safetyriskБезопасность и риск фармакотерапииSafety and Risk of Pharmacotherapy2312-78212619-1164Federal State Budgetary Institution ‘Scientific Centre for Expert Evaluation of Medicinal Products’ of the Ministry of Health of the Russian Federation (FSBI ‘SCEEMP’)safetyrisk-4Research ArticleОБЗОРЫ И ОРИГИНАЛЬНЫЕ СТАТЬИREVIEWS AND ORIGINAL ARTICLESК ВОПРОСУ О РАЗВИТИИ ВРОЖДЕННЫХ ПОРОКОВ У ДЕТЕЙ В УСЛОВИЯХ ПРОФИЛАКТИЧЕСКОГО ПРИЕМА МАТЕРЯМИ ФОЛИЕВОЙ КИСЛОТЫ В ПЕРИНАТАЛЬНОМ ПЕРИОДЕON THE QUESTION OF THE DEVELOPMENT OF FETAL CONGENITAL MALFORMATIONS IN THE CONDITIONS OF PREVENTIVE USE BY MOTHERS OF FOLIC ACID IN THE PERINATAL PERIODТороповаИрина АнатольевнаToropovaI. A.noemail@neicon.ruАляутдинРенад НиколаевичAlyautdinR. N.Alyautdin@expmed.ruАляутдинаОльга СергеевнаAlyautdinaO. S.noemail@neicon.ruРомановБорис КонстантиновичRomanovB. K.noemail@neicon.ru«Научный центр экспертизы средств медицинского применения» Министерства здравоохранения Российской ФедерацииРоссияFederal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products», Ministry of Health of the Russian FederationRussian FederationГБОУ ВПО Первый Московский государственный медицинский университет им. И.М. СеченоваРоссияI.M. Sechenov First Moscow State Medical UniversityRussian Federation201520022018011320Copyright © Торопова И.А., Аляутдин Р.Н., Аляутдина О.С., Романов Б.К., 20182018Торопова И.А., Аляутдин Р.Н., Аляутдина О.С., Романов Б.К.Toropova I.A., Alyautdin R.N., Alyautdina O.S., Romanov B.K.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.risksafety.ru/jour/article/view/4

Дефект нервной трубки относится к врожденным дефектам, возникающим при дефиците или нарушении обмена фолиевой кислоты. Профилактический прием фолиевой кислоты беременными женщинами позволил в значительной степени снизить частоту этих дефектов развития. Однако, несмотря на профилактические меры, сообщения о подобных серьезных нежелательных реакциях на фоне приема фолиевой кислоты продолжают регистрироваться. Анализ данных литературы показал, что причинами развития врожденных пороков может быть несвоевременное назначение фолатов, а также наличие полиморфизма гена, кодирующего 5, 10-метилентетрагидрофолатредуктазу. Рассмотрено влияние этого пролиморфизма на обмен фолиевой кислоты. Сделано предположение о том, что своевременное применение фолиевой кислоты, профилактическое генотипирование и в случае наличия полиморфизма 5, 10-метилентетрагидрофолатредуктазы, увеличение дозы фолиевой кислоты может снизить частоту указанных осложнений.

Neural tube defect relates to congenital defects caused by folic acid deficiency or violation of its exchange. Prophylactic administration of folic acid by pregnant women has greatly reduce the incidence of these malformations. However, despite preventive measures, reports of such serious adverse events continue to be recorded. The analysis showed that one of the possible causes of malformations may be the presence of the polymorphism of the gene encoding 5, 10-methylenetetrahydrofolate. The effect of this mutation on the metabolism of folic acid and possible recommendations to patients are discussed.

