Clever Geek Handbook
📜 ⬆️ ⬇️

Primary prevention of congenital malformations

Primary prevention of congenital malformations (CHD) is a set of measures for preconception and during pregnancy, aimed at eliminating or at least significantly reducing the risk of congenital malformations in the fetus. According to WHO , in many countries, congenital malformations are one of the most important causes of childhood mortality, chronic diseases, and disability. As of October 2012, 1 out of 33 newborns (approximately 3.2 million annually) has malformations. During the first 28 days of life, 270,000 children die every year from malformations. However, primary prevention is possible. Among the main methods are nutraceutical (taking physiological doses of folate , iodine , other micronutrients), vaccination and appropriate prenatal care. [one]

As recommended in the WHO newsletter, primary prevention of congenital malformations should include the following measures [1] :

  • Improving the nutrition of women throughout the reproductive period by ensuring the proper intake of vitamins and minerals (among which folate and iodine are most known).
  • Limit exposure to alcohol and thermal decomposition products of tobacco .
  • Elimination of the effects of teratogens (heavy metals, pesticides, certain medications).
  • Improving a woman’s somatic health (controlling insulin resistance , preventing gestational diabetes , reducing overweight, etc.).
  • Elimination of intrauterine infections (including vaccination against rubella virus).
  • Improving educational work with health workers and other staff involved in strengthening preventive measures against malformations.

The basis for the prevention of primary prevention of congenital malformations in most women (more than 60%) is the provision of nutrition for women during pregnancy in accordance with the recommended norms of consumption of macro- and micronutrients [2] . The work [3] systematized the available scientific information on the relationship of vitamins with malformations (analysis of more than 1000 articles in PUBMED, www.ncbi.nlm.nih.gov/pubmed). Based on a joint analysis of clinical and experimental data, it is shown that deficiencies of vitamins A, E, D, C and B vitamins (including folate, pyridoxine, and cyanocobalamin) during pregnancy significantly increase the risk of pregnancy pathologies and fetal malformations.

The experience of different countries in the prevention of CDF

The US Department of Health has set up a central web site sponsored by the agency, the National Guideline Clearinghouse (translated as the “National Guidelines Center”) [4] . This site summarizes the information on the thousands of recommendations that have been formulated by medical public organizations. Package No. 13400 “Prediction, prevention, and prognosis of preeclampsia” strongly recommends the use of multivitamin supplements with folates for the prevention of gestosis [5] , along with calcium preparations, abstinence from alcohol and smoking, and exercise. Oral intake of vitamins and minerals is recommended for the prevention of anemia [6] , postpartum hemorrhage (intake starting from the prenatal period) [7] and, in general, is a standard, recognized and undeniable component of antenatal care for healthy pregnant women [8] .

As recommended by the U.S. Department of Defense, female military personnel should take multivitamin supplements at least one month before pregnancy and in the first trimester. Pregnant women taking vitamin-mineral complexes (IUDs) due to certain health conditions (pernicious anemia - B12, convulsive disorders - folic acid, etc.) should continue taking these drugs during pregnancy. Pregnant women on a restrictive diet (vegetarians, diets for weight loss, etc.) should consult a dietitian and take an IUD for a personalized prescription [9] .

In accordance with the data of the Society of Obstetricians and Gynecologists of Canada (2007), a very paradoxical fact has been established: the highest compliance of taking vitamin-mineral complexes with folates (36% of the examined) was characterized by pregnant women without a history of DNT. At the same time, pregnant women who had a history of a child with DNT were characterized by lower compliance (26%). Moreover, patients in risk groups (women with risk factors for DNT, as well as those who smoked and took alcohol during pregnancy) were characterized by the lowest compliance (4%). Such observations make it necessary to provide additional explanations to patients about the important role of multivitamin preparations in the prevention of malformations. [ten]

Roles of individual vitamins in primary prevention of congenital malformations

Vitamin A (Retinol)

Vitamin A is a fat-soluble growth factor that has a significant effect on the transcription of hundreds of genes. Participates in the formation of the skeleton, ensures the normal existence of epithelial cells of the skin and mucous membranes of the eyes, respiratory, urinary tract, digestive tract and, of course, the function of vision. The embryo cannot synthesize retinol and depends on the delivery of retinol through the mother’s body [11] . Retinoids are important for the development of the heart in the early stages of embryonic development [12] . Ethanol causes malformations of various embryonic structures by blocking retinaldehyde dehydrogenase during gastrulation [13] .

