Значение дефицита железа и профилактики дефицита фолиевой кислоты при планировании беременности

Собрана и систематизирована опубликованная за последнее десятилетие информация по применению препаратов железа. Актуализирована потребность в длительном приеме препаратов железа и необходимость комплаентности пациенток. Сформулированы основные требования, предъявляемые к препаратам железа на сегодняшний день, а также акцентированы преимущества комбинаций органических солей железа с фолиевой кислотой в качестве наиболее оптимального и современного подхода к профилактике и лечению железодефицитных состояний при беременности.

1. Gopal M., Sunitha K., Arockiasamy J. et al. Micronutrient deficiency in pregnancy: time to think beyond iron and folic acid supplementation. Indian J Community Med. 2022;47(3):425–8. https://doi.org/10.4103/ijcm.ijcm_743_21.

2. Global nutrition targets 2025: low birth weight policy brief. Geneva: World Health Organization, 2012. Режим доступа: https://www.who.int/nutrition/topics/globaltargets_lowbirthweight_policybrief.pdf. [Дата обращения: 26.06.2025].

3. Choi R., Sun J., Yoo H. et al. A prospective study of serum trace elements in healthy korean pregnant women. Nutrients. 2016;8(11):749. https://doi.org/10.3390/nu8110749.

4. Grzeszczak K., Kwiatkowski S., Kosik-Bogacka D. The role of Fe, Zn, and Cu in pregnancy. Biomolecules. 2020;10(8):1176. https://doi.org/10.3390/biom10081176.

5. McCann S., Perapoch Amadó M., Moore S.E. The role of iron in brain development: a systematic review. Nutrients. 2020;12(7):2001. https://doi.org/10.3390/nu12072001.

6. Анемия. Всемирная организация здравоохранения, 2023. Режим доступа: https://www.who.int/news-room/fact-sheets/detail/anaemia. [Дата обращения: 26.06.2025].

7. Pasricha S.R., Tye-Din J., Muckenthaler M.U., Swinkels D.W. Iron deficiency. Lancet. 2021;397(10270):233–48. https://doi.org/10.1016/S0140-6736(20)32594-0.

8. Safiri S., Kolahi A.A., Noori M. et al. Burden of anemia and its underlying causes in 204 countries and territories, 1990-2019: results from the Global Burden of Disease Study 2019. J Hematol Oncol. 2021;14(1):185. https://doi.org/10.1186/s13045-021-01202-2.

9. Gοugοutsi V., Pouliakis A., Argyrios T. et al. The critical role of the early evaluation of iron and bitamin B12 deficiency in pregnancy. Cureus. 2024;16(8):e67592. https://doi.org/10.7759/cureus.67592.

10. Ferrazzi E., Tiso G., Di Martino D. Folic acid versus 5-methyl tetrahydrofolate supplementation in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2020;253:312–9. https://doi.org/10.1016/j.ejogrb.2020.06.012.

11. Михайлова О.И., Мирзабекова Д.Д., Кан Н.Е., Тютюнник В.Л. Нутритивная поддержка при беременности: возможность профилактики акушерских осложнений. Медицинский совет. 2021;(3):67–74. https://doi.org/10.21518/2079701X-2021-3-67-74.

12. Saragih I.D., Dimog E.F., Saragih I.S., Lin C.J. Adherence to Iron and Folic Acid Supplementation (IFAS) intake among pregnant women: a systematic review meta-analysis. Midwifery. 2022;104:103185. https://doi.org/10.1016/j.midw.2021.103185.

13. Lyoba W.B., Mwakatoga J.D., Festo C. et al. Adherence to iron-folic acid supplementation and associated factors among pregnant women in Kasulu Communities in North-Western Tanzania. Int J Reprod Med. 2020;2020:3127245. https://doi.org/10.1155/2020/3127245.

14. Грудницкая Е.Н. Микронутриентная поддержка женщин репродуктивного возраста (обзор литературы). Репродуктивное здоровье. Восточная Европа. 2021;11(1):91–100. https://doi.org/10.34883/PI.2021.11.1.023.

