It has been over 15 years since the Medical Research Council Vitamin Trial involving 33 centers around the world conclusively showed that 72% of recurrent NTD cases could be prevented by folic acid supplements in the periconceptional period . A further study  showed that the first occurrence of spina bifida could also be prevented by folic acid. However, not all NTDs are responsive to folic acid and inositol has been shown as a possible additional therapy, based on prevention of spina bifida in folate-resistant NTDs in mice as well as the PONTI human trial [186, 187]. Calcium formate too has been shown to have preventive effects on NTD in mice but evidence is not yet forthcoming in prevention of human NTDs [188–190]. There still remains room to study whether there are other supplements out there that can prevent spina bifida.