Both excess and deficiency of vitamin A leads to serious consequences for the fetus [14] . Increasing deficiency of vitamin A leads to a dose-dependent contraction of the hindbrain of the embryo [15] , impaired development of the larynx [16] , high perinatal mortality, severe ataxia, and blindness [17] ; borderline vitamin A deficiency leads to congenital kidney disease [18] .

Sufficient levels of vitamins A and E in newborns positively affect the formation of behavior and cognitive development of children [19] , prevent the development of hyaline membranes and violations of the formation of lung surfactant in newborns [20] . Higher levels of vitamin A consumed with food and multivitamins corresponded to a lower risk of cleft lip [21] .

Vitamin B1 (Thiamine)

Vitamin B1, being a coenzyme of decarboxylases, is involved in the oxidative decarboxylation of keto acids (pyruvic, α-ketoglutaric) in the Krebs cycle. With a deficiency of vitamin B1, the conversion of carbohydrates to lipids slows down, the synthesis of steroids and acetylcholine decreases, and energy metabolism suffers. Thiamine deficiency during pregnancy leads to increased death of the central nervous system neurons in the fetus [22] . Vitamin B1 deficiency in pregnant women is quite common [23] and is associated with an increased risk of congenital malformations, leads to premature birth [24] , and increases the risk of gestosis [25] , fetal neural tube defects, and other congenital malformations [26] . During the study of 377 cases of diaphragmatic hernia and 5008 controls, mothers of newborns filled out a nutrition questionnaire, which was used to evaluate nutrient intake during the year before pregnancy. Among women taking multivitamins, a higher intake of folic acid, vitamins B1, B2, B6, B12 and minerals of calcium, iron, magnesium and zinc corresponded to a reduced risk of developing diaphragmatic hernia [27] .

Vitamin B2 (Riboflavin)

Riboflavin - is a cofactor of the enzymes of energy metabolism. A low level of riboflavin in the diet led to a delay in the development of embryos; development of heart defects (defects of the interventricular septum, a decrease in the thickness of the walls of the left ventricle) [28] . Clinical studies of nutritional deficiency of riboflavin showed a 3-fold increased risk of developing limb defects. A study of 324 cases of children with limb defects and 4982 healthy infants showed that the lowest dietary intake of riboflavin corresponded to a 3-fold risk of defects (O. Sh. 2.9, 95% CI: 1.04-8.32) [29] . The dietary deficiency of riboflavin and nicotinamide, reflected in the levels of these vitamins in the blood, was higher in mothers who gave birth to children with congenital heart defects [30] . With riboflavin deficiency, the risk of gestosis in the pregnant woman [31] and cleft palate in the fetus [32] , craniostenosis [33] , and urinary system defects [30] increase.

Vitamin PP (niacin, nicotinic acid, nicotinamide)

Vitamin PP is involved in the regulation of cellular respiration, the release of energy from carbohydrates and fats and in protein metabolism, forming the commonly used coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). With niacin deficiency during pregnancy, numerous developmental abnormalities form [34] . Low dietary levels of riboflavin (less than 1.2 mg / day) and niacin (less than 13.5 mg / day) double the risk of having a baby with congenital heart defects. An increase in nicotinamide subsidy reduced the risk of developing malformations regardless of dietary folate intake. In a study of 190 mothers of newborns with malformations of the ventricles of the heart, dietary intake of nicotinamide was lower in mothers who gave birth to a child with this VLD (14.6 and 15.1 mg / day; P <0.05, the Netherlands, [30] ). The levels of consumption of thiamine (B1), pyridoxine (B6) and niacin (B3) in perception were much lower in mothers who gave birth to children with cleft palate than in those who gave birth to children without this developmental defect [35] . Nicotinamide prevents the onset and development of fetal asphyxiation [36] .

