British Journal of Nutrition

Full Papers

Human and Clinical Nutrition

Methylenetetrahydrofolate reductase (MTHFR) C677T, A1298C and G1793A genotypes, and the relationship between maternal folate intake, tibia lead and infant size at birth

Katarzyna Kordasa1 c1, Adrienne S. Ettingera2a3, Héctor Lamadrid-Figueroaa4, Martha M. Tellez-Rojoa4, Mauricio Hérnandez-Avilaa4, Howard Hua2a5 and Robert O. Wrighta2a3a6

a1 Pennsylvania State University, University Park, PA, USA

a2 Harvard School of Public Health, Boston, MA, USA

a3 Channing Laboratory, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, USA

a4 National Institute of Public Health, Cuernavaca, Morelos, Mexico

a5 University of Michigan School of Public Health, Ann Arbor, MI, USA

a6 Children's Hospital, Boston, MA, USA


Small size at birth continues to be a problem worldwide and many factors, including reduced folate intake and Pb exposure, are associated with it. However, single factors rarely explain the variability in birth weight, suggesting a need for more complex explanatory models. We investigated environment–gene interactions to understand whether folate intake and maternal Pb exposure were associated with smaller newborn size in 474 women with uncomplicated pregnancies delivering term infants in Mexico City. We examined if folate intake modified the negative effects of maternal Pb burden on birth size. We also asked if maternal and infant methylenetetrahydrofolate reductase (MTHFR) genotypes (C677T, A1298C and G1793A) modified the effects of folate intake or Pb exposure on birth size. Women were aged 24·6 (sd 5·1) years; 43·5 % were primiparous. Maternal blood Pb at delivery was 86 (sd 42) μg/l, with 26·7 % having levels ≥ 100 μg/l. Tibia Pb level was 9·9 (sd 9·8) μg/g. Of the women, 35·3 % had folate intakes < 400 μg/d. Birth weight was 3170 (sd 422) g. In covariate-adjusted regressions, higher folate intake was associated with higher birth weight (β 0·04; P < 0·05). Higher bone Pb was associated with lower birth weight (β − 4·9; P < 0·05). Folate intake did not modify the effects of Pb on birth size, nor did MTHFR modify the association between Pb or folate intake on birth size. Although modest, the relationship between maternal nutrition, Pb burden and birth size does underscore the importance of environmental exposures to child health because patterns of fetal growth may affect health outcomes well into adulthood.

(Received June 16 2008)

(Revised February 25 2009)

(Accepted February 25 2009)

(Online publication April 02 2009)


c1 Corresponding author: Dr Katarzyna Kordas, fax +1 814 865 5870, email


Abbreviations: MTHFR, methylenetetrahydrofolate reductase; SNP, single nucleotide polymorphism