Poladych I. Molecular mechanisms of vitamin–D associated obstetric complications (clinical and experimental study)

Українська версія

Thesis for the degree of Doctor of Science (DSc)

State registration number

0526U000167

Thesis Registration Form

0526U000167.pdf

Applicant for

Specialization

  • 14.01.01 - Акушерство та гінекологія

15-06-2026

Specialized Academic Board

Д 26.003.03

Bogomolets National Medical University

Essay

This research is devoted to addressing a pressing scientific issue in modern obstetrics, namely deepening scientific understanding of the role of vitamin D in the pathogenesis of obstetric complications. A comprehensive clinical and experimental study was conducted, which included a retrospective analysis of 888 cases of pregnancy and childbirth management from 2022 to 2024, a prospective examination of 222 pregnant women with varying vitamin D statuses, as well as experimental modeling of vitamin D deficiency and preeclampsia in 82 female Wistar rats. The research novelty and practical significance of this study lie in the fact that, for the first time, a comprehensive analysis has been conducted of the role of vitamin D in the formation of molecular, metabolic, immuno-inflammatory, and angiogenic mechanisms underlying the development of major obstetric complications. A high prevalence of vitamin D deficiency and insufficiency among pregnant women has been established, and the leading risk factors for the development of vitamin D deficiency have been identified, including excess body weight, seasonal variability in sun exposure, living in a metropolis, extragenital pathology, and endocrine disorders. It has been demonstrated that vitamin D deficiency is associated with a statistically significant increase in the incidence of preeclampsia, fetal growth restriction, threatened preterm labor, gestational diabetes, anemia, and other pregnancy complications, as well as adversely affecting the course of labor and the condition of newborns, as evidenced by an increased incidence of preterm delivery, surgical interventions, intrauterine fetal distress, low Apgar scores, and elevated rates of perinatal morbidity and early neonatal mortality. Based on current scientific and methodological findings, new data have been obtained regarding the pathogenic role of vitamin D deficiency in the development of calcium-phosphate metabolism disorders, angiogenic imbalance, and placental dysfunction. It has been established that a decrease in 25(OH)D levels is accompanied by the development of secondary hyperparathyroidism, decreased levels of calcium, phosphorus, and magnesium, as well as significant changes in placental biochemical markers. It has been demonstrated that an increased sFlt-1/PlGF ratio is one of the most powerful independent predictors of preeclampsia and fetal growth restriction, and the developed multifactorial prognostic model exhibits high discriminatory ability in predicting the development of preeclampsia. It has been experimentally demonstrated for the first time that vitamin D deficiency is one of the key triggers for the activation of NF-κB-dependent pro-inflammatory signaling cascades, which play a leading role in the development of placental dysfunction. It has been established that vitamin D deficiency is accompanied by increased expression of NF-κB p65, TNF-α, and IL-1β, disruption of local placental vitamin D metabolism, dysregulation of VDR, CYP27B1, and CYP24A1 expression, as well as the development of marked angiogenic imbalance. For the first time, the role of the RANKL/RANK/OPG cytokine system in the development of immunoinflammatory and vascular disorders under conditions of vitamin D deficiency and preeclampsia has been determined, and, for the first time in global practice, the levels of FGF23 in the blood serum and placenta of experimental animals have been studied, and its significance in the development of preeclampsia and mineral metabolism disorders has been characterized. It has been established that vitamin D deficiency is accompanied by a high incidence of embryo-fetal loss, intrauterine growth restriction, morphofunctional changes in the placenta, and critical destabilization of vascular and immune homeostasis under conditions simulating preeclampsia. Morphological and morphometric studies of placentas confirmed the presence of structural and functional changes in placental tissue during vitamin D deficiency, which have significant pathogenetic importance in the development of obstetric complications. The results obtained have significantly expanded current understanding of the role of vitamin D in the pathogenesis of obstetric complications and scientifically substantiated the feasibility of personalized correction of vitamin D deficiency in pregnant women. The practical significance of the study is confirmed by the possibility of using 25(OH)D levels, indicators of calcium-phosphate metabolism, the sFlt-1/PlGF ratio, NF-κB-associated and angiogenic markers for the early prediction of obstetric complications, the stratification of high-risk groups, and the optimization of preventive and therapeutic measures. The proposed approaches contribute to improving pregnancy management, reducing the incidence of severe gestational and perinatal complications.

