##plugins.themes.bootstrap3.article.main##

Normal pregnancy is characterized by a mild systemic inflammatory response and progressive increase in serum inflammatory cytokines that peak in the third trimester. During pregnancy pre-existing inflammatory conditions, acquired oxidative stress arising from the placenta malfunction and nutritional deficiencies can trigger intense systemic responses that lead to endothelial activation, dysfunction and preeclampsia. We investigated the principal nutritional, oxidative and inflammatory pathways that trigger the clinical manifestation of preeclampsia.

This case-control study included 250 women with preeclampsia and 150 normotensive pregnant women. Urinary Iodine concentration (IUC) and serum levels of Ferritin, Thyroid-stimulating Hormone (TSH), selenium, Nitric Oxide (NO) gamma glutamyl transferase (GGT), Rheumatoid factor, and high sense C-reactive protein (hs-CRP) of cases and controls were compared using the student’s t and the Mann-Whitney U tests. Principal component analysis was carried out to delineate the patterns of association between nutritional, inflammatory and oxidative markers and preeclampsia.

The main pathophysiological pathways identified were the interactions between selenium/iodine deficiency and elevated serum TSH (endothelial dysfunction); serum ferritin, GGT, CRP and low urinary iodine concentration (inflammatory oxidative stress); elevated serum hs-CRP and Rheumatoid factor subclinical inflammation and immune cell activation) and high T3/T4 ratio (acute TSH stimulation of thyroid with low thyroid iodine stores)

Combined selenium and iodine deficiency resulting into elevated TSH, low NO and preferential T3 secretion; acute inflammatory conditions associated with elevated serum GGT, CRP, and Ferritin; and subclinical inflammatory conditions characterized by autoimmunity are some of the major oxidant and inflammatory pathways associated with increased risk of preeclampsia.

Downloads

Download data is not yet available.

