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Vitamin D exposure during pregnancy, but not early childhood, is associated with risk of childhood wheezing

  • L. N. Anderson (a1) (a2), Y. Chen (a3), J. A. Omand (a2) (a4), C. S. Birken (a1) (a5) (a6) (a7), P. C. Parkin (a1) (a5) (a6) (a7), T. To (a1) (a5) (a6) (a8), J. L. Maguire (a2) (a3) (a4) (a6) (a7) and the TARGet Kids Collaboration...

The association between vitamin D and wheezing in early childhood is unclear. The primary objective of this study was to evaluate the association between vitamin D exposure, during both pregnancy and childhood, and early childhood wheezing. Secondary objectives were to evaluate the associations between vitamin D exposures and asthma and wheezing severity. We conducted a cohort study of children (0–5 years) recruited from 2008 to 2013 through the TARGet Kids! primary-care research network. Vitamin D exposures included maternal vitamin D supplement use during pregnancy, child vitamin D supplementation and children’s 25-hydroxyvitamin D (25(OH)D) concentrations. The outcomes measured were parent-reported childhood wheezing, diagnosed asthma and wheezing severity. Vitamin D supplement and wheezing data were available for 2478 children, and blood samples were available for 1275 children. Adjusted odds ratios (aOR) were estimated using logistic regression adjusted for age, sex, ethnicity, body mass index, birth weight, outdoor play, breastfeeding duration, daycare status, parental smoking and family history of asthma. Vitamin D supplementation during pregnancy was associated with lower odds of childhood wheezing (aOR=0.65; 95% CI: 0.46–0.93). In early childhood, neither 25(OH)D (aOR per 10 nmol/l=1.01; 95% CI: 0.96–1.06) nor vitamin D supplementation (aOR=1.00; 95% CI: 0.81–1.23) was associated with wheezing. No significant associations were observed with diagnosed asthma or wheezing severity. Vitamin D supplementation during pregnancy was associated with reduced odds of wheezing, but child vitamin D supplementation and childhood 25(OH)D were not associated with reduced wheezing. The timing of exposure may be important in understanding the association between vitamin D and childhood wheezing.

Corresponding author
*Address for correspondence: L. N. Anderson, The Hospital for Sick Children, Division of Paediatric Medicine, 686 Bay Street, Rm. 109832, Peter Gilgan Centre for Research and Learning, Toronto, Ontario, Canada M5G 0A4.(Email:
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TARGet Kids! Collaboration – Scientific Committee: Kawsari Abdullah, Laura N. Anderson, Catherine S. Birken, Cornelia M. Borkhoff, Sarah Carsley, Yang Chen, Matthew D’Ascanio, Mikael Katz-Lavigne, Kanthi Kavikondala, Grace Jieun Lee, Jonathon L. Maguire, Jessica Omand, Patricia C. Parkin, Navindra Persaud, Meta van den Heuvel, Weeda Zabih; Site Investigators: Jillian Baker, Tony Barozzino, Joey Bonifacio, Douglas Campbell, Sohail Cheema, Brian Chisamore, Karoon Danayan, Paul Das, Mary Beth Derocher, Anh Do, Michael Dorey, Sloane Freeman, Keewai Fung, Charlie Guiang, Curtis Handford, Hailey Hatch, Sheila Jacobson, Tara Kiran, Holly Knowles, Bruce Kwok, Sheila Lakhoo, Margarita Lam-Antoniades, Eddy Lau, Fok-Han Leung, Jennifer Loo, Sarah Mahmoud, Rosemary Moodie, Julia Morinis, Sharon Naymark, Patricia Neelands, James Owen, Michael Peer, Marty Perlmutar, Navindra Persaud, Andrew Pinto, Michelle Porepa, Nasreen Ramji, Noor Ramji, Alana Rosenthal, Janet Saunderson, Rahul Saxena, Michael Sgro, Susan Shepherd, Barbara Smiltnieks, Carolyn Taylor, Thea Weisdors, Sheila Wijayasinghe, Peter Wong, Ethel Ying, Elizabeth Young.

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1. To, T, Dell, S, Dick, P, Cicutto, L. The burden of illness experienced by young children associated with asthma: a population-based cohort study. J Asthma. 2008; 45, 4549.
2. Krahn, MD, Berka, C, Langlois, P, Detsky, AS. Direct and indirect costs of asthma in Canada, 1990. Can Med Assoc J. 1996; 154, 821831.
3. Crighton, EJ, Feng, J, Gershon, A, Guan, J, To, T. A spatial analysis of asthma prevalence in Ontario. Can J Public Health. 2012; 103, e384e389.