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Research papers

1. Поладич, І. В. і Говсєєв, Д. О. (2024). Особливості перебігу вагітності та пологів у вагітних із різним статусом вітаміну D. Український журнал Перинатологія і Педіатрія, 4(100), с. 56-62. https://doi.org/10.15574/PP.2024.4(100).5662

2. Поладич, І. В. і Говсєєв Д. О. (2024). Особливості вітамін D статусу у вагітних. Український журнал Здоров’я жінки, 4(173), с. 46-51. https://doi.org/10.15574/HW.2024.4(173).4651

3. Поладич, І. В. і Костенко, О. Ю. (2024). Особливості взаємозв’язку вітаміну D та анемії у вагітних. Український журнал Здоров’я жінки, 6(175), с. 50-56. https://doi.org/10.15574/HW.2024.6(175).5056

4. Поладич, І. і Говсєєв, Д. (2025). Вплив вітаміну D на розвиток акушерських ускладнень. Репродуктивне здоров’я жінки, (2), с. 8–13. https://doi.org/10.30841/2708-8731.2.2025.326493

5. Poladych, I. V. and Govsieiev, D.O. (2025). Vitamin D and p65-NF-κB: new pathogenetic mechanisms in the development of preeclampsia. Fiziol. Zh., 71(4), pp. 84-89. https://doi.org/10.15407/fz71.04.084

6. Поладич, І. В. і Авраменко, С. О. (2025). Вплив материнського вітаміну D на ріст плода та наслідки вагітності. Український журнал Перинатологія і Педіатрія, 1(101), с. 45-51. https://doi.org/10.15574/PP.2025.1(101).4551.

7. Poladych, I. V., Shymanskyi, I. O., Veliky, M. M. and Govsieiev, D. O. (2025). Experimental preeclampsia development depends on vitamin D3 status in female wistar rats. Ukr. Biochem. J., 97(4), pp. 34-42. https://doi.org/10.15407/ubj97.04.034

8. Poladych, I. V., Savosko, S. I., Grabovyi, O. M. and Govsieiev, D. O. (2025). Morphogenetic changes in the rat placenta under vitamin D3 deficiency. Reports of Morphology, 31(3), pp. 13-18. https://doi.org/10.31393/morphology-journal-2025-31(3)-02

9. Poladych, I.V. (2025). The effect of vitamin D3 deficiency and its correction on endothelial function in experimental preeclampsia. Fiziol. Zh., 71(5): pp. 47-55. https://doi.org/10.15407/fz71.05.047

10. Поладич, І. В. і Говсєєв, Д. О. (2025). Дефіцит вітаміну D і передчасні пологи: результати клінічного дослідження. Український журнал Здоров’я жінки, 2(177), с. 36-40. https://doi.org/10.15574/HW.2025.2(177).3640

11. Поладич, І. В. і Осадчук, С.В. (2025). Ангіогенний дисбаланс при прееклампсії: чи має значення рівень вітаміну D? Український журнал Здоров’я жінки, 3(178), с. 40-45; https://doi.org/10.15574/HW.2025.3(178).4045

12. Поладич, І. В. і Авраменко, С. О. (2025). Роль ядерного фактора каппа B у патогенезі затримки росту плода залежно від статусу вітаміну D3. Український журнал Здоров’я жінки, 4(179), с. 44-48; https://doi.org/10.15574/HW.2025.4(179).4448