15. Philip K.E.J., Sadaka A.S., Polkey M. et al. The prevalence and associated mortality of non-anaemic iron deficiency in older adults: a 14 years observational cohort study. Br J Haematol. 2020;189(3):566–72. https://doi.org/10.1111/bjh.16409.

16. Куликов И.А., Геворкян Г.А. Анализ выявляемости латентного дефицита железа и железодефицитной анемии в гинекологической практике и данные результатов лечения. Российский вестник акушера-гинеколога. 2023;23(3):117–26. https://doi.org/10.17116/rosakush202323031117.

17. Auerbach М., DeLoughery T.G. Diagnosis of iron deficiency and iron deficiency anemia in adults. Режим доступа: https://www.uptodate.com/contents/causes-and-diagnosis-of-iron-deficiency-and-iron-deficiency-anemia-in-adults. [Дата обращения: 26.06.2025].

18. Дикке Г.Б. Витаминно-минеральный комплекс для беременных: современная формула. Фарматека. 2021;28(6)100–7. https://doi.org/10.18565/pharmateca.2021.6.100-107.

19. Benson C.S., Shah A., Stanworth S.J. et al. The effect of iron deficiency and anaemia on women's health. Anaesthesia. 2021;76 Suppl 4:84–95. https://doi.org/10.1111/anae.15405.

20. Iriarte-Gahete M., Tarancon-Diez L., Garrido-Rodríguez V. et al. Absolute and functional iron deficiency: Biomarkers, impact on immune system, and therapy. Blood Rev. 2024;68:101227. https://doi.org/10.1016/j.blre.2024.101227.

21. Hilton C., Sabaratnam R., Drakesmith H., Karpe F. Iron, glucose and fat metabolism and obesity: an intertwined relationship. Int J Obes (Lond). 2003:47(7):554–63. https://doi.org/10.1038/s41366-023-01299-0.

22. Volani C., Doerrier C., Demetz E. et al. Dietary iron loading negatively affects liver mitochondrial function. Metallomics. 2017;9(11):1634–44. https://doi.org/10.1039/c7mt00177k.

23. Georgieff M.K., Krebs N.F., Cusick S.E. The benefits and risks of iron supplementation in pregnancy and childhood. Annu Rev Nutr. 2019;39:121–46. https://doi.org/10.1146/annurev-nutr-082018-124213.

24. Dixon S.J., Lemberg K.M., Lamprecht M.R. et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72. https://doi.org/10.1016/j.cell.2012.03.042.

25. Wyatt J., Fernando S.M., Powell S.G. et al. The role of iron in the pathogenesis of endometriosis: a systematic review. Hum Reprod Open. 2023(3):hoad033. https://doi.org/10.1093/hropen/hoad033.

26. Li Y., He Y., Cheng W. et al. Double-edged roles of ferroptosis in endometriosis and endometriosis-related infertility. Cell Death Discov. 2023;9(1):306. https://doi.org/10.1038/s41420-023-01606-8.

27. Tang D., Chen X., Kang R., Kroemer G. Ferroptosis: molecular mechanisms and health implications. Cell Res. 2021;31(2):107–25. https://doi.org/10.1038/s41422-020-00441-1.

28. Nemeth E., Ganz T. Hepcidin-ferroport in interaction controls systemic iron homeostasis. Int J Mol Sci. 2021;22(12);6493. https://doi.org/10.3390/ijms22126493.

29. Donovan A., Lima C.A., Pinkus J.L. et al. The iron exporter ferroportin/ Slc40a1 is essential for iron homeostasis. Cell Metab. 2025;1(3):191–200. https://doi.org/10.1016/j.cmet.2005.01.003.

30. Lopez A., Cocub P., Macdougall I.C., Peyrin-Biroulet L. Iron deficiency anemia. Lancet. 2015;387(10021):907–16. https://doi.org/10.1016/S0140-6736(15)60865-0.

