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.
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Data used to generate the result in this manuscript is available as a supplementary material in this manuscript.
References
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
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
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
Hatfield DL (2001) Selenium : its molecular biology and role in human health. Kluwer Academic Press
Kryukov GV, Castellano S, Novoselov SV et al (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443. https://doi.org/10.1126/SCIENCE.1083516
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
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
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
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
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
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
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
Farzin L, Sajadi F (2012) Comparison of serum trace element levels in patients with or without pre-eclampsia. J Res Med Sci 17:938
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Sedgwick P (2013) Meta-analyses: heterogeneity and subgroup analysis. BMJ 346 https://doi.org/10.1136/bmj.f4040
GRADE handbook. https://gdt.gradepro.org/app/handbook/handbook.html. Accessed 13 Dec 2021
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
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
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
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
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
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
Ferrer E, Alegría A, Barberá R et al (1999) Whole blood selenium content in pregnant women. Sci Total Environ 227:139–143
Duntas LH (2020) Selenium and at-risk pregnancy: challenges and controversies. Thyroid Res 13. https://doi.org/10.1186/S13044-020-00090-X
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
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
Mistry HD, Williams PJ (2011) The importance of antioxidant micronutrients in pregnancy. Oxid Med Cell Longev 2011https://doi.org/10.1155/2011/841749
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
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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.
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(Prisma checklist; Databases searching strategies; Characteristics of all studies of this systematic review and meta-analysis of selenium levels in preeclampsia).
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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
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DOI: https://doi.org/10.1007/s12011-022-03316-1