The Association Between Maternal Tibia Lead, Folate Intake, and MTHFR Genotype, and Child Birth Weight

Abstract

ISEE-644 Objective: Maternal lead exposure, folate intake, and mutations in methylenetetrahydrofolate (MTHFR) gene are known to affect birthweight (BW), but have not been investigated together. Materials and Methods: Our study sample consisted of Mexico City women (n = 487) with complete data on tibia lead (TPb), folate intake, MTHFR (C594T, C677T, A1298C), their child's BW, and covariates. Bone lead was measured using K-x-ray fluorescence; folate intake assessed with semiquantitative FFQ. We assumed autosomal dominant effect for MTHFR genotype. Associations of TPb, folate intake, and MTHFR genotypes with BW were analyzed, adjusting for covariates. Interactions between TPb, folate intake, and MTHFR genotype in predicting BW were investigated. Results: Mean TPb was 9.9 ± 9.8 μg/g bone; birth weight was 3166 ± 415 g; folate intake was 867 ± 891 μg/day. Allele frequencies were 3.9% (C594T), 59.1% (C677T), 10.9% (A1298C). All variants were in Hardy-Weinberg equilibrium. There was no main effect of folate or MTHFR genotype on BW. Each 1 μg/g increase in TPB was associated with a 4 g decrease in BW (P = 0.01); women with TPb >9.5 μg/g (median) had neonates 90 g lighter than those of women with TPb ≤9.5 μg/g. The associations between TPb and BW were as follows: by MTHFR genotype: 594CC (β = −5.0*), 594CT/TT (β = 8.9, interaction term for TPb*MTHFRP = 0.22); 677CC (β = −14.1*), 677CT/TT (β = −3.6*, interaction term P = 0.20); 1298AA (β = −6.1**), 1298AC/CC (β = 2.6, interaction term P = 0.20). Estimates for relationship between folate and BW did not differ by MTHFR genotype. Conclusions: We did not find 677CT/TT genotype or other MTHFR polymorphisms to be risk factors for lower BW. TPb consistently predicted lower BW in women. The relationship between TPb and BW appeared stronger in women with wild type MTHFR but was diminished in women who were variant carriers.