Abstract
Background: Pre-eclampsia poses a significant potential risk of hypertensive disorders during pregnancy, a leading cause of maternal deaths. Hyperuricemia is associated with adverse effects on endothelial function, normal cellular metabolism, and platelet aggregation and adhesion. This study was designed to compare serum urate levels in normotensive pregnant women to those with pregnancy-induced hypertension, and to evaluate its value as a potential predictive marker of hypertension severity during pregnancy.
Methods: A prospective, observational, case-control study conducted on 100 pregnant women in their third trimester. Pregnant women were classified into two groups (n=50) according to arterial blood pressure measurements: group I had normal blood pressure, and group II had a blood pressure of ≥ 140/90, which was further subdivided according to hypertension severity into IIa (pregnancy- induced hypertension, IIb (mild pre-eclampsia), and IIc (severe pre-eclampsia). Blood samples were obtained on admission. Serum urate, high sensitive C-reactive protein, and interleukin-1β levels, and lipid profile were compared among the groups.
Results: A significant increase in the mean values of serum urate, C-reactive protein, and interleukin- 1β levels was detected in gestational hypertensives. In addition, there was a positive correlation between serum urate levels and C-reactive protein and interleukin-1β, as well as between serum urate levels and hypertension severity.
Conclusion: Hyperuricemia and increased C-reactive protein and interleukin-1β serum levels correlate with the severity of pregnancy-induced hypertension, and these biomarkers may play a role in the pathogenesis of pre-eclampsia. Serum urate measurement is sensitive, reliable markers that correlate well with the severity of hypertension in pregnant females with pre-eclampsia.
Keywords: Pre-eclampsia, serum uric acid, inflammatory markers, high-sensitive C-reactive protein, IL-1β, pregnancy-induced hypertension.
Graphical Abstract
[1]
Chang J, Elam-Evans LD, Berg CJ, et al. Pregnancy-related mortality surveillance-United States, 1991-1999. MMWR Surveill Summ 2003; 52(2): 1-8.[PMID: 12825542]
[2]
Duley L. The global impact of pre-eclampsia and eclampsia. Semin Perinatol 2009; 33(3): 130-7.[http://dx.doi.org/10.1053/j.semperi.2009.02.010] [PMID: 19464502]
[3]
Kumar N, Singh AK. Maternal serum uric acid as a predictor of severity of hypertensive disorders of pregnancy: A Prospective Cohort Study. Curr Hypertens Rev 2019; 15(2): 154-60.[http://dx.doi.org/10.2174/1573402114666181112141953] [PMID: 30417791]
[4]
Campbell OM, Graham WJ. Lancet Maternal Survival Series steering group. Strategies for reducing maternal mortality: Getting on with what works. Lancet 2006; 368(9543): 1284-99.[http://dx.doi.org/10.1016/S0140-6736(06)69381-1] [PMID: 17027735]
[5]
Brown MA, Hague WM, Higgins J, et al. Australasian society for the study of hypertension in pregnancy. The detection, investigation and management of hypertension in pregnancy: Executive summary. Aust N Z J Obstet Gynaecol 2000; 40(2): 133-8.[http://dx.doi.org/10.1111/j.1479-828X.2000.tb01136.x] [PMID: 10925899]
[6]
Sibai BM. Diagnosis and management of gestational hypertension and preeclampsia. Obstet Gynecol 2003; 102(1): 181-92.[PMID: 12850627]
[7]
American College of Obstetricians and Gynecologists; Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 2013; 122(5): 1122-31.[PMID: 24150027]
[8]
Spencer J, Polavarapu S, Timms D. Regional and monthly variation in rates of pre-eclampsia at delivery among U.S. births. 29th Annual Meeting of the Society for Maternal-Fetal Medicine Abstract No 2942009; 26: 31.