Vitamin B6

Vitamin B6 is involved in the following nitrogen metabolism processes: transamination, deamination and decarboxylation of amino acids; tryptophan transformations; conversion of sulfur-containing and hydroxy amino acids. Pyridoxine deficiency is associated with an increased frequency of seizures, paresthesias, with an anxious state of the psyche, vomiting, tooth decay (evidence category “A”) [37] . A meta-analysis of 5 studies involving more than 1,600 women showed that regular use of vitamin B6 reduces the risk of resorption of tooth enamel in pregnant women and the risk of low fetal weight at birth [38] . B6 deficiency during pregnancy contributes to the development of fetal neural tube defects [39] and may contribute to the development of gestosis [29] . A study of 324 cases of children with limb defects and 4982 healthy infants showed that the lowest dietary intake of vitamin B6 corresponded to a 4-fold increase in the risk of limb defects (O. Sh. 3.9, 95% CI 1.08-13.78) [40] .

Folates (Folic Acid, Vitamin B9)

Vitamin B9 is needed to prevent anemia in pregnant women and fetal developmental defects, including the development of neural tube defects (DNT) through its effect on cell growth and differentiation. Influencing DNA methylation, folic acid plays an important role in cell division processes, which is especially important for tissues whose cells actively divide and differentiate (blood, epithelium) during pregnancy and fetal growth. [41] .

The role of folic acid preparations in lowering the risk of DNT (fetal neural tube defects) has been repeatedly proven in numerous clinical studies [42] . Folic acid supplementation prevents Down Syndrome [43] and congenital heart defects [44] . According to the National Italian Institute of Health, taking folic acid before and during pregnancy in an amount of 400 mcg / day or more prevents not only DNT, but also abnormalities in embryogenesis of the brain, cardiovascular system, urinary system, the formation of cleft palate, limb defects, defects of large arteries, and omphalocele - umbilical hernia [45] . Observations of the Norwegian cohort of 85,176 pregnant women who subsequently gave birth to a child showed that taking folic acid preparations starting from the period of pericopeception reduces the development of autism risk by 50% (O. Sh. 0.61, 95% CI 0.41-0.90) [46] .

Epidemiological data showed that a significant reduction in the risk of neural tube defects (DNT) is observed when the concentration of folate in red blood cells is more than 906 nmol / L. For the prevention of DNT, women are advised to take 400 mcg / day of folic acid in the period before conception, and when taking this dose of folic acid, the concentration of folate in red blood cells> 906 nmol / L is not reached after 4 weeks. A study of 46 healthy women who received 400 and 800 mcg / day of folic acid or placebo showed the feasibility of increasing the dosage of folic acid to 800 mcg. After taking 800 μg / day of folic for 16 weeks, the average time to reach the target level of folates in red blood cells (906 nmol / l or more) was 4.2 ± 3.5 weeks, at 400 μg / day - 8.1 ± 4.5 weeks [47]

The dose of folic acid should not exceed 800 ... 1000 mcg / day [48] . Firstly, a comparative analysis of studies on the use of folates for the prevention of DNT shows that the use of even such high doses of folic acid as 4000-5000 μg / day has almost the same result as the use of 400 μg / day - that is, 50% - An 80% reduction in the risk of fetal DNT [49] . Secondly, folic acid is not a natural form of folate and an excess of folic acid introduced with drugs will inhibit the transport of endogenous folate [50] . The latter occurs due to the inhibition of the metabolism enzymes of folate dihydrofolate reductase (DHFR) and thymidylate synthase (TS) and the carrier protein of the reduced folate carrier (RFC gene) [51] . Prevention of DNT and all other CMPs is more effective when folic acid is used in combination with other vitamins than when using folic acid monopreparations According to a large study (outcomes of more than 5000 pregnancies), folic acid monopreparations reduced the risk of congenital malformations by 70%, while the use of multivit mined complexes decreased risk of the CDF 90% [52] .

