Systematic review and meta-analysis of the associations between maternal methylenetetrahydrofolate reductase polymorphisms and preterm delivery

Aim: To date, reported associations between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and preterm delivery are conflicting. The present meta-analysis summarized the existing evidence and evaluated these associations.

Methods: Eligible studies were retrieved from Medline (PubMed), EMBASE, the Chinese Biomedical Literature Database and the Cochrane Library. We calculated pooled odds ratios (ORs) and 95% confidence interval (CIs) within five genetic models using either random-effects or fixed-effects models dependent on study heterogeneity. Potential publication bias was assessed using a Begg's test. Sensitivity analysis was performed to evaluate the stability of the results.

Results: Thirteen studies involving 4816 mothers who experienced preterm delivery and 34 506 normal controls were finally included. Significant associations between MTHFR C677T polymorphism and the risk of preterm delivery were detected overall (OR_T/C = 1.34, 95% CI 1.12-1.61; OR_TT/CC = 1.60, 95% CI 1.21-2.11; OR_CT/CC = 1.33, 95% CI 1.07-1.65; OR_{TT/(CC + CT)} = 1.41, 95% CI 1.11-1.78; OR_{(TT + CT)/CC} = 1.36, 95% CI 1.11-1.66) and in an Asian population (OR_T/C = 1.80, 95% CI 1.24-2.62; OR_TT/CC = 2.13, 95% CI 1.27-3.57; OR_CT/CC = 1.93, 95% CI 1.37-2.71; OR_{(TT + CT)/CC} = 2.03, 95% CI 1.49-2.77). Negative associations of the A1298C polymorphism were only observed among Asian pregnant women (OR_C/A = 0.66, 95% CI 0.50-0.88; OR_CC/AA = 0.10, 95% CI 0.02-0.53; OR_{CC/(AA + AC)} = 0.11, 95% CI 0.02-0.57; OR_{(CC + AC)/AA} = 0.68, 95% CI 0.49-0.94).

Conclusions: MTHFR 677 T may play a significant role in regard to the risk of preterm delivery, especially in the Asian population.