Predictors for preeclampsia in pregnant women with diabetes mellitus
Based on the literature data, the authors have investigated a number of biomarkers and determined their relationship to the development of preeclampsia in women with pre-gestational diabetes mellitus in the first trimester of pregnancy. Due to the fact that there are similar mechanisms for these conditions, the early diagnosis of preeclampsia is significantly difficult in this patient category. The authors have assessed maternal risk factors and biophysical and biochemical markers and showed their role in the prediction of preeclampsia. It has been established that in the presence of diabetes mellitus, the study of certain hormones and the markers of the inflammatory response, oxidative stress, and lipid metabolism, and adipokines may be of potential value for the prediction of preeclampsia. However, pregnancy-associated proteins and angiogenic and antiangiogenic factors, which are strong predictors of preeclampsia in women without diabetes mellitus, are shown to be a valid diagnostic tool in diabetes mellitus. Despite conflicting data, insufficient experience, and the extent of examinations, it is impossible to draw an unambiguous conclusion about the role of biomarkers in the assessment of preeclampsia in the first trimester of pregnancy complicated by diabetes mellitus.Kapustin R.V., Tsybuk E.M.
Conclusion. Thus, the active introduction of biomarkers into practice requires further and more detailed study of this area and optimization of research design.
Keywords
preeclampsia
diabetes mellitus
biomarkers
References
- Poon L.C., Shennan A., Hyett J.A., Kapur A., Hadar E., Divakar H. et al. The International Federation of Gynecology and Obstetrics (FIGO) initiative on pre-eclampsia: A pragmatic guide for first-trimester screening and prevention. Int. J. Gynaecol. Obstet. 2019; 145(Suppl. 1): 1-33. https://dx.doi.org/10.1002/ijgo.12802.
- International Diabetes Federation. IDF diabetes atlas. 9th ed. Brussels; 2019. Accessed April 12, 2020.
- Saito S., ed. Preeclampsia. Comprehensive cynecology and obstetrics. Springer Nature; 2018. https://dx.doi.org/10.1007/978-981-10-5891-2.
- Weissgerber T.L., Mudd L.M. Preeclampsia and diabetes. Curr. Diab. Rep. 2015; 15(3): 9. https://dx.doi.org/10.1007/s11892-015-0579-4.
- Ottanelli S., Napoli A., Clemenza S., Mecacci F., Lapolla A., Metzger B.E. Hypertension and preeclampsia in pregnancy complicated by diabetes. Gestational diabetes. A Decade after the HAPO Study. Front. Diabetes. 2020; 28: 171-82. https://dx.doi.org/10.1159/000480173.
- Redman C.W., Sargent I.L. Preeclampsia and the systemic inflammatory response. Semin. Nephrol. 2004; 24(6): 565-70. https://dx.doi.org/10.1016/s0270-9295(04)00127-5.
- Wright D., Akolekar R., Syngelaki A., Poon L.C., Nicolaides K.H. A competing risks model in early screening for preeclampsia. Fetal Diagn. Ther. 2012; 32(3): 171-8. https://dx.doi.org/10.1159/000338470.
- Ekbom P., Damm P., Feldt-Rasmussen B., Feldt-Rasmussen U., Mølvig J., Mathiesen E.R. Pregnancy outcome in type 1 diabetic women with microalbuminuria. Diabetes Care. 2001; 24(10): 1739-44. https://dx.doi.org/10.2337/diacare.24.10.1739.
- Vestgaard M., Sommer M.C., Ringholm L., Damm P., Mathiesen E.R. Prediction of preeclampsia in type 1 diabetes in early pregnancy by clinical predictors: a systematic review. J. Matern. Fetal Neonatal Med. 2018; 31(14): 1933-9. https://dx.doi.org/10.1080/14767058.2017.1331429.
- O'Gorman N., Nicolaides K.H., Poon L.C. The use of ultrasound and other markers for early detection of preeclampsia. Womens Health (London). 2016; 12(2): 199-207. https://dx.doi.org/10.2217/whe.15.95.
