Nutritional and environmental factors in human spina bifida - An emphasis on myo-inositol.
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KUN Katholieke Universiteit Nijmegen, 04 oktober 2004
Promotores : Zielhuis, G.A., Merkus, J.M.W.M., Mariman, E.C.M. Co-promotor : Steegers-Theunissen, R.P.M.
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SubjectUMCN 1.5: Interventional oncology; UMCN 5.2: Endocrinology and reproduction
This thesis describes the results of a nation wide case-control triad study carried out in collaboration with nine spina bifida centers and a patient organization (VSOP/BOSK) focused on the role of myo-inositol and zinc, environmental factors and related genes in the pathogenesis of spina bifida. Moreover, fundamental studies concerning the kinetics of myo-inositol, its course during pregnancy and concentration in amniotic fluid are described. We recruited 132 families with a child suffering from a nonsyndromic spina bifida and 236 control families who were enrolled via acquaintances of the case-families and via posters and leaflets at nurseries and public health centers. The investigation comprised the collection of nutritional and lifestyle data by questionnaires and blood sampling for biochemical and genetic determinants. Maternal myo-inositol concentrations of <13.2 æmol/L, glucose concentrations =4.5 mmol/L, zinc concentrations of <190 ìmol/L and serum vitamin B12 concentrations of 185 pmol/L were associated with 2.6-fold, 4.6-fold, 2.9-fold and 3.5-fold increased risks of spina bifida offspring, respectively. No differences were observed between spina bifida children and controls. Furthermore, low dietary intakes of iron, magnesium, niacin, fibers, plant proteins and polysaccharides were associated with a 2 to 5-fold increased risk for spina bifida offspring. Also, a set of amendable risk factors was defined which may facilitate preconceptional counseling. Two genetic studies related to inositol and zinc metabolism were inconclusive. In conclusion, it is too early to launch supplementation programs with myo-inositol and zinc in addition to folic acid. However, women at risk for a low myo-inositol status, zinc deficiency or deranged carbohydrate metabolism, in particular diabetic women, should be preconceptionally screened and treated to optimize the preconceptional status of these nutrients. If, however, adjuvant myo-inositol and/or zinc supplementation is preconceptionally administered, we emphasize that careful monitoring and documentation is essential to evaluate this treatment on efficacy and safety aspects in both the mother and fetus.
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