Optimization of the prevention of perinatal pathology in women with gestational endotheliopathy

Authors

DOI:

https://doi.org/10.18370/2309-4117.2022.66.46-53

Keywords:

pregnancy, gestational endotheliopathy, endothelial dysfunction, perinatal pathology, vascular-endothelial growth factor, placental growth factor, endoglin, preeclampsia, acetylsalicylic acid, vitamin D, Metida

Abstract

Objectives: to evaluate the clinical effectiveness of the Metida for the prevention of perinatal pathology in pregnant women with gestational endotheliopathy and with the risk of preeclampsia.
Materials and methods. 68 pregnant women with verified gestational endotheliopathy and with risk of preeclampsia > 1:150 participated in a prospective clinical comparative study. The patients were divided into subgroups: the first subgroup included 30 women who from 11–13 weeks of pregnancy received acetylsalicylic acid 100 mg/day and vitamin D 2000 IU/day; the II subgroup included 38 pregnant women who from 11–13 weeks of gestation received acetylsalicylic acid 100 mg/day, vitamin D 2000 IU/day and Metida (300 mg of elemental magnesium, 30 mg of vitamin B6). 28 practically healthy pregnant women of the control group received vitamin D 1000 IU/day. The clinical effectiveness of therapy was evaluated by comparing the number of cases of perinatal pathology; cases of intrauterine suffering of the fetus; the dynamics of indicators of laboratory-instrumental research methods (markers of the risk of perinatal pathology) and the pregnancy outcomes.
Results. Metida as an additional preventive therapy made it possible to significantly reduce the number of cases of placental dysfunction (р = 0.01) and intrauterine suffering of the fetus (р = 0.02) compared to standard preventive therapy. There was also a 6-fold reduction in the incidence of preeclampsia and premature birth due to magnesium supplementation, compared to pregnant women who received only acetylsalicylic acid and vitamin D. There was a significant decrease in serum indicators of markers of endothelial dysfunction in women with gestational endotheliopathy as a result of taking magnesium: vascular endothelial growth factor (p < 0.00001), endoglin (p < 0.00001) compared to patients who did not receive magnesium, and there was also normalization of the of 25(OH)D level in blood serum compared to the control group (p = 0.33).
Conclusions. Additional Mg supplementation during pregnancy may reduce the likelihood of perinatal pathology in high-risk patients and help normalize serum markers of endothelial dysfunction in women with high risk of preeclampsia.