- Холин А.М., Муминова К.Т., Нагоев Т.М., Ходжаева З.С., Гус А.И. Прогнозирование преэклампсии в первом триместре на основе клинико-анамнестических факторов, биомаркеров и 3D-энергетической допплеровской оценки васкуляризации плацентарного ложа. Акушерство и гинекология. 2018; 8: 56-65. [Kholin A.M., Muminova K.T., Nagoev T.M., Khodzhaeva Z.S., Gus A.I. First trimester prediction of preeclampsia based on maternal factors, biomarkers and 3D power doppler of placental bed vascularization. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; 8: 56-65. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.8.56-65.
- Bracero L.A., Schulman H. Doppler studies of the uteroplacental circulation in pregnancies complicated by diabetes. Ultrasound Obstet. Gynecol. 1991; 1(6): 391-4. https://dx.doi.org/10.1046/j.1469-0705.1991.01060391.x.
- Sun I.Y., Overgaard M.T., Oxvig C., Giudice L.C. Pregnancy-associated plasma protein A proteolytic activity is associated with the human placental trophoblast cell membrane. J. Clin. Endocrinol. Metab. 2002; 87(11): 5235-40. https://dx.doi.org/10.1210/jc.2002-020561.
- Anderson U.D., Olsson M.G., Kristensen K.H., Åkerström B., Hansson S.R. Review: Biochemical markers to predict preeclampsia. Placenta. 2012; 33(Suppl.): S42-7. https://dx.doi.org/10.1016/j.placenta.2011.11.021.
- Kharfi A., Giguère Y., De Grandpré P., Moutquin J.M., Forest J.C. Human chorionic gonadotropin (hCG) may be a marker of systemic oxidative stress in normotensive and preeclamptic term pregnancies. Clin. Biochem. 2005; 38(8): 717-21. https://dx.doi.org/10.1016/j.clinbiochem.2005.04.011.
- Savvidou M.D., Syngelaki A., Muhaisen M., Emelyanenko E., Nicolaides K.H. First trimester maternal serum free β-human chorionic gonadotropin and pregnancy-associated plasma protein A in pregnancies complicated by diabetes mellitus. BJOG. 2012; 119(4): 410-6. https://dx.doi.org/10.1111/j.1471-0528.2011.03253.x.
- Kapustin R.V., Kascheeva T.K., Alekseenkova E.N., Shelaeva E.V. Are the first-trimester levels of PAPP-A and fb-hCG predictors for obstetrical complications in diabetic pregnancy? J. Matern. Fetal Neonatal Med. 2020; March 30: 1-7. https://dx.doi.org/10.1080/14767058.2020.1743658.
- Muttukrishna S., Knight P.G., Groome N.P., Redman C.W., Ledger W.L. Activin A and inhibin A as possible endocrine markers for pre-eclampsia. Lancet. 1997; 349(9061): 1285-8. https://dx.doi.org/10.1016/s0140-6736(96)09264-1.
- Ekbom P., Damm P., Andersson A.M., Skakkebaek N.E., Feldt-Rasmussen U., Mathiesen E.R. Serum levels of activin A and inhibin A are not related to the increased susceptibility to pre-eclampsia in type I diabetic pregnancies. Acta Obstet. Gynecol. Scand. 2006; 85(2): 143-7. https://dx.doi.org/10.1080/00016340500345311.
- Sebire N.J., Roberts L., Noble P., Wallace E., Nicolaides K.H. Raised maternal serum inhibin A concentration at 10 to 14 weeks of gestation is associated with pre-eclampsia. BJOG. 2000; 107(6): 795-7. https://dx.doi.org/10.1111/j.1471-0528.2000.tb13343.x.
- Tihtonen K.M., Kööbi T., Vuolteenaho O., Huhtala H.S., Uotila J.T. Natriuretic peptides and hemodynamics in preeclampsia. Am. J. Obstet. Gynecol. 2007; 196(4): 328. e1-328. e3287. https://dx.doi.org/10.1016/j.ajog.2006.11.033.