31. Cramer W.A. Structure-function of the cytochrome b6f lipoprotein complex: a scientific odyssey and personal perspective. Photosynth Res. 2019;139(1–3):53–65. https://doi.org/10.1007/s11120-018-0585-x.

32. Zhang Y., Lu Y., Jin L. Iron metabolism and ferroptosis in physiological and pathological pregnancy. Int J Mol Sci. 2022;23(16):9395. https://doi.org/10.3390/ijms23169395.

33. Drakesmith H., Nemeth E., Ganz T. Ironing out ferroportin. Cell Metab. 2015;22(5):777–87. https://doi.org/10.1016/j.cmet.2015.09.006.

34. Nemeth E., Ganz T. Hepcidin and iron in health and disease. Annu Rev Med. 2023;74:261–77. https://doi.org/10.1146/annurev-med-043021-032816.

35. Zanella I., Paiardi G., Di Lorenzo D., Biasiotto G. Iron absorption in celiac disease and nutraceutical effect of 7-hydroxymatairesinol. Mini-review. Molecules (Basel, Switzerland). 2020;25(9):2041. https://doi.org/10.3390/molecules25092041.

36. Aschemeyer S., Qiao B., Stefanova D. et al. Structure-function analysis of ferroportin defines the binding site and an alternative mechanism of action of hepcidin. Blood. 2018;131(8):899–910. https://doi.org/10.1182/blood-2017-05-786590.

37. Nemeth E., Tuttle M.S., Powelson J. et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science. 2004;306(5704):2090–3. https://doi.org/10.1126/science.1104742.

38. Billesbolle C.B., Azumaya C.M., Kretsch R.C. et al. Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms. Nature. 2020;586(7831):807–11. https://doi.org/10.1038/s41586-020-2668-z.

39. Camaschella C. Iron deficiency. Blood. 2019;133(1):30–9. Blood. 2023;141(6):682. https://doi.org/10.1182/blood.2022018610.

40. Haase M., Bellomo R., Haase-Fielitz A. Novel biomarkers, oxidative stress, and the role of labile iron toxicity in cardiopulmonary bypass-associated acute kidney injury. JACC. 2010;55(19):2024–33. https://doi.org/10.1016/j.jacc.2009.12.046.

41. Auerbach М. Anemia in pregnancy. Режим доступа: https://www.uptodate.com/contents/anemia-in-pregnancy. [Дата обращения: 26.06.2025].

42. Pavord S., Daru J., Prasannan N. et al.; BSH Committee. UK guidelines on the management of iron deficiency in pregnancy. Br J Haematol. 2020;188(6):819–30. https://doi.org/10.1111/bjh.16221.

43. Dewey K.G., Oaks B.M. U-shaped curve for risk associated with maternal hemoglobin, iron status, or iron supplementation. Am J Clin Nutr. 2017;106(Suppl 6):1694S–1702S. https://doi.org/10.3945/ajcn.117.156075.

44. Chang Y.H., Chen W.H., Su C. et al. Maternal iron deficiency programs rat offspring hypertension in relation to renin-angiotensin system and oxidative stress. Int J Mol Sci. 2022;23(15):8294. https://doi.org/10.3390/ijms23158294.

45. Fisher A.L., Nemeth E. Iron homeostasis during pregnancy. Am J Clin Nutr. 2017;106(Suppl 6):1567S–1574S. https://doi.org/10.3945/ajcn.117.155812.

46. Tran P.V., Kennedy B.C., Pisansky M.T. et al. Prenatal choline supplementation diminishes early-life iron deficiency-induced reprogramming of molecular networks associated with behavioral abnormalities in the adult rat hippocampus. J Nutr. 2016;146(3):484–93. https://doi.org/10.3945/jn.115.227561.

47. Cao C., Fleming M.D. Localization and kinetics of the transferrin-dependent iron transport machinery in the mouse placenta. Curr Dev Nutr. 2021;5(4):nzab025. https://doi.org/10.1093/cdn/nzab025.

