Применение фолиевой кислоты или поливитаминов в периконцептуальный период относится к эффективным способам первичной профилактики пороков развития нервной трубки. Результаты проведенных в Венгрии рандомизированных и когортных контролируемых исследований показали, что применение поливитаминных добавок в периконцептуальный период достоверно снижает распространенность пороков развития в исследуемых популяциях. Эти наблюдения были подтверждены многими, но не всеми обсервационными исследованиями (т.е. исследованиями эффективности терапии в условиях, когда выбор контрольной группы не представляется возможным).
Сравнение данных рандомизированного исследования, проведенного в Венгрии с применением поливитаминов, содержащих 0,8 мг/сут фолиевой кислоты, и многолетних данных венгерской службы наблюдения за врожденными аномалиями позволило сделать важный вывод: поливитамины, содержащие 0,8 мг/сут фолиевой кислоты, были более эффективны в профилактике пороков развития нервной трубки, чем высокие дозы монопрепарата фолиевой кислоты. В то время как и поливитамины, и монопрепарат фолиевой кислоты предотвращают пороки развития сердечно-сосудистой системы, только поливитамины профилактируют обструктивные нарушения мочевых путей, пороки развития конечностей и врожденный пилоростеноз. Тем не менее фолиевая кислота эффективно предотвращала развитие некоторых форм ректального/анального стеноза/атрезии и формирование ротолицевой расщелины. Наблюдения еще раз подтверждают тот факт, что применение поливитаминов в периконцептуальном периоде статистически значимо снижает частоту встречаемости разных врожденных пороков развития, в том числе дефектов нервной трубки.
Ключевые слова: фолиевая кислота, поливитамины, профилактика, пороки развития нервной трубки, другие врожденные дефекты.
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The use of folic acid or poly-vitamins in periconceptional period is the effective method of primary prophylaxis of neural tube defects. The results of the randomized and cohort controlled studies in Hungary showed that the use of poly-vitamin supplements in periconceptional period significantly reduces incidence of birth defects in test populations. The observations were confirmed with numerous, but not all observation studies (i.e. efficacy studies in which control group was not provided). The comparison of results of the randomized study which was carried out in Hungary with poly-vitamins containing 0.8 mg of folic acid/day, and long-term data of the Hungarian Supervision Service on congenital abnormalities allowed to make the important conclusion: poly-vitamins which contained 0.8mg of folic acid/day were more effective in prophylaxis of neural tube defects than high doses of monotherapy with folic acid. While both poly-vitamins and monotherapy with folic acid prevented birth defects of cardiovascular system, only poly-vitamins prevented obstructive urinary disorders, malformations of the extremities and congenital pyloric stenosis. Nevertheless, folic acid effectively prevented development of some forms of rectal/anal stenosis/atresia and formation of orofacial cleft. The observations again confirmed the fact that the use of poly-vitamins in peroconceptual period reliably reduced incidence of various birth defects including neural tube defects.
1. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council vitamin study. Lancet 1991; 338: 131–7.
2. Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992; 327: 1832–5.
3. Czeizel AE. Prevention of congenital abnormalities by periconceptional multivitamin supplementation. Brit Med J 1993; 306: 1645–8.
4. Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996; 62: 179–83.
5. Czeizel AE. Periconceptional folic acid-containing multivitamin supplementation. Eur J Obstet Gynecol Reprod Biol 1998; 75: 151–61.
6. Botto LD, Olney RS, Erickson JD. Vitamin supplements and the risk for congenital anomalies other than neural-tube defects. Am J Med Genet 2004; 1250: 12–21.
7. Czeizel AE, Dobó M, Vargha P. Hungarian intervention two-cohort controlled trial of periconceptional multivitamin supplementation to prevent certain congenital abnormalities: Birth Defects Research Part B. Developmental and Repro ductive Toxicology. Submitted.
8. Mulinare J, Erickson JD, James LM, Berry RJ. Does periconceptional use of multivitamins reduce the occurrence of birth defects? Am J Epidemiol 1995; 141: 53.
9. Tolarova M. Periconceptional supplementation with vitamins and folic acid to prevent recurrence of cleft lip. Lancet 1982; 2: 217.
10. Hayes C, Werler MM, Willett WC, Mitchell AA. Case-control study of periconceptional folic acid supplementation and oral clefts. Am J Epidemiol 1996; 143: 1229–34.
11. Werler MM, Hayes C, Louik C. Multivitamin use and risk of birth defects. Am J Epidemiol 1999; 150: 675–82.
12. Myers MF, Li S, Correa-Villasenon A et al. Folic acid supplementation and risk for imperforate anus in China. Am J Epidemiol 2001; 154: 1051–6.
13. Botto LD, Mulinare J, Erickson JD. Occurrence of omphalocele in relation to maternal multivitamin use: A population-based study. Pediatrics 2002; 109: 904–8.
14. Czeizel AE. Reducing risk of birth defects with periconceptional micronutrient supplementation. In: Delange FM, West KP. Micronutrient Deficiencies in the First Months of Life- Nestle Nutrition Workshop Series Pediatric Program. Basel: Verey/S. Karger AG, 2003; p. 309–25.
15. Wald NJ, Law MR, Morris JK, Wald DS. Quantifying the effects of folic acid. Lancet 2001; 358: 2069–73.
16. Wald NJ. Folic acid and the prevention of neural-tube defects. Lancet 2004; 350: 101–3.
17. Czeizel AE, Rockenbauer M, Siffel Cs, Varga E. Description and mission evaluation of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Teratology 2001; 63: 176–85.
