title: Folic acid use in pregnancy and the development of atopy, asthma, and lung function in childhood.
abstract: BACKGROUND
  Recently, folic acid supplementation during pregnancy was implicated as a potential risk factor for atopic diseases in childhood.
  
  
  OBJECTIVE
  To investigate whether folic acid supplementation and higher intracellular folic acid (ICF) levels during pregnancy increase the risk of childhood atopic diseases.
  
  
  METHODS
  In the KOALA Birth Cohort Study (N=2834), data on eczema and wheeze were collected by using repeated questionnaires at 3, 7, 12, and 24 months, 4 to 5 years, and 6 to 7 years after delivery. Atopic dermatitis and total and specific immunoglobulin E levels were determined at age 2 years and asthma and lung function at age 6 to 7 years. We defined folic acid use as stand-alone and/or multivitamin supplements according to the period of use before and/or during pregnancy. ICF levels were determined in blood samples taken at ∼35 weeks of pregnancy (n=837). Multivariable logistic and linear regression analyses were conducted, with generalized estimating equation models for repeated outcomes.
  
  
  RESULTS
  Maternal folic acid supplement use during pregnancy was not associated with increased risk of wheeze, lung function, asthma, or related atopic outcomes in the offspring. Maternal ICF level in late pregnancy was inversely associated with asthma risk at age 6 to 7 years in a dose-dependent manner (P for trend=.05).
  
  
  CONCLUSIONS
  Our results do not confirm any meaningful association between folic acid supplement use during pregnancy and atopic diseases in the offspring. Higher ICF levels in pregnancy tended, at most, toward a small decreased risk for developing asthma.
authors.affiliation: Department of Epidemiology, Maastricht University, CAPHRI School for Public Health and Primary Care, Maastricht, The Netherlands.
authors.forename: Fabienne J H
authors.initials: FJ
authors.lastname: Magdelijns
authors.forename: Monique
authors.initials: M
authors.lastname: Mommers
authors.forename: John
authors.initials: J
authors.lastname: Penders
authors.forename: Luc
authors.initials: L
authors.lastname: Smits
authors.forename: Carel
authors.initials: C
authors.lastname: Thijs
mesh_terms: D001249:Asthma / Q000139:chemically induced* / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D005492:Folic Acid / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced* / Q000503:physiopathology; D011446:Prospective Studies; D012129:Respiratory Function Tests; D012307:Risk Factors; D014803:Vitamin B Complex / Q000009:adverse effects*
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid