Skip to main content
Log in

Association of Selenium Levels with Preeclampsia: A Systematic Review and Meta-analysis

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Several observational studies have shown inconclusive findings on the association between selenium levels and preeclampsia. This systematic review and meta-analysis was conducted to clarify the association between selenium levels and preeclampsia. The databases PubMed, Google Scholar, ScienceDirect, and the Cochrane Library were searched for studies which investigated selenium levels with preeclampsia and which were published up to April 2022. The overall standardized mean differences (SMD) of selenium levels between cases and controls were measured. Sensitivity analysis, reporting bias, subgroup analysis, and meta-regression were performed for the estimate. The meta-analysis was calculated using the “meta” package in the open-source software R. A total of 26 studies with 1855 preeclampsia cases compared with 3728 healthy pregnant controls were included. The level of selenium was significantly lower in cases of preeclampsia compared with the controls [SMD =  − 0.85; 95% confidence interval (CI): (− 1.46, − 0.25); P =  < 0.01). As there was significant heterogeneity [I2 = 96%, Cochran’s Q = 620.47; P =  < 0.01], the random effects model was used. A stratified meta-analysis revealed that selenium levels were significantly lower in the cases compared with the controls among pregnant women from the African continent [SMD =  − 1.15 (− 1.65, − 0.65); P =  < 0.01]. Likewise, the same pattern was observed among women from middle- and low-income countries [SMD =  − 1.32 (− 2.22, − 0.42); P =  < 0.01]. None of the investigated factors (Modified Newcastle–Ottawa Scale quality score, year of publication, and sample size) showed significant association with the selenium SMD. The level of certainty of this evidence is “low certainty,” as calculated by the GRADEpro GDT online tool. This meta-analysis with low level of evidence certainty revealed that low selenium level is associated significantly with preeclampsia. This pattern is also observed in women from the African continent and women from low- or middle-income countries. Further studies with different prospective designs and detailed patient characteristics are needed to consolidate this evidence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

Data Availability

Data used to generate the result in this manuscript is available as a supplementary material in this manuscript.

References

  1. Abalos E, Cuesta C, Grosso AL et al (2013) Global and regional estimates of preeclampsia and eclampsia: a systematic review. Eur J Obstet Gynecol Reprod Biol 170:1–7. https://doi.org/10.1016/J.EJOGRB.2013.05.005

    Article  PubMed  Google Scholar 

  2. Steegers EAP, Von Dadelszen P, Duvekot JJ, Pijnenborg R (2010) Pre-eclampsia. Lancet (London, England) 376:631–644. https://doi.org/10.1016/S0140-6736(10)60279-6

    Article  PubMed  Google Scholar 

  3. Meazaw MW, Chojenta C, Muluneh MD, Loxton D (2020) Systematic and meta-analysis of factors associated with preeclampsia and eclampsia in sub-Saharan Africa. PLoS One 15. https://doi.org/10.1371/JOURNAL.PONE.0237600

  4. Hatfield DL (2001) Selenium : its molecular biology and role in human health. Kluwer Academic Press

  5. Kryukov GV, Castellano S, Novoselov SV et al (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443. https://doi.org/10.1126/SCIENCE.1083516

    Article  CAS  PubMed  Google Scholar 

  6. Bellinger FP, Raman AV, Reeves MA, Berry MJ (2009) Regulation and function of selenoproteins in human disease. Biochem J 422:11–22. https://doi.org/10.1042/BJ20090219

    Article  CAS  PubMed  Google Scholar 

  7. Rumbold A, Duley L, Crowther C, Haslam R (2005) Antioxidants for preventing pre-eclampsia. Cochrane database Syst Rev. https://doi.org/10.1002/14651858.CD004227.PUB2

  8. Muzembo BA, Deguchi Y, Ngatu NR et al (2015) Selenium and exposure to fibrogenic mineral dust: a mini-review. Environ Int 77:16–24. https://doi.org/10.1016/J.ENVINT.2015.01.002

    Article  CAS  PubMed  Google Scholar 

  9. Atamer Y, Koçyigit Y, Yokus B et al (2005) Lipid peroxidation, antioxidant defense, status of trace metals and leptin levels in preeclampsia. Eur J Obstet Gynecol Reprod Biol 119:60–66. https://doi.org/10.1016/J.EJOGRB.2004.06.033

    Article  CAS  PubMed  Google Scholar 

  10. Businge CB, Longo-Mbenza B, Kengne AP (2021) Exploration of the underlying nutritional, inflammatory and oxidative stress pathological mechanisms in preeclampsia using principal component analysis. Eur J Med Heal Sci 3:19–24. https://doi.org/10.24018/EJMED.2021.3.4.932

    Article  Google Scholar 

  11. Emam AAH, Attia AM (2020) Selected trace elements in Egyptian females with preeclampsia. Int J Med Arts 2:811–819. https://doi.org/10.21608/IJMA.2020.32767.1137

    Article  Google Scholar 

  12. Eze SC, Ododo NA, Ugwu EO, et al. (2020) Serum selenium levels of pre-eclamptic and normal pregnant women in Nigeria: a comparative study. PLoS One 15. https://doi.org/10.1371/JOURNAL.PONE.0238263

  13. Farzin L, Sajadi F (2012) Comparison of serum trace element levels in patients with or without pre-eclampsia. J Res Med Sci 17:938

    PubMed  PubMed Central  Google Scholar 

  14. Ghaemi SZ, Forouhari S, Dabbaghmanesh MH et al (2013) (2013) A prospective study of selenium concentration and risk of preeclampsia in pregnant Iranian women: a nested case–control study. Biol Trace Elem Res 1522(152):174–179. https://doi.org/10.1007/S12011-013-9614-Y

    Article  Google Scholar 

  15. Haque MM, Moghal MMR, Sarwar MS et al (2016) Low serum selenium concentration is associated with preeclampsia in pregnant women from Bangladesh. J Trace Elem Med Biol 33:21–25. https://doi.org/10.1016/J.JTEMB.2015.08.002

    Article  CAS  PubMed  Google Scholar 

  16. Ilechukwu O, Onuegbu J, Olisekodiaka J, Ezeani C (2021) Evaluation of plasma selenium, zinc and malondialdehyde levels in newly diagnosed preeclamptic women at a teaching hospital. ULUTAS Med J 7:86. https://doi.org/10.5455/UMJ.20210422011242

    Article  Google Scholar 

  17. Katz O, Paz-Tal O, Lazer T et al (2012) Severe pre-eclampsia is associated with abnormal trace elements concentrations in maternal and fetal blood. J Matern Fetal Neonatal Med 25:1127–1130. https://doi.org/10.3109/14767058.2011.624221

    Article  CAS  PubMed  Google Scholar 

  18. Lewandowska M, Więckowska B, Sajdak S, Lubiński J (2020) First trimester microelements and their rrelationships with pregnancy outcomes and complications. Nutrients 12. https://doi.org/10.3390/NU12041108

  19. Maleki A, Fard MK, Zadeh DH et al (2011) The relationship between plasma level of Se and preeclampsia. Hypertens pregnancy 30:180–187. https://doi.org/10.3109/10641950903322931

    Article  CAS  PubMed  Google Scholar 

  20. Mazloomi S, Khodadadi I, Alimohammadi S, Shafiee G (2020) Correlation of thioredoxin reductase (TrxR) and nitric oxide synthase (NOS) activities with serum trace elements in preeclampsia. 43:120–124. https://doi.org/10.1080/10641963.2020.1817476

  21. Mistry HD, Wilson V, Ramsay MM et al (2008) Reduced selenium concentrations and glutathione peroxidase activity in preeclamptic pregnancies. Hypertension 52:881–888. https://doi.org/10.1161/HYPERTENSIONAHA.108.116103

    Article  CAS  PubMed  Google Scholar 

  22. Dahabiyeh LA, Tooth D, Kurlak LO, et al. (2020) A pilot study of alterations in oxidized angiotensinogen and antioxidants in pre-eclamptic pregnancy. Sci Rep 10. https://doi.org/10.1038/S41598-020-58930-7

  23. Gromadzinska J, Wasowicz W, Krasomski G et al (1998) Selenium levels, thiobarbituric acid-reactive substance concentrations and glutathione peroxidase activity in the blood of women with gestosis and imminent premature labour. Analyst 123:35–40. https://doi.org/10.1039/A705396G

    Article  CAS  PubMed  Google Scholar 

  24. da Silva AC, Martins-Costa SH, Valério EG, Lopes Ramos JG (2017) Comparison of serum selenium levels among hypertensive and normotensive pregnant women. Hypertens pregnancy 36:64–69. https://doi.org/10.1080/10641955.2016.1237645

    Article  CAS  PubMed  Google Scholar 

  25. Enebe JT, Dim CC, Ugwu EO, et al. (2020) Serum antioxidant micronutrient levels in pre-eclamptic pregnant women in Enugu, south-East Nigeria: a comparative cross-sectional analytical study. BMC Pregnancy Childbirth 20. https://doi.org/10.1186/S12884-020-03081-W

  26. Kim J, Kim YJ, Lee R et al (2012) Serum levels of zinc, calcium, and iron are associated with the risk of preeclampsia in pregnant women. Nutr Res 32:764–769. https://doi.org/10.1016/J.NUTRES.2012.09.007

    Article  CAS  PubMed  Google Scholar 

  27. Liu T, Zhang M, Guallar E, et al. (2019) Trace minerals, heavy metals, and preeclampsia: findings from the Boston Birth Cohort. J Am Heart Assoc 8. https://doi.org/10.1161/JAHA.119.012436

  28. Maduray K, Moodley J, Soobramoney C et al (2017) Elemental analysis of serum and hair from pre-eclamptic South African women. J Trace Elem Med Biol 43:180–186. https://doi.org/10.1016/J.JTEMB.2017.03.004

    Article  CAS  PubMed  Google Scholar 

  29. Mistry H, Kurlak L, Gill C et al (2013) PP027. Alterations in maternal antioxidant micronutrient concentrations in women prior to developing pre-eclampsia. Pregnancy Hypertens 3:76–77. https://doi.org/10.1016/J.PREGHY.2013.04.054

    Article  PubMed  Google Scholar 

  30. Mistry HD, Gill CA, Kurlak LO et al (2015) Association between maternal micronutrient status, oxidative stress, and common genetic variants in antioxidant enzymes at 15 weeks׳ gestation in nulliparous women who subsequently develop preeclampsia. Free Radic Biol Med 78:147–155. https://doi.org/10.1016/J.FREERADBIOMED.2014.10.580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Moraes PH, Palei A, Sandrim V et al (2010) P52 Comparative assessment of levels of selenium in preeclampsia and gestational hypertension. Pregnancy Hypertens An Int J Women’s Cardiovasc Heal 1:S56. https://doi.org/10.1016/S2210-7789(10)60218-8

    Article  Google Scholar 

  32. Rayman MP, Abou-Shakra FR, Ward NI, Redman CWG (1996) Comparison of selenium levels in pre-eclamptic and normal pregnancies. Biol Trace Elem Res 55:9–20. https://doi.org/10.1007/BF02784164

    Article  CAS  PubMed  Google Scholar 

  33. Rezende VB, Barbosa F, Palei AC et al (2015) Correlations among antiangiogenic factors and trace elements in hypertensive disorders of pregnancy. J Trace Elem Med Biol 29:130–135. https://doi.org/10.1016/J.JTEMB.2014.06.011

    Article  CAS  PubMed  Google Scholar 

  34. Uotila JT, Tuimala RJ, Aarnio TM et al (1993) Findings on lipid peroxidation and antioxidant function in hypertensive complications of pregnancy. Br J Obstet Gynaecol 100:270–276. https://doi.org/10.1111/J.1471-0528.1993.TB15242.X

    Article  CAS  PubMed  Google Scholar 

  35. Xu M, Guo D, Gu H et al (2016) Selenium and preeclampsia: a systematic review and meta-analysis. Biol Trace Elem Res 171:283–292. https://doi.org/10.1007/S12011-015-0545-7

    Article  CAS  PubMed  Google Scholar 

  36. Salameh JP, Bossuyt PM, McGrath TA et al (2020) Preferred reporting items for systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA): explanation, elaboration, and checklist. BMJ 370:2632

    Article  Google Scholar 

  37. American College of Obstetricians, Task Force on Hypertension in Pregnancy (2013) Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. In: Obstetrics and gynecology. Obstet Gynecol, pp 1122–1131

  38. Wells G, Shea B, O’Connell D, et al. Ottawa Hospital Research Institute. In: Newcastle-Ottawa Scale Assess. Qual. nonrandomised Stud. meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 10 Dec 2021

  39. Munn Z, Tufanaru C, Aromataris E (2014) JBIʼs systematic reviews. AJN, Am J Nurs 114:49–54. https://doi.org/10.1097/01.NAJ.0000451683.66447.89

    Article  PubMed  Google Scholar 

  40. Wan X, Wang W, Liu J, Tong T (2014) Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol 14. https://doi.org/10.1186/1471-2288-14-135

  41. Balduzzi S, Rücker G, Schwarzer G (2019) How to perform a meta-analysis with R: a practical tutorial. Evid Based Ment Health 22:153–160. https://doi.org/10.1136/ebmental-2019-300117