[9]
Lim KH, Steinberg G, Ramus RM. Preeclampsia. Emedicine 2011. (online) (cited2011). Updated 2015, Dec 28.emedicine.medscape.com/article/1476919-overview
[10]
Rock KL, Kataoka H, Lai JJ. Uric acid as a danger signal in gout and its comorbidities. Nat Rev Rheumatol 2013; 9(1): 13-23.[http://dx.doi.org/10.1038/nrrheum.2012.143] [PMID: 22945591]
[11]
Sakr HI, Khowailed AA, Farghaly ME, Kamel MM, Farid EZ. Endothelial-Platelet Dysfunction as an Indicator of Pre-Eclampsia and its Severity. Med J Cairo Univ 2019; 87(June): 1775-82.[http://dx.doi.org/10.21608/mjcu.2019.53964]
[12]
Yuk HJ, Lee YS, Ryu HW, Kim SH, Kim DS. Effects of Toona sinensis Leaf Extract and Its Chemical Constituents on Xanthine Oxidase Activity and Serum Uric Acid Levels in Potassium Oxonate-Induced Hyperuricemic Rats. Molecules 2018; 23(12): 3254.[http://dx.doi.org/10.3390/molecules23123254] [PMID: 30544886]
[13]
Roberts WL, Sedrick R, Moulton L, Spencer A, Rifai N. Evaluation of four automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Clin Chem 2000; 46(4): 461-8.[http://dx.doi.org/10.1093/clinchem/46.4.461] [PMID: 10759469]
[14]
López-Mejías R, Genre F, Remuzgo-Martínez S, et al. Interleukin 1 beta (IL1ß) rs16944 genetic variant as a genetic marker of severe renal manifestations and renal sequelae in Henoch-Schönlein purpura. Clin Exp Rheumatol 2016; 34(3)(Suppl. 97): S84-8.[PMID: 26842496]
[15]
Elshaer SL, Mohamed IN, Coucha M, et al. Deletion of TXNIP Mitigates High-Fat Diet-Impaired Angiogenesis and Prevents Inflammation in a Mouse Model of Critical Limb Ischemia. Antioxidants 2017; 6(3): 47.[http://dx.doi.org/10.3390/antiox6030047] [PMID: 28661427]
[16]
Huang EW, Liu CZ, Liang SJ, et al. Endophilin-A2-mediated increase in scavenger receptor expression contributes to macrophage-derived foam cell formation. Atherosclerosis 2016; 254: 133-41.[http://dx.doi.org/10.1016/j.atherosclerosis.2016.10.009] [PMID: 27741419]
[17]
Lee SM, Kim CW, Kim JK, Shin HJ, Baik JH. GCG-rich tea catechins are effective in lowering cholesterol and triglyceride concentrations in hyperlipidemic rats. Lipids 2008; 43(5): 419-29.[http://dx.doi.org/10.1007/s11745-008-3167-4] [PMID: 18365267]
[18]
Chan YH. Biostatistics 102: quantitative data-parametric & non- parametric tests. Singapore Med J 2003; 44(8): 391-6.[PMID: 14700417]
[19]
Chan YH. Biostatistics 104: Chanorrelational analysis. Singapore Med J 2003; 44(12): 614-9.[PMID: 14770254]
[20]
Hawkins TL-A, Roberts JM, Mangos GJ, Davis GK, Roberts LM, Brown MA. Plasma uric acid remains a marker of poor outcome in hypertensive pregnancy: A retrospective cohort study. BJOG 2012; 119(4): 484-92.[http://dx.doi.org/10.1111/j.1471-0528.2011.03232.x] [PMID: 22251368]
[21]
Niraula A, Lamsal M, Majhi S, Khan SA, Basnet P. Significance of Serum Uric Acid in Pregnancy Induced Hypertension by the National Medical Association 2017; 109(3): 198-202.
[22]
Lamarca B. Endothelial dysfunction. An important mediator in the pathophysiology of hypertension during pre-eclampsia. Minerva Ginecol 2012; 64(4): 309-20.[PMID: 22728575]
[23]
União Europeia. A promoção da economia social como um fator essencial de desenvolvimento económico e social da Europa - Conclusões do Conselho (7 de dezembro de 2015). BMC Public Health 2015; 9: 1-9.
[24]
Patel T, Dudhat A. Relationship of serum uric acid level to maternal and perinatal outcome in patients with hypertensive disorders of pregnancy. Gujarat Med J 2014; 69(2): 1e3.
[25]
Bainbridge SA, Roberts JM. Uric acid as a pathogenic factor in preeclampsia. Placenta 2008; 29(Suppl. A): S67-72.[http://dx.doi.org/10.1016/j.placenta.2007.11.001] [PMID: 18093648]
[26]
Walsh SW. Eicosanoids in preeclampsia. Prostaglandins Leukot Essent Fatty Acids 2004; 70(2): 223-32.[http://dx.doi.org/10.1016/j.plefa.2003.04.010] [PMID: 14683695]
[27]
Kataoka H, Yang K, Rock KL. The xanthine oxidase inhibitor Febuxostat reduces tissue uric acid content and inhibits injury-induced inflammation in the liver and lung. Eur J Pharmacol [Internet] 2015; 5746: 174-9.[http://dx.doi.org/10.1016/j.ejphar.2014.11.013]
[28]
Sultana R, Ahmed S, Sultana N, Fazlul SM, Atia F. Association of serum uric acid with pre-eclampsia. A Case Control Study Delta Med Col J 2013; 1(2): 46-50.
[29]
Powers RW, Bodnar LM, Ness RB, et al. Uric acid concentrations in early pregnancy among preeclamptic women with gestational hyperuricemia at delivery. Am J Obstet Gynecol 2006; 194(1): 160.[http://dx.doi.org/10.1016/j.ajog.2005.06.066] [PMID: 16389026]
[30]
Kuwabara M. Hyperuricemia, cardiovascular disease, and hypertension. Pulse (Basel) 2016; 3(3-4): 242-52.[http://dx.doi.org/10.1159/000443769] [PMID: 27195245]
[31]
Iliesiu A, Campeanu A, Dusceac D. Serum uric acid and cardiovascular disease. Maedica. J Clin Med 2010; 5(3): 186-92.
[32]
Feig DI, Kang DH, Johnson RJ. Uric acid and cardiovascular riskn. Engl J Med 2009; 359(17): 1811-21.