- Ringholm L., Pedersen-Bjergaard U., Thorsteinsson B., Boomsma F., Damm P., Mathiesen E.R. Atrial Natriuretic Peptide (ANP) in early pregnancy is associated with development of preeclampsia in type 1 diabetes. Diabetes Res. Clin. Pract. 2011; 93(3): e106-9. https://dx.doi.org/10.1016/j.diabres.2011.06.007.
- Brewer J., Liu R., Lu Y., Scott J., Wallace K., Wallukat G. et al. Endothelin-1, oxidative stress, and endogenous angiotensin II: mechanisms of angiotensin II type I receptor autoantibody-enhanced renal and blood pressure response during pregnancy. Hypertension. 2013; 62(5): 886-92. https://dx.doi.org/10.1161/HYPERTENSIONAHA.113.01648.
- Ringholm L., Pedersen-Bjergaard U., Thorsteinsson B., Boomsma F., Damm P., Mathiesen E.R. A high concentration of prorenin in early pregnancy is associated with development of pre-eclampsia in women with type 1 diabetes. Diabetologia. 2011; 54(7): 1615-9. https://dx.doi.org/10.1007/s00125-011-2087-7.
- Wang A., Rana S., Karumanchi S.A. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda). 2009; 24: 147-58. https://dx.doi.org/10.1152/physiol.00043.2008.
- Ahmad S., Ahmed A. Elevated placental soluble vascular endothelial growth factor receptor-1 inhibits angiogenesis in preeclampsia. Circ. Res. 2004; 95(9): 884-91. https://dx.doi.org/10.1161/01.RES.0000147365.86159.f5.
- Ходжаева З.С., Холин А.М., Шувалова М.П., Иванец Т.Ю., Демура С.А., Галичкина И.В. Российская модель оценки эффективности теста на преэклампсию sFlt-1/PlGF. Акушерство и гинекология. 2019; 2: 52-8. [Khodzhaeva Z.S., Kholin A.M., Shuvalova M.P., Ivanets T.Y., Demura S.A., Galichkina I.V. A Russian model for evaluating the efficiency of the sFlt-1/PlGF test for preeclampsia. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2019; 2: 52-8. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.2.52-58.
- Venkatesha S., Toporsian M., Lam C., Hanai J., Mammoto T., Kim Y.M. et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat. Med. 2006; 12(6): 642-9. https://dx.doi.org/10.1038/nm1429.
- Yu Y., Jenkins A.J., Nankervis A.J., Hanssen K.F., Scholz H., Henriksen T. et al. Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women. Diabetologia. 2009; 52(1): 160-8. https://dx.doi.org/10.1007/s00125-008-1182-x.
- Cohen A.L., Wenger J.B., James-Todd T., Lamparello B.M., Halprin E., Serdy S. et al. The association of circulating angiogenic factors and HbA1c with the risk of preeclampsia in women with preexisting diabetes. Hypertens. Pregnancy. 2014; 33(1): 81-92. https://dx.doi.org/10.3109/10641955.2013.837175.
- Holmes V.A., Young I.S., Patterson C.C., Maresh, M.J., Pearson D.W. et al. The role of angiogenic and antiangiogenic factors in the second trimester in the prediction of preeclampsia in pregnant women with type 1 diabetes. Diabetes Care. 2013; 36(11): 3671-7. https://dx.doi.org/10.2337/dc13-0944.
- Salazar Garcia M.D., Mobley Y., Henson J., Davies M., Skariah A., Dambaeva S. et al. Early pregnancy immune biomarkers in peripheral blood may predict preeclampsia. J. Reprod. Immunol. 2018; 125: 25-31. https://dx.doi.org/10.1016/j.jri.2017.10.048.
- De Jonge L.L., Steegers E.A.P., Ernst G.D.S., Lindeman J., Russcher H., Hofman A. et al. C-reactive protein levels, blood pressure and the risks of gestational hypertensive complications. J. Hypertens. 2011; 29(12): 2413-21. https://dx.doi.org/10.1097/hjh.0b013e32834c58e5.
- Du M., Basu A., Fu D., Wu M., Centola M., Jenkins A.J. et al. Serum inflammatory markers and preeclampsia in type 1 diabetes: a prospective study. Diabetes Care. 2013; 36(7): 2054-61. https://dx.doi.org/10.2337/dc12-1934.
- Hauguel-de Mouzon S., Lepercq J., Catalano P. The known and unknown of leptin in pregnancy. Am. J. Obstet. Gynecol. 2006; 194(6): 1537-45. https://dx.doi.org/10.1016/j.ajog.2005.06.064.
- Song Y., Gao J., Qu Y., Wang S., Wang X., Liu J. Serum levels of leptin, adiponectin and resistin in relation to clinical characteristics in normal pregnancy and preeclampsia. Clin. Chim. Acta. 2016; 458: 133-7. https://dx.doi.org/10.1016/j.cca.2016.04.036.
- Kelly C.B., Hookham M.B., Yu J.Y., Lockhart S.M., Du M., Jenkins A.J. et al. Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes. Diabetologia. 2017; 60(12): 2514-24. https://dx.doi.org/10.1007/s00125-017-4415-z.
- Nien J.K., Mazaki-Tovi S., Romero R., Erez O., Kusanovic J.P., Gotsch F. et al. Adiponectin in severe preeclampsia. J. Perinat. Med. 2007; 35(6): 503-12. https://dx.doi.org/10.1515/JPM.2007.121.
- D'Anna R., Baviera G., Corrado F., Giordano D., Di Benedetto A., Jasonni V.M. Plasma adiponectin concentration in early pregnancy and subsequent risk of hypertensive disorders. Obstet. Gynecol. 2005; 106(2): 340-4. https://dx.doi.org/10.1097/01.AOG.0000168441.79050.03.
- Wotherspoon A.C., Young I.S., McCance D.R., Patterson C.C., Maresh M.J., Pearson D.W. et al. Serum fatty acid binding protein 4 (FABP4) predicts pre-eclampsia in women with type 1 diabetes. Diabetes Care. 2016; 39(10): 1827-9. https://dx.doi.org/10.2337/dc16-0803.
- Капустин Р.В., Аржанова О.Н., Тиселько А.В. Оксидативный стресс у беременных с сахарным диабетом. Сахарный диабет. 2017; 20(6): 461-71. [Kapustin R.V., Arzhanova O.N., Tiselko A.V. Oxidative stress in pregnant women with diabetes mellitus. Diabetes mellitus. 2017; 20(6): 461-71. (in Russian)]. https://doi.org/ 10.14341/DM8669.
- Lappas M., Hiden U., Desoye G., Froehlich J., Hauguel-de Mouzon S., Jawerbaum A. The role of oxidative stress in the pathophysiology of gestational diabetes mellitus. Antioxid. Redox Signal. 2011; 15(12): 3061-100. https://dx.doi.org/10.1089/ars.2010.3765.
- Ahmad I.M., Zimmerman M.C., Moore T.A. Oxidative stress in early pregnancy and the risk of preeclampsia. Pregnancy Hypertens. 2019; 18: 99-102. https://doi.org/10.1016/j.preghy.2019.09.014.
- Kalea A.Z., Schmidt A.M., Hudson B.I. RAGE: a novel biological and genetic marker for vascular disease. Clin. Sci. (Lond.). 2009; 116(8): 621-37. https://dx.doi.org/10.1042/CS20080494.
- Yu Y., Hanssen K.F., Kalyanaraman V., Chirindel A., Jenkins A.J., Nankervis A.J. et al. Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes. BJOG. 2012; 119(12): 1512-20. https://dx.doi.org/10.1111/j.1471-0528.2012.03463.x.
- Harsem N.K., Braekke K., Staff A.C. Augmented oxidative stress as well as antioxidant capacity in maternal circulation in preeclampsia. Eur. J. Obstet. Gynecol. Reprod. Biol. 2006; 128(1-2): 209-15. https:/dx./doi.org/10.1016/j.ejogrb.2005.11.014.