References

  1. C.W. Redman and I.L. Sargent. Preeclampsia and the systemic inflammatory response. Semin Nephrol, vol 24, no. 6, pp. 565-70. 2004.
     Google Scholar
  2. G.P. Sacks, K. Studena, K. Sargent and C.W. Redman. Normal pregnancy and preeclampsia both produce inflammatory changes in peripheral blood leukocytes akin to those of sepsis. Am J Obstet Gynecol, vol. 179, no. 1, pp. 80-6. 1998.
     Google Scholar
  3. C.W. Redman, G.P. Sacks and I.L. Sargent. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol, vol. 180, no. 2 Pt 1, pp. 499-506. 1999.
     Google Scholar
  4. A.L. Tranquilli, G. Dekker, L. Magee, J. Roberts, B.M. Sibai, W. Steyn, et al. The classification, diagnosis and management of the hypertensive disorders of pregnancy: A revised statement from the ISSHP. Pregnancy Hypertens, vol. 4, no. 2, pp. 97-104. 2014.
     Google Scholar
  5. T.G. Pickering, J.E. Hall, L.J. Appel, B.E. Falkner, J.W. Graves, M.N. Hill MN, et al. Recommendations for blood pressure measurement in humans: an AHA scientific statement from the Council on High Blood Pressure Research Professional and Public Education Subcommittee. J Clin Hypertens (Greenwich), vol. 7, no. 2, pp. 102-109. 2005.
     Google Scholar
  6. D.B. Ngo, L. Dikassa, W. Okitolonda, T.D. Kashala, C. Gervy, J. Dumont, et al. Selenium status in pregnant women of a rural population (Zaire) in relationship to iodine deficiency. Trop Med Int Health, vol. 2, no. 6, pp. 572-81, 1997.
     Google Scholar
  7. D. Glinoer. The regulation of thyroid function during normal pregnancy: importance of the iodine nutrition status. Best Pract Res Clin Endocrinol Metab, vol. 18, no. 2, pp. 133-52. 2004
     Google Scholar
  8. M. Zimmermann. The Effects of Iodine Deficiency in Pregnancy and Infancy. Paediatric and perinatal epidemiology, vol. 26, Suppl 1, pp. 108-17. 2012.
     Google Scholar
  9. P.P. Smyth. Role of iodine in antioxidant defence in thyroid and breast disease. Biofactors, vol. 19, no. 3-4, pp. 121-130. 2003.
     Google Scholar
  10. 10. Johansen JS, Harris AK, Rychly DJ, Ergul A. Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Cardiovasc Diabetol. 2005;4:5.
     Google Scholar
  11. L. Tian, L. Zhang, J. Liu, T. Guo, C. Gao and J. Ni. Effects of TSH on the function of human umbilical vein endothelial cells. J Mol Endocrinol, vol 52, no. 2, pp. 215-222. 2014.
     Google Scholar
  12. A. Dardano, L. Ghiadoni, Y. Plantinga, N. Caraccio, A. Bemi, E. Duranti, et al. Recombinant human thyrotropin reduces endothelium-dependent vasodilation in patients monitored for differentiated thyroid carcinoma. J Clin Endocrinol Metab, vol. 91, no. 10, pp. 4175-8. 2006.
     Google Scholar
  13. E. Lioudaki, N.G. Mavroeidi, D.P. Mikhailidis, E.S. Ganotakis. Subclinical hypothyroidism and vascular risk: an update. Hormones (Athens), vol. 12, no. 4, pp. 495-506. 2013.
     Google Scholar
  14. D.H. O'Leary and J.F. Polak JF. Intima-media thickness: a tool for atherosclerosis imaging and event prediction. Am J Cardiol, vol. 90, no. 10c, pp. 18l-21l. 2002.
     Google Scholar
  15. E. Lapice, S. Maione, L. Patti, P. Cipriano, A.A. Rivellese, G. Riccardi G, et al. Abdominal adiposity is associated with elevated C-reactive protein independent of BMI in healthy nonobese people. Diabetes Care, vol. 32, no. 9, pp. 1734-6. 2009.
     Google Scholar
  16. R. Anty, S. Bekri, N. Luciani, M.C. Saint-Paul, M. Dahman, A. Iannelli, et al. The inflammatory C-reactive protein is increased in both liver and adipose tissue in severely obese patients independently from metabolic syndrome, Type 2 diabetes, and NASH. Am J Gastroenterol, vol. 101, no. 8, pp.1824-33. 2006.
     Google Scholar
  17. WHO. C-reactive protein concentrations as a marker of inflammation or infection for interpreting biomarkers of micronutrient status. Geneva: World Health Organization; 2014.
     Google Scholar
  18. M.C. Dao, S. Sen, C. Iyer, D. Klebenov and S.N. Meydani. Obesity during pregnancy and fetal iron status: is Hepcidin the link? J Perinatol, vol. 33, no. 3, pp. 177-81. 2013.
     Google Scholar
  19. V. Manolov, B. Marinov, M. Velizarova, B. Atanasova, V. Vasilev, K. Tzatchev, et al. Anemia in pregnancy and serum hepcidin levels. Int J adv Res, vol 3, no.1, pp.758-61. 2015.
     Google Scholar
  20. G. Toldi, B. Stenczer, A. Molvarec, Z. Takáts, G. Beko, J. Rigó Jr., et al. Hepcidin concentrations and iron homeostasis in preeclampsia. Clin Chem Lab Med, vol.48, no. 10, pp. 1423-6. 2010.
     Google Scholar
  21. R. Drozdz, C. Parmentier, H. Hachad, P. Leroy, G. Siest and M. Wellman. gamma-Glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system. Free Radic Biol Med, vol 25, no. 7, pp. 786-92, 1998.
     Google Scholar
  22. M. Enoiu, H. Aberkane, J.F. Salazar, P. Leroy, J. Groffen, G. Siest, et al. Evidence for the pro-oxidant effect of gamma-glutamyltranspeptidase-related enzyme. Free Radic Biol Med, vol. 29, no. 9, pp. 825-33, 2000.
     Google Scholar
  23. R. Winkler, S. Griebenow and W. Wonisch. Effect of iodide on total antioxidant status of human serum. Cell Biochem Funct, vol. 18, no. 2, pp. 143-6. 2000.
     Google Scholar
  24. M. Gulaboglu, B. Borekci and I. Delibas I. Urine iodine levels in preeclamptic and normal pregnant women. Biol Trace Elem Res, vol. 136, no. 3, pp. 249-57. 2010.
     Google Scholar
  25. C.Y. Chen, C.P. Chen and K.H. Lin. Biological functions of thyroid hormone in placenta. Int J Mol Sci, vol. 16, no. 2, pp. 4161-79. 2015.
     Google Scholar
  26. C.W. Redman and I.L. Sargent. Placental debris, oxidative stress and pre-eclampsia. Placenta. 2000;21(7):597-602. 2000.
     Google Scholar
  27. A. De Vivo, G. Baviera, D. Giordano, G. Todarello, F. Corrado and R. Deanna. PlGF and sFlt-1 as markers for predicting pre-eclampsia. Acta Obstet Gynecol Scand, vol. 87, no. 8, pp. 837-42. 2008.
     Google Scholar
  28. R. Burns, F. Azizi, M. Hedayati, P. Mirmiran, C. O'Herlihy and P.P. Smyth. Is placental iodine content related to dietary iodine intake? Clin Endocrinol (Oxf), vol. 75, no. 2, pp. 261-4. 2011.
     Google Scholar
  29. S. Venkatesha, M. Toporsian, C. Lam, J. Hanai J, T. Mammoto, Y.M. Kim, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med, vol.12, no. 6, pp. 642-9. 2006.
     Google Scholar
  30. T.A. Pearson, G.A. Mensah, Y. Hong and S.C. Smith. CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease. Circulation, Vol. 110, no. 25, pp. e543-e4. 2004.
     Google Scholar
  31. M. Shipley, A. Rahman, D. O’Gradaigh and R. Conway. “Rheumatology and bone disease”. In Kumar and Clark’s Clinical Medicine. 7th edn. P. Kumar and M. Clark eds. London Elsevier Saunders, 2012, ch 11, pp. 493–560.
     Google Scholar
  32. D. Glinoer. The regulation of thyroid function in pregnancy: pathways of endocrine adaptation from physiology to pathology. Endocr Rev, vol. 18, no. 3, pp. 404-33.1997.
     Google Scholar