4. Garner, R, Kohen, D. Changes in the prevalence of asthma among Canadian children. Health Rep. 2008; 19, 4550.
5. Sears, MR. Epidemiology of childhood asthma. Lancet. 1997; 350, 10151020.
6. Ginde, AA, Mansbach, JM, Camargo, CA Jr. Vitamin D, respiratory infections, and asthma. Curr Allergy Asthma Rep. 2009; 9, 8187.
7. Litonjua, AA. Vitamin D deficiency as a risk factor for childhood allergic disease and asthma. Curr Opin Allergy Clin Immunol. 2012; 12, 179185.
8. Hollams, EM. Vitamin D and atopy and asthma phenotypes in children. Curr Opin Allergy Clin Immunol. 2012; 12, 228234.
9. Lau, S. What is new in the prevention of atopy and asthma? Curr Opin Allergy Clin Immunol. 2013; 13, 181186.
10. Yong, SB, Wu, CC, Wang, L, Yang, KD. Influence and mechanisms of maternal and infant diets on the development of childhood asthma. Pediatr Neonatol. 2013; 54, 511.
11. De Luca, G, Olivieri, F, Melotti, G, et al. Fetal and early postnatal life roots of asthma. J Matern Fetal Neonatal Med. 2010; 23(Suppl. 3), 8083.
12. Devereux, G. Early life events in asthma--diet. Pediatr Pulmonol. 2007; 42, 663673.
13. Devereux, G, Litonjua, AA, Turner, SW, et al. Maternal vitamin D intake during pregnancy and early childhood wheezing. Am J Clin Nutr. 2007; 85, 853859.
14. Miyake, Y, Sasaki, S, Tanaka, K, Hirota, Y. Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants. Eur Respir J. 2010; 35, 12281234.
15. Erkkola, M, Kaila, M, Nwaru, BI, et al. Maternal vitamin D intake during pregnancy is inversely associated with asthma and allergic rhinitis in 5-year-old children. Clin Exp Allergy. 2009; 39, 875882.
16. Camargo, CA, Rifas-Shiman, SL, Litonjua, AA, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 years of age. Am J Clin Nutr. 2007; 85, 788795.
17. Maslova, E, Hansen, S, Jensen, CB, et al. Vitamin D intake in mid-pregnancy and child allergic disease – a prospective study in 44,825 Danish mother-child pairs. BMC Pregnancy Childbirth. 2013; 13, 199.
18. Zosky, GR, Hart, PH, Whitehouse, AJ, et al. Vitamin D deficiency at 16 to 20 weeks’ gestation is associated with impaired lung function and asthma at 6 years of age. Ann Am Thorac Soc. 2014; 11, 571577.
19. Gale, CR, Robinson, SM, Harvey, NC, et al. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr. 2008; 62, 6877.
20. Pike, KC, Inskip, HM, Robinson, S, et al. Maternal late-pregnancy serum 25-hydroxyvitamin D in relation to childhood wheeze and atopic outcomes. Thorax. 2012; 67, 950956.
21. Morales, E, Romieu, I, Guerra, S, et al. Maternal vitamin D status in pregnancy and risk of lower respiratory tract infections, wheezing, and asthma in offspring. Epidemiology. 2012; 23, 6471.
22. Magnus, MC, Stene, LC, Håberg, SE, et al. Prospective study of maternal mid-pregnancy 25-hydroxyvitamin D level and early childhood respiratory disorders. Paediatr Perinat Epidemiol. 2013; 27, 532541.
23. Baïz, N, Dargent-Molina, P, Wark, JD, Souberbielle, JC, Annesi-Maesano, I, Group EM-CCS. Cord serum 25-hydroxyvitamin D and risk of early childhood transient wheezing and atopic dermatitis. J Allergy Clin Immunol. 2014; 133, 147153.
24. Camargo, CA, Ingham, T, Wickens, K, et al. Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics. 2011; 127, e180e187.
25. Gergen, PJ, Teach, SJ, Mitchell, HE, et al. Lack of a relation between serum 25-hydroxyvitamin D concentrations and asthma in adolescents. Am J Clin Nutr. 2013; 97, 12281234.
26. Tolppanen, AM, Sayers, A, Granell, R, et al. Prospective association of 25-hydroxyvitamin d3 and d2 with childhood lung function, asthma, wheezing, and flexural dermatitis. Epidemiology. 2013; 24, 310319.
27. Hollams, EM, Hart, PH, Holt, BJ, et al. Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. Eur Respir J. 2011; 38, 13201327.
28. Brehm, JM, Acosta-Pérez, E, Klei, L, et al. Vitamin D insufficiency and severe asthma exacerbations in Puerto Rican children. Am J Respir Crit Care Med. 2012; 186, 140146.
29. Brehm, JM, Schuemann, B, Fuhlbrigge, AL, et al. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J Allergy Clin Immunol. 2010; 126, 5258, e55.
