Cord blood 25(OH)-vitamin D deficiency and childhood asthma, allergy and eczema: the COPSAC2000 birth cohort study

Bo L Chawes, Klaus Bønnelykke, Pia F Jensen, Ann-Marie M Schoos, Lene Heickendorff, Hans Bisgaard, Bo L Chawes, Klaus Bønnelykke, Pia F Jensen, Ann-Marie M Schoos, Lene Heickendorff, Hans Bisgaard

Abstract

Background: Epidemiological studies have suggested an association between maternal vitamin D dietary intake during pregnancy and risk of asthma and allergy in the offspring. However, prospective clinical studies on vitamin D measured in cord blood and development of clinical end-points are sparse.

Objective: To investigate the interdependence of cord blood 25-hydroxyvitamin D (25(OH)-Vitamin D) level and investigator-diagnosed asthma- and allergy-related conditions during preschool-age.

Methods: Cord blood 25(OH)-Vitamin D level was measured in 257 children from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2000) at-risk mother-child cohort. Troublesome lung symptoms (TROLS), asthma, respiratory infections, allergic rhinitis, and eczema, at age 0-7 yrs were diagnosed exclusively by the COPSAC pediatricians strictly adhering to predefined algorithms. Objective assessments of lung function and sensitization were performed repeatedly from birth.

Results: After adjusting for season of birth, deficient cord blood 25(OH)-Vitamin D level (<50 nmol/L) was associated with a 2.7-fold increased risk of recurrent TROLS (HR = 2.65; 95% CI = 1.02-6.86), but showed no association with respiratory infections or asthma. We saw no association between cord blood 25(OH)-Vitamin D level and lung function, sensitization, rhinitis or eczema. The effects were unaffected from adjusting for multiple lifestyle factors.

Conclusion: Cord blood 25(OH)-Vitamin D deficiency associated with increased risk of recurrent TROLS till age 7 years. Randomized controlled trials of vitamin D supplementation during pregnancy are needed to prove causality.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Kaplan Meier survival curve showing…
Figure 1. Kaplan Meier survival curve showing the risk of developing recurrent troublesome lung symptoms (TROLS) at age 0–7 yrs stratified by cord blood 25(OH)-Vitamin D level.
Figure 2. Kaplan Meier survival curve showing…
Figure 2. Kaplan Meier survival curve showing the risk of developing lower respiratory tract infections (LRTI) at age 0–3 yrs stratified by cord blood 25(OH)-Vitamin D level.
Figure 3. Kaplan Meier survival curve showing…
Figure 3. Kaplan Meier survival curve showing the risk of developing eczema at age 0–7 yrs stratified by cord blood 25(OH)-Vitamin D level.