дефект нервной трубкифолиевая кислота510-метилентетрагидрофолатредуктазагипергомоцистеинемияneural tube defectfolic acidmethylentetrahydrofolate reductasehyperhomocysteinemiaReferencesThaler C.J. Folate мetabolism and human reproduction. Geburtshilfe Frauenheilkd. 74(9): 845-851.Thaler CJ. Folate мetabolism and human reproduction. Geburtshilfe Frauenheilkd. 74(9): 845-851.Frosst P., Blom H.J., Milos R., et al. A candidate genetic risk factor for vascular disease: a common mutation in methylene-tetrahydrofolate reductase. Nat Genet. 1995; 10: 111-113.Frosst P, Blom HJ, Milos R, et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet. 1995;10:111–113.Kang S.S., Zhou J., Wong P.W., et al. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet. 1988; 43: 414-421.Kang SS, Zhou J, Wong PW, et al. Intermediate homocysteinemia: a thermolabile variant of methylenetetrahydrofolate reductase. Am J Hum Genet. 1988;43:414–421.McAndrew P.E., Brandt J.T., Pearl D.K., et al. The incidence of the gene for thermolabile methylene tetrahydrofolate reductase in African Americans. Thromb Res. 1996; 83: 195-198.McAndrew PE, Brandt JT, Pearl DK, et al. The incidence of the gene for thermolabile methylene tetrahydrofolate reductase in African Americans. Thromb Res. 1996;83:195–198.Verhoeff B.J., Trip M.D., Prins M.H., et al. The effect of a common methylenetetrahydrofolate reductase mutation on levels of homocysteine, folate, vitamin B12 and on the risk of premature atherosclerosis. Atherosclerosis. 1998; 141: 161-166.Verhoeff BJ, Tri p MD, Prins MH, et al. The effect of a common methylenetetrahydrofolate reductase mutation on levels of homocysteine, folate, vitamin B12 and on the risk of premature atherosclerosis. Atherosclerosis. 1998;141:161–166.Harmon D.L., Woodside J.V., Yarnell J.W., et al. The common thermolabile variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia. QJM. 1996; 89: 571-577.Harmon DL, Woodside JV, Yarnell JW, et al. The common thermolabile variant of methylene tetrahydrofolate reductase is a major determin ant of mild hyperhomocystein aemia. QJM. 1996;89:571–577.Jacques P.F., Bostom A.G., Williams R.R., et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996; 93: 7-9.Jacques PF, Bostom AG, Williams RR, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation. 1996; 93:7–9.Ströhle A., Wolters M., Hahn A. Nährstoff -supplemente - Molichkeiten und Grenzen. Teil 2: Ausgewuhlte Risikogruppen - Supplemente in der Schwangerschaft. Med Monatsschr Pharm. 2013; 36: 252-266.Ströhle A, Wolters M, Hahn A. Nährstoffsupplemente – Möglichkeiten und Grenzen. Teil 2: Ausgewählte Risikogruppen – Supplemente in der Schwangerschaft. Med Mon atsschr Pharm. 2013;36:252–266.Nelen W.L., Blom H.J., Thomas C.M., et al. Methylenetetrahydrofolate reductase polymorphism affects the change in homocysteine and folate concentrations resulting from low dose folic acid supplementation in women with unexplained recurrent miscarriages. J Nutr. 1998; 128: 1336-1341.Nelen WL, Blom HJ, Thomas CM, et al. Methylenetetrahydrofolate reductase polymorphism affects the change in homocysteine and folate concentrations resulting from low dose folic acid supplementation in women with unexplained recurrent miscarriages. J Nutr. 1998;128:1336–1341.Hibbard B.M., Hibbard E.D., Jeffcoate T.N. Folic acid and reproduction. Acta Obstet. Gynecol. Scand. 1965, 44, 375-400.Hibbard BM, Hibbard ED, Jeffcoate TN. Folic acid and reproduction. Acta Obstet. Gynecol. Scand. 