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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 …