The Effect of Oral Selenium Supplementation on C-Reactive Protein (CRP) Serum Levels in Pregnant Women: A Systematic Review and Meta-analysis on Clinical Trials

Authors
Ali Gholami
Mitra Hariri
Abstract
Introduction: Since new evidence shows the anti-inflammatory effects of selenium, the aim of the present study was to conduct a systematic review and meta-analysis of clinical trial articles on the effect of selenium on serum C-reactive protein (CRP) levels in pregnant women.

Methods: In this study, Clinicaltrials.gov, ISI web of science, Cochrane Library, PubMed, and Scopus databases were searched until April 2024, and all randomized clinical trials that investigated the effect of selenium on serum CRP levels in pregnant women were selected. The DerSimonian and Laird random-effects model was used to calculate the overall effect size and heterogeneity. Cochran’s Q-test and I-squared tests were also used to assess statistical heterogeneity between studies.

Results: The results of the meta-analysis conducted on the clinical trial studies showed that selenium supplementation reduced the serum CRP level by 3.99 mg/L, which was statistically significant (confidence interval (CI): -2.30, -5.6; 0.001˂P), and the heterogeneity between studies was also significant (0.001˂P).

Conclusion The results showed that selenium supplementation can significantly reduce serum CRP levels in pregnant women. However, it seems that more studies in different parts of the world are still needed to confirm the beneficial effects or side effects of selenium supplementation on CRP levels among pregnant women due to the significant heterogeneity among studies.
Keywords
Meta-analysis
Systematic review
C-reactive protein
Selenium
1. Maresh M. Medical complications in pregnancy. Baillieres Clin Obstet Gynaecol. 1990;4(1):129-47.
2. McNestry C, Killeen SL, Crowley RK, McAuliffe FM. Pregnancy complications and later life women's health. Acta Obstet Gynecol Scand. 2023;102(5):523-31.
3. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130-7.
4. Wilson BJ, Watson MS, Prescott GJ, Sunderland S, Campbell DM, Hannaford P, Smith WC. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. Bmj. 2003;326(7394):845.
5. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Bmj. 2007;335(7627):974.
6. Levine RJ, Vatten LJ, Horowitz GL, Qian C, Romundstad PR, Yu KF, Hollenberg AN, Hellevik AI, Asvold BO, Karumanchi SA. Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study. Bmj. 2009;339:b4336.
7. Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999;222(3):222-35.
8. Serdar Z, Gür E, Develioğlu O, Colakoğullari M, Dirican M. Placental and decidual lipid peroxidation and antioxidant defenses in preeclampsia. Lipid peroxidation in preeclampsia. Pathophysiology. 2002;9(1):21.
9. Sikkema JM, van Rijn BB, Franx A, Bruinse HW, de Roos R, Stroes ES, van Faassen EE. Placental superoxide is increased in pre-eclampsia. Placenta. 2001;22(4):304-8.
10. Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol. 1999;180(2 Pt 1):499-506.
11. Brosnan MJ. One step beyond: glutathione peroxidase and endothelial dysfunction. Hypertension. 2008;51(4):825-6.
12. Mistry HD, Wilson V, Ramsay MM, Symonds ME, Broughton Pipkin F. Reduced selenium concentrations and glutathione peroxidase activity in preeclamptic pregnancies. Hypertension. 2008;52(5):881-8.
13. Atamer Y, Koçyigit Y, Yokus B, Atamer A, Erden AC. Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2005;119(1):60-6.
14. Harlev A, Wiznitzer A. New insights on glucose pathophysiology in gestational diabetes and insulin resistance. Curr Diab Rep. 2010;10(3):242-7.
15. Lowe LP, Metzger BE, Dyer AR, Lowe J, McCance DR, Lappin TR, Trimble ER, Coustan DR, Hadden DR, Hod M, Oats JJ, Persson B. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations of maternal A1C and glucose with pregnancy outcomes. Diabetes Care. 2012;35(3):574-80.
16. Sayın R, Aslan M, Kucukoglu ME, Luleci A, Atmaca M, Esen R, Demir H. Serum prolidase enzyme activity and oxidative stress levels in patients with diabetic neuropathy. Endocrine. 2014;47(1):146-51.
17. Maxwell SR, Thomason H, Sandler D, LeGuen C, Baxter MA, Thorpe GH, Jones AF, Barnett AH. Poor glycaemic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus. Ann Clin Biochem. 1997;34 ( Pt 6):638-44.
