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Background MTHFR gene may be a key epigenetic regulation-related factor crucial during embryogenesis. We performed a meta-analysis to determine the association of fetal MTHFR C677T polymorphism with neural tube defects (NTDs). Methods A comprehensive literature search of the PubMed, Embase, and CNKI database was performed up to April 10, 2020. Results A total of 19 case-control studies with 2,228 NTDs cases and 4,220 controls were identified. Pooled data revealed that the fetal MTHFR C677T polymorphism was significantly highly correlated with development of NTDs in the overall population. Stratified analysis showed a significant association among Caucasians and Asians, but not in mixed populations. There was a significant association between the MTHFR C677T polymorphism and spina bifida risk. No publication bias was found under any genetic model. Conclusions Our pooled data support the fetal MTHFR C677T polymorphism association with risk of NTDs, especially among Caucasians and Asians.

Association of Fetal MTHFR C677T Polymorphism with Susceptibility to Neural Tube Defects: A Systematic Review and Update Meta-Analysis