Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children

Ann Am Thorac Soc. 2016 Feb;13(2):223-30. doi: 10.1513/AnnalsATS.201508-549OC.


Background: Little is known about folate and atopy or severe asthma exacerbations. We examined whether folate deficiency is associated with number of positive skin tests to allergens or severe asthma exacerbations in a high-risk population and further assessed whether such association is explained or modified by vitamin D status.

Methods: Cross-sectional study of 582 children aged 6 to 14 years with (n = 304) and without (n = 278) asthma in San Juan, Puerto Rico. Folate deficiency was defined as plasma folate less than or equal to 20 ng/ml. Our outcomes were the number of positive skin tests to allergens (range, 0-15) in all children and (in children with asthma) one or more severe exacerbations in the previous year. Logistic and negative binomial regression models were used for the multivariate analysis. All multivariate models were adjusted for age, sex, household income, residential proximity to a major road, and (for atopy) case/control status; those for severe exacerbations were also adjusted for use of inhaled corticosteroids and vitamin D insufficiency (a plasma 25[OH]D < 30 ng/ml).

Measurements and main results: In a multivariate analysis, folate deficiency was significantly associated with an increased degree of atopy and 2.2 times increased odds of at least one severe asthma exacerbation (95% confidence interval for odds ratio, 1.1-4.6). Compared with children who had normal levels of both folate and vitamin D, those with both folate deficiency and vitamin D insufficiency had nearly eightfold increased odds of one or more severe asthma exacerbation (95% confidence interval for adjusted odds ratio, 2.7-21.6).

Conclusions: Folate deficiency is associated with increased degree of atopy and severe asthma exacerbations in school-aged Puerto Ricans. Vitamin D insufficiency may further increase detrimental effects of folate deficiency on severe asthma exacerbations.

Keywords: Puerto Ricans; asthma; children; folate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adrenal Cortex Hormones / therapeutic use
  • Asthma / drug therapy
  • Asthma / epidemiology*
  • Asthma / physiopathology
  • Bronchodilator Agents / therapeutic use
  • Child
  • Disease Progression
  • Female
  • Folic Acid / blood
  • Folic Acid Deficiency / epidemiology*
  • Forced Expiratory Volume
  • Humans
  • Hypersensitivity / diagnosis
  • Hypersensitivity / epidemiology*
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Puerto Rico / epidemiology
  • Severity of Illness Index
  • Skin Tests
  • Vital Capacity
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / epidemiology*


  • Adrenal Cortex Hormones
  • Bronchodilator Agents
  • Vitamin D
  • Folic Acid
  • 25-hydroxyvitamin D