Extended combined screening for preeclampsia prediction in women with diabetes mellitus

Abstract

BACKGROUND: Early screening for preeclampsia has shown high efficiency for low-risk groups, however, the presence of systemic vascular disease in patients with diabetes mellitus complicates their use and requires the development of additional approaches to predicting preeclampsia in this group of patients.

AIM: The aim of this study was to evaluate the effectiveness of early prediction of preeclampsia with extended combined screening in patients with pregestational types of diabetes mellitus.

MATERIALS AND METHODS: This study included 75 pregnant women: 40 patients with type 1 diabetes mellitus, and 35 patients with type 2 diabetes mellitus. To determine the risk of further preeclampsia development, we evaluated biochemical, biophysical and anamnestic factors, along with the serum levels of placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin at 11⁺⁰ to 13⁺⁶ gestational weeks. The main outcome assessed was the development of preeclampsia.

RESULTS: In patients with further development of preeclampsia (35% in type 1 and 40 % in type 2 diabetic women), we observed higher soluble fms-like tyrosine kinase 1 / placental growth factor ratios, as well as elevated serum soluble endoglin (type 1 diabetes mellitus) and soluble fms-like tyrosine kinase 1 (type 2 diabetes mellitus) levels. Isolated determination of placental growth factor showed no significant differences in the levels of this angiogenic factor in preeclampsia. A multivariate predictive model for preeclampsia demonstrated high prognostic parameters: for patients with type 1 diabetes mellitus, area under the curve was 0.96 (95% confidence interval 0.93–1.00), with positive predictive value 76.7% and negative predictive value 90.1%; for patients with type 2 diabetes mellitus, area under the curve was 0.94 (95% confidence interval 0.86–1.00), with positive predictive value 88.5% and negative predictive value 97.1%.

CONCLUSIONS: Specific biochemical and biophysical markers of preeclampsia combined with maternal risk factors and assessment of carbohydrate metabolism can increase the predictive value of early screening studies for preeclampsia in women with pregestational diabetes mellitus.

Keywords

preeclampsia / diabetes mellitus / placenta growth factor / soluble fms-like tyrosine kinase-1 / soluble endoglin / the ratio of the activity of soluble fms-like tyrosine kinase-1 to the level of placental growth factor

References

[1] International Diabetes Federation. IDF Diabetes Atlas. Brussels; 2021 [cited 2023 Mar 21]. Available from: http://www.indiaenvironmentportal.org.in/files/file/diabetes%20atlas%202021.pdf

[2] International Diabetes Federation. IDF diabetes atlas. Brussels; 2021 [дата обращения 21.03.2023]. Доступ по ссылке: http://www.indiaenvironmentportal.org.in/files/file/diabetes%20atlas%202021.pdf

[3] Weissgerber TL, Mudd LM. Preeclampsia and diabetes. Curr Diab Rep. 2015;15(3):9. DOI: 10.1007/s11892-015-0579-4

[4] Weissgerber T.L., Mudd L.M. Preeclampsia and diabetes // Curr. Diab. Rep. 2015. Vol. 15. No. 3. P. 9. DOI: 10.1007/s11892-015-0579-4

[5] Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda). 2009;24:147–158. DOI: 10.1152/physiol.00043.2008

[6] Wang A., Rana S., Karumanchi S.A. Preeclampsia: the role of angiogenic factors in its pathogenesis // Physiology (Bethesda). 2009. Vol. 24. P. 147–158. DOI: 10.1152/physiol.00043.2008

[7] Nirupama R, Divyashree S, Janhavi P, et al. Preeclampsia: pathophysiology and management. J Gynecol Obstet Hum Reprod. 2021;50(2). DOI: 10.1016/j.jogoh.2020.101975

[8] Nirupama R., Divyashree S., Janhavi P., et al. Preeclampsia: pathophysiology and management // J. Gynecol. Obstet. Hum. Reprod. 2021. Vol. 50. No. 2. DOI: 10.1016/j.jogoh.2020.101975

[9] Chau K, Hennessy A, Makris A. Placental growth factor and pre-eclampsia. J Hum Hypertens. 2017;31(12):782–786. DOI: 10.1038/jhh.2017.61

[10] Chau K., Hennessy A., Makris A. Placental growth factor and preeclampsia // J. Hum. Hypertens. 2017. Vol. 31. No. 12. P. 782–786. DOI: 10.1038/jhh.2017.61

[11] Rana S, Burke SD, Karumanchi SA. Imbalances in circulating angiogenic factors in the pathophysiology of preeclampsia and related disorders. Am J Obstet Gynecol. 2022;226(2):S1019–S1034. DOI: 10.1016/j.ajog.2020.10.022

[12] Rana S., Burke S.D., Karumanchi S.A. Imbalances in circulating angiogenic factors in the pathophysiology of preeclampsia and related disorders // Am. J. Obstet. Gynecol. 2022. Vol. 226. No. 2. P. S1019–S1034. DOI: 10.1016/j.ajog.2020.10.022

[13] Perucci LO, Gomes KB, Freitas LG, et al. Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis factor alpha receptors in different clinical manifestations of preeclampsia. PLoS One. 2014;9(5). DOI: 10.1371/journal.pone.0097632

