Evaluation of lupus anticoagulant, damage, and remission as predictors of pregnancy complications in systemic lupus erythematosus: the French GR2 study

Maddalena Larosa, Véronique Le Guern, Gaëlle Guettrot-Imbert, Nathalie Morel, Noémie Abisror, Chafika Morati-Hafsaoui, Pauline Orquevaux, Elisabeth Diot, Andrea Doria, Françoise Sarrot-Reynauld, Nicolas Limal, Viviane Queyrel, Odile Souchaud-Debouverie, Laurent Sailler, Maëlle Le Besnerais, Tiphaine Goulenok, Anna Molto, Emmanuelle Pannier-Metzger, Loic Sentilhes, Luc Mouthon, Estibaliz Lazaro, Nathalie Costedoat-Chalumeau, GR2 Group, Béatrice Banneville, Antoine Baudet, Constance Beaudouin-Bazire, Cristina Belizna, Rakiba Belkhir, Ygal Benhamou, Alice Berezne, Sabine Berthier, Emilie Berthoux, Holy Bezanahary, Lisa Biale, Boris Bienvenu, Claire Blanchard-Delaunay, Anne Calas, Pascal Cathebras, Claire Cazalets, Benjamin Chaigne, Olivia Chandesris, Jérémy Chatelais, Emmanuel Chatelus, Elodie Chauvet, Fleur Cohen, Pascal Coquerelle, Marion Couderc, Mathilde de Menthon, Claire de Moreuil, Juliette Delforge, Azeddine Dellal, Catherine Deneux-Tharaux, Amélie Denis, Emmanuelle Dernis, Alban Deroux, Sandra Desouches, Guillaume Direz, Maxime Dougados, Marine Driessen, Aurélie Du Thanh, Laetitia Dunogeant, Cécile Durant, Isabelle Durieu, Elisabeth Elefant, Marc Fabre, Olivier Fain, Nicole Ferreira-Maldent, René-Marc Flipo, Aline Frazier, Antoine Froissart, Sophie Georgin-Lavialle, Elisabeth Gervais, Bertrand Godeau, François Goffinet, Anne Gompel, Laure Gossec, Phillipe Goupille, Claire Grange, Constance Guillaud-Danis, Eric Hachulla, Aurélie Hummel, Moez Jallouli, Patrick Jego, Stéphane Jobard, Laurence Josselin-Mahr, Noémie Jourde-Chiche, Anne-Sophie Korganow, Marc Lambert, Vincent Langlois, Delphine Lariviere, Claire Larroche, Céline Lartigau-Roussin, Augustin Latourte, Christian Lavigne, Thomas Le Gallou, Gaëlle Leroux, Hervé Levesque, Frédéric Lioté, Laurence Loeuillet, Jonathan London, Valentine Loustau, Emmanuel Maheu, Matthieu Mahevas, Hélène Maillard, Xavier Mariette, Hubert Marotte, Nicolas Martin-Silva, Nihal Martis, Agathe Masseau, François Maurier, Arsène Mekinian, Sara Melboucy-Belkhir, Martin Michaud, Marc Michel, Jacques Morel, Guillaume Moulis, Jérémy Ora, Elisabeth Pasquier, Jean-Loup Pennaforte, Antoinette Perlat, Hélène Petit Bauer, Laurent Perard, Evangeline Pillebout, Jean-Maxime Piot, Geneviève Plu-Bureau, Vincent Poindron, Agnès Portier, Gregory Pugnet, Loïc Raffray, Alexis Regent, Christophe Richez, Mélanie Roriz, Gaëtan Sauvetre, Léa Savey, Nicolas Schleinitz, Jeremy Sellam, Raphaele Seror, Vincent Sobanski, Christelle Sordet, Martin Soubrier, Katia Stankovic-Stojanovic, Nathalie Tieulé, Thierry Thomas, Marie-Agnès Timsit, Vassilis Tsatsaris, Maria Letizia Urban, Geoffrey Urbanski, Cécile Yelnik, Maddalena Larosa, Véronique Le Guern, Gaëlle Guettrot-Imbert, Nathalie Morel, Noémie Abisror, Chafika Morati-Hafsaoui, Pauline Orquevaux, Elisabeth Diot, Andrea Doria, Françoise Sarrot-Reynauld, Nicolas Limal, Viviane Queyrel, Odile Souchaud-Debouverie, Laurent Sailler, Maëlle Le Besnerais, Tiphaine Goulenok, Anna Molto, Emmanuelle Pannier-Metzger, Loic Sentilhes, Luc Mouthon, Estibaliz Lazaro, Nathalie Costedoat-Chalumeau, GR2 Group, Béatrice Banneville, Antoine Baudet, Constance Beaudouin-Bazire, Cristina Belizna, Rakiba Belkhir, Ygal Benhamou, Alice Berezne, Sabine Berthier, Emilie Berthoux, Holy Bezanahary, Lisa Biale, Boris Bienvenu, Claire Blanchard-Delaunay, Anne Calas, Pascal Cathebras, Claire Cazalets, Benjamin Chaigne, Olivia Chandesris, Jérémy Chatelais, Emmanuel Chatelus, Elodie Chauvet, Fleur Cohen, Pascal Coquerelle, Marion Couderc, Mathilde de Menthon, Claire de Moreuil, Juliette Delforge, Azeddine Dellal, Catherine Deneux-Tharaux, Amélie Denis, Emmanuelle Dernis, Alban Deroux, Sandra Desouches, Guillaume Direz, Maxime Dougados, Marine Driessen, Aurélie Du Thanh, Laetitia Dunogeant, Cécile Durant, Isabelle Durieu, Elisabeth Elefant, Marc Fabre, Olivier Fain, Nicole Ferreira-Maldent, René-Marc Flipo, Aline Frazier, Antoine Froissart, Sophie Georgin-Lavialle, Elisabeth Gervais, Bertrand Godeau, François Goffinet, Anne Gompel, Laure Gossec, Phillipe Goupille, Claire Grange, Constance Guillaud-Danis, Eric Hachulla, Aurélie Hummel, Moez Jallouli, Patrick Jego, Stéphane Jobard, Laurence Josselin-Mahr, Noémie Jourde-Chiche, Anne-Sophie Korganow, Marc Lambert, Vincent Langlois, Delphine Lariviere, Claire Larroche, Céline Lartigau-Roussin, Augustin Latourte, Christian Lavigne, Thomas Le Gallou, Gaëlle Leroux, Hervé Levesque, Frédéric Lioté, Laurence Loeuillet, Jonathan London, Valentine Loustau, Emmanuel Maheu, Matthieu Mahevas, Hélène Maillard, Xavier Mariette, Hubert Marotte, Nicolas Martin-Silva, Nihal Martis, Agathe Masseau, François Maurier, Arsène Mekinian, Sara Melboucy-Belkhir, Martin Michaud, Marc Michel, Jacques Morel, Guillaume Moulis, Jérémy Ora, Elisabeth Pasquier, Jean-Loup Pennaforte, Antoinette Perlat, Hélène Petit Bauer, Laurent Perard, Evangeline Pillebout, Jean-Maxime Piot, Geneviève Plu-Bureau, Vincent Poindron, Agnès Portier, Gregory Pugnet, Loïc Raffray, Alexis Regent, Christophe Richez, Mélanie Roriz, Gaëtan Sauvetre, Léa Savey, Nicolas Schleinitz, Jeremy Sellam, Raphaele Seror, Vincent Sobanski, Christelle Sordet, Martin Soubrier, Katia Stankovic-Stojanovic, Nathalie Tieulé, Thierry Thomas, Marie-Agnès Timsit, Vassilis Tsatsaris, Maria Letizia Urban, Geoffrey Urbanski, Cécile Yelnik

