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Clinical Rheumatology

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01-01-2021 | Systemic Lupus Erythematosus | Original Article

Clinical features associated with pregnancy outcomes in women with positive antiphospholipid antibodies and previous adverse pregnancy outcomes: a real-world prospective study

Authors: Xinyi Li, Xiaoli Deng, Hongji Duan, Lin Zeng, Jiansuo Zhou, Chang Liu, Xiaoyue Guo, Xiangyuan Liu

Published in: Clinical Rheumatology | Issue 1/2021

Abstract

Objective

This study aims to analyze factors related to pregnancy outcomes in women with positive antiphospholipid antibodies and previous adverse pregnancy outcomes (APOs) prospectively.

Methods

Patients’ characteristics were described. Factors associated with obstetric complications were analyzed using logistic regression analysis.

Results

A total of 128 females with 73.4% non-criteria obstetric antiphospholipid syndrome (NC-OAPS) were included. APOs accounted for 38.3%, of which 65.3% were fetal losses. Live birth rates in criteria OAPS and NC-OAPS were similar (76.5% and 74.5%). For the whole patients, antinuclear antibody (ANA) titer ≥ 1:160 (OR 5.064, 95% CI (1.509, 16.995), P = 0.009) was a risk factor for APOs and low molecular weight heparin (LMWH) use (OR 0.149, 95% CI (0.029, 0.775), P = 0.024)) was a protective factor. Age (OR 1.159, 95% CI (1.011, 1.329), P = 0.034) and previous APOs ≥ 3 times (OR 3.772, 95% CI (1.14, 12.435), P = 0.029) were risk factors for fetal loss, and LMWH use (OR 0.068, 95% CI (0.009, 0.486), P = 0.007) was a protective factor. Regular rheumatology visits was a protective factor for APOs and fetal loss (OR 0.085, 95% CI (0.024, 0.306), P < 0.001; OR 0.019, 95% CI (0.004, 0.104), P < 0.001). The proportion of it decreased in APOs and fetal loss groups (53.1% and 28.1%). Glucocorticoid use was a risk factor for APOs in NC-OAPS and higher serum C3 levels in the first gestational trimester was a protective factor for fetal loss (OR 3.703, 95% CI (1.402, 9.777), P = 0.008; OR 0.041, 95% CI (0.002, 0.947), P = 0.046).

Conclusion

Age, APO history, ANA titer, LWMH and glucocorticoid use, serum C3 levels, and regular rheumatology visits were related to obstetric complications.

Key Points

• This was one of the few prospective studies focused on patients with positive antiphospholipid antibodies and previous adverse pregnancy outcomes. The majority were NC-OAPS patients.

• The study first evaluated the impact of rheumatologists’ monitoring based on individual disease assessments on pregnancy outcomes. The live birth proportion was similar in patients with criteria OAPS and NC-OAPS when treated.

• Age, APO history (≥ 3 times), ANA titer (≥ 1:160), LMWH use, glucocorticoid use, and serum C3 were factors related to obstetric complications.

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Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, Jacobsen S, Lakos G, Tincani A, Kontopoulou-Griva I, Galeazzi M, Meroni PL, Derksen RH, de Groot PG, Gromnica-Ihle E, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC, Quere I, Hachulla E, Vasconcelos C, Roch B, Fernandez-Nebro A, Boffa MC, Hughes GR, Ingelmo M, Euro-Phospholipid Project G (2002) Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum 46(4):1019–1027. https://doi.org/10.1002/art.10187CrossRefPubMed

Schreiber K, Hunt BJ (2016) Pregnancy and antiphospholipid syndrome. Semin Thromb Hemost 42(07):780–788. https://doi.org/10.1055/s-0036-1592336CrossRefPubMed

Deguchi M, Yamada H, Sugiura-Ogasawara M, Morikawa M, Fujita D, Miki A, Makino S, Murashima A (2017) Factors associated with adverse pregnancy outcomes in women with antiphospholipid syndrome: a multicenter study. J Reprod Immunol 122:21–27. https://doi.org/10.1016/j.jri.2017.08.001CrossRefPubMed