18. Zhang CXW, Candia AA, Sferruzzi-Perri AN. Placental inflammation, oxidative stress, and fetal outcomes in maternal obesity. Trends in Endocrinology & Metabolism. 2024.
19. Ba C, Martin-Romero FJ, Kumaraswamy E, Moustafa M, H Z, Dl H. Selenium: its molecular biology and role in human health. 2001. p. 23-32.
20. Rayman MP. Selenium and human health. Lancet. 2012;379(9822):1256-68.
21. Boddy A. Bioactive Compounds and Cancer. Br J Clin Pharmacol. 72: Copyright © 2011 The British Pharmacological Society.; 2011. p. 170-1.
22. Ferrer E, Alegría A, Barberá R, Farré R, Lagarda MJ, Monleon J. Whole blood selenium content in pregnant women. Sci Total Environ. 1999;227(2-3):139-43.
23. Mihailović M, Cvetković M, Ljubić A, Kosanović M, Nedeljković S, Jovanović I, Pesut O. Selenium and malondialdehyde content and glutathione peroxidase activity in maternal and umbilical cord blood and amniotic fluid. Biol Trace Elem Res. 2000;73(1):47-54.
24. Rayman MP, Bode P, Redman CW. Low selenium status is associated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom. Am J Obstet Gynecol. 2003;189(5):1343-9.
25. Ernst GDS, de Jonge LL, Hofman A, Lindemans J, Russcher H, Steegers EAP, Jaddoe VWV. C-reactive protein levels in early pregnancy, fetal growth patterns, and the risk for neonatal complications: the Generation R Study. American Journal of Obstetrics and Gynecology. 2011;205(2):132.e1-.e12.
26. Asemi Z, Jamilian M, Mesdaghinia E, Esmaillzadeh A. Effects of selenium supplementation on glucose homeostasis, inflammation, and oxidative stress in gestational diabetes: Randomized, double-blind, placebo-controlled trial. Nutrition. 2015;31(10):1235-42.
27. Mesdaghinia E, Rahavi A, Bahmani F, Sharifi N, Asemi Z. Clinical and Metabolic Response to Selenium Supplementation in Pregnant Women at Risk for Intrauterine Growth Restriction: Randomized, Double-Blind, Placebo-Controlled Trial. Biol Trace Elem Res. 2017;178(1):14-21.
28. Mesdaghinia E, Shahin F, Ghaderi A, Shahin D, Shariat M, Banafshe H. The Effect of Selenium Supplementation on Clinical Outcomes, Metabolic Profiles, and Pulsatility Index of the Uterine Artery in High-Risk Mothers in Terms of Preeclampsia Screening with Quadruple Test: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial : Selenium and preeclampsia. Biol Trace Elem Res. 2023;201(2):567-76.
29. Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab. 2007;92(4):1263-8.
30. Rayman MP, Searle E, Kelly L, Johnsen S, Bodman-Smith K, Bath SC, Mao J, Redman CWG. Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: A randomised, controlled pilot trial. British Journal of Nutrition. 2014;112(1):99-111.
31. Tara F, Maamouri G, Rayman MP, Ghayour-Mobarhan M, Sahebkar A, Yazarlu O, Ouladan S, Tavallaie S, Azimi-Nezhad M, Shakeri MT, Boskabadi H, Oladi M, Sangani MT, Razavi BS, Ferns G. Selenium supplementation and the incidence of preeclampsia in pregnant Iranian women: a randomized, double-blind, placebo-controlled pilot trial. Taiwan J Obstet Gynecol. 2010;49(2):181-7.
32. Higgins JP, Altman DG. Assessing Risk of Bias in Included Studies. Cochrane Handbook for Systematic Reviews of Interventions2008. p. 187-241.
33. Deeks JJ, Higgins JP, Altman DG, Group obotCSM. Analysing data and undertaking meta-analyses. Cochrane Handbook for Systematic Reviews of Interventions2019. p. 241-84.
34. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Medical Research Methodology. 2005;5(1):13.
35. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-88.
36. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629-34.
37. Begg CB, Berlin JA. Publication bias and dissemination of clinical research. J Natl Cancer Inst. 1989;81(2):107-15.
38. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-58.
39. Gholami A, Amirkalali B, Baradaran HR, Hariri M. A systematic review and dose-response meta-analysis of the effect of selenium supplementation on serum concentration of C-reactive protein. J Trace Elem Med Biol. 2023;80:127273.