[14] Perucci L.O., Gomes K.B., Freitas L.G., et al. Soluble endoglin, transforming growth factor-Beta 1 and soluble tumor necrosis factor alpha receptors in different clinical manifestations of preeclampsia // PLoS One. 2014. Vol. 9. No. 5. DOI: 10.1371/journal.pone.0097632

[15] Majali-Martinez A, Weiss-Fuchs U, Miedl H, et al. Type 1 diabetes mellitus and the first trimester placenta: hyperglycemia-induced effects on trophoblast proliferation, cell cycle regulators, and invasion. Int J Mol Sci. 2021;22(20). DOI: 10.3390/ijms222010989

[16] Majali-Martinez A., Weiss-Fuchs U., Miedl H., et al. Type 1 diabetes mellitus and the first trimester placenta: hyperglycemia-induced effects on trophoblast proliferation, cell cycle regulators, and invasion // Int. J. Mol. Sci. 2021. Vol. 22, No. 20. DOI: 10.3390/ijms222010989

[17] Ottanelli S, Napoli A, Clemenza S, et al. Hypertension and preeclampsia in pregnancy complicated by diabetes. In: Gestational diabetes. A decade after the HAPO study. Ed. by A. Lapolla, B.E. Metzger. Vol. 28. Basel: Karger; 2020: 171–182. DOI: 10.1159/000480173

[18] Ottanelli S., Napoli A., Clemenza S., et al. Hypertension and preeclampsia in pregnancy complicated by diabetes // Gestational Diabetes. A Decade after the HAPO Study / Ed. by A. Lapolla, B.E. Metzger. Vol. 28. Basel: Karger, 2020. P. 171–182. DOI: 10.1159/000480173

[19] Powers RW, Jeyabalan A, Clifton RG, et al. Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies. PLoS One. 2010;5(10). DOI: 10.1371/journal.pone.0013263

[20] Powers R.W., Jeyabalan A., Clifton R.G., et al. Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies // PLoS One. 2010. Vol. 5. No. 10. DOI: 10.1371/journal.pone.0013263

[21] Cohen AL, Wenger JB, James-Todd T, 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. DOI: 10.3109/10641955.2013.837175

[22] Cohen A.L., Wenger J.B., James-Todd T., et al. The association of circulating angiogenic factors and HbA1c with the risk of preeclampsia in women with preexisting diabetes // Hypertens Pregnancy. 2014. Vol. 33. No. 1. P. 81–92. DOI: 10.3109/10641955.2013.837175

[23] Yu Y, Jenkins AJ, Nankervis AJ, et al. Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women. Diabetologia. 2009. Vol. 52. No. 1. P. 160–168. DOI: 10.1007/s00125-008-1182-x

[24] Yu Y., Jenkins A.J., Nankervis A.J., et al. Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women // Diabetologia. 2009. Vol. 52. No. 1. P. 160–168. DOI: 10.1007/s00125-008-1182-x

[25] Tan MY, Syngelaki A, Poon LC, et al. Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation. Ultrasound Obstet Gynecol. 2018;52(2):186–195. DOI: 10.1002/uog.19112

[26] Tan M.Y., Syngelaki A., Poon L.C., et al. Screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks’ gestation // Ultrasound Obstet. Gynecol. 2018. Vol. 52. No. 2. P. 186–195. DOI: 10.1002/uog.19112

[27] Crovetto F, Figueras F, Triunfo S, et al. First trimester screening for early and late preeclampsia based on maternal characteristics, biophysical parameters, and angiogenic factors. Prenat Diagn. 2015;35(2):183–191. DOI: 10.1002/pd.4519

[28] Crovetto F., Figueras F., Triunfo S., et al. First trimester screening for early and late preeclampsia based on maternal characteristics, biophysical parameters, and angiogenic factors // Prenat. Diagn. 2015. Vol. 35. No. 2. P. 183–191. DOI: 10.1002/pd.4519

[29] Standards of specializes diabetes care. Ed. by I.I. Dedov, M.V. Shestakova, A.Yu. Mayorov. Moscow; 2021. (In Russ.) [cited 2023 Mar 21]. Available from: https://www.endocrincentr.ru/sites/default/files/specialists/science/clinic-recomendations/alg_book_10_final_.pdf

[30] Алгоритмы специализированной медицинской помощи больным сахарным диабетом / под ред. И.И. Дедова, М.В. Шестаковой, А.Ю. Майорова. Вып. 10. Москва, 2021 [дата обращения 21.03.2023]. Доступ по ссылке: https://www.endocrincentr.ru/sites/default/files/specialists/science/clinic-recomendations/alg_book_10_final_.pdf

[31] Brown MA, Magee LA, Kenny LC, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(1):24–43. DOI: 10.1161/HYPERTENSIONAHA.117.10803

[32] Brown M.A., Magee L.A., Kenny L.C., et al. Hypertensive disorders of pregnancy: isshp classification, diagnosis, and management recommendations for international practice // Hypertension. 2018. Vol. 72. No. 1. P. 24–43. DOI: 10.1161/HYPERTENSIONAHA.117.10803