- Cuffe J.S., Xu Z.C., Perkins A.V. Biomarkers of oxidative stress in pregnancy complications. Biomark, Med. 2017; 11(3): 295-306. https://dx.doi.org/10.2217/bmm-2016-0250.
- Harsem N.K., Braekke K., Torjussen T., Hanssen K., Staff A.C. Advanced glycation end products in pregnancies complicated with diabetes mellitus or preeclampsia. Hypertens. Pregnancy. 2008; 27(4): 374-86. https://dx.doi.org/10.1080/10641950802000968.
- Johnston P.C., Powell L.A., McCance D.R., Pogue K., McMaster C., Gilchrist S. et al. Placental protein tyrosine nitration and MAPK in type 1 diabetic pre-eclampsia: Impact of antioxidant vitamin supplementation. J. Diabetes Complications. 2013; 27(4): 322-7. https://dx.doi.org/10.1016/j.jdiacomp.2013.02.001.
- Böger R.H., Diemert A., Schwedhelm E., Lüneburg N., Maas R., Hecher K. The role of nitric oxide synthase inhibition by asymmetric dimethylarginine in the pathophysiology of preeclampsia. Gynecol. Obstet. Invest. 2010; 69(1): 1-13. https://dx.doi.org/10.1159/000245940.
- Sertkaya A.C., Kafkasli A., Turkcuoglu I., Karabulut A.B. Asymmetric dimethylarginine level in hyperglycemic gestation. Endocrine. 2011; 40(2): 237-42. https://dx.doi.org/10.1007/s12020-011-9461-6.
- El Khouly N.I., Sanad Z.F., Saleh S.A., Shabana A.A., Elhalaby A.F., Badr E.E. Value of first-trimester serum lipid profile in early prediction of preeclampsia and its severity: A prospective cohort study. Hypertens. Pregnancy. 2016; 35(1): 73-81. https:/dx./doi.org/10.3109/10641955.2015.1115060.
- Enquobahrie D.A., Williams M.A., Butler C.L., Frederick I.O., Miller R.S., Luthy D.A. Maternal plasma lipid concentrations in early pregnancy and risk of preeclampsia. Am. J. Hypertens. 2004; 17(7): 574-81. https://dx.doi.org/10.1016/j.amjhyper.2004.03.666.
- Toescu V., Nuttall S.L., Martin U., Kendall M.J., Dunne F. Oxidative stress and normal pregnancy. Clin. Endocrinol. (Oxf.). 2002; 57(5): 609-13. https://dx.doi.org/10.1046/j.1365-2265.2002.01638.x.
- Basu A., Alaupovic P., Wu M., Jenkins A.J., Yu Y., Nankervis A.J. et al. Plasma lipoproteins and preeclampsia in women with type 1 diabetes: a prospective study. J. Clin. Endocrinol. Metab. 2012; 97(5): 1752-62. https://dx.doi.org/10.1210/jc.2011-3255.
Received 16.06.2020
Accepted 05.10.2020
About the Authors
Roman V. Kapustin, PhD, MD, Secretary Scientific, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, St. Petersburg, Russia; Associate Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, Medical Faculty, St. Petersburg State University, St. Petersburg, Russia.Tel.: +7(812)328-98-68. E-mail: kapustin.roman@gmail.com. 199034, Russia, Saint Petersburg, Mendeleevskaya Line, 3.
Elizaveta M. Tcybuk, student, Department of Obstetrics, Gynecology and Reproduction, Faculty of Medicine, St. Petersburg State University, St. Petersburg, Russia.
Tel.: +7(911)193-55-60. E-mail: elizavetatcybuk@gmail.com. 199034, Russia, Saint Petersburg, Universitetskaya nab., 7–9.
For citation: Kapustin R.V., Tsybuk E.M. Predictors for preeclampsia in pregnant women with diabetes mellitus.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2020; 12: 54-61 (in Russian)
https://dx.doi.org/10.18565/aig.2020.12.54-61