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Maternal periconceptional supplementation with folic acid significantly reduces the risk of an NTD\u2010affected pregnancy, but does not prevent all NTDs, and \u201cfolic acid non\u2010responsive\u201d NTDs continue to occur. Similarly, among mouse models of NTDs, some are responsive to folic acid but others are not.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Among nutritional factors, inositol deficiency causes cranial NTDs in mice while supplemental inositol prevents spinal and cranial NTDs in the <jats:italic>curly tail<\/jats:italic> (<jats:italic>Grhl3<\/jats:italic> hypomorph) mouse, rodent models of hyperglycemia or induced diabetes, and in a folate\u2010deficiency induced NTD model. NTDs also occur in mice lacking expression of certain inositol kinases. Inositol\u2010containing phospholipids (phosphoinositides) and soluble inositol phosphates mediate a range of functions, including intracellular signaling, interaction with cytoskeletal proteins, and regulation of membrane identity in trafficking and cell division.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:italic>Myo<\/jats:italic>\u2010inositol has been trialed in humans for a range of conditions and appears safe for use in human pregnancy. In pilot studies in Italy and the United Kingdom, women took inositol together with folic acid preconceptionally, after one or more previous NTD\u2010affected pregnancies. In nonrandomized cohorts and a randomized double\u2010blind study in the United Kingdom, no recurrent NTDs were observed among 52 pregnancies reported to date.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>Larger\u2010scale fully powered trials are needed to determine whether supplementation with inositol and folic acid would more effectively prevent NTDs than folic acid alone. 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