Vitamin B12

Folate metabolism and DNA methylation processes, which are so important for cell growth, are impaired when each of these three vitamins B6, B9 or B12 is deficient. The leading transmethylation reactions involving B12 are the synthesis of thymidine (DNA synthesis) and methionine from homocysteine [53] . B12-hypovitaminosis almost certainly occurs in pregnant women with a strict vegetarian diet and in pregnant women with intestinal flora dysbiosis and low stomach acidity. A deficiency of vitamin B12 in pregnant women negatively affects folate metabolism and increases the risk of congenital defects of the fetus, especially neural tube defects [54] . A study of 203 mothers who gave birth to a baby with a cleft lip and / or cleft palate and 178 mothers without defects showed that the Western diet (high meat, pizza, legumes and potatoes, low fruit) is associated with an increased risk these VLD (O. Sh. 1.9; 95% D.I. 1.2-3.1). According to the authors, the “western” type of diet was associated with lower levels of folate (P = 0.02), vitamin B6 (P = 0.001), vitamin B12 (P = 0.02) and elevated levels of homocysteine ​​in blood plasma (P = 0.05) [55] .

The prevalence of vitamin deficiencies that affect the risk of coronary artery

According to large studies involving tens of thousands of people, most adults consume less folate than established by the norms [56] . In particular, a study of folate consumption by the German population during 1997–2000 showed that, on average, adult folate consumption was less than 80% of the daily recommended folate rate in Germany. Moreover, in 25% of women of childbearing age, the folate content in erythrocytes and blood plasma is reduced [57] . Studies of the Institute of Nutrition RAMS indicate a widespread deficiency of vitamins among pregnant women in all regions of our country. Deficiency of B vitamins is detected in 20-100% of patients, ascorbic acid - in 13-50%, carotenoids - 25-94% with a relatively good supply of vitamins A and E [58] [59] . The most common deficiency is iron, iodine, calcium, zinc, chromium, folic acid, biotin, vitamins A, D, B1, B6. [60]

The combined use of vitamins for the prevention of congenital malformations

The results of the analysis of the data of the National study on the prevention of birth defects (NBDPS, USA, 1997-2003) showed that a higher intake of B vitamins (folate, vitamins B1, B2, B6 and B12), minerals (calcium, iron, magnesium, zinc) and vitamin E reduced the risk of congenital malformations by 30-70% [27] . Surveillance in a cohort of 280127 pregnant women in Norway showed that supplementation with folic acid reduces the risk of placental abruption by 26%. However, the greatest effectiveness of prevention was observed when taking folic acid as part of multivitamin preparations: the risk decreased by 32% (O. Sh. 0.68, 95% CI 0.56-0.83) [61] [62] .

A study in Hungary of more than 5000 pregnancies showed that the use of multivitamins for the prevention of neural tube defects and other developmental abnormalities showed a decrease in the occurrence of DNT by 92%, malformations of the cardiovascular system by 42%, as well as a significant decrease in other developmental defects. Multivitamins containing 0.4–0.8 mg / day of folic acid were more effective in the prevention of neural tube malformations than high doses of folic acid monotherapy [118] [52] .

