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This meta-analysis was performed to clarify controversial associations of the  MTHFR  677   C &gt; T gene polymorphism in maternal and foetal tissue with neonatal defects. It was reported the association of  MTHFR  677 C &gt; T gene polymorphism with frequencies of neonatal defects including congenital heart disease (CHD), neural tube defects (NTD), non-syndromic cleft lip and palate (NSCL/P), and Down syndrome (DS). Depending on the neonatal defect subtypes,  MTHFR  677 C &gt; T gene polymorphism was associated with NTD, CHD (except for codominant mode of inheritance (TC/CC) and dominant mode of inheritance (TT + TC/CC);  p  = .167 and  p  = .054, respectively), DS, and NSCL/P (codominant mode of inheritance (TC/CC),  p  = .032) in the maternal group. However, in the neonatal group, the  MTHFR  677 C &gt; T gene polymorphism was only associated with the frequency of NTD and CHD. Maternal and neonatal  MTHFR  677 C &gt; T gene polymorphisms appear to be associated with neonatal defects but differ by defect types.IMPACT STATEMENTWhat is already known on this subject?  Neonatal defects are a signifcant problem and are related to genes involved in the metabolism of homocysteine and folate.What do the results of this study add?  The  MTHFR  677C &gt; T polymorphism in maternal and neonatal subjects was significantly associated with neonatal defects. When the neonatal subjects were stratified based on disease, the maternal  MTHFR  677C &gt; T polymorphism was found to be significantly correlated with all four neonatal defects. In contrast, the polymorphism in newborns was significantly associated with neural tube defects.What are the implications of these findings for clinical practice and/or further research?  We believe that our study makes a significant contribution to the literature because it collectively analysed neural tube defects, congenital heart disease, cleft lip and palate, and Down syndrome in relation to the 677C &gt; T polymorphism of  MTHFR . Thus, we anticipate that this study will serve as a valuable resource for future investigations of neonatal defect prevention and maternal inheritance in newborn diseases. What is already known on this subject?  Neonatal defects are a signifcant problem and are related to genes involved in the metabolism of homocysteine and folate. What do the results of this study add?  The  MTHFR  677C &gt; T polymorphism in maternal and neonatal subjects was significantly associated with neonatal defects. When the neonatal subjects were stratified based on disease, the maternal  MTHFR  677C &gt; T polymorphism was found to be significantly correlated with all four neonatal defects. In contrast, the polymorphism in newborns was significantly associated with neural tube defects. What are the implications of these findings for clinical practice and/or further research?  We believe that our study makes a significant contribution to the literature because it collectively analysed neural tube defects, congenital heart disease, cleft lip and palate, and Down syndrome in relation to the 677C &gt; T polymorphism of  MTHFR . Thus, we anticipate that this study will serve as a valuable resource for future investigations of neonatal defect prevention and maternal inheritance in newborn diseases.

Association of MTHFR 677C > T gene polymorphism with neonatal defects: a meta-analysis of 81444 subjects