13. Poladych, I. V., Shymanskyi, I. O., Khomenko, A. V., Veliky, M. M. and Govsieiev, D. O. (2026). Fibroblast growth factor 23, calcium and phosphate serum levels in experimental preeclampsia: impact of vitamin D3 status. Ukr. Biochem. J., 98(1), pp. 37-48. https://doi.org/10.15407/ubj98.01.037

14. Поладич, І. (2024). Вплив гіповітамінозу D на активність р-65 субодиниці ядерного фактору kB у патогенезі плацентарної дисфункції. Журнал «Медична наука України» (НМУ), 20(4), с. 27-35. https://doi.org/10.32345/2664-4738.4.2024.04

15. Poladych, I. V. (2024). Vitamin D in the genesis of preeclampsia: current understanding of the problem (literature review). Bulletin of problems in biology and medicine, 4(175), pp. 113-122. https://doi.org/10.29254/2077-4214-2024-4-175-113-122

16. Поладич, І. і Говсєєв, Д. (2025). Роль вітаміну D у регуляції фертильності: експериментальне дослідження. Журнал «Медична наука України» (НМУ), 21(1), с. 71-76. https://doi.org/10.32345/2664-4738.1.2025.09

17. Poladych, I. and Govsieiev, D. (2025). Vitamin D deficiency as a risk factor for preeclampsia: The role of vitamin D receptor and cytochrome P450 family 27 subfamily B member 1. Bulletin of Problems in Biology and Medicine, 1(176), pp. 288-297. https://doi.org/10.29254/2077-4214-2025-1-176-288-297

18. Poladych, I. V. and Antoniuk, M. I. (2025). Markers of calcium-phosphorus metabolism as prognostic factors of obstetric complications. Bulletin of problems in biology and medicine, 2(177), pp. 253-260. https://doi.org/10.29254/2077-4214-2025-2-177-253-260

19. Поладич, І. (2025). Особливості кальцієво-фосфорного обміну у вагітних щурів із різним вітамін-D статусом. Журнал «Медична наука України» (НМУ), 21(3), с. 106-112. https://doi.org/10.32345/2664-4738.3.2025.11

20. Poladych, I. V. (2025). Fibroblast growth factor 23 in pregnant rats with different vitamin D3 status. Bulletin of problems in biology and medicine, 3(178), pp. 213-220. https://doi.org/10.29254/2077-4214-2025-3-178-213-220

21. Poladych, I. (2025). Vitamin D deficiency as a trigger of inflammation and preterm birth. Bulletin of Medical and Biological Research, 7(3), pp. 73-79. https://doi.org/10.63341/bmbr/3.2025.73

22. Poladych, I. V. and Avramenko, S. О. (2025). The effects of vitamin D3 deficiency on calcium–phosphate homeostasis and the RANKL/OPG regulatory system: experimental study. Bulletin of problems in biology and medicine, 4(179), pp. 178-186. https://doi.org/10.29254/2077-4214-2025-4-179-178-186

23. Поладич, І. В., Савосько, С. І., Грабовий, О. М. і Шиманський, І. О. (2025, 29–30 травня). Вплив дефіциту вітаміну D на морфологенез плаценти. Тканинні реакції в нормі, експерименті та клініці-2025: тези Всеукраїнської науково-практичної конференції з міжнародною участю (с. 224–225)

24. Поладич, І. В. і Костенко, О. Ю. (2023). Роль вітаміну D в генезі звичних репродуктивних втрат. Український журнал Здоров’я жінки, 5(168), с. 34–41. https://doi.org/10.15574/HW.2023.168.34

25. Поладич, І. В. і Говсєєв, Д. О. (2024). Сучасне уявлення про роль вітаміну D у генезі передчасних пологів (огляд літератури). Український журнал Здоров’я жінки, 5(174), с. 66–72. https://doi.org/10.15574/HW.2024.5(174).6672

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