40. Rayman MP. The importance of selenium to human health. Lancet. 2000;356(9225):233-41.
41. Duntas LH. Selenium and inflammation: underlying anti-inflammatory mechanisms. Horm Metab Res. 2009;41(6):443-7.
42. Hunter DJ, Morris JS, Chute CG, Kushner E, Colditz GA, Stampfer MJ, Speizer FE, Willett WC. Predictors of selenium concentration in human toenails. Am J Epidemiol. 1990;132(1):114-22.
43. Stoffaneller R, Morse NL. A review of dietary selenium intake and selenium status in Europe and the Middle East. Nutrients. 2015;7(3):1494-537.
44. Kieliszek M, Bano I, Zare H. A Comprehensive Review on Selenium and Its Effects on Human Health and Distribution in Middle Eastern Countries. Biol Trace Elem Res. 2022;200(3):971-87.
45. Avan A, Tavakoly Sany SB, Ghayour-Mobarhan M, Rahimi HR, Tajfard M, Ferns G. Serum C-reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice. J Cell Physiol. 2018;233(11):8508-25.
46. Ilktac A, Kalkan S, Caliskan S. C-reactive protein and procalcitonin levels in prostate cancer. Int J Clin Pract. 2021;75(4):e13935.
47. Allin KH, Nordestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci. 2011;48(4):155-70.
48. Fontenelle LC, Cardoso de Araújo DS, da Cunha Soares T, Clímaco Cruz KJ, Henriques GS, Marreiro DDN. Nutritional status of selenium in overweight and obesity: A systematic review and meta-analysis. Clin Nutr. 2022;41(4):862-84.
49. Thomson CD, Robinson MF, Butler JA, Whanger PD. Long-term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase (EC 1.11.1.9) in blood components of New Zealand women. Br J Nutr. 1993;69(2):577-88.
50. Levander OA, Alfthan G, Arvilommi H, Gref CG, Huttunen JK, Kataja M, Koivistoinen P, Pikkarainen J. Bioavailability of selenium to Finnish men as assessed by platelet glutathione peroxidase activity and other blood parameters. Am J Clin Nutr. 1983;37(6):887-97.
1. Maresh M. Medical complications in pregnancy. Baillieres Clin Obstet Gynaecol. 1990;4(1):129-47.
2. McNestry C, Killeen SL, Crowley RK, McAuliffe FM. Pregnancy complications and later life women's health. Acta Obstet Gynecol Scand. 2023;102(5):523-31.
3. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130-7.
4. Wilson BJ, Watson MS, Prescott GJ, Sunderland S, Campbell DM, Hannaford P, Smith WC. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. Bmj. 2003;326(7394):845.
5. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Bmj. 2007;335(7627):974.
6. Levine RJ, Vatten LJ, Horowitz GL, Qian C, Romundstad PR, Yu KF, Hollenberg AN, Hellevik AI, Asvold BO, Karumanchi SA. Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study. Bmj. 2009;339:b4336.
7. Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999;222(3):222-35.
8. Serdar Z, Gür E, Develioğlu O, Colakoğullari M, Dirican M. Placental and decidual lipid peroxidation and antioxidant defenses in preeclampsia. Lipid peroxidation in preeclampsia. Pathophysiology. 2002;9(1):21.
9. Sikkema JM, van Rijn BB, Franx A, Bruinse HW, de Roos R, Stroes ES, van Faassen EE. Placental superoxide is increased in pre-eclampsia. Placenta. 2001;22(4):304-8.
10. Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol. 1999;180(2 Pt 1):499-506.
11. Brosnan MJ. One step beyond: glutathione peroxidase and endothelial dysfunction. Hypertension. 2008;51(4):825-6.
12. Mistry HD, Wilson V, Ramsay MM, Symonds ME, Broughton Pipkin F. Reduced selenium concentrations and glutathione peroxidase activity in preeclamptic pregnancies. Hypertension. 2008;52(5):881-8.
13. Atamer Y, Koçyigit Y, Yokus B, Atamer A, Erden AC. Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2005;119(1):60-6.
14. Harlev A, Wiznitzer A. New insights on glucose pathophysiology in gestational diabetes and insulin resistance. Curr Diab Rep. 2010;10(3):242-7.
15. Lowe LP, Metzger BE, Dyer AR, Lowe J, McCance DR, Lappin TR, Trimble ER, Coustan DR, Hadden DR, Hod M, Oats JJ, Persson B. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations of maternal A1C and glucose with pregnancy outcomes. Diabetes Care. 2012;35(3):574-80.