Abstract

Objectives: The specific roles of remission status, lupus low disease activity state (LLDAS), and damage accrual on the prognosis of pregnancies in women with SLE are unknown. We analysed their impact on maternal flares and adverse pregnancy outcomes (APOs).

Methods: We evaluated all women (≥18 years) with SLE enrolled in the prospective GR2 study with an ongoing singleton pregnancy at 12 weeks (one pregnancy/woman). Several sets of criteria were used to define remission, disease activity and damage. APOs included: foetal/neonatal death, placental insufficiency with preterm delivery and small-for-gestational-age birth weight. First trimester maternal and disease features were tested as predictors of maternal flares and APOs.

Results: The study included 238 women (98.3% on hydroxychloroquine (HCQ)) with 230 live births. Thirty-five (14.7%) patients had at least one flare during the second/third trimester. At least one APOs occurred in 34 (14.3%) women. Hypocomplementemia in the first trimester was the only factor associated with maternal flares later in pregnancy (P=0.02), while several factors were associated with APOs. In the logistic regression models, damage by SLICC-Damage Index [odds ratio (OR) 1.8, 95% CI: 1.1, 2.9 for model 1 and OR 1.7, 95% CI: 1.1, 2.8 for model 2] and lupus anticoagulant (LA, OR 4.2, 95% CI: 1.8, 9.7 for model 1; OR 3.7, 95% CI: 1.6, 8.7 for model 2) were significantly associated with APOs.

Conclusion: LA and damage at conception were predictors of APOs, and hypocomplementemia in the first trimester was associated with maternal flares later in pregnancy in this cohort of pregnant patients mostly with well-controlled SLE treated with HCQ.

Trial registration: ClinicalTrials.gov, https://ichgcp.net/clinical-trials-registry/NCT02450396" title="See in ClinicalTrials.gov">NCT02450396.

Keywords: adverse pregnancy outcome; damage; pregnancy; remission; systemic lupus erythematosus.

© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology.

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Source: PubMed

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