Mendelian Randomization Analysis of the Effect of Maternal Homocysteine During Pregnancy, as Represented by Maternal MTHFR C677T Genotype, on Birth Weight

BACKGROUND: 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. METHODS: 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. RESULTS: MTHFR C677T genotype showed a dose–response association with homocysteine concentration for each additional T allele (P(trend) < 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). CONCLUSIONS: Our results suggest an adverse relationship between maternal homocysteine level and birth weight. A reduction in homocysteine levels might positively affect birth outcomes.