Author Biographies

D.H. Konkov, National Pirogov Memorial Medical University, Vinnytsia

MD, professor, Obstetrics and Gynecology Department No. 1

S.М. Kosianenko, National Pirogov Memorial Medical University, Vinnytsia

PhD, associate professor, Obstetrics and Gynecology Department No. 2

R.S. Ostreniuk, National Pirogov Memorial Medical University, Vinnytsia

Senior teacher, Department of Bioсhemistry and General Chemistry

O.L. Lovkina, National Pirogov Memorial Medical University, Vinnytsia

PhD, associate professor, Obstetrics and Gynecology Department No. 2

References

  1. Konkov, D.G., Bulavenko, O.V., Taran, O.A. “Features of the trimesteral dynamics of vasotonic regulation in gestational endotheliopathy.” Perinatology and pediatric 4.72 (2017): 70–7. DOI: 10.15574/PP.2017.72.70
  2. Konkov, D.G. The pathogenesis and prevention of perinatal losses due to endothelial dysfunction: Thesis for the doctor’s degree of medical. Vinnytsia (2015): 38 р.
  3. Konkov, D.G. “The features of pregnancy in women with subchorionic hematomas in the background of gestational endotheliopathy.” Medicine of Ukraine 2.168 (2013): 54–7.
  4. Konkov, D.G., Bevz, G.V., Piskun, A.Y., Bodnarchuk, O.V. “Prospective directions for creating a strategy for effective medicine prevention of preeclampsia (Literature review).” Reproductive health of woman 3.58 (2022): 49–61. DOI: 10.30841/2708-8731.3.2022.262376
  5. Konkov, D.G., Medved, V.I., Chaika, G.V., Rud, V.O. Microalbuminuria as a predictor of gestational pathology: study guide. Vinnytsya. TVORY (2022): 46 р.
  6. Konkov, D.G., Bulavenko, O.V., Bodnarchuk, O.V., Klimas, L.A. “The peculiarities of vitamin D status and clinical characteristic in women with moderate obesity in gestational endotheliopathy.” Reports of Vinnytsia National Medical University. 26.2 (2022): 239–47. DOI: 10.31393/reports-vnmedical-2022-26(2)-12
  7. Ministry of Health of Ukraine. Order from 24.01.2022 № 151 “On Approving the Unified clinical protocol of primary, secondary (specialized) and tertiary (highly specialized) medical care “Hypertensive disorders during pregnancy, childbirth and the postpartum period”.
  8. Arikan, G.M., Panzitt, T., Gücer, F., et al. “Course of maternal serum magnesium levels in low-risk gestations and in preterm labor and delivery.” Fetal Diagn Ther 14.6 (1999): 332–6. DOI: 10.1159/000020952
  9. Belkaniya, G.S., Dilenyan, L.R., Konkov, D.G., et al. “An anthropogenic model of cardiovascular system adaptation to the Earth’s gravity as the conceptual basis of pathological anthropology.” J Physiol Anthropol 40.1 (2021): 9. DOI: 10.1186/s40101-021-00260-2
  10. Bullarbo, M., Ödman, N., Nestler, A., et al. “Magnesium supplementation to prevent high blood pressure in pregnancy: a randomised placebo control trial.” Arch Gynecol Obstet 288.6 (2013): 1269–74. DOI: 10.1007/s00404-013-2900-2
  11. Carmeliet, G., Bouillon, R. “How Important Is Vitamin D for Calcium Homeostasis During Pregnancy and Lactation?” Journal of bone and mineral research 33.1 (2018): 13–5. DOI: 10.1002/jbmr.3344
  12. Chaemsaithong, P., Pooh, R.K., Zheng, M., et al. “Prospective evaluation of screening performance of first-trimester prediction models for preterm preeclampsia in an Asian population.” Am J Obstet Gynecol 221.6 (2019): 650.e1-650.e16. DOI: 10.1016/j.ajog.2019.09.041
  13. Chaemsaithong, P., Sahota, D.S., Poon, L.C. “First trimester preeclampsia screening and prediction.” Am J Obstet Gynecol 226.2S (2022): S1071–97.e2. DOI: 10.1016/j.ajog.2020.07.020
  14. Dahle, L.O., Berg, G., Hammar, M., et al. “The effect of oral magnesium substitution on pregnancy-induced leg cramps.” Am J Obstet Gynecol 173.1 (1995): 175–80. DOI: 10.1016/0002-9378(95)90186-8
  15. de Araújo, C.A.L., Ray, J.G., Figueiroa, J.N., Alves, J.G. “BRAzil magnesium (BRAMAG) trial: a double-masked randomized clinical trial of oral magnesium supplementation in pregnancy.” BMC Pregnancy Childbirth 20.1 (2020): 234. DOI: 10.1186/s12884-020-02935-7
