Inositol and folate resistant neural tube defects

Folic acid supplementation is widely used to prevent neural tube defects (NTDs). ^{1, 2} Yet not all cases of NTD appear to respond to folic acid. For instance, in the randomised controlled trial sponsored by the Medical Research Council, ¹ six NTD recurrences were noted among 593 women (1%) who received full folic acid supplementation, compared with 21 recurrences among 602 unsupplemented pregnancies (3.5%). Hence, in this study, 28% of NTD cases failed to be prevented by folic acid. Currently, no alternative therapy is available for such "folic acid resistant" NTDs.

Studies in mice provide evidence for folate sensitive and folate resistant NTD types. NTDs in mice homozygous for mutations of the Pax3 , Cart1 , and crooked tail genes can be prevented by folic acid, ^{3- 5} whereas NTDs in the curly tail mutant mouse are resistant to folic acid. ⁶ A potentially novel therapy for folate resistant NTD was suggested by our finding that treatment of pregnant females with myo -inositol, during early pregnancy, can prevent the majority of NTD cases in the curly tail mouse. ⁷ Dietary inositol also reduces the frequency of NTDs in a diabetic rat model. ⁸

Here, we report the first use of periconceptional inositol in human pregnancy, in association with a history of folate resistant NTD. Two unrelated, healthy, Italian parents of European origin (mother aged 25, father aged 30) elected to terminate two consecutive pregnancies following ultrasound findings of myelomeningocele. These NTDs occurred despite administration of 4 mg folic acid daily,...