Angiogenic markers could predict adverse pregnancy outcomes

Ying Xing1, Lina Wen1, Jia Zhang1, Haiyan Li1, Jing Ma1
1Department of Gynecology and Obstetrics, Department of Gynecology, Department of Pediatrics, Second Hospital of Hebei Medical University, Shijiazhuang, China

Tóm tắt

Adverse pregnancy outcomes (APOs) have been a devastating actuality in clinic. However, the pre-onset risk factors, that correlated with pregnancy failure, including antiphospholipid antibodies (APLs) and angiogenic factors, remain unclear. A retrospective study was performed in this research, and data from 145 pregnant women were collected during their pregnancy. Patients were finally divided into non-APO group (n = 89) and APO group (n = 56) according to their pregnancy outcomes. The associations among their characteristics, laboratory tests, therapies, and outcomes were analyzed. Univariate analysis demonstrated that patients with APOs showed significant prevalence of lupus anticoagulant (LAC) positive (P < 0.001), antiphospholipid syndrome (P = 0.030), and heparin prior to pregnancy (P = 0.041). LAC positive was correlated with shorter gestational age (P = 0.043) and gestational weeks of pre-term delivery (P = 0.011). Increased ratio of soluble vascular endothelial growth factor receptor-1/placental growth factor in pregnancies with APLs was correlated with the APOs and worse neonatal outcomes, including gestational age (P = 0.028), fetal death (P = 0.011), gestational weeks of pre-term delivery (P = 0.002), and birth weight percentile (P = 0.016). Angiogenic markers in pregnancies with APLs were correlated with the incidence of APOs.