Notes

  1. ↑ 1 2 Malformations. Newsletter No. 370 (Neopr.) . World Health Organization (October 2012). Date of treatment October 24, 2013.
  2. ↑ Methodical recommendations 2.3.1.2432-08. Norms of physiological needs for energy and nutrients for various groups of the population of the Russian Federation.
  3. ↑ Gromova O. A. Congenital malformations as a result of vitamin deficiency: systematic analysis and practical conclusions. Obstetrics and Gynecology, 2013, No. 7, S.93-100.
  4. ↑ National Guideline Clearinghouse, http://www.guideline.gov/ Archived August 19, 2014 on the Wayback Machine
  5. ↑ Prediction, prevention, and prognosis of preeclampsia, 2008 Mar. NGC: 006811 Society of Obstetricians and Gynaecologists of Canada, http://www.guideline.gov/ Archived August 19, 2014 on the Wayback Machine
  6. ↑ Anemia in pregnancy. 2008 Jul. NGC: 006764 American College of Obstetricians and Gynecologists, http://www.guideline.gov/ Archived August 19, 2014 on the Wayback Machine
  7. ↑ Postpartum hemorrhage. 2006 Oct. NGC: 005702 American College of Obstetricians and Gynecologists
  8. ↑ Antenatal care. Routine care for the healthy pregnant woman. 2003 Oct (revised 2008 Mar). NGC: 007174 National Collaborating Center for Women's and Children's Health.
  9. ↑ VA / DoD clinical practice guideline for management of pregnancy. 2002 Oct (revised 2009). NGC: 007714
  10. ↑ Richard-Tremblay AA, Sheehy O, Audibert F, Ferreira E, Bérard A. Concordance between periconceptional folic acid supplementation and Canadian Clinical Guidelines. J Popul Ther Clin Pharmacol. 2012; 19 (2): e150-9.
  11. ↑ Marceau G, Gallot D, Lemery D, Sapin V. Metabolism of retinol during mammalian placental and embryonic development. Vitam Horm. 2007; 75: 97-115.
  12. ↑ Pan J, Baker KM. Retinoic acid and the heart. Vitam Horm. 2007; 75: 257-283.
  13. ↑ Kot-Leibovich H, Fainsod A. Ethanol induces embryonic malformations by competing for retinaldehyde dehydrogenase activity during vertebrate gastrulation. Dis Model Mech. 2009; 2 (5-6): 295-305.
  14. ↑ Gromova O.A., Torshin I. Yu., Dosing of Vitamin A during Pregnancy, Gynecology, 2010, No. 10, P. 43-38.
  15. ↑ Zile MH. Function of vitamin A in vertebrate embryonic development. J Nutr. 2001; 131 (3): 705-708.
  16. ↑ Tateya I, Tateya T, Surles RL, Tanumihardjo S, Bless DM. Prenatal vitamin A deficiency causes laryngeal malformation in rats. Ann Otol Rhinol Laryngol. 2007; 116 (10): 785-792.
  17. ↑ Hill B, Holroyd R, Sullivan M. Clinical and pathological findings associated with congenital hypovitaminosis A in extensively grazed beef cattle. Aust Vet J. 2009; 87 (3): 94-98.
  18. ↑ Lelievre-Pegorier M, Vilar J, Ferrier ML, Mild Vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney int. 1998; 54 (5): 1455-1462.
  19. ↑ Chen K, Zhang X, Wei XP, Antioxidant vitamin status during pregnancy in relation to cognitive development in the first two years of life. Early Hum Dev. 2009 Jul; 85 (7): 421-7.
  20. ↑ Askin DF, Diehl-Jones W. Pathogenesis and prevention of chronic lung disease in the neonate. Crit Care Nurs Clin North Am. 2009 Mar; 21 (1): 11-25.
  21. ↑ Mitchell LE, Murray JC, O'Brien S, Christensen K. Retinoic acid receptor alpha gene variants, multivitamin use, and liver intake as risk factors for oral clefts: a population-based case-control study in Denmark, 1991-1994. Am J Epidemiol. 2003; 158 (1): 69-76.
  22. ↑ Oliveira FA. Thiamine deficiency during pregnancy leads to cerebellar neuronal death in rat offspring: role of voltage-dependent K + channels. Brain Res. 2007; 1134 (1): 79-86
