Genetic polymorphism of MTHFR C677T with preterm birth and low birth weight susceptibility: a meta-analysis

This study aimed at clarifying the association of maternal and neonatal methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms with preterm birth (PTB) and low birth weight (LBW) susceptibility, respectively.

A systematic search of Embase, Medline, China Biological Medicine Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang Database was performed before June, 2016. The frequencies of maternal and neonatal MTHFR C677T genotypes in the cases and controls and other information were extracted by two independent investigators. Odds ratios (ORs) with 95% confidence intervals (CIs) were adopted to estimate the relationships between MTHFR C677T polymorphisms and PTB as well as LBW by random or fixed effect models.

Twenty-five studies from 20 articles concerning maternal and neonatal MTHFR C677T gene polymorphism with PTB and LBW were included in this study. Maternal MTHFR C677T polymorphism was associated with PTB risk under allele contrast (T vs. C, OR = 1.36, 95% CI 1.02-1.81), homozygote (TT vs. CC, OR = 1.70, 95% CI 1.07-2.68), and recessive (TT vs. CT + CC, OR = 1.49, 95% CI 1.00-2.22) model, but not dominant or heterozygote model. Maternal MTHFR C677T polymorphism was also associated with LBW risk under allele contrast (OR = 1.69, 95% CI 1.25-2.28), homozygote (OR = 2.26, 95% CI 1.44-3.54), dominant (OR = 1.71, 95% CI 1.19-2.47), recessive (OR = 1.79, 95% CI 1.42-2.26) model, but not heterozygote model. No associations between neonatal MTHFR C677T polymorphism and PTB or LBW were found under all genetic models.

Identification of maternal MTHFR C677T mutation may play a key role for primary prevention of PTB as well as LBW and screening pregnant women of high risk in developing countries.