    Article  PubMed  Google Scholar 

  42. Sedgwick P (2013) Meta-analyses: heterogeneity and subgroup analysis. BMJ 346 https://doi.org/10.1136/bmj.f4040

  43. GRADE handbook. https://gdt.gradepro.org/app/handbook/handbook.html. Accessed 13 Dec 2021

  44. Ferguson EL, Gadowsky SL, Huddle JM et al (1995) An interactive 24-h recall technique for assessing the adequacy of trace mineral intakes of rural Malawian women; its advantages and limitations. Eur J Clin Nutr 49:565–578

    CAS  PubMed  Google Scholar 

  45. Kong F, Ma L, Chen S et al (2016) Serum selenium level and gestational diabetes mellitus: a systematic review and meta-analysis. Nutr J 15:1–10. https://doi.org/10.1186/S12937-016-0211-8

    Article  CAS  Google Scholar 

  46. Osorio-Yáñez C, Gelaye B, Enquobahrie DA et al (2018) Dietary intake and urinary metals among pregnant women in the Pacific Northwest. Environ Pollut 236:680–688. https://doi.org/10.1016/J.ENVPOL.2018.01.110

    Article  PubMed  Google Scholar 

  47. Levander OA, Moser PB, Morris VC (1987) Dietary selenium intake and selenium concentrations of plasma, erythrocytes, and breast milk in pregnant and postpartum lactating and nonlactating women. Am J Clin Nutr 46:694–698. https://doi.org/10.1093/AJCN/46.4.694

    Article  CAS  PubMed  Google Scholar 

  48. Gerla PJ, Sharif MU, Korom SF (2011) Geochemical processes controlling the spatial distribution of selenium in soil and water, west central South Dakota, USA. Environ Earth Sci 62:1551–1560. https://doi.org/10.1007/S12665-010-0641-0/FIGURES/3

    Article  CAS  Google Scholar 

  49. Da Silva EG, Mataveli LRV, Zezzi Arruda MA (2013) Speciation analysis of selenium in plankton, Brazil nut and human urine samples by HPLC-ICP-MS. Talanta 110:53–57. https://doi.org/10.1016/J.TALANTA.2013.02.014

    Article  PubMed  Google Scholar 

  50. Ferrer E, Alegría A, Barberá R et al (1999) Whole blood selenium content in pregnant women. Sci Total Environ 227:139–143

    Article  CAS  PubMed  Google Scholar 

  51. Duntas LH (2020) Selenium and at-risk pregnancy: challenges and controversies. Thyroid Res 13. https://doi.org/10.1186/S13044-020-00090-X

  52. Wolonciej M, Milewska E, Roszkowska-Jakimiec W (2016) Trace elements as an activator of antioxidant enzymes. Postepy Hig Med Dosw (Online) 70:1483–1498. https://doi.org/10.5604/17322693.1229074

    Article  PubMed  Google Scholar 

  53. Horan MK, McGowan CA, Gibney ER, et al. (2015) The association between maternal dietary micronutrient intake and neonatal anthropometry - secondary analysis from the ROLO study. Nutr J 14. https://doi.org/10.1186/S12937-015-0095-Z

  54. Mistry HD, Williams PJ (2011) The importance of antioxidant micronutrients in pregnancy. Oxid Med Cell Longev 2011https://doi.org/10.1155/2011/841749

  55. Lewandowska M, Sajdak S, Lubí Nski J (2019) Serum selenium level in early healthy pregnancy as a risk marker of pregnancy induced hypertension. https://doi.org/10.3390/nu11051028

Download references

Author information

Authors and Affiliations

Authors

Contributions

HZH, SZH, and IA conceptualized and designed the study. HZH and SZH conducted the search. IA performed as a judge for dispute. HZH and IA performed the statistical analyses. HZH, SZH, and IA drafted the paper. All authors reviewed the draft and approved this version of the paper.

Corresponding author

Correspondence to Hamdan Z. Hamdan.

Ethics declarations

Ethical Approval

Since this was a systematic review and meta-analysis, ethical approval is not required.

Consent to Participate

Not applicable.

Consent for Publication

Not applicable.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 64 KB)

Supplementary file 1

Supplementary file 1

(Prisma checklist; Databases searching strategies; Characteristics of all studies of this systematic review and meta-analysis of selenium levels in preeclampsia).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hamdan, H.Z., Hamdan, S.Z. & Adam, I. Association of Selenium Levels with Preeclampsia: A Systematic Review and Meta-analysis. Biol Trace Elem Res 201, 2105–2122 (2023). https://doi.org/10.1007/s12011-022-03316-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-022-03316-1

Keywords

Navigation