Objective: Folic acid supplement use is recommended in pregnancy to reduce the risk of neural tube defect but concerns have been raised that increasing folic acid intake may select for embryos with genotypes that increase disease risk in the offspring. Our aim was to test for this effect. Design: Observational prospective cohort study. Setting: Aberdeen Maternity Hospital. Population or Sample: Women born before the introduction of folic acid advice (1970-80) and carrying singleton pregnancies (n = 1234) and their offspring (n = 1083) born after (2001-03). Methods: We measured the genotype (MTHFR C677T and A1298C, MTR A2756G, MTRR A66G and TCN G776C) of mothers and their offspring, maternal supplement intake, intake of folate and vitamin B12 from natural foods and maternal blood folate and B12 status at 19 weeks of gestation. Main outcome measures: B vitamin related genotype of the offspring. Results: There were no significant differences in any of the five genotype frequencies between mothers and their babies. There was no deviation from Hardy-Weinberg equilibrium in either generation and no change in the frequency of doubly homozygous MTHFR variants (677 TT/1298 CC). The genotype of the offspring was not related to maternal periconceptual supplement use, folate intake from foods or plasma and red cell folate measured at 19 weeks of gestation. Conclusions: We found no evidence to support the concern that folic acid fortification or supplement use in pregnancy results in selection of deleterious genotypes. © 2008 The Authors.