  23. ↑ Rees G, Brooke Z, Doyle W, Costeloe K. The nutritional status of women in the first trimester of pregnancy. JR Soc Promot Health. 2005 Sep; 125 (5): 232-8.
  24. ↑ Link G, Zempleni J, Bitsch I. The intrauterine turnover of thiamin in preterm and full-term infants. Int J Vitam Nutr Res. 1998; 68 (4): 242-8.
  25. ↑ Emonts P, Seaksan S, Seidel L, Thoumsin H, Gaspard U, Albert A, Foidart JM. Prediction of maternal predisposition to preeclampsia. Hypertens Pregnancy. 2008; 27 (3): 237-45.
  26. ↑ Cabrera RM, Hill DS, Etheredge AJ, Finnell RH. Investigations into the etiology of neural tube defects. Birth Defects Res C Embryo Today. 2004 Dec; 72 (4): 330-44.
  27. ↑ 1 2 Yang W, Shaw GM, Carmichael SL, Rasmussen SA, Waller DK, Pober BR, Anderka M; National Birth Defects Prevention Study. Nutrient intakes in women and congenital diaphragmatic hernia in their offspring. Birth Defects Res A Clin Mol Teratol. 2008 Mar; 82 (3): 131-8.
  28. ↑ Chan J, Deng L, Mikael LG. Low dietary choline and low dietary riboflavin during pregnancy influence reproductive outcomes and heart development in mice. Am J Clin Nutr. 2010; 91 (4): 1035-43.
  29. ↑ 1 2 Ronnenberg AG, Venners SA, Xu X, Chen C, Wang L, Guang W, Huang A, Wang X. Preconception B-vitamin and homocysteine ​​status, conception, and early pregnancy loss. Am J Epidemiol. 2007 Aug 1; 166 (3): 304-12.
  30. ↑ 1 2 3 Smedts HP, Rakhshandehroo M, Verkleij-Hagoort AC, de Vries JH, Ottenkamp J, Steegers EA, Steegers-Theunissen RP. Maternal intake of fat, riboflavin and nicotinamide and the risk of having offspring with congenital heart defects. Eur J Nutr. 2008; 47 (7): 357-65.
  31. ↑ Neugebauer J. Riboflavin supplementation and preeclampsia. Int J Gynaecol Obstet. 2006 May; 93 (2): 136-7.
  32. ↑ 69. Shaw GM. Rasmussen SA.Maternal nutrient intakes and risk of orofacial clefts. Epidemiology. 2006 May; 17 (3): 285-91.
  33. ↑ Carmichael SL, Rasmussen SA, Lammer EJ, Ma C, Shaw GM. Craniosynostosis and nutrient intake during pregnancy. Birth Defects Res A Clin Mol Teratol. 2010.
  34. ↑ CHAMBERLAIN JG, NELSON MM. Multiple congenital abnormalities in the rat resulting from acute maternal niacin deficiency during pregnancy. Proc Soc Exp Biol Med. 1963;112:836.
  35. ↑ Krapels IP, van Rooij IA, Ocke MC. Maternal nutritional status and the risk for orofacial cleft offspring in humans. J Nutr. 2004;134(11):3106-3113.
  36. ↑ Bustamante D, Morales P, Pereyra JT. Nicotinamide prevents the effect of perinatal asphyxia on dopamine release evaluated with in vivo microdialysis 3 months after birth. Exp Brain Res. 2007 Mar;177(3):358-69.
  37. ↑ Формулярная система. Федеральное руководство, ГеотарМед, М., 2010, 996С. .
  38. ↑ Thaver D, Saeed MA, Bhutta ZA.Pyridoxine (vitamin B6) supplementation in pregnancy.Cochrane Database Syst Rev. 2006 Apr 19;(2):CD000179. .
  39. ↑ Candito M, Rivet R, Herbeth B. Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: a multicenter case-control study. Am J Med Genet A. 2008;146A(9):1128-1133. .
  40. ↑ Robitaille J, Carmichael SL, Shaw GM, Olney RS. Maternal nutrient intake and risks for transverse and longitudinal limb deficiencies: data from the National Birth Defects Prevention Study, 1997—2003. Birth Defects Res A Clin Mol Teratol. 2009;85(9):773-779.
  41. ↑ Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr. 2008;87(3):517-533.
  42. ↑ Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull. 2008;29(2 Suppl:S101-11).
  43. ↑ Patterson D. Folate metabolism and the risk of Down syndrome.Downs Syndr Res Pract. 2008 Oct;12(2):93-7. .