[33]
Sabry MM, Mahmoud MM, Shoukry HS, Rashed L, Kamar SS, Ahmed MM. Interactive effects of apelin, renin-angiotensin system and nitric oxide in treatment of obesity-induced type 2 diabetes mellitus in male albino rats. Arch Physiol Biochem 2019; 125(3): 244-54.[http://dx.doi.org/10.1080/13813455.2018.1453521] [PMID: 29564917]
[34]
Anand NN, Padma V, Prasad A, Alam KC, Javid MS. Serum uric acid in new and recent onset primary hypertension. J Pharm Bioallied Sci 2015; 7(Suppl. 1): S4-8.[http://dx.doi.org/10.4103/0975-7406.155763] [PMID: 26015744]
[35]
Prasad M, Matteson EL, Herrmann J, et al. Uric acid is associated with inflammation, coronary microvascular dysfunction, and adverse outcomes in postmenopausal women. Hypertension 2017; 69(2): 236-42.[http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.08436] [PMID: 27993955]
[36]
Kumru S, Godekmerdan A, Kutlu S, Ozcan Z. Correlation of maternal serum high-sensitive C-reactive protein levels with biochemical and clinical parameters in preeclampsia. Eur J Obstet Gynecol Reprod Biol 2006; 124(2): 164-7.[http://dx.doi.org/10.1016/j.ejogrb.2005.05.007] [PMID: 16054746]
[37]
Ali Z, Bokhari FA, Zaki S, Zargham U, Tauseef A, Khakan S. Correlation of CRP levels in third trimester with fetal birth weight in preeclamptic and normotensive pregnant women. J Coll Physicians Surg Pak 2015; 25(2): 111-4.[PMID: 25703754]
[38]
Abi Nahed R, Reynaud D, Borg AJ, et al. NLRP7 is increased in human idiopathic fetal growth restriction and plays a critical role in trophoblast differentiation. J Mol Med (Berl) 2019; 97(3): 355-67.[http://dx.doi.org/10.1007/s00109-018-01737-x] [PMID: 30617930]
[39]
Brien ME, Duval C, Palacios J, et al. Uric acid crystals induce placental inflammation and alters trophoblast function via an IL-1-dependent pathway implication for FGR. J Immunol 2017; 198(1): 443-51.[http://dx.doi.org/10.4049/jimmunol.1601179] [PMID: 27903743]
[40]
Mulla MJ, Myrtolli K, Potter J, et al. Uric acid induces trophoblast IL-1β production via the inflammasome: implications for the pathogenesis of preeclampsia. Am J Reprod Immunol 2011; 65(6): 542-8.[http://dx.doi.org/10.1111/j.1600-0897.2010.00960.x] [PMID: 21352397]
[41]
Amash A, Holcberg G, Sapir O, Huleihel M. Placental secretion of interleukin-1 and interleukin-1 receptor antagonist in preeclampsia: effect of magnesium sulfate. J Interferon Cytokine Res 2012; 32(9): 432-41.[http://dx.doi.org/10.1089/jir.2012.0013] [PMID: 22909148]
[42]
Rusterholz C, Gupta AK, Huppertz B, Holzgreve W, Hahn S. Soluble factors released by placental villous tissue: Interleukin-1 is a potential mediator of endothelial dysfunction. Am J Obstet Gynecol 2005; 192(2): 618-24.[http://dx.doi.org/10.1016/j.ajog.2004.08.029] [PMID: 15696012]
[43]
Bakheeta MS, Seddikb MI, Eldarweshc A. Evaluation of TNF-A, nitric oxide, lipid profile, urea and creatinine serum levels for prediction of preeclampsia. Int J Res in Pharm and Biosci 2016; 3(5): 27-36.
[44]
Anita CH, Bhagyalakshmi A, Rekha C, Sujatharani A. A study of malondialdehyde and lipid profile in pregnancy-induced hypertension. Int J Pharm Bio Sci 2015; 6(4): 167-75.
[45]
Kalar MU, Fatima I, Nabila K, et al. Prevalence and predictors of postnatal depression in mothers of Karachi. Karachi Int J Collaborat Res Int Med Public health 2012; 4(5): 830-9.
[46]
Monica N, Kunder M, Shashidhar KN, Devi JG, Harish R. Biochemical evaluation of serum lipid profile and serum uric acid in preeclampsia. A Case-Control Study IOSR. J Pharm (Cairo) 2016; 6(10): 41-4.
[47]
Agarwal V, Gupta BK, Vishnu A, Mamtatyagi , Shiprasolanki , Kiran J. Association of lipid profile and uric acid with pre-eclampsia of third trimester in nullipara women. J Clin Diagn Res 2014; 8(7): CC04-7.[http://dx.doi.org/10.7860/JCDR/2014/7901.4533] [PMID: 25177559]
[48]
Gohil JT, Patel PK, Gupta P. Estimation of lipid profile in subjects of preeclampsia. J Obstet Gynaecol India 2011; 61(4): 399-403.[http://dx.doi.org/10.1007/s13224-011-0057-0] [PMID: 22851820]
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