16. Sayın R, Aslan M, Kucukoglu ME, Luleci A, Atmaca M, Esen R, Demir H. Serum prolidase enzyme activity and oxidative stress levels in patients with diabetic neuropathy. Endocrine. 2014;47(1):146-51.
17. Maxwell SR, Thomason H, Sandler D, LeGuen C, Baxter MA, Thorpe GH, Jones AF, Barnett AH. Poor glycaemic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus. Ann Clin Biochem. 1997;34 ( Pt 6):638-44.
18. Zhang CXW, Candia AA, Sferruzzi-Perri AN. Placental inflammation, oxidative stress, and fetal outcomes in maternal obesity. Trends in Endocrinology & Metabolism. 2024.
19. Ba C, Martin-Romero FJ, Kumaraswamy E, Moustafa M, H Z, Dl H. Selenium: its molecular biology and role in human health. 2001. p. 23-32.
20. Rayman MP. Selenium and human health. Lancet. 2012;379(9822):1256-68.
21. Boddy A. Bioactive Compounds and Cancer. Br J Clin Pharmacol. 72: Copyright © 2011 The British Pharmacological Society.; 2011. p. 170-1.
22. Ferrer E, Alegría A, Barberá R, Farré R, Lagarda MJ, Monleon J. Whole blood selenium content in pregnant women. Sci Total Environ. 1999;227(2-3):139-43.
23. Mihailović M, Cvetković M, Ljubić A, Kosanović M, Nedeljković S, Jovanović I, Pesut O. Selenium and malondialdehyde content and glutathione peroxidase activity in maternal and umbilical cord blood and amniotic fluid. Biol Trace Elem Res. 2000;73(1):47-54.
24. Rayman MP, Bode P, Redman CW. Low selenium status is associated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom. Am J Obstet Gynecol. 2003;189(5):1343-9.
25. Ernst GDS, de Jonge LL, Hofman A, Lindemans J, Russcher H, Steegers EAP, Jaddoe VWV. C-reactive protein levels in early pregnancy, fetal growth patterns, and the risk for neonatal complications: the Generation R Study. American Journal of Obstetrics and Gynecology. 2011;205(2):132.e1-.e12.
26. Asemi Z, Jamilian M, Mesdaghinia E, Esmaillzadeh A. Effects of selenium supplementation on glucose homeostasis, inflammation, and oxidative stress in gestational diabetes: Randomized, double-blind, placebo-controlled trial. Nutrition. 2015;31(10):1235-42.
27. Mesdaghinia E, Rahavi A, Bahmani F, Sharifi N, Asemi Z. Clinical and Metabolic Response to Selenium Supplementation in Pregnant Women at Risk for Intrauterine Growth Restriction: Randomized, Double-Blind, Placebo-Controlled Trial. Biol Trace Elem Res. 2017;178(1):14-21.
28. Mesdaghinia E, Shahin F, Ghaderi A, Shahin D, Shariat M, Banafshe H. The Effect of Selenium Supplementation on Clinical Outcomes, Metabolic Profiles, and Pulsatility Index of the Uterine Artery in High-Risk Mothers in Terms of Preeclampsia Screening with Quadruple Test: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial : Selenium and preeclampsia. Biol Trace Elem Res. 2023;201(2):567-76.
29. Negro R, Greco G, Mangieri T, Pezzarossa A, Dazzi D, Hassan H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol Metab. 2007;92(4):1263-8.
30. Rayman MP, Searle E, Kelly L, Johnsen S, Bodman-Smith K, Bath SC, Mao J, Redman CWG. Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: A randomised, controlled pilot trial. British Journal of Nutrition. 2014;112(1):99-111.
31. Tara F, Maamouri G, Rayman MP, Ghayour-Mobarhan M, Sahebkar A, Yazarlu O, Ouladan S, Tavallaie S, Azimi-Nezhad M, Shakeri MT, Boskabadi H, Oladi M, Sangani MT, Razavi BS, Ferns G. Selenium supplementation and the incidence of preeclampsia in pregnant Iranian women: a randomized, double-blind, placebo-controlled pilot trial. Taiwan J Obstet Gynecol. 2010;49(2):181-7.
32. Higgins JP, Altman DG. Assessing Risk of Bias in Included Studies. Cochrane Handbook for Systematic Reviews of Interventions2008. p. 187-241.
