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J Epidemiol. 2013 Sep 5;23(5):371-5. Epub 2013 Jul 13.

Mendelian randomization analysis of the effect of maternal homocysteine during pregnancy, as represented by maternal MTHFR C677T genotype, on birth weight.

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  • 1Department of Preventive Medicine, School of Medicine, Ewha Womans University, Seoul, Korea.



We used Mendelian randomization analysis to investigate the causal relationship between maternal homocysteine level, as represented by maternal methylenetetrahydrofolate reductase (MTHFR) C677T genotype, with the birth weight of offspring.


We recruited women at 24 to 28 weeks' gestation who visited Ewha Womans University Hospital for prenatal care during the period from August 2001 to December 2003. A total of 473 newborns with a gestational age of at least 37 weeks were analyzed in this study. We excluded twin births and children of women with a history of gestational diabetes, gestational hypertension, or chronic renal disease. The association of maternal homocysteine concentration with the birth weight of infants was analyzed using 2-stage regression.


MTHFR C677T genotype showed a dose-response association with homocysteine concentration for each additional T allele (Ptrend < 0.01). Birth weight decreased from 120 to 130 grams as maternal homocysteine level increased, while controlling for confounding factors; however, the association was of marginal significance (P = 0.06).


Our results suggest an adverse relationship between maternal homocysteine level and birth weight. A reduction in homocysteine levels might positively affect birth outcomes.

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