Table 1.

NTDs prevention: take home messeges

NTDs	NTDs constitute a major health burden, responsible for about 0.5-2/1000 pregnancies worldwide and still representing a preventable cause of still birth, neonatal, and infant death, or significant lifelong sequelae.
Folate and folic acid sources	Folate is a water-soluble B vitamin naturally present in foods such as dark green leafy vegetables, legumes, and oranges. Folic acid is the synthetic form of folate. Folic acid is nowadays available as multivitamin, or single supplement and as essential nutrient used for cereal grain products fortification.
Folate and NTDs prevention	Women of childbearing age are at risk of having a pregnancy affected by NTDs, with variable rates from country to country. Convincing evidence shows that the fulfilment of adequate folate levels during the most critical periconceptional period (4 weeks before conception through the first trimester) can substantially decrease the prevalence of NTDs. In this context, maternal diet may play a key role in protection against these major congenital abnormalities and the Mediterranean dietary pattern seems to be associated with the highest risk reduction.
Mediterranean diet and Nutritional transition process	The Mediterranean dietary pattern represents an important source of methyl donors, like folate, essential cofactors in several pathways of cellular processes implicated in placental and fetal growth and development. Despite the evidences, we are nowadays assisting to the progressive abandonment of Mediterranean diet in favour of more unhealthy north American eating habits.
Prevention strategies	A balanced diet and a healthy life-style alone, despite the benefits, seem to be not enough for the prevention of NTDs. The main question is which intervention, between folic acid supplementation, foods fortification or both, linked to a healthy life-style and diet pattern may represent the best method in preventing NTDs. The relative failure of the periconceptional folic acid supplementation policy has led many countries to introduce mandatory fortification of flour with folic acid. Studies following fortification showed a significant decline in the NTDs rates in those countries.
Folate metabolism status assessment	There are no universally accepted cut-off points to define deficiency of folate. Erythrocyte folate concentration (EFC), is definitely the best available indicator to assess long-term measure of folate intakes and tissue folate stores. The latest scientific evidence suggests that a EFC above 1000 nmol/l is the level required for optimal NTDs prevention.
Chronical exposure to Folic acid supplementation: adverse effects?	Literature data report a possible association between long lasting high blood folate levels and an increased risk of many pathologic conditions like many types of cancer, asthma, cognitive problems and autism as well as the coverage of vitamin B12 deficiency anemia. Nevertheless, no clear consensus and concrete statistical evidence regarding the safety of folic acid has been met, due to discrepancies between results from different studies.
Conclusions	Basing on the experience gained in the US, the benefit in terms of clear reduction of NTDs incidence seem to be significantly higher than the risks associated with the assumption, for a long period, of an amount of folic acid exceeding the basic necessities. The introduction of a well established program of daily consumer foods fortified with folic acid combined with an efficient information and awareness campaign promoting a healthy and balanced diet before and during pregnancy may represent an important strategy to reduce the incidence of these pathologies.