[THE DIFFERENTIATED APPROACH TO PREVENTION OF NEURAL TUBE DEFECTS IN CHILDREN]

Neural tube defects occupy second place in frequency after the defects of the cardiovascular system. The folate metabolism violation and hyperhomocysteinemia in women are proved to be the leading risk factors for the NTD of the fetus. Polymorphism of the 5,10-methylenetetrahydrofolate reductase gene (MTHFR) is a genetic determinant of folate metabolism violation. Admission of folic acid in a standard dose of 0.4 mg and / or the use of fortified foods does not allow reaching the protective level of folic acid if there is a mutation of the MTHFR gene or when several risk factors combine, which requires a higher dose of folic acid. The aim of the study is to develop an algorithm for the identification of women of reproductive age with the risk of having a child with NTD and to apply differentiated approach to the choice of a preventive dose of folic acid. A retrospective analysis of NTD cases in the Odessa region (Ukraine) for 2000-2013 was carried out. The frequency of the birth of children with CNS defects and NTD, risk factors of NTD in children were studied. Mothers and their children with NTD were evaluated for the level of folic acid, homocysteine and the presence of C677T and A1298C MTHFR polymorphisms. The incidence of spina bifida aperta is 4.9 per 10,000 newborns. Two groups of significant risk factors for the NTD in children were identified: 1) risk factors that can be eliminated - the absence of preconceptional prevention of NTD with folic acid (AR 0.4), second-hand tobacсo smoking (AR 0.33), fever/hot baths in the first trimester of pregnancy (AR 0.64), use of well water for cooking (AP 0.44); 2) risk factors that can not be eliminated, and which indicate a genetic risk of NTD - a family history of a stroke, heart attack, thrombosis, congenital malformations, malignant tumors (AR 0.54-0.7), an obstetrical history of miscarriage (AR 0.56 ), mother's diseases (varicose disease, obesity), NTD in other children in this family (AR 0.74). The mothers of children with NTD showed a decreased level of folic acid and an increased level of homocysteine in addition to the correlation of hyperhomocysteinemia with the mutations of the MTHFR gene. The algorithm for assessing the individual risk of having a child with NTD includes the evaluation of risk factors. If a genetic factor of folate metabolism violation or environmental risk factors that can not be eliminated are found, we recommend an additional examination. It includes determining the level of homocysteine and the MTHFR polymorphisms (in the case of hyperhomocysteinemia), which will identify the required dose of folic acid.