48. Lakhal-Littleton S. Advances in understanding the crosstalk between mother and fetus on iron utilization. Semin Hematol. 2021;58(3):153–60. https://doi.org/10.1053/j.seminhematol.2021.06.003.

49. O'Brien K.O. Maternal, fetal and placental regulation of placental iron trafficking. Placenta. 2022;125:47–53. https://doi.org/10.1016/j.placenta.2021.12.018.

50. Best C.M., Pressman E.K., Cao C. et al. Maternal iron status during pregnancy compared with neonatal iron status better predicts placental iron transporter expression in humans. FASEB J. 2016;30(10):3541–50. https://doi.org/10.1096/fj.201600069R.

51. Delaney K.M., Cao C., Guillet R. et al. Fetal iron uptake from recent maternal diet and the maternal RBC iron pool. Am J Clin Nutr. 2022;115(4):1069–79. https://doi.org/10.1093/ajcn/nqac020.

52. Sangkhae V., Nemeth E. Regulation of the iron homeostatic hormone hepcidin. Adv Nutr (Bethesda, Md.). 2017;8(1):126–36. https://doi.org/10.3945/an.116.013961.

53. Hess S.Y., Zimmermann M.B., Arnold M. et al. Iron deficiency anemia reduces thyroid peroxidase activity in rats. J Nutr. 2002;132(7):1951–5. https://doi.org/10.1093/jn/132.7.1951.

54. Szczepanek-Parulska E., Hernik A., Ruchała M. Anemia in thyroid diseases. Pol Arch Intern Med. 2017;127(5):352–60. https://doi.org/10.20452/pamw.3985.

55. Soliman A.T., De Sanctis V., Yassin M. et al. Chronic anemia and thyroid function. Acta Biomed. 2017;88(1):119–27. https://doi.org/10.23750/abm.v88i1.6048.

56. Golde D.W., Bersch N., Chopra I.J., Cline M.J. Thyroid hormones stimulate erythropoiesis in vitro. Br J Haematol. 1977;37(2):173–7. https://doi.org/10.1111/j.1365-2141.1977.tb06833.x.

57. Maggio M., De Vita F., Fisichella A. et al. The role of the multiple hormonal dysregulation in the onset of "Anemia of Aging": focus on testosterone, IGF-1, and thyroid hormones. Int J Endocrinol. 2015;2015:292574. https://doi.org/10.1155/2015/292574.

58. Zimmermann M.B., Köhrle J. The impact of iron and selenium deficiencies on iodine and thyroid metabolism: biochemistry and relevance to public health. Thyroid. 2002;12(10):867–78. https://doi.org/10.1089/105072502761016494.

59. Brigham D.E., Beard J.L. Effect of thyroid hormone replacement in iron-deficient rats. Am J Physiol. 1995;269(5 Pt 2):R1140–1147. https://doi.org/10.1152/ajpregu.1995.269.5.R1140.

60. Beard J.L., Brigham D.E., Kelley S.K., Green M.H. Plasma thyroid hormone kinetics are altered in iron-deficient rats. J Nutr. 1998;128(8):1401–8. https://doi.org/10.1093/jn/128.8.1401.

61. Garofalo V., Condorelli R.A., Cannarella R. et al. Relationship between iron deficiency and thyroid function: a systematic review and meta-analysis. Nutrients. 2023;15(22):4790. https://doi.org/10.3390/nu15224790.

62. Luo J., Wang X., Yuan L., Guo L. Iron deficiency, a risk factor of thyroid disorders in reproductive-age and pregnant women: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2021;12:629831. https://doi.org/10.3389/fendo.2021.629831.

63. Yan M.X., Zhao Y., Zhao D.D. et al. The association of folic acid, iron nutrition during pregnancy and congenital heart disease in Northwestern China: a matched case-control study. Nutrients. 2022;14(21):4541. https://doi.org/10.3390/nu14214541.

