BackgroundTo investigate the association of folate metabolism gene polymorphism with neural tube defects (NTDs) in Chinese population.MethodsThe subjects were divided into two groups, 495 children with NTDs (NTD group) and 255 healthy children (control group).ResultsThe levels of folic acid, s-adenosine methionine (SAM), and Sam/s-adenosine homocysteine (SAH) in NTD group were lower than those in control group. There were significant differences in hey, SAH, and Sam levels between two groups, but there was no significant difference in folic acid content. High fever in early pregnancy, taking antiepileptic drugs, father’s exposure to organic solvents, folic acid deficiency, and mother’s diabetes were the important risk factors in NTDs. MTHFR 677C > T gene was a risk factor for NTD in children, while 1298A > C gene was a protective factor.ConclusionFolic acid metabolism markers were different in NTD children and their mothers, and the overall trend showed that folate, SAM, and SAM/SAH levels were decreased, while Hcy and SAH levels were increased; MTHFR 677C > T gene of SNPs was a risk factor for the occurrence of NTDs, and MTHFR 1298A > C gene was a protective factor, and the environmental risk factor had a synergistic effect on occurrence of NTDs.