Cavalli Pietro, Tonni Gabriele, Grosso Enrico, Poggiani Carlo
Servizio di Genetica, AO Istituti Ospitalieri, Cremona, Italy.
Birth Defects Res A Clin Mol Teratol. 2011 Nov;91(11):962-5. doi: 10.1002/bdra.22853. Epub 2011 Sep 28.
Neural tube defects (NTDs), most commonly spina bifida and anencephaly, can be prevented with periconceptional intake of folic acid in about 70% of cases. Recurrence of NTDs despite supplementation of high dose of folic acid further suggests that a proportion of NTD cases might be resistant to folic acid. Moreover, heterogeneity of NTDs has been suggested in animal studies, indicating that only some sub-type of NTDs should be considered sensitive to folate intake. Inositol isomers (particularly myo- and chiro-inositol) can prevent folate-resistant NTDs in the curly-tail mutant mouse, suggesting that some cases of human NTDs might benefit from inositol supplementation. In humans, lower inositol blood concentration was found in pregnant women carrying NTD fetuses, whereas a periconceptional combination therapy with folic acid associated with inositol has been linked to normal live births, despite high NTD recurrence risk. Fifteen pregnancies from 12 Caucasian women from different parts of Italy with at least one previous NTD-affected pregnancy underwent periconceptional combined myo-inositol and folic acid supplementation. Maternal serum α-feto-protein levels were found in the normal range, and normal results on ultrasound examination were found in all the pregnancies that followed. No collateral effects or intense uterine contractions were demonstrated in this pilot study in any of the pregnancies after inositol supplementation, and seventeen babies were born without any type of NTD.
神经管缺陷（NTDs），最常见的是脊柱裂和无脑儿，约70%的病例可通过孕前摄入叶酸来预防。尽管补充了高剂量叶酸，NTDs仍会复发，这进一步表明一部分NTDs病例可能对叶酸有抗性。此外，动物研究提示了NTDs的异质性，这表明只有某些NTDs亚型应被视为对叶酸摄入敏感。肌醇异构体（特别是肌醇和手性肌醇）可预防卷尾突变小鼠中对叶酸耐药的NTDs，这表明一些人类NTDs病例可能受益于肌醇补充。在人类中，怀有NTD胎儿的孕妇血液中的肌醇浓度较低，而尽管NTD复发风险很高，但孕前将叶酸与肌醇联合治疗与正常活产有关。来自意大利不同地区的12名白人女性有至少一次先前受NTD影响的妊娠，她们的15次妊娠在孕前接受了肌醇和叶酸联合补充。发现母体血清甲胎蛋白水平在正常范围内，且随后的所有妊娠超声检查结果均正常。在这项初步研究中，补充肌醇后的任何一次妊娠均未出现副作用或强烈宫缩，17名婴儿出生时未患任何类型的NTD。