18. Czeizel AE. The first 25 years of the Hungarian Congenital Abnormality Registry. Teratology 1997; 55: 299–305.
19. Czeizel AE, Petik D, Vargha P. Validation studies of drug exposures in pregnant women. Pharmacoepid Drug Safety 2003; 12: 409–16.
20. Smithells RW, Sheppard S, Wild J, Schorah CJ. Prevention of neural tube defect recurrences in Yorkshire: final report. Lancet 1989; 2: 498–9.
21. McNulty H, McKinely MC, Wilson B et al. Impaired functioning of thermolabilemethylenetetrahydrofolatereductase is dependent on riboflavin status: Implications for riboflavin requirements. Am J Clin Nutr 2002; 76: 436–41.
22. Jacques PF, Boston AG, Wilson PWT et al. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 2001; 73: 613–21.
23. Kirke PN, Molloy AM, Daly LE et al. Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med 1993; 86: 703–8.
24. Berry RJ, Li Z, Erickson JD et al. Prevention of neural-tube defects with folic acid in China. China-US Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 1999; 341: 1485–90.
25. Czeizel AE, Tímár L, Sárközi A. Dose-dependent effect of folic acid on the prevention of orofacial clefts. Pediatrics 1999; 104: e66.
26. Rockenbauer M, Olsen J, Czeizel AE et al. Recall bias in a case-control study on the use of medicine during pregnancy. Epidemiology 2001; 12: 461–6.
________________________________________________
1. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council vitamin study. Lancet 1991; 338: 131–7.
2. Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992; 327: 1832–5.
3. Czeizel AE. Prevention of congenital abnormalities by periconceptional multivitamin supplementation. Brit Med J 1993; 306: 1645–8.
4. Czeizel AE. Reduction of urinary tract and cardiovascular defects by periconceptional multivitamin supplementation. Am J Med Genet 1996; 62: 179–83.
5. Czeizel AE. Periconceptional folic acid-containing multivitamin supplementation. Eur J Obstet Gynecol Reprod Biol 1998; 75: 151–61.
6. Botto LD, Olney RS, Erickson JD. Vitamin supplements and the risk for congenital anomalies other than neural-tube defects. Am J Med Genet 2004; 1250: 12–21.
7. Czeizel AE, Dobó M, Vargha P. Hungarian intervention two-cohort controlled trial of periconceptional multivitamin supplementation to prevent certain congenital abnormalities: Birth Defects Research Part B. Developmental and Repro ductive Toxicology. Submitted.
8. Mulinare J, Erickson JD, James LM, Berry RJ. Does periconceptional use of multivitamins reduce the occurrence of birth defects? Am J Epidemiol 1995; 141: 53.
9. Tolarova M. Periconceptional supplementation with vitamins and folic acid to prevent recurrence of cleft lip. Lancet 1982; 2: 217.
10. Hayes C, Werler MM, Willett WC, Mitchell AA. Case-control study of periconceptional folic acid supplementation and oral clefts. Am J Epidemiol 1996; 143: 1229–34.
11. Werler MM, Hayes C, Louik C. Multivitamin use and risk of birth defects. Am J Epidemiol 1999; 150: 675–82.
12. Myers MF, Li S, Correa-Villasenon A et al. Folic acid supplementation and risk for imperforate anus in China. Am J Epidemiol 2001; 154: 1051–6.
13. Botto LD, Mulinare J, Erickson JD. Occurrence of omphalocele in relation to maternal multivitamin use: A population-based study. Pediatrics 2002; 109: 904–8.
14. Czeizel AE. Reducing risk of birth defects with periconceptional micronutrient supplementation. In: Delange FM, West KP. Micronutrient Deficiencies in the First Months of Life- Nestle Nutrition Workshop Series Pediatric Program. Basel: Verey/S. Karger AG, 2003; p. 309–25.
15. Wald NJ, Law MR, Morris JK, Wald DS. Quantifying the effects of folic acid. Lancet 2001; 358: 2069–73.
16. Wald NJ. Folic acid and the prevention of neural-tube defects. Lancet 2004; 350: 101–3.
17. Czeizel AE, Rockenbauer M, Siffel Cs, Varga E. Description and mission evaluation of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-1996. Teratology 2001; 63: 176–85.
18. Czeizel AE. The first 25 years of the Hungarian Congenital Abnormality Registry. Teratology 1997; 55: 299–305.
19. Czeizel AE, Petik D, Vargha P. Validation studies of drug exposures in pregnant women. Pharmacoepid Drug Safety 2003; 12: 409–16.
20. Smithells RW, Sheppard S, Wild J, Schorah CJ. Prevention of neural tube defect recurrences in Yorkshire: final report. Lancet 1989; 2: 498–9.
21. McNulty H, McKinely MC, Wilson B et al. Impaired functioning of thermolabilemethylenetetrahydrofolatereductase is dependent on riboflavin status: Implications for riboflavin requirements. Am J Clin Nutr 2002; 76: 436–41.
22. Jacques PF, Boston AG, Wilson PWT et al. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 2001; 73: 613–21.
23. Kirke PN, Molloy AM, Daly LE et al. Maternal plasma folate and vitamin B12 are independent risk factors for neural tube defects. Q J Med 1993; 86: 703–8.
24. Berry RJ, Li Z, Erickson JD et al. Prevention of neural-tube defects with folic acid in China. China-US Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 1999; 341: 1485–90.
25. Czeizel AE, Tímár L, Sárközi A. Dose-dependent effect of folic acid on the prevention of orofacial clefts. Pediatrics 1999; 104: e66.
26. Rockenbauer M, Olsen J, Czeizel AE et al. Recall bias in a case-control study on the use of medicine during pregnancy. Epidemiology 2001; 12: 461–6.
Авторы
Э.Цейцель
Университет наук Этвеша Лоранда, Будапешт, Венгрия