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

BACKGROUND: 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. OBJECTIVE: To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI. DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

[1]  Bernhard Resch,et al.  Burden of respiratory syncytial virus infection in young children. , 2012, World journal of clinical pediatrics.

[2]  O. Ruuskanen,et al.  Low serum 25-hydroxyvitamin D levels are associated with increased risk of viral coinfections in wheezing children , 2010, Journal of Allergy and Clinical Immunology.

[3]  C. Hawrylowicz,et al.  Regulatory T cells, inflammation and the allergic response—The role of glucocorticoids and Vitamin D , 2010, The Journal of Steroid Biochemistry and Molecular Biology.

[4]  J. Rossen,et al.  Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community† , 2010, Journal of medical virology.

[5]  S. Madhi,et al.  Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis , 2010, The Lancet.

[6]  C. Camargo,et al.  Vitamin D status of newborns in New Zealand , 2010, British Journal of Nutrition.

[7]  M. Kenward,et al.  Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring , 2010, Diabetologia.

[8]  C. Geisler,et al.  Vitamin D controls T cell antigen receptor signaling and activation of human T cells , 2010, Nature Immunology.

[9]  H. Bauchner,et al.  Widespread Vitamin D Deficiency in Urban Massachusetts Newborns and Their Mothers , 2010, Pediatrics.

[10]  R. Black,et al.  Vitamin D status and acute lower respiratory infection in early childhood in Sylhet, Bangladesh , 2010, Acta paediatrica.

[11]  J. Taylor,et al.  Use of Supplemental Vitamin D Among Infants Breastfed for Prolonged Periods , 2010, Pediatrics.

[12]  G. Hunninghake,et al.  Vitamin D Decreases Respiratory Syncytial Virus Induction of NF-κB–Linked Chemokines and Cytokines in Airway Epithelium While Maintaining the Antiviral State , 2009, The Journal of Immunology.

[13]  M. Ege,et al.  Maternal vitamin D intake during pregnancy increases gene expression of ILT3 and ILT4 in cord blood , 2009, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[14]  D. Kromhout,et al.  Towards an adequate intake of vitamin D. An advisory report of the Health Council of the Netherlands , 2009, European Journal of Clinical Nutrition.

[15]  H. Bischoff-Ferrari Vitamin D: what is an adequate vitamin D level and how much supplementation is necessary? , 2009, Best practice & research. Clinical rheumatology.

[16]  C. Camargo,et al.  Serum 25-Hydroxyvitamin D Levels Among US Children Aged 1 to 11 Years: Do Children Need More Vitamin D? , 2009, Pediatrics.

[17]  A. Rosenberg,et al.  Vitamin D deficiency in young children with severe acute lower respiratory infection , 2009, Pediatric pulmonology.

[18]  A. Litonjua Childhood asthma may be a consequence of vitamin D deficiency , 2009, Current opinion in allergy and clinical immunology.

[19]  J. Ilonen,et al.  Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5‐year‐old children , 2009, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[20]  A. Kaya,et al.  Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers , 2009, European Journal of Clinical Nutrition.

[21]  J. Wallace,et al.  Vitamin D deficiency and insufficiency in pregnant women: a longitudinal study. , 2009, The British journal of nutrition.

[22]  Carlos A Camargo,et al.  Demographic differences and trends of vitamin D insufficiency in the US population, 1988-2004. , 2009, Archives of internal medicine.

[23]  C. Homer,et al.  Vitamin D, PTH and calcium levels in pregnant women and their neonates , 2009, Clinical endocrinology.

[24]  S. Long Respiratory pathogens in children with and without respiratory symptoms , 2009 .

[25]  L. Nagy,et al.  1,25-Dihydroxyvitamin D3 Is an Autonomous Regulator of the Transcriptional Changes Leading to a Tolerogenic Dendritic Cell Phenotype12 , 2009, The Journal of Immunology.

[26]  S. Vohra,et al.  Vitamin D status is not associated with the risk of hospitalization for acute bronchiolitis in early childhood , 2009, European Journal of Clinical Nutrition.

[27]  E. Simões,et al.  A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33–35 weeks of gestational age, based on data from the Spanish FLIP study , 2008, Respiratory research.

