Folic acid is a synthetic form of folate used in supplements and fortified foods (like wheat and maize flour) to reduce the occurrence of neural tube defects (NTDs). These include spina bifida (or cleft spine), where there is an opening in one or more of the bones (vertebrae) of the spinal column, and anencephaly where the head (cephalic) end of the neural tube fails to close. Supplementation with folic acid is internationally recommended to women from the moment they are trying to conceive until 12 weeks of pregnancy. Another option recommended by the World Health Organization (WHO) is that women of reproductive age take weekly iron and folic acid supplements, especially in populations where the prevalence of anaemia is above 20%. Supplementation may also reduce other birth defects such as cleft lip with or without cleft palate and congenital cardiovascular defects. Recently, 5-methyl-tetrahydrofolate (5-MTHF) has been proposed as an alternative to folic acid supplementation. This is because most dietary folate and folic acid are metabolised to 5-MTHF. Some women have gene characteristics which reduce folate concentration in blood.
This review confirms that folic acid supplementation prevents the first and second time occurrence of NTDs and shows there is not enough evidence to determine if folic acid prevents other birth defects. Information about the safety of other current and alternative supplementation schemes and any possible effects on other outcomes for mothers and babies is also lacking. This review of five trials, involving 6105 women (1949 with a history of a pregnancy affected by a NTD and 4156 with no history of NTDs), shows the protective effect of daily folic acid supplementation in doses ranging from 0.36 mg (360 µg) to 4 mg (4000 µg) a day, with and without other vitamins and minerals, before conception and up to 12 weeks of pregnancy, for preventing the recurrence of these diseases. There were insufficient data to evaluate the effects on other outcomes such as cleft lip and palate. More research is needed on different types of supplementation programmes and the use of different types of supplements (such as 5-methyl-tetrahydrofolate -5-MTHF), particularly in countries where folic acid fortification of staple foods like wheat or maize flour is not mandatory and where the prevalence of NTDs is still high.