title: Neonatal folate, homocysteine, vitamin B12 levels and methylenetetrahydrofolate reductase variants in childhood asthma and eczema.
abstract: OBJECTIVE
  To assess the associations of folate, homocysteine and vitamin B12 levels of children at birth and their methylenetetrahydrofolate reductase (MTHFR) variants with asthma and eczema in childhood.
  
  
  METHODS
  This study was embedded in a population-based prospective cohort study (n = 2,001). Neonatal cord blood folate, homocysteine and vitamin B12 levels were measured, and MTHFR C677T and A1298C genotyped. Wheezing and physician-diagnosed eczema were annually obtained by questionnaire until 4 years. At 6 years, we collected information on physician-diagnosed asthma ever and self-reported eczema ever, measured fractional exhaled nitric oxide (FeNO), and interrupter resistance (Rint). Data were analysed with generalized estimating equations or logistic regression: continuous outcomes with linear regression models.
  
  
  RESULTS
  Folate, homocysteine and vitamin B12 levels of children at birth were not associated with wheezing or eczema until 4 years, asthma and eczema ever, or FeNO or Rint at 6 years. In children carrying C677T mutations in MTHFR, higher folate levels were associated with an increased risk of eczema (repeated eczema until 4 years: OR 1.40 (95% CI 1.09-1.80) (SD change) P-interaction = 0.003, eczema ever at 6 years: OR 1.41 (0.97-2.03) P-interaction = 0.011). No interactions between MTHFR and child folate and homocysteine levels were observed for wheezing and asthma.
  
  
  CONCLUSIONS
  Folate, homocysteine and vitamin B12 levels of children at birth did not affect asthma- and eczema-related outcomes up to the age of 6 years. Further studies are warranted to establish the role of MTHFR variants in these associations.
authors.affiliation: The Generation R Study Group, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: R J P
authors.initials: RJ
authors.lastname: van der Valk
authors.forename: J C
authors.initials: JC
authors.lastname: Kiefte-de Jong
authors.forename: A M M
authors.initials: AM
authors.lastname: Sonnenschein-van der Voort
authors.forename: L
authors.initials: L
authors.lastname: Duijts
authors.forename: E
authors.initials: E
authors.lastname: Hafkamp-de Groen
authors.forename: H A
authors.initials: HA
authors.lastname: Moll
authors.forename: H
authors.initials: H
authors.lastname: Tiemeier
authors.forename: E A P
authors.initials: EA
authors.lastname: Steegers
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: V W V
authors.initials: VW
authors.lastname: Jaddoe
authors.forename: J C
authors.initials: JC
authors.lastname: de Jongste
mesh_terms: D001249:Asthma / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000097:blood / Q000235:genetics*; D005260:Female; D005312:Fetal Blood; D005492:Folic Acid / Q000097:blood*; D005500:Follow-Up Studies; D005819:Genetic Markers; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D006710:Homocysteine; D005492:Folic Acid; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12