33. Deeks JJ, Higgins JP, Altman DG, Group obotCSM. Analysing data and undertaking meta-analyses. Cochrane Handbook for Systematic Reviews of Interventions2019. p. 241-84.
34. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Medical Research Methodology. 2005;5(1):13.
35. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177-88.
36. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Bmj. 1997;315(7109):629-34.
37. Begg CB, Berlin JA. Publication bias and dissemination of clinical research. J Natl Cancer Inst. 1989;81(2):107-15.
38. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21(11):1539-58.
39. Gholami A, Amirkalali B, Baradaran HR, Hariri M. A systematic review and dose-response meta-analysis of the effect of selenium supplementation on serum concentration of C-reactive protein. J Trace Elem Med Biol. 2023;80:127273.
40. Rayman MP. The importance of selenium to human health. Lancet. 2000;356(9225):233-41.
41. Duntas LH. Selenium and inflammation: underlying anti-inflammatory mechanisms. Horm Metab Res. 2009;41(6):443-7.
42. Hunter DJ, Morris JS, Chute CG, Kushner E, Colditz GA, Stampfer MJ, Speizer FE, Willett WC. Predictors of selenium concentration in human toenails. Am J Epidemiol. 1990;132(1):114-22.
43. Stoffaneller R, Morse NL. A review of dietary selenium intake and selenium status in Europe and the Middle East. Nutrients. 2015;7(3):1494-537.
44. Kieliszek M, Bano I, Zare H. A Comprehensive Review on Selenium and Its Effects on Human Health and Distribution in Middle Eastern Countries. Biol Trace Elem Res. 2022;200(3):971-87.
45. Avan A, Tavakoly Sany SB, Ghayour-Mobarhan M, Rahimi HR, Tajfard M, Ferns G. Serum C-reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice. J Cell Physiol. 2018;233(11):8508-25.
46. Ilktac A, Kalkan S, Caliskan S. C-reactive protein and procalcitonin levels in prostate cancer. Int J Clin Pract. 2021;75(4):e13935.
47. Allin KH, Nordestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci. 2011;48(4):155-70.
48. Fontenelle LC, Cardoso de Araújo DS, da Cunha Soares T, Clímaco Cruz KJ, Henriques GS, Marreiro DDN. Nutritional status of selenium in overweight and obesity: A systematic review and meta-analysis. Clin Nutr. 2022;41(4):862-84.
49. Thomson CD, Robinson MF, Butler JA, Whanger PD. Long-term supplementation with selenate and selenomethionine: selenium and glutathione peroxidase (EC 1.11.1.9) in blood components of New Zealand women. Br J Nutr. 1993;69(2):577-88.
50. Levander OA, Alfthan G, Arvilommi H, Gref CG, Huttunen JK, Kataja M, Koivistoinen P, Pikkarainen J. Bioavailability of selenium to Finnish men as assessed by platelet glutathione peroxidase activity and other blood parameters. Am J Clin Nutr. 1983;37(6):887-97.
1. Maresh M. Medical complications in pregnancy. Baillieres Clin Obstet Gynaecol. 1990;4(1):129-47.
2. McNestry C, Killeen SL, Crowley RK, McAuliffe FM. Pregnancy complications and later life women's health. Acta Obstet Gynecol Scand. 2023;102(5):523-31.
3. Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009;33(3):130-7.
4. Wilson BJ, Watson MS, Prescott GJ, Sunderland S, Campbell DM, Hannaford P, Smith WC. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. Bmj. 2003;326(7394):845.
5. Bellamy L, Casas JP, Hingorani AD, Williams DJ. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. Bmj. 2007;335(7627):974.
6. Levine RJ, Vatten LJ, Horowitz GL, Qian C, Romundstad PR, Yu KF, Hollenberg AN, Hellevik AI, Asvold BO, Karumanchi SA. Pre-eclampsia, soluble fms-like tyrosine kinase 1, and the risk of reduced thyroid function: nested case-control and population based study. Bmj. 2009;339:b4336.
7. Hubel CA. Oxidative stress in the pathogenesis of preeclampsia. Proc Soc Exp Biol Med. 1999;222(3):222-35.
8. Serdar Z, Gür E, Develioğlu O, Colakoğullari M, Dirican M. Placental and decidual lipid peroxidation and antioxidant defenses in preeclampsia. Lipid peroxidation in preeclampsia. Pathophysiology. 2002;9(1):21.
