Inositol supplementation in pregnancies at risk of apparently folate‐resistant NTDs

Cavalli, Pietro; Tedoldi, Sara; Riboli, Barbara

doi:10.1002/bdra.20454

Cited by 28 publications

(28 citation statements)

References 30 publications

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Section: Discussionmentioning

confidence: 99%

“…A report by Cavalli et al [39] discussed the "folic resistance" hypothesis among some women. That is, while prenatal folic acid supplementation prevented about 70% of neural tube defects in one dataset [40], there are cases of folate-resistant and folate-sensitive NTD subtypes, which are supported by animal models [39]. In a case series, Cavalli and colleagues [39] supplemented women with high NTD recurrence risk with periconceptional inositol and folic acid to prevent reputed folate-resistant fetal NTDs.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Does prenatal micronutrient supplementation improve children's mental development? A systematic review

Leung

Wiens

Kaplan

2011

BMC Pregnancy Childbirth

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BackgroundAlthough maternal nutrient status influences all aspects of fetal development including the brain, the impact of micronutrient supplementation on the baby's mental function is a topic of debate. This systematic review assesses the effect of single and multiple micronutrient supplementation during pregnancy on offspring mental development.MethodsEleven electronic literature databases were searched using key terms of various combinations and filter string terms. Reference lists of articles selected for review were scanned for citations fitting the same inclusion criteria. Each stage of the literature retrieval and review process was conducted independently by two reviewers. The CONSORT checklist was used to assess study quality.ResultsA total of 1316 articles were retrieved from the electronic database search, of which 18 met the inclusion criteria and were evaluated. The selected studies were randomized controlled trials published from 1983 to 2010, with high variance in sample size, intervention type, and outcome measures. The median CONSORT score was 15 (range 12 - 19). Due to inconsistent interventions and outcome measures among the studies, no conclusive evidence was found that enhancing the intrauterine environment through micronutrient supplementation was associated with child mental development in a number of dimensions. There was some evidence to support n-3 fatty acids or multi-micronutrients having some positive effect on mental development, but the evidence for single nutrients was much weaker.ConclusionsThe study of children's mental outcomes as a function of prenatal supplementation is still relatively new, but the results of this systematic review suggest that further work with multiple micronutrients and/or n-3 fatty acids should be conducted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Does prenatal micronutrient supplementation improve children's mental development? A systematic review

Leung

Wiens

Kaplan

2011

BMC Pregnancy Childbirth

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“…Curly tail responds to inositol, SELH/Bc responds to an unidentified consistent difference between two commercial diets, and Axd responds to methionine (Table 2). Inositol supplementation is being explored in some human pregnancies at risk for NTDs (Cavalli et al, 2008).…”

Section: Partial Answers From Mouse Models To Questions About Human Nmentioning

confidence: 99%

Insights into prevention of human neural tube defects by folic acid arising from consideration of mouse mutants

Harris

2008

Birth Defects Research

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Almost 30 years after the initial study by Richard W. Smithells and coworkers, it is still unknown how maternal periconceptional folic acid supplementation prevents human neural tube defects (NTDs). In this article, questions about human NTD prevention are considered in relation to three groups of mouse models: NTD mutants that respond to folate, NTD mutants and strains that do not respond to folate, and mutants involving folate-pathway genes. Of the 200 mouse NTD mutants, only a few have been tested with folate; half respond and half do not. Among responsive mutants, folic acid supplementation reduces exencephaly and/or spina bifida aperta frequency in the Sp(2H), Sp, Cd, Cited2, Cart1, and Gcn5 mutants. Prevention ranges from 35 to 85%. The responsive Sp(2H) (Pax3) mutant has abnormal folate metabolism, but the responsive Cited2 mutant does not. Neither folic nor folinic acid reduces NTD frequency in Axd, Grhl3, Fkbp8, Map3k4, or Nog mutants or in the curly tail or SELH/Bc strains. Spina bifida frequency is reduced in Axd by methionine and in curly tail by inositol. Exencephaly frequency is reduced in SELH/Bc by an alternative commercial ration. Mutations in folate-pathway genes do not cause NTDs, except for 30% exencephaly in folate-treated Folr1. Among folate-pathway mutants, neural tube closure is normal in Cbs, Folr2, Mthfd1, Mthfd2, Mthfr, and Shmt1 mutants. Embryos die by midgestation in Folr1, Mtr, Mtrr, and RFC1 mutants. The mouse models point to genetic heterogeneity in the ability to respond to folic acid and also to heterogeneity in genetic cause of NTDs that can be prevented by folic acid.

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“…The first case report described a couple whose third, healthy child was born after inositol and folic acid supplementation (49). The second report described 3 sets of parents at high risk for having a child with an NTD who gave birth to a total of 5 healthy children after inositol and folic acid supplementation (50).…”

Section: Discussionmentioning

confidence: 99%

Neural tube defects in mice with reduced levels of inositol 1,3,4-trisphosphate 5/6-kinase

Wilson

Hugge

Bielińska

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Inositol 1,3,4-trisphosphate 5/6-kinase (ITPK1) is a key regulatory enzyme at the branch point for the synthesis of inositol hexakisphosphate (IP6), an intracellular signaling molecule implicated in the regulation of ion channels, endocytosis, exocytosis, transcription, DNA repair, and RNA export from the nucleus. IP6 also has been shown to be an integral structural component of several proteins. We have generated a mouse strain harboring a ␤-galactosidase (␤gal) gene trap cassette in the second intron of the Itpk1 gene. Animals homozygous for this gene trap are viable, fertile, and produce less ITPK1 protein than wild-type and heterozygous animals. Thus, the gene trap represents a hypomorphic rather than a null allele. Using a combination of immunohistochemistry, in situ hybridization, and ␤gal staining of mice heterozygous for the hypomorphic allele, we found high expression of Itpk1 in the developing central and peripheral nervous systems and in the paraxial mesoderm. Examination of embryos resulting from homozygous matings uncovered neural tube defects (NTDs) in some animals and axial skeletal defects or growth retardation in others. On a C57BL/6 ؋ 129(P2)Ola background, 12% of midgestation embryos had spina bifida and/or exencephaly, whereas wild-type animals of the same genetic background had no NTDs. We conclude that ITPK1 is required for proper development of the neural tube and axial mesoderm.exencephaly ͉ hypomorphic allele ͉ inositol signaling ͉ spina bifida

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Inositol supplementation in pregnancies at risk of apparently folate‐resistant NTDs

Cited by 28 publications

References 30 publications

Does prenatal micronutrient supplementation improve children's mental development? A systematic review

Does prenatal micronutrient supplementation improve children's mental development? A systematic review

Insights into prevention of human neural tube defects by folic acid arising from consideration of mouse mutants

Neural tube defects in mice with reduced levels of inositol 1,3,4-trisphosphate 5/6-kinase

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