MTHFR and neural tube defect: There were several studies in relation to the interaction of maternal MTHFR gene and smoke exposure on the risk of adverse pregnancy outcomes including low birth weight [41] and major birth defects such as neural tube defects, oral clefting [34] and CHD [42], and the mechanisms might be due to low folate status associated with genetic polymorphisms of MTHFR gene and smoke exposure [43].