  44. ↑ Bailey LB, Berry RJ.Folic acid supplementation and the occurrence of congenital heart defects, orofacial clefts, multiple births, and miscarriage.Am J Clin Nutr. 2005 May;81(5):1213S-1217S.
  45. ↑ Salerno P, Bianchi F, Pierini A, Baldi F, Folic acid and congenital malformation: scientific evidence and public health strategies. Ann Ig. 2008 Nov-Dec;20(6):519-30. .
  46. ↑ Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Davey Smith G, Øyen AS, Susser E, Stoltenberg C. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA. 2013 Feb 13;309(6):570-7.
  47. ↑ Brämswig S, Prinz-Langenohl R, Lamers Y, Tobolski O, Wintergerst E, Berthold HK, Pietrzik K. Supplementation with a multivitamin containing 800 microg of folic acid shortens the time to reach the preventive red blood cell folate concentration in healthy women. Int J Vitam Nutr Res. 2009 Mar;79(2):61-70. doi: 10.1024/0300-9831.79.2.61.
  48. ↑ Громова О. А., Торшин И. Ю. Витамины и микроэлементы: между Сциллой и Харибдой, 2013, МЦНМО, 702 С.
  49. ↑ Громова О. А., Торшин И. Ю. Применение фолиевой кислоты в акушерстве и гинекологии, 2009, М., РСЦ ЮНЕСКО, 73 С. .
  50. ↑ Nijhout HF, Reed MC, Budu P, Ulrich CM. A mathematical model of the folate cycle: new insights into folate homeostasis. J Biol Chem. 2004;279(53):55008-16.
  51. ↑ Ifergan I, Assaraf YG. Molecular mechanisms of adaptation to folate deficiency. Vitam Horm. 2008;79:99-143. .
  52. ↑ 1 2 Czeizel AE. The primary prevention of birth defects: Multivitamins or folic acid? Int J Med Sci 2004; 1:50-61.
  53. ↑ Terroine T. Biochemical anomalies and teratogenicavitaminosis. Annee Biol 1967; 6 (7): 329-59. .
  54. ↑ Molloy AM, Kirke PN, Troendle JF.Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defect prevalence and no folic Acid fortification. Pediatrics. 2009 Mar;123(3):917-23. .
  55. ↑ Vujkovic M, Ocke MC, van der Spek PJ, Maternal Western dietary patterns and the risk of developing a cleft lip with or without a cleft palate. Obstet Gynecol. 2007;110(2 Pt 1:378-384.
  56. ↑ Raiten DJ, Fisher KD.Assessment of folate methodology used in the Third National Health and Nutrition Examination Survey (NHANES III, 1988—1994).J Nutr. 1995 May;125(5):1371S-1398S. .
  57. ↑ Gonzalez-Gross M, Prinz-Langenohl R, Pietrzik K.Folate status in Germany 1997—2000.Int J Vitam Nutr Res. 2002 Dec;72(6):351-9.
  58. ↑ Коденцова, В. М., Вржесинская О. А., Витамины в питании беременных, Гинекология, Том 4, N1, ─ 2002.
  59. ↑ Маталыгина. О. А. Питание беременных и кормящих женщин. Решенные и нерешенные проблемы. Вопросы современной педиатрии 2008, Том 7, № 5, С. 23-29.
  60. ↑ Хорошилов И. Е., Успенский Ю. В. Новые подходы в лечебном питании беременных и кормящих женщин Гинекология. 2008. № 4. С. 67-77.
  61. ↑ Nilsen RM, Vollset SE, Rasmussen SA, Ueland PM, Daltveit AK. Folic acid and multivitamin supplement use and risk of placental abruption: a population-based registry study. Am J Epidemiol. 2008 Apr 1;167(7):867-74.
  62. ↑ Werler MM, Hayes C, Louik C. Multivitamin use and risk of birth defects. Am J Epidemiol. 1999; 150:675-682
Источник — https://ru.wikipedia.org/w/index.php?title=Первичная_профилактика_врождённых_пороков_развития&oldid=100054329


More articles:

  • Georgian, Irakli Aleksandrovich
  • Superflake Returns
  • Schliben, Karl Leopold von
  • My love is sadness
  • Qatar Football Championship 1997/1998
  • Macropsis fuscinervis
  • Muhgabur, Pierre-Xavier
  • Kudashov, George Maximovich
  • Blitz, Karel
  • 2nd Virginia Infantry Regiment

All articles

Clever Geek | 2019