Abstract
Aims: The study aim was to evaluate pregnancy outcomes in patients with antiphospholipid syndrome (APS) and to determine which clinical parameters present risk factors for adverse pregnancy outcomes in these patients.
Methods: The study included 55 patients with APS treated at the Clinic for Ob/Gyn, Clinical Center of Serbia, from 2006 to 2012. The control group consisted of 55 healthy pregnant women. Data regarding previous pregnancies and conception method were registered. Immunological and laboratory tests were performed. Pregnancy outcomes, including miscarriage, intrauterine fetal death, hypertensive disorders, diabetes mellitus, phlebothrombosis, fetal growth restriction, premature delivery, delivery method, perinatal asphyxia, respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis were followed.
Results: The premature delivery rate in APS patients was 31.8%, and pregnancy loss was 18.2%. Significantly more patients with APS had thrombocytopenia, pregnancy losses, intrauterine growth restriction, and perinatal asphyxia compared with the control group. More miscarriages, preterm delivery, lower birth weight, preeclampsia, and IgM anticardiolipin antibody levels significantly correlated with adverse pregnancy outcomes. Although rare, respiratory distress syndrome can also worsen neonatal health status. According to ROC analysis, previous miscarriages correctly explained 66.3% of adverse pregnancy outcome cases. We generated four equations of adverse pregnancy outcome risk factors.
Conclusions: The most important prognostic factor for pregnancy outcome in APS patients is the number of previous miscarriages. Using appropriate current therapeutic protocol can enable live birth of a healthy newborn in most cases.
References
[1] Blank M, Shoenfeld Y. Antiphospholipid antibody-mediated reproductive failure in antiphospholipid syndrome. Clin Rev Allergy Immunol. 2010;38:141–7.10.1007/s12016-009-8146-xSearch in Google Scholar PubMed
[2] Bramham K, Hunt BJ, Germain S, Calatayud I, Khamashta MA, Bewely S, et al. Pregnancy outcome in different clinical phenotypes of antiphospholipid syndrome. Lupus. 2010;19:58–64.10.1177/0961203309347794Search in Google Scholar PubMed
[3] Branch DW, Khamashta MA. Antiphospholipid syndrome: obstetric diagnosis, management and controversies. Obstet Gynecol. 2003;101:1333–44.Search in Google Scholar
[4] Cervera R, Piette JC, Font J, Khamasta MA, Shoenfeld Y, Camps MT, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients. Arthritis Rheum. 2002;46:1019–27.10.1002/art.10187Search in Google Scholar PubMed
[5] Cervera R, Serrano R, Pons-Estel GJ, Ceberio-Hualde L, Shoenfeld Y, de Ramon E, et al. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients. Ann Rheum Dis. 2013 doi:10.1136/annrheumdis-2013-204838.10.1136/annrheumdis-2013-204838Search in Google Scholar PubMed
[6] Clark EAS, Silver RM, Branch W. Do Antiphospholipid antibodies cause preeclampsia and HELLP syndrome? Curr Rheumatol Rep. 2007;9:219–25.10.1007/s11926-007-0035-9Search in Google Scholar PubMed
[7] Cohen D, Buurma A, Goemaere NN, Girardi G, le Cessie S, Scherjon S, et al. Classical complement activation as a footprint for murine and human antiphospholipid antibody-induced fetal loss. J Pathol. 2011;225:502–11.10.1002/path.2893Search in Google Scholar PubMed
[8] Danza A, Ruiz-Iratostra G, Khamashta M. Antiphospholipid syndrome in obstetrics. Best Pract Res Clin Obstet Gynecol. 2012;26:65–76.10.1016/j.bpobgyn.2011.10.006Search in Google Scholar PubMed
[9] De Jesus GR, Rodrigues G, de Jesus NR, Levy RA. Pregnancy morbidity in antiphospholipid syndrome: what is the impact of treatment? Curr Rheumatol Rep. 2014;16:403.10.1007/s11926-013-0403-6Search in Google Scholar PubMed
[10] Di Prima FA, Valenti O, Hyseni E, Giorgio E, Faraci M, Renda E, et al. Antiphospholipid syndrome during pregnancy: the state of the art. J Prenat Med. 2011;5:41–53.Search in Google Scholar
[11] Di Simone N, Castellani R, Raschi E, Borghi MO, Meroni PL, Caruso A. Anti-beta-2 glycoprotein I antibodies affect Bcl-2 and Bax trophoblast expression without evidence of apoptosis. Ann NY Acad Sci. 2006;1069:364–76.10.1196/annals.1351.034Search in Google Scholar PubMed