64. Guideline: optimal serum serum and red blood cell folate concentrations in women of reproductive age for prevention of neural tube defects. Geneva: World Health Organization, 2015. Режим доступа: https://www.who.int/publications/i/item/9789241549042. [Дата обращения: 26.06.2025].

65. World Health Organization Model List of Essential Medicines, 20th List (April 2017). Geneva: World Health Organization, 2017. Режим доступа: https://www.who.int/publications/i/item/eml-20. [Дата обращения: 26.06.2025].

66. Bailey L.B. Folate and vitamin B12 recommended intakes and status in the United States. Nutr Rev. 2004;62(6 Pt 2):S14–S20. https://doi.org/10.1111/j.1753-4887.2004.tb00065.x.

67. Johnson M.A. If high folic acid aggravates vitamin B12 deficiency what should be done about it? Nutr Rev. 2007;65(10):451–8. https://doi.org/10.1111/j.1753-4887.2007.tb00270.x.

68. WHO Guidelines Approved by the Guidelines Review Committee. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization, 2016. Режим доступа: https://pubmed.ncbi.nlm.nih.gov/28079998. [Дата обращения: 26.06.2025].

69. Hanson M.A., Bardsley A., De-Regil L.M. et al. The International Federation of Gynecology and Obstetrics (FIGO) recommendations on adolescent, preconception, and maternal nutrition: "Think Nutrition First". Int J Gynaecol Obstet. 2015;131 Suppl 4:S213–53. https://doi.org/10.1016/S0020-7292(15)30034-5.

70. Kennedy D., Koren G. Identifying women who might benefit from higher doses of folic acid in pregnancy. Can Fam Physician. 2012;58(4):394–7.

71. Wahyuwibowo J., Aziz A., Safitri E. et al. Iron-folate supplementation during pregnancy for prevent oxidative stress in pregnant rats: level of MDA, creatinine, glucose, erythrocite, blood pressure, body weight and number of offspring. Pharmacog J. 2020;12(1):186–91. https://doi.org/10.5530/pj.2020.12.28.

72. Ших Е.В., Махова А.А., Еременко Н.Н. и др. Рациональные комбинации в фармакотерапии железодефицита. Вопросы гинекологии, акушерства и перинатологии. 2023;22(3):108–16. https://doi.org/10.20953/1726-1678-2023-3-108-116.

73. Baddam S., Khan K.M., Jialal I. Folic acid deficiency. 2025 Jun 25. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2025 Jan 25.

74. Roche M.L., Samson K.L.I., Green T.J. et al. Perspective: Weekly Iron and Folic Acid Supplementation (WIFAS): a critical review and rationale for inclusion in the essential medicines list to accelerate anemia and neural tube defects reduction. Adv Nutr. 2021;12(2):334–42. https://doi.org/10.1093/advances/nmaa169.

75. Джобава Э.М., Кнышева И.Г., Артизанова Д.П. Дефицит железа во время беременности: эффективность терапии и ключевые точки клинической практики. Акушерство и гинекология. 2023;(3):109–12. https://doi.org/10.18565/aig.2023.64.

76. Джобава Э.М., Кнышева И.Г., Артизанова Д.П. Дефицит железа в практике врача-гинеколога: эффективность терапии. Акушерство, Гинекология и Репродукция. 2023;17(2):202–9. https://doi.org/10.17749/2313-7347/ob.gyn.rep.2023.402.

77. Лукина Е.А., Ледина А.В., Роговская С.И. Железодефицитная анемия: взгляд гематолога и гинеколога. Оптимизируем диагностику и лечебную тактику. РМЖ. Мать и дитя. 2020;3(4):248–53. https://doi.org/10.32364/2618-8430-2020-3-4-248-253.

78. Stanworth S.J., Churchill D., Sweity S. et al. The impact of different doses of oral iron supplementation during pregnancy: a pilot randomized trial. Blood Adv. 2024;8(21):5683–94. https://doi.org/10.1182/bloodadvances.2024013408.