Ruffatti A, Tonello M, Del Ross T, Cavazzana A, Grava C, Noventa F, Tona F, Iliceto S, Pengo V (2006) Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity. Thromb Haemost 96(3):337–341. https://doi.org/10.1160/TH06-05-0287CrossRefPubMed

Saccone G, Berghella V, Maruotti GM, Ghi T, Rizzo G, Simonazzi G, Rizzo N, Facchinetti F, Dall'Asta A, Visentin S, Sarno L, Xodo S, Bernabini D, Monari F, Roman A, Eke AC, Hoxha A, Ruffatti A, Schuit E, Martinelli P, PREGNANTS working group (2017) Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome: the PREGNANTS study. Am J Obstet Gynecol 216(5):525 e1–525.e12. https://doi.org/10.1016/j.ajog.2017.01.026CrossRef

Ruffatti A, Favaro M, Calligaro A, Zambon A, Del Ross T (2019) Management of pregnant women with antiphospholipid antibodies. Expert Rev Clin Immunol 15(4):347–358. https://doi.org/10.1080/1744666X.2019.1565995CrossRefPubMed

Mekinian A, Loire-Berson P, Nicaise-Roland P, Lachassinne E, Stirnemann J, Boffa MC, Chollet-Martin S, Carbillon L, Fain O (2012) Outcomes and treatment of obstetrical antiphospholipid syndrome in women with low antiphospholipid antibody levels. J Reprod Immunol 94(2):222–226. https://doi.org/10.1016/j.jri.2012.02.004CrossRefPubMed

Antovic A, Sennstrom M, Bremme K, Svenungsson E (2018) Obstetric antiphospholipid syndrome. Lupus Sci Med 5(1):e000197. https://doi.org/10.1136/lupus-2016-000197CrossRefPubMedPubMedCentral

Chauleur C, Galanaud JP, Alonso S, Cochery-Nouvellon E, Balducchi JP, Mares P, Fabbro-Peray P, Gris JC (2010) Observational study of pregnant women with a previous spontaneous abortion before the 10th gestation week with and without antiphospholipid antibodies. J Thromb Haemost 8(4):699–706. https://doi.org/10.1111/j.1538-7836.2010.03747.xCrossRefPubMed

10.

Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA (2006) International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 4(2):295–306. https://doi.org/10.1111/j.1538-7836.2006.01753.xCrossRef

11.

Silver RM, Parker CB, Reddy UM, Goldenberg R, Coustan D, Dudley DJ, Saade GR, Stoll B, Koch MA, Conway D, Bukowski R, Hogue CJ, Pinar H, Moore J, Willinger M, Branch DW (2013) Antiphospholipid antibodies in stillbirth. Obstet Gynecol 122(3):641–657. https://doi.org/10.1097/AOG.0b013e3182a1060eCrossRefPubMedPubMedCentral

12.

Palma Dos Reis CR, Cardoso G, Carvalho C, Nogueira I, Borges A, Serrano F (2019) Prediction of adverse pregnancy outcomes in women with systemic lupus erythematosus. Clin Rev Allergy Immunol. https://doi.org/10.1007/s12016-019-08762-9

13.

Gynecologists ACoOa (2000) Intrauterine growth restriction. Obstet Gynecol 95:1–12

14.

Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, Bruce IN, Isenberg D, Wallace DJ, Nived O, Sturfelt G, Ramsey-Goldman R, Bae SC, Hanly JG, Sánchez-Guerrero J, Clarke A, Aranow C, Manzi S, Urowitz M, Gladman D, Kalunian K, Costner M, Werth VP, Zoma A, Bernatsky S, Ruiz-Irastorza G, Khamashta MA, Jacobsen S, Buyon JP, Maddison P, Dooley MA, van Vollenhoven RF, Ginzler E, Stoll T, Peschken C, Jorizzo JL, Callen JP, Lim SS, Fessler BJ, Inanc M, Kamen DL, Rahman A, Steinsson K, Franks AG, Sigler L, Hameed S, Fang H, Pham N, Brey R, Weisman MH, McGwin G, Magder LS (2012) Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 64(8):2677–2686. https://doi.org/10.1002/art.34473CrossRefPubMedPubMedCentral

15.

Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, Cuadrado MJ, Dorner T, Ferrer-Oliveras R, Hambly K, Khamashta MA, King J, Marchiori F, Meroni PL, Mosca M, Pengo V, Raio L, Ruiz-Irastorza G, Shoenfeld Y, Stojanovich L, Svenungsson E, Wahl D, Tincani A, Ward MM (2019) EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 78(10):1296–1304. https://doi.org/10.1136/annrheumdis-2019-215213CrossRefPubMed

16.

Sammaritano LR, Bermas BL, Chakravarty EE, Chambers C, Clowse MEB, Lockshin MD, Marder W, Guyatt G, Branch DW, Buyon J, Christopher-Stine L, Crow-Hercher R, Cush J, Druzin M, Kavanaugh A, Laskin CA, Plante L, Salmon J, Simard J, Somers EC, Steen V, Tedeschi SK, Vinet E, White CW, Yazdany J, Barbhaiya M, Bettendorf B, Eudy A, Jayatilleke A, Shah AA, Sullivan N, Tarter LL, Birru Talabi M, Turgunbaev M, Turner A, D'Anci KE (2020) 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases. Arthritis Rheumatol 72(4):529–556. https://doi.org/10.1002/art.41191CrossRefPubMed

17.

Viall CA, Chamley LW (2015) Histopathology in the placentae of women with antiphospholipid antibodies: a systematic review of the literature. Autoimmun Rev 14(5):446–471. https://doi.org/10.1016/j.autrev.2015.01.008CrossRefPubMed

18.

Mulla MJ, Brosens JJ, Chamley LW, Giles I, Pericleous C, Rahman A, Joyce SK, Panda B, Paidas MJ, Abrahams VM (2009) Antiphospholipid antibodies induce a pro-inflammatory response in first trimester trophoblast via the TLR4/MyD88 pathway. Am J Reprod Immunol 62(2):96–111. https://doi.org/10.1111/j.1600-0897.2009.00717.xCrossRefPubMedPubMedCentral

19.

Bramham K, Thomas M, Nelson-Piercy C, Khamashta M, Hunt BJ (2011) First-trimester low-dose prednisolone in refractory antiphospholipid antibody-related pregnancy loss. Blood 117(25):6948–6951. https://doi.org/10.1182/blood-2011-02-339234CrossRefPubMed

20.

Zhou Z, Teng J, Sun Y, Liu H, Cheng X, Su Y, Yang C, Ye J (2019) Characteristics of pregnancy complications and treatment in obstetric antiphospholipid syndrome in China. Clin Rheumatol 38(11):3161–3168. https://doi.org/10.1007/s10067-019-04670-7CrossRefPubMed

21.

Alijotas-Reig J, Esteve-Valverde E, Ferrer-Oliveras R, Saez-Comet L, Lefkou E, Mekinian A, Belizna C, Ruffatti A, Hoxha A, Tincani A, Nalli C, Marozio L, Maina A, Espinosa G, Rios-Garces R, Cervera R, Carolis S, Monteleone G, Latino O, Udry S, Lurba EL, Garrido-Gimenez C, Trespidi L, Gerosa M, Chighizola CB, Rovere-Querini P, Canti V, Mayer-Pickel K, Tabacco S, Arnau A, Trape J, Ruiz-Hidalgo D, Sos L, Farran-Codina I (2019) Comparative study of obstetric antiphospholipid syndrome (OAPS) and non-criteria obstetric APS (NC-OAPS): report of 1640 cases from the EUROAPS registry. Rheumatology (Oxford) kez419. https://doi.org/10.1093/rheumatology/kez419

22.

Thurman JM, Kraus DM, Girardi G, Hourcade D, Kang HJ, Royer PA, Mitchell LM, Giclas PC, Salmon J, Gilkeson G, Holers VM (2005) A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice. Mol Immunol 42(1):87–97. https://doi.org/10.1016/j.molimm.2004.07.043CrossRefPubMed

23.