Từ khóa


Tài liệu tham khảo

Kyei NNA, Boakye D, Gabrysch S. Maternal mycotoxin exposure and adverse pregnancy outcomes: a systematic review. Mycotoxin Res. 2020;36:243–55. Ge GM, Leung MTY, Man KKC, Leung WC, Ip P, Li GHY, Wong ICK, Kung AWC, Cheung CL. Maternal thyroid dysfunction during pregnancy and the risk of adverse outcomes in the offspring: a systematic review and meta-analysis. J Clin Endocr Metab. 2020. https://doi.org/10.1210/clinem/dgaa555. Cutts JC, Agius PA, Zaw L, Powell R, Moore K, Draper B, Simpson JA, Fowkes FJI. Pregnancy-specific malarial immunity and risk of malaria in pregnancy and adverse birth outcomes: a systematic review. BMC Med. 2020;18:14. Griffin M, Heazell AEP, Chappell LC, Zhao J, Lawlor DA. The ability of late pregnancy maternal tests to predict adverse pregnancy outcomes associated with placental dysfunction (specifically fetal growth restriction and pre-eclampsia): a protocol for a systematic review and meta-analysis of prognostic accuracy studies. Syst Rev. 2020;9:78. Rodriguez-Almaraz ME, Herraiz I, Gomez-Arriaga PI, Vallejo P, Gonzalo-Gil E, Usategui A, Lopez-Jimenez EA, Galindo A, Galindo M. The role of angiogenic biomarkers and uterine artery doppler in pregnant women with systemic lupus erythematosus or antiphospholipid syndrome. Pregnancy Hypertens. 2018;11:99–104. Arslan E, Branch DW. Antiphospholipid syndrome: Diagnosis and management in the obstetric patient. Best Pract Res Clin Obstet Gynaecol. 2020;64:31–40. Pignatelli P, Ettorre E, Menichelli D, Pani A, Violi F, Pastori D. Seronegative antiphospholipid syndrome: refining the value of “non-criteria” antibodies for diagnosis and clinical management. Haematologica. 2020;105:562–72. De Carolis S, Tabacco S, Rizzo F, Giannini A, Botta A, Salvi S, Garufi C, Benedetti Panici P, Lanzone A. Antiphospholipid syndrome: an update on risk factors for pregnancy outcome. Autoimmun Rev. 2018;17:956–66. Gibbins KJ, Mumford SL, Sjaarda LA, Branch DW, Perkins NJ, Ye A, Schisterman EF, Silver RM. Preconception antiphospholipid antibodies and risk of subsequent early pregnancy loss. Lupus. 2018;27:1437–45. Sciascia S, Hunt BJ, Talavera-Garcia E, Lliso G, Khamashta MA, Cuadrado MJ: The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am J Obstet Gynecol. 2016;214:273 e271–273 e278. Fischer-Betz R, Specker C. Pregnancy in systemic lupus erythematosus and antiphospholipid syndrome. Best Pract Res Clin Rheumatol. 2017;31:397–414. Andreoli L, Bertsias GK, Agmon-Levin N, Brown S, Cervera R, Costedoat-Chalumeau N, Doria A, Fischer-Betz R, Forger F, Moraes-Fontes MF, Khamashta M, King J, Lojacono A, Marchiori F, Meroni PL, Mosca M, Motta M, Ostensen M, Pamfil C, Raio L, Schneider M, Svenungsson E, Tektonidou M, Yavuz S, Boumpas D, Tincani A. EULAR recommendations for women’s health and the management of family planning, assisted reproduction, pregnancy and menopause in patients with systemic lupus erythematosus and/or antiphospholipid syndrome. Ann Rheum Dis. 2017;76:476–85. Graupner O, Karge A, Flechsenhar S, Seiler A, Haller B, Ortiz JU, Lobmaier SM, Axt-Fliedner R, Enzensberger C, Abel K, Kuschel B. Role of sFlt-1/PlGF ratio and feto-maternal doppler for the prediction of adverse perinatal outcome in late-onset pre-eclampsia. Arch Gynecol Obstet. 2020;301:375–85. Kim MY, Buyon JP, Guerra MM, Rana S, Zhang D, Laskin CA, Petri M, Lockshin MD, Sammaritano LR, Branch DW, Porter TF, Merrill JT, Stephenson MD, Gao Q, Karumanchi SA, Salmon JE. Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: results of the PROMISSE study. Am J Obstet Gynecol. 2016;214:108 e101-108 e114. Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennstrom M, Olovsson M, Brennecke SP, Stepan H, Allegranza D, Dilba P, Schoedl M, Hund M, Verlohren S. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016;374:13–22. Triggianese P, Lattavo G, Chimenti MS, Conigliaro P, Perricone R, Perricone C, De Carolis C. Reproductive outcomes 20 years after the intravenous immunoglobulin treatment in women with recurrent pregnancy losses. Am J Reprod Immunol. 