  16. Doyle, W., Crawford, M.A., Wynn, A.H., Wynn, S.W. “Maternal magnesium intake and pregnancy outcome.” Magnes Res 2 (1989): 205–10.
  17. Duley, L., Gülmezoglu, A.M., Henderson-Smart, D.J., Chou, D. “Magnesium sulphate and other anticonvulsants for women with pre-eclampsia.” Cochrane Database Syst Rev 11 (2010): CD000025. DOI: 10.1002/14651858.CD000025.pub2
  18. Fogacci, S., Fogacci, F., Banach, M., et al. “Lipid and Blood Pressure Meta-analysis Collaboration (LBPMC) Group. Vitamin D supplementation and incident preeclampsia: A systematic review and meta-analysis of randomized clinical trials.” Clin Nutr 39.6 (2020): 1742–52. DOI: 10.1016/j.clnu.2019.08.015
  19. Harrison, V., Fawcus, S., Jordaan, E. “Magnesium supplementation and perinatal hypoxia: outcome of a parallel group randomised trial in pregnancy.” BJOG 114.8 (2007): 994–1002. DOI: 10.1111/j.1471-0528.2007.01409.x
  20. Henderson, J.T., Vesco, K.K., Senger, C.A., et al. Aspirin use to prevent preeclampsia and related morbidity and mortality [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2021 Sep. Report No.: 21-05274-EF-1.
  21. The Fetal Medicine Foundation. Risk for preeclampsia. Available from: [https://fetalmedicine.org/ research/assess/preeclampsia/first-trimester].
  22. Kieboom, B.C., Kiefte-de Jong, J.C., Eijgelsheim, M., et al. “Proton pump inhibitors and hypomagnesemia in the general population: a population-based cohort study.” Am J Kidney Dis 66.5 (2015): 775–82. DOI: 10.1053/j.ajkd.2015.05.012
  23. Kieboom, B.C.T., Zietse, R., Ikram, M.A., et al. “Thiazide but not loop diuretics is associated with hypomagnesaemia in the general population.” Pharmacoepidemiol Drug Saf 27.11 (2018): 1166–73. DOI: 10.1002/pds.4636
  24. Kinshella, M.W., Sarr, C., Sandhu, A., et al. “PRECISE Network. Calcium for pre-eclampsia prevention: a systematic review and network meta-analysis to guide personalised antenatal care.” BJOG (2022). DOI: 10.1111/1471-0528.17222
  25. Kivioja, A., Toivonen, E., Tyrmi, J., et al. “Increased Risk of Preeclampsia in Women With a Genetic Predisposition to Elevated Blood Pressure.” Hypertension 79.9 (2022): 2008–15. DOI: 10.1161/HYPERTENSIONAHA.122.18996
  26. Konkov, D.G., Belkania, G.S., Piskun, A., Adamchuk, N. “The features of haemodynamic pregnancy support witn gestational endotheliopathy: poster review.” The proceedings of the e-posters of XXVIII European Congress of Perinatal Medicine 22–25 June 2022 , Lisbon, Portugal. ID 64.
  27. Konkov, D.G., Piskun, A.O., Taran, O.A., Kostur, G.V. “Specialties of hystomorphometrical changes in placenta of women with early and late preeclampsia.” Wiad Lek 73.1 (2020): 151–5.
  28. Konkov, D.G., Klivak, V.V., Taran, O.A., Lastovetska, O.B. “The modern clinical features of effective prevention of gestational and fetal pathology.” Reproductive endocrinology 5.55 (2020): 29–37. DOI: 10.18370/2309-4117.2020.55.29-37
  29. Lai, J., Syngelaki, A., Nicolaides, K.H., et al. “Impact of new definitions of preeclampsia at term on identification of adverse maternal and perinatal outcomes.” Am J Obstet Gynecol 224.5 (2021): 518.e1-518.e11. DOI: 10.1016/j.ajog.2020.11.004
  30. Li, S., Tian, H. “Oral low-dose magnesium gluconate preventing pregnancy induced hypertension.” Zhonghua Fu Chan Ke Za Zhi 32.10 (1997): 613–5.
  31. Liamis, G., Hoorn, E.J., Florentin, M., Milionis, H. “An overview of diagnosis and management of drug-induced hypomagnesemia.” Pharmacol Res Perspect 9.4 (2021): e00829. DOI: 10.1002/prp2.829
  32. Dalton, L.M., Ní Fhloinn, D.M., Gaydadzhieva, G.T., et al. “Magnesium in pregnancy.” Nutr Rev 74.9 (2016): 549–57. DOI: 10.1093/nutrit/nuw018
  33. Makrides, M., Crosby, D.D., Bain, E., Crowther, C.A. “Magnesium supplementation in pregnancy.” The Cochrane database of systematic reviews 4 (2014): CD000937. DOI: 10.1002/14651858.CD000937.pub2
