The Role of Angiogenic and Antiangiogenic Factors in the Second Trimester in the Prediction of Preeclampsia in Pregnant Women with Type 1 Diabetes

Overview

Journal Diabetes Care

Specialty Endocrinology

Date 2013 Aug 8

PMID 23920083

Citations 11

Authors

Valerie A Holmes

Ian S Young

Christopher C Patterson

Michael J A Maresh

Donald W M Pearson

James D Walker

David R McCance

Affiliations

Soon will be listed here.

Abstract

Objective: To assess the association between circulating angiogenic and antiangiogenic factors in the second trimester and risk of preeclampsia in women with type 1 diabetes.

Research Design And Methods: Maternal plasma concentrations of placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), and soluble endoglin (sEng) were available at 26 weeks of gestation in 540 women with type 1 diabetes enrolled in the Diabetes and Preeclampsia Intervention Trial.

Results: Preeclampsia developed in 17% of pregnancies (n = 94). At 26 weeks of gestation, women in whom preeclampsia developed later had significantly lower PlGF (median [interquartile range]: 231 pg/mL [120-423] vs. 365 pg/mL [237-582]; P < 0.001), higher sFlt-1 (1,522 pg/mL [1,108-3,393] vs. 1,193 pg/mL [844-1,630] P < 0.001), and higher sEng (6.2 ng/mL [4.9-7.9] vs. 5.1 ng/mL[(4.3-6.2]; P < 0.001) compared with women who did not have preeclampsia. In addition, the ratio of PlGF to sEng was significantly lower (40 [17-71] vs. 71 [44-114]; P < 0.001) and the ratio of sFlt-1 to PlGF was significantly higher (6.3 [3.4-15.7] vs. 3.1 [1.8-5.8]; P < 0.001) in women who later developed preeclampsia. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to a logistic model containing established risk factors (area under the curve [AUC], 0.813) significantly improved the predictive value (AUC, 0.850 and 0.846, respectively; P < 0.01) and significantly improved reclassification according to the integrated discrimination improvement index (IDI) (IDI scores 0.086 and 0.065, respectively; P < 0.001).

Conclusions: These data suggest that angiogenic and antiangiogenic factors measured during the second trimester are predictive of preeclampsia in women with type 1 diabetes. The addition of the ratio of PlGF to sEng or the ratio of sFlt-1 to PlGF to established clinical risk factors significantly improves the prediction of preeclampsia in women with type 1 diabetes.

Citing Articles

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References

Levine R, Maynard S, Qian C, Lim K, England L, Yu K . Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004; 350(7):672-83. DOI: 10.1056/NEJMoa031884. View

Pencina M, DAgostino Sr R, DAgostino Jr R, Vasan R . Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2007; 27(2):157-72. DOI: 10.1002/sim.2929. View

Sibai B, Koch M, Freire S, Silva J, Rudge M, Martins-Costa S . Serum inhibin A and angiogenic factor levels in pregnancies with previous preeclampsia and/or chronic hypertension: are they useful markers for prediction of subsequent preeclampsia?. Am J Obstet Gynecol. 2008; 199(3):268.e1-9. DOI: 10.1016/j.ajog.2008.06.071. View

McCance D, Holmes V, Maresh M, Patterson C, Walker J, Pearson D . Vitamins C and E for prevention of pre-eclampsia in women with type 1 diabetes (DAPIT): a randomised placebo-controlled trial. Lancet. 2010; 376(9737):259-66. PMC: 2911677. DOI: 10.1016/S0140-6736(10)60630-7. View

McKeeman G, Ardill J, Caldwell C, Hunter A, Mcclure N . Soluble vascular endothelial growth factor receptor-1 (sFlt-1) is increased throughout gestation in patients who have preeclampsia develop. Am J Obstet Gynecol. 2004; 191(4):1240-6. DOI: 10.1016/j.ajog.2004.03.004. View

Persson M, Norman M, Hanson U . Obstetric and perinatal outcomes in type 1 diabetic pregnancies: A large, population-based study. Diabetes Care. 2009; 32(11):2005-9. PMC: 2768194. DOI: 10.2337/dc09-0656. View

Romero R, Nien J, Espinoza J, Todem D, Fu W, Chung H . A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a.... J Matern Fetal Neonatal Med. 2008; 21(1):9-23. PMC: 2587364. DOI: 10.1080/14767050701830480. View

Hlatky M, Greenland P, Arnett D, Ballantyne C, Criqui M, Elkind M . Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association. Circulation. 2009; 119(17):2408-16. PMC: 2956982. DOI: 10.1161/CIRCULATIONAHA.109.192278. View

Meis P, Goldenberg R, Mercer B, Iams J, Moawad A, Miodovnik M . The preterm prediction study: risk factors for indicated preterm births. Maternal-Fetal Medicine Units Network of the National Institute of Child Health and Human Development. Am J Obstet Gynecol. 1998; 178(3):562-7. DOI: 10.1016/s0002-9378(98)70439-9. View

10.

Powers R, Jeyabalan A, Clifton R, van Dorsten P, Hauth J, Klebanoff M . Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (PlGF) in preeclampsia among high risk pregnancies. PLoS One. 2010; 5(10):e13263. PMC: 2952583. DOI: 10.1371/journal.pone.0013263. View

11.

Maynard S, Karumanchi S . Angiogenic factors and preeclampsia. Semin Nephrol. 2011; 31(1):33-46. PMC: 3063446. DOI: 10.1016/j.semnephrol.2010.10.004. View

12.

Jensen D, Damm P, Moelsted-Pedersen L, Ovesen P, Westergaard J, Moeller M . Outcomes in type 1 diabetic pregnancies: a nationwide, population-based study. Diabetes Care. 2004; 27(12):2819-23. DOI: 10.2337/diacare.27.12.2819. View

13.

Levine R, Lam C, Qian C, Yu K, Maynard S, Sachs B . Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006; 355(10):992-1005. DOI: 10.1056/NEJMoa055352. View

14.

Maynard S, Min J, Merchan J, Lim K, Li J, Mondal S . Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003; 111(5):649-58. PMC: 151901. DOI: 10.1172/JCI17189. View

15.

Duley L, Henderson-Smart D, Meher S, King J . Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2007; (2):CD004659. DOI: 10.1002/14651858.CD004659.pub2. View

16.

Yu Y, Jenkins A, Nankervis A, Hanssen K, Scholz H, Henriksen T . Anti-angiogenic factors and pre-eclampsia in type 1 diabetic women. Diabetologia. 2008; 52(1):160-8. DOI: 10.1007/s00125-008-1182-x. View

17.

. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol. 2000; 183(1):S1-S22. View

18.

Brown M, Lindheimer M, de Swiet M, Van Assche A, Moutquin J . The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy. 2002; 20(1):IX-XIV. DOI: 10.1081/PRG-100104165. View

19.

Duley L . The global impact of pre-eclampsia and eclampsia. Semin Perinatol. 2009; 33(3):130-7. DOI: 10.1053/j.semperi.2009.02.010. View

20.

Perni U, Sison C, Sharma V, Helseth G, Hawfield A, Suthanthiran M . Angiogenic factors in superimposed preeclampsia: a longitudinal study of women with chronic hypertension during pregnancy. Hypertension. 2012; 59(3):740-6. DOI: 10.1161/HYPERTENSIONAHA.111.181735. View