{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:07:10Z","timestamp":1787022430497,"version":"build-2736575974"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2016,2,1]],"date-time":"2016-02-01T00:00:00Z","timestamp":1454284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cross-sectional study of 582 children aged 6 to 14 years with (n\u2009=\u2009304) and without (n\u2009=\u2009278) 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\u201315) 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\u2009&amp;lt;\u200930 ng\/ml).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>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\u20134.6). 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\u201321.6).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1513\/annalsats.201508-549oc","type":"journal-article","created":{"date-parts":[[2015,11,12]],"date-time":"2015-11-12T15:12:37Z","timestamp":1447341157000},"page":"223-230","source":"Crossref","is-referenced-by-count":18,"title":["Folate Deficiency, Atopy, and Severe Asthma Exacerbations in Puerto Rican Children"],"prefix":"10.1093","volume":"13","author":[{"given":"Joshua","family":"Blatter","sequence":"first","affiliation":[{"name":"Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Brehm","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Sordillo","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick","family":"Forno","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Boutaoui","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edna","family":"Acosta-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Behavioral Sciences Research Institute and Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Alvarez","sequence":"additional","affiliation":[{"name":"Behavioral Sciences Research Institute and Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"Col\u00f3n-Semidey","sequence":"additional","affiliation":[{"name":"Behavioral Sciences Research Institute and Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott T.","family":"Weiss","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto A.","family":"Litonjua","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glorisa","family":"Canino","sequence":"additional","affiliation":[{"name":"Behavioral Sciences Research Institute and Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Celed\u00f3n","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Medicine, Allergy, and Immunology, Department of Pediatrics, Children\u2019s Hospital of Pittsburgh of University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,2,1]]},"reference":[{"key":"2026020402572696300_bib1","first-page":"1","article-title":"Trends in asthma prevalence, health care use, and mortality in the United States, 2001-2010","volume":"94","author":"Akinbami","year":"2012","journal-title":"NCHS Data Brief"},{"key":"2026020402572696300_bib2","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/S2213-2600(13)70126-7","article-title":"Diet and asthma: vitamins and methyl donors","volume":"1","author":"Han","year":"2013","journal-title":"Lancet Respir Med"},{"key":"2026020402572696300_bib3","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1164\/rccm.201302-0317PP","article-title":"Folate and asthma","volume":"188","author":"Blatter","year":"2013","journal-title":"Am J Respir Crit Care Med"},{"key":"2026020402572696300_bib4","first-page":"3462","article-title":"In utero supplementation with methyl donors enhances allergic airway disease in mice","volume":"118","author":"Hollingsworth","year":"2008","journal-title":"J Clin Invest"},{"key":"2026020402572696300_bib5","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1016\/j.jaci.2009.04.023","article-title":"Has mandatory folic acid supplementation of foods increased the risk of asthma and allergic disease?","volume":"123","author":"Ownby","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"2026020402572696300_bib6","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.3945\/ajcn.113.065623","article-title":"Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis","volume":"98","author":"Crider","year":"2013","journal-title":"Am J Clin Nutr"},{"key":"2026020402572696300_bib7","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1016\/j.jaci.2012.10.046","article-title":"Relationships between folate and inflammatory features of asthma","volume":"131","author":"Lin","year":"2013","journal-title":"J Allergy Clin Immunol"},{"key":"2026020402572696300_bib8","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/nure.12121","article-title":"Fruit and vegetable intake and risk of wheezing and asthma: a systematic review and meta-analysis","volume":"72","author":"Seyedrezazadeh","year":"2014","journal-title":"Nutr Rev"},{"key":"2026020402572696300_bib9","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.jaci.2009.03.007","article-title":"Higher serum folate levels are associated with a lower risk of atopy and wheeze","volume":"123","author":"Matsui","year":"2009","journal-title":"J Allergy Clin Immunol"},{"key":"2026020402572696300_bib10","doi-asserted-by":"crossref","first-page":"205","DOI":"10.2169\/internalmedicine.50.4424","article-title":"Study of folate status among Egyptian asthmatics","volume":"50","author":"Farres","year":"2011","journal-title":"Intern Med"},{"key":"2026020402572696300_bib11","first-page":"1","article-title":"National surveillance for asthma: United States, 1980-2004","volume":"56","author":"Moorman","year":"2007","journal-title":"MMWR Surveill Summ"},{"issue":"S2","key":"2026020402572696300_bib12","first-page":"168","article-title":"The use of folic acid for the prevention of birth defects in Puerto Rico","volume":"18","author":"Garcia-Fragoso","year":"2008","journal-title":"Ethn Dis"},{"key":"2026020402572696300_bib13","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1164\/rccm.201203-0431OC","article-title":"Vitamin D insufficiency and severe asthma exacerbations in Puerto Rican children","volume":"186","author":"Brehm","year":"2012","journal-title":"Am J Respir Crit Care Med"},{"key":"2026020402572696300_bib14","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1097\/01.chi.0000227878.58027.3d","article-title":"A study of disruptive behavior disorders in Puerto Rican youth: I. 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