[33] Bhide A, Acharya G, Baschat A, et al. ISUOG practice guidelines (updated): use of Doppler velocimetry in obstetrics. Ultrasound Obstet Gynecol. 2021;58(2):331–339. DOI: 10.1002/uog.23698

[34] Bhide A., Acharya G., Baschat A., et al. ISUOG practice guidelines (updated): use of Doppler velocimetry in obstetrics // Ultrasound Obstet. Gynecol. 2021. Vol. 58. No. 2. P. 331–339. DOI: 10.1002/uog.23698

[35] Smirnov IV, Gryazeva IV, Vasileva MY, et al. New highly sensitive sandwich ELISA system for soluble endoglin quantification in different biological fluids. Scand J Clin Lab Invest. 2018;78(6):515–523. DOI: 10.1080/00365513.2018.1516892

[36] Smirnov I.V., Gryazeva I.V., Vasileva M.Y., et al. New highly sensitive sandwich ELISA system for soluble endoglin quantification in different biological fluids // Scand. J. Clin. Lab. Invest. 2018. Vol. 78. No. 6. P. 515–523. DOI: 10.1080/00365513.2018.1516892

[37] Kapustin RV, Kopteeva EV, Alekseenkova EN, et al. Prediction of preeclampsia based on maternal serum endoglin level in women with pregestational diabetes mellitus. Hypertens Pregnancy. 2022;41(3–4):173–180. DOI: 10.1080/10641955.2022.2068574

[38] Kapustin R.V., Kopteeva E.V., Alekseenkova E.N., et al. Prediction of preeclampsia based on maternal serum endoglin level in women with pregestational diabetes mellitus // Hypertens Pregnancy. 2022. Vol. 41. No. 3–4. P. 173–180. DOI: 10.1080/10641955.2022.2068574

[39] Kapustin RV, Tcybuk EM, Chepanov SV, et al. Evaluation of sFlt-1 and PlGF for predicting preeclampsia in pregnant women with diabetes mellitus. Journal of Obstetrics and Women’s Diseases. 2021;70(4):43–56. (In Russ). DOI: 10.17816/JOWD64108

[40] Капустин Р.В., Цыбук Е.М., Чепанов С.В., и др. Оценка уровня растворимой fms-подобной тирозинкиназы-1 и плацентарного фактора роста для предикции развития преэклампсии у беременных с сахарным диабетом // Журнал акушерства и женских болезней. 2021. Т. 70. № 4. C. 43–56. DOI: 10.17816/JOWD64108

[41] Levine RJ, Lam C, Qian C, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355(10):992–1005. DOI: 10.1056/NEJMoa055352

[42] Levine R.J., Lam C., Qian C., et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia // N. Engl. J. Med. 2006. Vol. 355. No. 10. P. 992–1005. DOI: 10.1056/NEJMoa055352

[43] Cohen A, Lim KH, Lee Y, et al. Circulating levels of the antiangiogenic marker soluble FMS-like tyrosine kinase 1 are elevated in women with pregestational diabetes and preeclampsia: angiogenic markers in preeclampsia and preexisting diabetes. Diabetes Care. 2007;30(2):375–377. DOI: 10.2337/dc06-1514

[44] Cohen A., Lim K.H., Lee Y., et al. Circulating levels of the antiangiogenic marker soluble FMS-like tyrosine kinase 1 are elevated in women with pregestational diabetes and preeclampsia: angiogenic markers in preeclampsia and preexisting diabetes // Diabetes Care. 2007. Vol. 30. No. 2. P. 375–377. DOI: 10.2337/dc06-1514

[45] Moore Simas TA, Crawford SL, Solitro MJ, et al. Angiogenic factors for the prediction of preeclampsia in high-risk women. Am J Obstet Gynecol. 2007;197(3):244.e1–244.e2448. DOI: 10.1016/j.ajog.2007.06.030

[46] Moore Simas T.A., Crawford S.L., Solitro M.J., et al. Angiogenic factors for the prediction of preeclampsia in high-risk women // Am. J. Obstet. Gynecol. 2007. Vol. 197. No. 3. P. 244.e1–244.e2448. DOI: 10.1016/j.ajog.2007.06.030

[47] Zen M, Padmanabhan S, Zhang K, et al. Urinary and serum angiogenic markers in women with preexisting diabetes during pregnancy and their role in preeclampsia prediction. Diabetes Care. 2020;43(1):67–73. DOI: 10.2337/dc19-0967

[48] Zen M., Padmanabhan S., Zhang K., et al. Urinary and serum angiogenic markers in women with preexisting diabetes during pregnancy and their role in preeclampsia prediction // Diabetes Care. 2020. Vol. 43. No. 1. P. 67–73. DOI: 10.2337/dc19-0967

[49] Holmes VA, Young IS, Patterson CC, 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):3671–3677. DOI: 10.2337/dc13-0944

[50] Holmes V.A., Young I.S., Patterson C.C., 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. Vol. 36. No. 11. P. 3671–3677. DOI: 10.2337/dc13-0944

RIGHTS & PERMISSIONS

Eсо-Vector