Neonatal folate, homocysteine, vitamin B12 levels and methylenetetrahydrofolate reductase variants in childhood asthma and eczema

R J P van der Valk, J C Kiefte-de Jong, A M M Sonnenschein-van der Voort, L Duijts, E Hafkamp-de Groen, H A Moll, H Tiemeier, E A P Steegers, A Hofman, V W V Jaddoe, J C de Jongste
Allergy 2013, 68 (6): 788-95

OBJECTIVES: 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.

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