References

    1. Holick MF (2007) Vitamin D deficiency. N Engl J Med 357: 266–281.
    1. Eder W, Ege MJ, von ME (2006) The asthma epidemic. N Engl J Med 355: 2226–2235.
    1. Hollams EM (2012) Vitamin D and atopy and asthma phenotypes in children. Curr Opin Allergy Clin Immunol 12: 228–234.
    1. Zosky GR, Berry LJ, Elliot JG, James AL, Gorman S, et al. (2011) Vitamin D deficiency causes deficits in lung function and alters lung structure. Am J Respir Crit Care Med 183: 1336–1343.
    1. Litonjua AA, Weiss ST (2007) Is vitamin D deficiency to blame for the asthma epidemic? J Allergy Clin Immunol 120: 1031–1035.
    1. Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST, et al. (2007) Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr 85: 788–795.
    1. Devereux G, Litonjua AA, Turner SW, Craig LC, McNeill G, et al. (2007) Maternal vitamin D intake during pregnancy and early childhood wheezing. Am J Clin Nutr 85: 853–859.
    1. Morales E, Romieu I, Guerra S, Ballester F, Rebagliato M, et al. (2012) Maternal vitamin D status in pregnancy and risk of lower respiratory tract infections, wheezing, and asthma in offspring. Epidemiology 23: 64–71.
    1. Camargo CA Jr, Ingham T, Wickens K, Thadhani R, Silvers KM, et al. (2011) Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics 127: e180–e187.
    1. Liu X, Arguelles L, Zhou Y, Wang G, Chen Q, et al. (2013) Longitudinal trajectory of vitamin D status from birth to early childhood in the development of food sensitization. Pediatr Res 74: 321–326.
    1. Baiz N, rgent-Molina P, Wark JD, Souberbielle JC, nnesi-Maesano I (2013) Cord serum 25-hydroxyvitamin D and risk of early childhood transient wheezing and atopic dermatitis. J Allergy Clin Immunol.
    1. Jones AP, Palmer D, Zhang G, Prescott SL (2012) Cord blood 25-hydroxyvitamin D3 and allergic disease during infancy. Pediatrics 130: e1128–e1135.
    1. Bisgaard H (2004) The Copenhagen Prospective Study on Asthma in Childhood (COPSAC): design, rationale, and baseline data from a longitudinal birth cohort study. Ann Allergy Asthma Immunol 93: 381–389.
    1. Bisgaard H, Hermansen MN, Loland L, Halkjaer LB, Buchvald F (2006) Intermittent inhaled corticosteroids in infants with episodic wheezing. N Engl J Med 354: 1998–2005.
    1. Bisgaard H, Hermansen MN, Buchvald F, Loland L, Halkjaer LB, et al. (2007) Childhood asthma after bacterial colonization of the airway in neonates. N Engl J Med 357: 1487–1495.
    1. Maunsell Z, Wright DJ, Rainbow SJ (2005) Routine isotope-dilution liquid chromatography-tandem mass spectrometry assay for simultaneous measurement of the 25-hydroxy metabolites of vitamins D2 and D3. Clin Chem 51: 1683–1690.
    1. Hojskov CS, Heickendorff L, Moller HJ (2010) High-throughput liquid-liquid extraction and LCMSMS assay for determination of circulating 25(OH) vitamin D3 and D2 in the routine clinical laboratory. Clin Chim Acta 411: 114–116.
    1. Bisgaard H, Pipper CB, Bonnelykke K (2011) Endotyping early childhood asthma by quantitative symptom assessment. J Allergy Clin Immunol.
    1. Bisgaard H, Bonnelykke K, Sleiman PM, Brasholt M, Chawes B, et al. (2009) Chromosome 17q21 gene variants are associated with asthma and exacerbations but not atopy in early childhood. Am J Respir Crit Care Med 179: 179–185.
    1. Chawes BL, Buchvald F, Bischoff AL, Loland L, Hermansen M, et al. (2010) Elevated Exhaled Nitric Oxide in High-risk Neonates Precedes Transient Early but not Persistent Wheeze. Am J Respir Crit Care Med 182: 138–142.
    1. Vissing NH, Chawes BL, Bisgaard H (2013) Increased risk of pneumonia and bronchiolitis after bacterial colonization of the airways as neonates. Am J Respir Crit Care Med 188: 1246–1252.
    1. Chawes BL, Kreiner-Moller E, Bisgaard H (2009) Objective assessments of allergic and nonallergic rhinitis in young children. Allergy 64: 1547–1553.
    1. Chawes BL, Kreiner-Moller E, Bisgaard H (2010) Upper and Lower Airway Patency are Associated in Young Children. Chest 137: 1332–1337.
    1. Chawes BL, Bonnelykke K, Kreiner-Moller E, Bisgaard H (2010) Children with allergic and nonallergic rhinitis have a similar risk of asthma. J Allergy Clin Immunol 126: 567–573.
    1. Braun-Fahrlander C, Wuthrich B, Gassner M, Grize L, Sennhauser FH, et al. (1997) Validation of a rhinitis symptom questionnaire (ISAAC core questions) in a population of Swiss school children visiting the school health services. SCARPOL-team. Swiss Study on Childhood Allergy and Respiratory Symptom with respect to Air Pollution and Climate. International Study of Asthma and Allergies in Childhood. Pediatr Allergy Immunol 8: 75–82.
    1. Bisgaard H, Simpson A, Palmer CN, Bonnelykke K, McLean I, et al. (2008) Gene-environment interaction in the onset of eczema in infancy: filaggrin loss-of-function mutations enhanced by neonatal cat exposure. PLoS Med 5: e131.
    1. Halkjaer LB, Loland L, Buchvald FF, Agner T, Skov L, et al. (2006) Development of atopic dermatitis during the first 3 years of life: the Copenhagen prospective study on asthma in childhood cohort study in high-risk children. Arch Dermatol 142: 561–566.
    1. Chawes BL, Poorisrisak P, Johnston SL, Bisgaard H (2012) Neonatal bronchial hyperresponsiveness precedes acute severe viral bronchiolitis in infants. J Allergy Clin Immunol 130: 354–361.
    1. Loland L, Buchvald FF, Halkjaer LB, Anhoj J, Hall GL, et al. (2006) Sensitivity of bronchial responsiveness measurements in young infants. Chest 129: 669–675.
    1. Loland L, Bisgaard H (2008) Feasibility of repetitive lung function measurements by raised volume rapid thoracoabdominal compression during methacholine challenge in young infants. Chest 133: 115–122.
    1. Bisgaard H, Jensen SM, Bonnelykke K (2012) Interaction between Asthma and Lung Function Growth in Early Life. Am J Respir Crit Care Med.
    1. Ballardini N, Nilsson C, Nilsson M, Lilja G (2006) ImmunoCAP Phadiatop Infant—a new blood test for detecting IgE sensitisation in children at 2 years of age. Allergy 61: 337–343.
    1. Wickman M, Ahlstedt S, Lilja G, van Hage HM (2003) Quantification of IgE antibodies simplifies the classification of allergic diseases in 4-year-old children. A report from the prospective birth cohort study—BAMSE. Pediatr Allergy Immunol 14: 441–447.
    1. Sorensen M, Bisgaard H, Stage M, Loft S (2007) Biomarkers of exposure to environmental tobacco smoke in infants. Biomarkers 12: 38–46.
    1. Sichert-Hellert W, Wenz G, Kersting M (2006) Vitamin intakes from supplements and fortified food in German children and adolescents: results from the DONALD study. J Nutr 136: 1329–1333.
    1. Miyake Y, Sasaki S, Tanaka K, Hirota Y (2010) Dairy food, calcium and vitamin D intake in pregnancy, and wheeze and eczema in infants. Eur Respir J 35: 1228–1234.
    1. Wjst M (2006) The vitamin D slant on allergy. Pediatr Allergy Immunol 17: 477–483.
    1. Litonjua AA (2009) Childhood asthma may be a consequence of vitamin D deficiency. Curr Opin Allergy Clin Immunol 9: 202–207.
    1. Yim S, Dhawan P, Ragunath C, Christakos S, Diamond G (2007) Induction of cathelicidin in normal and CF bronchial epithelial cells by 1,25-dihydroxyvitamin D(3). J Cyst Fibros 6: 403–410.

Source: PubMed

3
Subskrybuj