9. Sikkema JM, van Rijn BB, Franx A, Bruinse HW, de Roos R, Stroes ES, van Faassen EE. Placental superoxide is increased in pre-eclampsia. Placenta. 2001;22(4):304-8.
10. Redman CW, Sacks GP, Sargent IL. Preeclampsia: an excessive maternal inflammatory response to pregnancy. Am J Obstet Gynecol. 1999;180(2 Pt 1):499-506.
11. Brosnan MJ. One step beyond: glutathione peroxidase and endothelial dysfunction. Hypertension. 2008;51(4):825-6.
12. Mistry HD, Wilson V, Ramsay MM, Symonds ME, Broughton Pipkin F. Reduced selenium concentrations and glutathione peroxidase activity in preeclamptic pregnancies. Hypertension. 2008;52(5):881-8.
13. Atamer Y, Koçyigit Y, Yokus B, Atamer A, Erden AC. Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2005;119(1):60-6.
14. Harlev A, Wiznitzer A. New insights on glucose pathophysiology in gestational diabetes and insulin resistance. Curr Diab Rep. 2010;10(3):242-7.
15. Lowe LP, Metzger BE, Dyer AR, Lowe J, McCance DR, Lappin TR, Trimble ER, Coustan DR, Hadden DR, Hod M, Oats JJ, Persson B. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations of maternal A1C and glucose with pregnancy outcomes. Diabetes Care. 2012;35(3):574-80.
16. Sayın R, Aslan M, Kucukoglu ME, Luleci A, Atmaca M, Esen R, Demir H. Serum prolidase enzyme activity and oxidative stress levels in patients with diabetic neuropathy. Endocrine. 2014;47(1):146-51.
17. Maxwell SR, Thomason H, Sandler D, LeGuen C, Baxter MA, Thorpe GH, Jones AF, Barnett AH. Poor glycaemic control is associated with reduced serum free radical scavenging (antioxidant) activity in non-insulin-dependent diabetes mellitus. Ann Clin Biochem. 1997;34 ( Pt 6):638-44.
18. Zhang CXW, Candia AA, Sferruzzi-Perri AN. Placental inflammation, oxidative stress, and fetal outcomes in maternal obesity. Trends in Endocrinology & Metabolism. 2024.
19. Ba C, Martin-Romero FJ, Kumaraswamy E, Moustafa M, H Z, Dl H. Selenium: its molecular biology and role in human health. 2001. p. 23-32.
20. Rayman MP. Selenium and human health. Lancet. 2012;379(9822):1256-68.
21. Boddy A. Bioactive Compounds and Cancer. Br J Clin Pharmacol. 72: Copyright © 2011 The British Pharmacological Society.; 2011. p. 170-1.
22. Ferrer E, Alegría A, Barberá R, Farré R, Lagarda MJ, Monleon J. Whole blood selenium content in pregnant women. Sci Total Environ. 1999;227(2-3):139-43.
23. Mihailović M, Cvetković M, Ljubić A, Kosanović M, Nedeljković S, Jovanović I, Pesut O. Selenium and malondialdehyde content and glutathione peroxidase activity in maternal and umbilical cord blood and amniotic fluid. Biol Trace Elem Res. 2000;73(1):47-54.
24. Rayman MP, Bode P, Redman CW. Low selenium status is associated with the occurrence of the pregnancy disease preeclampsia in women from the United Kingdom. Am J Obstet Gynecol. 2003;189(5):1343-9.
25. Ernst GDS, de Jonge LL, Hofman A, Lindemans J, Russcher H, Steegers EAP, Jaddoe VWV. C-reactive protein levels in early pregnancy, fetal growth patterns, and the risk for neonatal complications: the Generation R Study. American Journal of Obstetrics and Gynecology. 2011;205(2):132.e1-.e12.
26. Asemi Z, Jamilian M, Mesdaghinia E, Esmaillzadeh A. Effects of selenium supplementation on glucose homeostasis, inflammation, and oxidative stress in gestational diabetes: Randomized, double-blind, placebo-controlled trial. Nutrition. 2015;31(10):1235-42.
27. Mesdaghinia E, Rahavi A, Bahmani F, Sharifi N, Asemi Z. Clinical and Metabolic Response to Selenium Supplementation in Pregnant Women at Risk for Intrauterine Growth Restriction: Randomized, Double-Blind, Placebo-Controlled Trial. Biol Trace Elem Res. 2017;178(1):14-21.
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