2020;83:e13224. Triggianese P, Conigliaro P, Chimenti MS, Barbato C, Greco E, Kroegler B, De Carolis C, Perricone R. Systemic sclerosis: exploring the potential interplay between thyroid disorders and pregnancy outcome in an italian cohort. Isr Med Assoc J. 2017;19:473–7. Cui L, Shu C, Liu Z, Tong W, Cui M, Wei C, Tang JJ, Liu X, Hu J, Jiang J, He J, Zhang DY, Ye F, Li Y. The expression of serum sEGFR, sFlt-1, sEndoglin and PLGF in preeclampsia. Preg Hypertens. 2018;13:127–32. Cochery-Nouvellon E, Mercier E, Bouvier S, Balducchi JP, Quere I, Perez-Martin A, Mousty E, Letouzey V, Gris JC. Obstetric antiphospholipid syndrome: early variations of angiogenic factors are associated with adverse outcomes. Haematologica. 2017;102:835–42. Mayer-Pickel K, Stern C, Eberhard K, Lang U, Obermayer-Pietsch B, Cervar-Zivkovic M. Angiogenic factors in pregnancies of women with antiphospholipid syndrome and systemic lupus erythematosus. J Reprod Immunol. 2018;127:19–23. Akdogan N, Demircan C, Bolek EC, Gokoz O, Karaduman A. Indeterminate cell histiocytosis in a patient with systemic lupus erythematosus and antiphospholipid antibody syndrome: an unusual association. Lupus. 2020;29:74–8. Negrini S, Pappalardo F, Murdaca G, Indiveri F, Puppo F. The antiphospholipid syndrome: from pathophysiology to treatment. Clin Exp Med. 2017;17:257–67. Czwalinna A, Bergmann F. Prevention of pregnancy complications in antiphospholipid syndrome. Hamostaseologie. 2020;40:174–83. Lo HW, Chen CJ, Tsai EM. Pregnancy outcomes for women with non-criteria antiphospholipid syndrome after anticoagulant therapy. Eur J Obstet Gynecol Reprod Biol. 2020;244:205–7. Hoxha A, Favaro M, Calligaro A, Del Ross T, Ruffatti AT, Infantolino C, Tonello M, Mattia E, Ruffatti A. Upgrading therapy strategy improves pregnancy outcome in antiphospholipid syndrome: a cohort management study. Thromb Haemost. 2020;120:36–43. Emmi L, Bergamini C, Spinelli A, Liotta F, Marchione T, Caldini A, Fanelli A, De Cristofaro MT, Dal Pozzo G. Possible pathogenetic role of activated platelets in the primary antiphospholipid syndrome involving the central nervous system. Ann N Y Acad Sci. 1997;823:188–200. Baroni G, Banzato A, Bison E, Denas G, Zoppellaro G, Pengo V. The role of platelets in antiphospholipid syndrome. Platelets. 2017;28:762–6. Liu X, Qiu Y, Yu ED, Xiang S, Meng R, Niu KF, Zhu H. Comparison of therapeutic interventions for recurrent pregnancy loss in association with antiphospholipid syndrome: a systematic review and network meta-analysis. Am J Reprod Immunol. 2020;83:e13219. Islam MA, Alam F, Wong KK, Kamal MA, Gan SH. Thrombotic management of antiphospholipid syndrome: towards novel targeted therapies. Curr Vasc Pharmacol. 2017;15:313–26. Carmi O, Berla M, Shoenfeld Y, Levy Y. Diagnosis and management of catastrophic antiphospholipid syndrome. Expert Rev Hematol. 2017;10:365–74. Chaturvedi S, McCrae KR. Diagnosis and management of the antiphospholipid syndrome. Blood Rev. 2017;31:406–17. Petri M. Pregnancy and systemic lupus erythematosus. Best Pract Res Clin Obstet Gynaecol. 2020;64:24–30. Jeon HS, Lee SM, Jung YM, Oh S, Park JK, Lee EB, Park CW, Park JS, Han D, Jun JK. Proteomic biomarkers in mid-trimester amniotic fluid associated with adverse pregnancy outcomes in patients with systemic lupus erythematosus. PLoS One. 2020;15:e0235838. Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum. 2012;64:2311–8. Lightstone L, Hladunewich MA. Lupus nephritis and pregnancy: concerns and management. Semin Nephrol. 2017;37:347–53. Lecarpentier E, Vieillefosse S, Haddad B, Fournier T, Leguy MC, Guibourdenche J, Tsatsaris V. Placental growth factor (PlGF) and sFlt-1 during pregnancy: physiology, assay and interest in preeclampsia. Ann Biol Clin (Paris). 2016;74:259–67. Kwiatkowski S, Kwiatkowska E, Torbe A. The role of disordered angiogenesis tissue markers (sflt-1, Plgf) in present day diagnosis of preeclampsia. Ginekol Pol. 2019;90:173–6. Zhao M, Zhu Z, Liu C, Zhang Z. Dual-cutoff of sFlt-1/PlGF ratio in the stratification of preeclampsia: a systematic review and meta-analysis. Arch Gynecol Obstet. 2017;295:1079–87. Vieillefosse S, Guibourdenche J, Atallah A, Haddad B, Fournier T, Tsatsaris V, Lecarpentier E. Predictive and prognostic factors of preeclampsia: Interest of PlGF and sFLT-1. J Gynecol Obstet Biol Reprod (Paris). 2016;45:999–1008.