1965, 44, 375–400.Smithells R.W. Multivitamins for the prevention of neural tube defects. How convincing is the evidence? Drugs. 1989; 38: 849-854.Smithells RW. Multivitamins for the prevention of neural tube defects. How convincing is the evidence? Drugs. 1989;38:849–854.Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991; 338: 131-137.Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991;338:131–137.Wagner C. Biochemical role of folate in cellular metabolism. In: Bailey L.B., ed. Folate in health and disease. New York, NY: Marcel Dekker, 1995: 23- 42.Wagner C. Biochemical role of folate in cellular metabolism. In: Bailey LB, ed. Folate in health and disease. New York, NY: Marcel Dekker, 1995:23– 42.Chanarin I. The megaloblastic anaemias. London, United Kingdom: Blackwell, 1969; 786 - 829.Chan arin I. The megaloblastic an aemias. London, United Kingdom: Blackwell, 1969;786 – 829.McPartlin J., Halligan A., Scott J.M., Darling M., Weir D.G. Accelerated folate breakdown in pregnancy. Lancet 1993; 341: 148 -9.McPartlin J, Halligan A, Scott JM, Darling M, Weir DG. Accelerated folate breakdown in pregn ancy. Lancet 1993;341:148 –9.McPartlin J., Halligan A., Scott J.M., Darling M., Weir D.G. Accelerated folate breakdown in pregnancy. Lancet 1993; 341: 148 -9.Fleming AF. Urin ary excretion of folate in pregn ancy. J Obstet Gyn aecol Br Comm 1972;79:916 –20.Fleming A.F. Urinary excretion of folate in pregnancy. J Obstet Gynaecol Br Comm 1972; 79: 916 -20.Tamura T., Picciano M. Folate and human reproduction. Am.J.Clin. Nutr., 2006;83:993–1016.Tamura T., Picciano M. Folate and human reproduction. Am.J.Clin. Nutr., 2006; 83: 993-1016. variant of methylenetetrahydrofolate reductase. Am J Hum Genet. 1988; 43: 414-421.Baymuradova SM, Bitsadze VO, Marov SV, et al. The role of anti phospholi pid syndrome and genetic thrombophilia in the pathogenesis of toxaemia. Tromboz, gemostaz i reologiya. 2002. № 4. Р. 69 (in Russian).Баймурадова С.М., Бицадзе В.О., Маров С.В. и соавт. Роль антифосфолипидного синдрома и генетических форм тромбофилий в патогенезе гестозов беременных. Тромбоз, гемостаз и реология. 2002. № 4. С. 69.Van der Put NM, Steegers-Theunissen RP, Frosst P, Trijbels FJ, Eskes TK, van den Heuvel LP, Mariman EC, den Heyer M, Rozen R, Blom HJ Mutated methylene- tetrahydrofolate reductase as a risk factor for spin a bifida. Lancet 1995, 346, 1070–1071.Van der Put N.M., Steegers-Theunissen R.P., Frosst P., Trijbels F.J., Eskes T.K., van den Heuvel L.P., Mariman E.C., den Heyer M., Rozen R., Blom H.J. Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 1995, 346, 1070-1071.Holmes V. Homocysteine Is Lower in the Third Trimester of Pregn ancy in Women with Enhanced Folate Status from Continued Folic Acid Supplementation. Clin. Chem. 2005, 51, 629-634.Holmes V. Homocysteine Is Lower in the Third Trimester of Pregnancy in Women with Enhanced Folate Status from Continued Folic Acid Supplementation. Clin. Chem. 2005, 51, 629-634.Park SB, Georgiades A. Changes in body composition predict homocysteine changes and hyperhomocysteinemia in Korea.J Korean Med Sci. 2013.7:1015-20.Park S.B., Georgiades A. Changes in body composition predict homocysteine changes and_hyperhomocysteinemia_in Korea.J Korean Med Sci. 2013.7: 1015-20.Park S.B., Georgiades A. Changes in body composition predict homocysteine changes and_hyperhomocysteinemia_in Korea.J Korean Med Sci. 2013.7: 1015-20.

The authors declare that there are no conflicts of interest present.