Shamonki JM, Salmon JE, Hyjek E, Baergen RN (2007) Excessive complement activation is associated with placental injury in patients with antiphospholipid antibodies. Am J Obstet Gynecol 196(2):167.e161–167.e165. https://doi.org/10.1016/j.ajog.2006.10.879CrossRef

24.

Velásquez M, Rojas M, Abrahams VM, Escudero C, Cadavid ÁP (2018) Mechanisms of endothelial dysfunction in antiphospholipid syndrome: association with clinical manifestations. Front Physiol 9:1840. https://doi.org/10.3389/fphys.2018.01840CrossRefPubMedPubMedCentral

25.

Chaturvedi S, Brodsky RA, McCrae KR (2019) Complement in the pathophysiology of the antiphospholipid syndrome. Front Immunol 10:499. https://doi.org/10.3389/fimmu.2019.00449CrossRef

26.

De Carolis S, Botta A, Santucci S, Garofalo S, Martino C, Perrelli A, Salvi S, Ferrazzani S, Caforio L, Scambia G (2009) Predictors of pregnancy outcome in antiphospholipid syndrome: a review. Clin Rev Allergy Immunol 38(2–3):116–124. https://doi.org/10.1007/s12016-009-8144-zCrossRef

27.

Kim MY, Guerra MM, Kaplowitz E, Laskin CA, Petri M, Branch DW, Lockshin MD, Sammaritano LR, Merrill JT, Porter TF, Sawitzke A, Lynch AM, Buyon JP, Salmon JE (2018) Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis 77(4):549–555. https://doi.org/10.1136/annrheumdis-2017-212224CrossRefPubMedPubMedCentral

28.

Shoenfeld Y, Carp HJ, Molina V, Blank M, Cervera R, Balasch J, Tincani A, Faden D, Lojacono A, Doria A, Konova E, Meroni PL (2006) Autoantibodies and prediction of reproductive failure. Am J Reprod Immunol 56(5–6):337–344. https://doi.org/10.1111/j.1600-0897.2006.00434.xCrossRefPubMed

29.

Ruiz JE, Cubillos J, Mendoza JC, Espinel FJ, Kwak JY, Beer AE (1995) Autoantibodies to phospholipids and nuclear antigens in non-pregnant and pregnant Colombian women with recurrent spontaneous abortions. J Reprod Immunol 28(1):41–51. https://doi.org/10.1016/0165-0378(94)00906-nCrossRefPubMed

30.

Ticconi C, Rotondi F, Veglia M, Pietropolli A, Bernardini S, Ria F, Caruso A, Di Simone N (2010) Antinuclear autoantibodies in women with recurrent pregnancy loss. Am J Reprod Immunol 64(6):384–392. https://doi.org/10.1111/j.1600-0897.2010.00863.xCrossRefPubMed

31.

Ticconi C, Pietropolli A, Borelli B, Bruno V, Piccione E, Bernardini S, Di Simone N (2016) Antinuclear autoantibodies and pregnancy outcome in women with unexplained recurrent miscarriage. Am J Reprod Immunol 76(5):396–399. https://doi.org/10.1111/aji.12560CrossRefPubMed

32.

de Jesus GR, dos Santos FC, Oliveira CS, Mendes-Silva W, de Jesus NR, Levy RA (2012) Management of obstetric antiphospholipid syndrome. Curr Rheumatol Rep 14(1):79–86. https://doi.org/10.1007/s11926-011-0218-2CrossRefPubMed

Title: Clinical features associated with pregnancy outcomes in women with positive antiphospholipid antibodies and previous adverse pregnancy outcomes: a real-world prospective study
Authors: Xinyi Li
Xiaoli Deng
Hongji Duan
Lin Zeng
Jiansuo Zhou
Chang Liu
Xiaoyue Guo
Xiangyuan Liu
Publication date: 01-01-2021
Publisher: Springer International Publishing
Keywords: Systemic Lupus Erythematosus
Eclampsia
Glucocorticoid
Antiphospholipid Syndrome
Antiphospholipid Syndrome
Low Molecular Weight Heparin
Published in: Clinical Rheumatology / Issue 1/2021
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI: https://doi.org/10.1007/s10067-020-05203-3

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