[28]  J. Aitken,et al.  Prevalence and determinants of Australian adolescents' and adults' weekend sun protection and sunburn, summer 2003-2004. , 2008, Journal of the American Academy of Dermatology.

[29]  C. Uiterwaal,et al.  Respiratory Pathogens in Children with and without Respiratory Symptoms , 2008, The Journal of Pediatrics.

[30]  W. Grant Variations in vitamin D production could possibly explain the seasonality of childhood respiratory infections in Hawaii. , 2008, The Pediatric infectious disease journal.

[31]  J. Mora,et al.  Vitamin effects on the immune system: vitamins A and D take centre stage , 2008, Nature Reviews Immunology.

[32]  Jeannette M. Perez-Rossello,et al.  Prevalence of vitamin D deficiency among healthy infants and toddlers. , 2008, Archives of pediatrics & adolescent medicine.

[33]  A. Akobeng,et al.  Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis , 2008, Archives of Disease in Childhood.

[34]  S. Vohra,et al.  Vitamin D receptor polymorphisms and the risk of acute lower respiratory tract infection in early childhood. , 2008, The Journal of infectious diseases.

[35]  Matthew J. Spittal,et al.  Use of Sun-Protective Clothing at Outdoor Leisure Settings from 1992 to 2002: Serial Cross-sectional Observation Survey , 2008, Cancer Epidemiology Biomarkers & Prevention.

[36]  John H. White,et al.  Cell defenses and the sunshine vitamin. , 2007, Scientific American.

[37]  W. Johns,et al.  To the moon and beyond. , 2007, Scientific American.

[38]  T. Dwyer,et al.  Vitamin D levels in people with multiple sclerosis and community controls in Tasmania, Australia , 2007, Journal of Neurology.

[39]  W. Willett,et al.  The urgent need to recommend an intake of vitamin D that is effective. , 2007, The American journal of clinical nutrition.

[40]  A. Litonjua,et al.  Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. , 2007, The American journal of clinical nutrition.

[41]  P. Lips,et al.  High prevalence of vitamin D deficiency in pregnant non-Western women in The Hague, Netherlands. , 2006, The American journal of clinical nutrition.

[42]  M. Holick High prevalence of vitamin D inadequacy and implications for health. , 2006, Mayo Clinic proceedings.

[43]  A. Sadovnick,et al.  Vitamin D intake and incidence of multiple sclerosis , 2004, Neurology.

[44]  M. Uskoković,et al.  Tolerogenic dendritic cells induced by vitamin D receptor ligands enhance regulatory T cells inhibiting allograft rejection and autoimmune diseases. , 2004, Journal of cellular biochemistry.

[45]  S. Filteau,et al.  Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y , 2004, European Journal of Clinical Nutrition.

[46]  Peter B. Jones,et al.  Vitamin D supplementation during the first year of life and risk of schizophrenia: a Finnish birth cohort study , 2004, Schizophrenia Research.

[47]  W. Willett,et al.  Vitamin D intake and incidence of multiple sclerosis , 2004, Neurology.

[48]  E. Simões Respiratory syncytial virus infection , 1999, The Lancet.

[49]  Gerritsen,et al.  Validation of a screening questionnaire for atopy with serum IgE tests in a population of pregnant Dutch women , 1998, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[50]  T. M. Nguyen,et al.  Evidence for a vitamin D paracrine system regulating maturation of developing rat lung epithelium. , 1996, The American journal of physiology.

[51]  J. Pike,et al.  1,25-dihydroxyvitamin D3 receptors in rat lung during the perinatal period: regulation and immunohistochemical localization. , 1990, Endocrinology.

[52]  M. Thomasset,et al.  Vitamin D-Dependent Calcium-Binding Proteins (CaBPs) in Human Fetuses: Comparative Distribution of 9K CaBP mRNA and 28K CaBP during Development , 1987, Pediatric Research.

[53]  B. Hollis,et al.  Evaluation of the total fetomaternal vitamin D relationships at term: evidence for racial differences. , 1984, The Journal of clinical endocrinology and metabolism.

[54]  R. Rao,et al.  Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring , 2011 .

[55]  L. Shulman Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States , 2010 .

[56]  M. Dufour,et al.  1,25(OH)2D3 stimulates phospholipid biosynthesis and surfactant release in fetal rat lung explants. , 1990, Biology of the neonate.