30. Carsley, S, Borkhoff, CM, Maguire, JL, et al. Cohort profile: The Applied Research Group for Kids (TARGet Kids!). Int J Epidemiol. 2014; doi:10.1093/ije/dyu123 [epub ahead of print].
31. Godel, JC, Canadian Paediatric Society FN, Inuit and Metis Health Committee. Vitamin D supplementation: recommendations for Canadian mothers and infants. Paediatr Child Health. 2007; 12, 583589.
32. Carter, GD, Carter, R, Jones, J, Berry, J. How accurate are assays for 25-hydroxyvitamin D? Data from the international vitamin D external quality assessment scheme. Clin Chem. 2004; 50, 21952197.
33. Maunsell, Z, Wright, DJ, Rainbow, SJ. Routine isotope-dilution liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of the 25-hydroxy metabolites of vitamins D2 and D3. Clin Chem. 2005; 51, 16831690.
34. Singh, RJ, Taylor, RL, Reddy, GS, Grebe, SK. C-3 epimers can account for a significant proportion of total circulating 25-hydroxyvitamin D in infants, complicating accurate measurement and interpretation of vitamin D status. J Clin Endocrinol Metab. 2006; 91, 30553061.
35. Institutes of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium. In Dietary Reference Intakes for Calcium and Vitamin D (eds. Ross AC, Taylor CL, Yaktine AL, et al.), 2011. Washington, DC: The National Academies Press.
36. Asher, MI, Keil, U, Anderson, HR, et al. International Study of Asthma and Allergies in Childhood (ISAAC): rationale and methods. Eur Respir J. 1995; 8, 483491.
37. Wilkins, R. PCCF+ Version 5E User’s Guide. Automated Geographic Coding Based on the Statistics Canada Postal Code Conversion Files, Including Postal Codes through March 2009. Ottawa: 2009.
38. Mei, Z, Grummer-Strawn, LM, Pietrobelli, A, et al. Validity of body mass index compared with other body-composition screening indexes for the assessment of body fatness in children and adolescents. Am J Clin Nutr. 2002; 75, 978985.
39. Group WMGRS. WHO Child Growth Standards based on length/height, weight and age. Acta Paediatr Suppl. 2006; 450, 7685.
40. Little, RJA, Rubin, DB. Statistical Analysis with Missing Data, 2nd edn, 2002. Wiley: Hoboken, NJ.
41. Goldring, ST, Griffiths, CJ, Martineau, AR, et al. Prenatal vitamin D supplementation and child respiratory health: a randomised controlled trial. PLoS One. 2013; 8, e66627.
42. Demirel, S, Guner, SN, Celiksoy, MH, Sancak, R. Is vitamin D insufficiency to blame for recurrent wheezing? Int Forum Allergy Rhinol. 2014; 4, 980985.
43. Ozaydin, E, Butun, MF, Cakir, BC, Kose, G. The association between vitamin d status and recurrent wheezing. Indian J Pediatr. 2013; 80, 907910.
44. Stenberg Hammar, K, Hedlin, G, Konradsen, JR, et al. Subnormal levels of vitamin D are associated with acute wheeze in young children. Acta Paediatr Suppl. 2014; 103, 856861.
45. Niruban, SJ, Alagiakrishnan, K, Beach, J, Senthilselvan, A. Association of vitamin D with respiratory outcomes in Canadian children. Eur J Clin Nutr. 2014; 68, 13341340.
46. Bener, A, Ehlayel, MS, Bener, HZ, Hamid, Q. The impact of Vitamin D deficiency on asthma, allergic rhinitis and wheezing in children: an emerging public health problem. J Family Community Med. 2014; 21, 154161.
47. Uysalol, M, Uysalol, EP, Yilmaz, Y, et al. Serum level of vitamin D and trace elements in children with recurrent wheezing: a cross-sectional study. BMC Pediatr. 2014; 14, 270.
48. Zosky, GR, Berry, LJ, Elliot, JG, et al. Vitamin D deficiency causes deficits in lung function and alters lung structure. Am J Respir Crit Care Med. 2011; 183, 13361343.
49. Nguyen, M, Trubert, CL, Rizk-Rabin, M, et al. 1,25-Dihydroxyvitamin D3 and fetal lung maturation: immunogold detection of VDR expression in pneumocytes type II cells and effect on fructose 1,6 bisphosphatase. J Steroid Biochem Mol Biol. 2004; 89–90, 9397.
50. Nguyen, TM, Guillozo, H, Marin, L, et al. Evidence for a vitamin D paracrine system regulating maturation of developing rat lung epithelium. Am J Physiol. 1996; 271(3 Pt 1), L392L399.
51. Becker, A, Berube, D, Chad, Z, et al. Diagnosis of asthma. Can Med Assoc J. 2005; 173(6 Suppl), S15S19.
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