Abstract
The use of folic acid in the periconceptional period can prevent about 70% of neural tube defects (NTDs). In the remaining cases, no medical prevention is available, and those conditions should be defined as folate-resistant NTDs. Rodent models suggest that some folate-resistant NTDs can be prevented by inositol (myoinositol and chiroinositol) supplementation prior to pregnancy. Should folic acid be combined with myoinositol periconceptional supplementation to reduce the overall risk of NTDs even in humans? Hereafter, we discuss the results from the PONTI study that strongly support both the effectiveness and safety of myoinositol periconceptional supplementation in preventing human NTDs. We further report on the largest case series of pregnancies treated with myoinositol and folic acid. At our institution, a sequential study during 12 years involved mothers at risk of fetal NTDs, and 29 babies from 27 pregnancies were born after periconceptional combined myoinositol and folic acid supplementation. No case of NTDs was observed, despite the high recurrence risk in the mothers. Taken together, those data suggest that periconceptional folic acid plus myoinositol can reduce both the occurrence and recurrence risks of NTDs in a greater number of cases than folic acid alone.
Highlights
According to EUROCAT (European Surveillance of Congenital Anomalies) data, the EU prevalence of major congenital abnormalities is 23.9 per 1000 births
Should folic acid be combined with myoinositol periconceptional supplementation to reduce the overall risk of neural tube defects (NTDs) even in humans? Hereafter, we discuss the results from the PONTI study that strongly support both the effectiveness and safety of myoinositol periconceptional supplementation in preventing human NTDs
Based on the results reported before, the PONTI (Prevention of Neural Tube Defects by Inositol) study was designed as a pilot study, aiming to demonstrate the feasibility of a randomized clinical trial (RCT) to evaluate the effectiveness of inositol plus folic acid in preventing a greater number of NTDs as compared to folic acid alone, according to the previous experimental hypothesis
Summary
According to EUROCAT (European Surveillance of Congenital Anomalies) data, the EU prevalence of major congenital abnormalities is 23.9 per 1000 births. Among those defects, the frequency of nervous system defects has been calculated at 2.3 per 1000, and the prevalence of neural tube defects (NTDs) is 0.9 per 1000 (years 2003–2007) [1]. Folic acid fortification reduces the risk of NTDs (OR 0.54, CI 95% 0.46–0.63) [6] Given those data, it comes without saying that about 30% of NTDs should be considered “resistant” to folic acid fortification and supplementation, and no intervention is available in those cases that are resistant to folic acid intake. Inositol is a fundamental nutrient required by human cells in culture to grow and survive
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