[12] Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev. 2005;2:CD002859.10.1002/14651858.CD002859.pub2Search in Google Scholar PubMed PubMed Central
[13] Giannakopoulos B, Krilis SA. The Pathogenesis of the antiphospholipid syndrome. N Engl J Med. 2013;368:1033–44.10.1056/NEJMra1112830Search in Google Scholar PubMed
[14] Harper BE, Willis R, Pierangeli SS. Pathophysiologial mechanisms in antiphospholipid syndrome. J Clin Rheumatol. 2011;6:157–71.10.2217/ijr.11.9Search in Google Scholar PubMed PubMed Central
[15] Kutteh WH, Hinote CD. Antiphospholipid antibody syndrome. Obstet Gynecol Clin North Am. 2014;41:113–32.10.1016/j.ogc.2013.10.004Search in Google Scholar PubMed
[16] Le Thi Thuong D, Tieulie N, Costedoat N, Andreu MR, Wechsler B, Vauthier-Brouzes D, et al. The HELLP syndrome in the antiphospholipid syndrome: retrospective study of 16 cases in 15 women. Ann Rheum Dis. 2005;64:273–8.10.1136/ard.2003.019000Search in Google Scholar PubMed PubMed Central
[17] Mak IY, Brosens JJ, Christian M, Hills FA, Chamley L, Regan L, et al. Regulated expression of signal transducer and activator of transcription, Stat5, and its enhancement of PRL expression in human endometrial stromal cells in vitro. J Clin Endocrinol Metab. 2002;87:2581–8.10.1210/jcem.87.6.8576Search in Google Scholar PubMed
[18] Marchetti T, Cohen M, de Moerloose P. Obstetrical antiphospholipid syndrome: from the pathogenesis to the clinical and therapeutic implications. Clin Dev Immunol. 2013;doi:10.1155/2013/159124.10.1155/2013/159124Search in Google Scholar PubMed PubMed Central
[19] Matsubayashi H, Sugi T, Arai T, Shida M, Kondo A, Suzuki T, et al. IgG-antiphospholipid antibodies in follicular fluid of IVF-ET patients are related to low fertilization rate of their oocytes. Am J Reprod Immunol. 2006;55:341–8.10.1111/j.1600-0897.2006.00374.xSearch in Google Scholar PubMed
[20] Mulla MJ, Myrtolli K, Brosens JJ, Chamley LW, Kwak-Kim JY, Paidas MJ, et al. Antiphospholipid antibodies limit trophoblast migration by reducing IL-6 production and STAT3 activity. Am J Reprod Immunol. 2010;63:339–48.10.1111/j.1600-0897.2009.00805.xSearch in Google Scholar PubMed
[21] Myakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295–308.10.1111/j.1538-7836.2006.01753.xSearch in Google Scholar PubMed
[22] Nodler J, Moolamalla SR, Ledger EM, Nuwayhid BS, Mulla ZD. Elevated antiphospholipid antibody titres and adverse pregnancy outcomes: analysis of a population-based hospital dataset. BMC Pregnancy Childbirth. 2009;9:11.10.1186/1471-2393-9-11Search in Google Scholar PubMed PubMed Central
[23] Qublan HS, Eid SS, Ababneh HA, Amarin ZO, Smadi AZ, Al-Khafaji FF, et al. Acquired and inherited thrombophilia: implication in recurrent IVF and embryo transfer failure. Hum Reprod. 2006;21:2694–8.10.1093/humrep/del203Search in Google Scholar PubMed
[24] Sanmarco M, Bardin N, Camoin L, Beziane A, Dignat-George F, Gammere M, et al. Antigenic profile, prevalence, and clinical significance of antiphospholipid antibodies in women referred for in vitro fertilization. Ann NY Acad Sci. 2007;1108:457–65.10.1196/annals.1422.048Search in Google Scholar PubMed
[25] Serrano F, Nogueira I, Borges A, Branco J. Primary antiphospholipid syndrome: pregnancy outcome in a Portugese population. Acta Reumatol Port. 2009;34:492–97.Search in Google Scholar
[26] Stone S, Hunt BJ, Khamashta MA, Bewely SJ, Nelson-Piercy C. Primary antiphospholipid syndrome in pregnancy: an analysis of outcome in a cohort of 33 women treated with a rigorous protocol. J Thromb Haemost. 2005;3:243–5.10.1111/j.1538-7836.2005.01185.xSearch in Google Scholar PubMed
[27] Tincani A, Lojacono A, Taglietti M, Motta M, Biasini C, Decca L, et al. Pregnancy and neonatal outcome in antiphospholipid syndrome. Lupus. 2002;11:649.10.1191/0961203302lu269oaSearch in Google Scholar PubMed
[28] Van Horn JT, Craven C, Ward K, Branch DW, Silver RM. Histologic features of placentas and abortion specimens from women with antiphospholipid and antiphospholipid-like syndromes. Placenta. 2004;25:642–8.10.1016/j.placenta.2003.12.006Search in Google Scholar PubMed
The authors stated that there are no conflicts of interest regarding the publication of this article.
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