  34. Margioula-Siarkou, G., Margioula-Siarkou, C., et al. “Soluble endoglin concentration in maternal blood as a diagnostic biomarker of preeclampsia: A systematic review and meta-analysis.” Eur J Obstet Gynecol Reprod Biol 258 (2021): 366–81. DOI: 10.1016/j.ejogrb.2021.01.039
  35. Mittendorf, R., Dambrosia, J., Dammann, O., et al. “Association between maternal serum ionized magnesium levels at delivery and neonatal intraventricular hemorrhage.” J Pediatr 140.5 (2002): 540–6. DOI: 10.1067/mpd.2002.123283
  36. Pietro, L., Guida, J.P.S., Nobrega, G.M., et al. “Placental Findings in Preterm and Term Preeclampsia: An Integrative Review of the Literature.” Rev Bras Ginecol Obstet 43.7 (2021): 560–9. DOI: 10.1055/s-0041-1730292
  37. Pilz, S., Trummer, C., Pandis, M., et al. “Vitamin D: Current Guidelines and Future Outlook.” Anticancer research 38.2 (2018): 1145–51. DOI: 10.21873/anticanres.12333
  38. Piskun, A., Konkov, D.G., Litvinov, S. “The characteristics of placental angiogenesis-related markers in early and late preeclampsia: poster review.” The proceedings of the e-posters of XXVIII European Congress of Perinatal Medicine 22–25 June 2022, Lisbon, Portugal. ID 73.
  39. Rolnik, D.L., Nicolaides, K.H., Poon, L.C. “Prevention of preeclampsia with aspirin.” Am J Obstet Gynecol 226.2S (2022): S1108–19. DOI: 10.1016/j.ajog.2020.08.045
  40. Roman, A., Desai, N., Rochelson, B., et al. “Maternal magnesium supplementation reduces intrauterine growth restriction and suppresses inflammation in a rat model.” Am J Obstet Gynecol 208 (2013): 383.e1 7.
  41. Rudnicki, M., Frölich, A., Rasmussen, W.F., McNair, P. “The effect of magnesium on maternal blood pressure in pregnancy-induced hypertension. A randomized double-blind placebo-controlled trial.” Acta Obstet Gynecol Scand 70.6 (1991): 445–50. DOI: 10.3109/00016349109007158
  42. Schoonderwoerd, M.J.A., Goumans, M.J.T.H., Hawinkels, L.J.A.C. “Beyond the Endothelium.” Biomolecules 10.2 (2020): 289. DOI: 10.3390/biom10020289
  43. Shaikh, K., Das, C.M., Baloch, G.H., et al. “Magnesium associated complications in pregnant women.” World Appl Sci J 17 (2012): 1074–8.
  44. Spätling, L., Spätling, G. “Magnesium supplementation in pregnancy. A double-blind study.” Br J Obstet Gynaecol 95.2 (1988): 120–5.
  45. Tomimori-Gi, K., Katsuragi, S., Kodama, Y., et al. “Low-dose aspirin therapy improves decidual arteriopathy in pregnant women with a history of preeclampsia.” Virchows Arch (2022). DOI: 10.1007/s00428-022-03388-3
  46. Wagner, C.L., Hollis, B.W., Kotsa, K., et al. “Vitamin D administration during pregnancy as prevention for pregnancy, neonatal and postnatal complications.” Rev Endocr Metab Disord 18.3 (2017): 307–22. DOI: 10.1007/s11154-017-9414-3
  47. Whittington, C.M., Danastas, K., Grau, G.Е., et al. “Expression of VEGF 111 and other VEGF-A variants in the rat uterus is correlated with stage of pregnancy.” J Comp Physiol B 187.2 (2018): 353–60. DOI: 10.1007/s00360-016-1040-y
  48. Yip, K.C., Luo, Z., Huang, X., et al. “The role of aspirin dose and initiation time in the prevention of preeclampsia and corresponding complications: a meta-analysis of RCTs.” Arch Gynecol Obstet 305.6 (2022): 1465–79. DOI: 10.1007/s00404-021-06349-4
  49. Yuan, J., Yu, Y., Zhu, T., et al. “Oral magnesium supplementation for the prevention of preeclampsia: a meta-analysis or randomized controlled trials.” Biol Trace Elem Res 200.8 (2022): 3572–81. DOI: 10.1007/s12011-021-02976-9
  50. Zarean, E., Tarjan, A. “Effect of Magnesium supplement on pregnancy outcomes: A Randomized Control Trial.” Adv Biomed Res 6 (2017): 109. DOI: 10.4103/2277-9175.213879

Published

2022-08-10

How to Cite

Konkov, D., Kosianenko, S., Ostreniuk, R., & Lovkina, O. (2022). Optimization of the prevention of perinatal pathology in women with gestational endotheliopathy. REPRODUCTIVE ENDOCRINOLOGY, (66), 46–53. https://doi.org/10.18370/2309-4117.2022.66.46-53

Issue

Section

Pregnancy and childbirth