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