Evaluation of lupus anticoagulant, damage, and remission as predictors of pregnancy complications in systemic lupus erythematosus: the French GR2 study
Authors: Larosa Maddalena , Le Guern Véronique , Guettrot-Imbert Gaëlle , Morel Nathalie , Abisror Noémie , Morati-Hafsaoui Chafika , Orquevaux Pauline , Diot Elisabeth , Doria Andrea , Sarrot-Reynauld Françoise , Limal Nicolas , Queyrel Viviane , Souchaud-Debouverie Odile , Sailler Laurent , Le Besnerais Maëlle , Goulenok Tiphaine , Molto Anna , Pannier-Metzger Emmanuelle , Sentilhes Loic , Mouthon Luc , Lazaro Estibaliz , Costedoat-Chalumeau Nathalie ,   the GR2 Group, Banneville Béatrice , Baudet Antoine , Beaudouin-Bazire Constance , Belizna Cristina , Belkhir Rakiba , Benhamou Ygal , Berezne Alice , Berthier Sabine , Berthoux Emilie , Bezanahary Holy , Biale Lisa , Bienvenu Boris , Blanchard-Delaunay Claire , Calas Anne , Cathebras Pascal , Cazalets Claire , Chaigne Benjamin , Chandesris Olivia , Chatelais Jérémy , Chatelus Emmanuel , Chauvet Elodie , Cohen Fleur , Coquerelle Pascal , Couderc Marion , de Menthon Mathilde , de Moreuil Claire , Delforge Juliette , Dellal Azeddine , Deneux-Tharaux Catherine , Denis Amélie , Dernis Emmanuelle , Deroux Alban , Desouches Sandra , Direz Guillaume , Dougados Maxime , Driessen Marine , Du Thanh Aurélie , Dunogeant Laetitia , Durant Cécile , Durieu Isabelle , Elefant Elisabeth , Fabre Marc , Fain Olivier , Ferreira-Maldent Nicole , Flipo René-Marc , Frazier Aline , Froissart Antoine , Georgin-Lavialle Sophie , Gervais Elisabeth , Godeau Bertrand , Goffinet François , Gompel Anne , Gossec Laure , Goupille Phillipe , Grange Claire , Guillaud-Danis Constance , Hachulla Eric , Hummel Aurélie , Jallouli Moez , Jego Patrick , Jobard Stéphane , Josselin-Mahr Laurence , Jourde-Chiche Noémie , Korganow Anne-Sophie , Lambert Marc , Langlois Vincent , Lariviere Delphine , Larroche Claire , Lartigau-Roussin Céline , Latourte Augustin , Lavigne Christian , Le Gallou Thomas , Leroux Gaëlle , Levesque Hervé , Lioté Frédéric , Loeuillet Laurence , London Jonathan , Loustau Valentine , Maheu Emmanuel , Mahevas Matthieu , Maillard Hélène , Mariette Xavier , Marotte Hubert , Martin-Silva Nicolas , Martis Nihal , Masseau Agathe , Maurier François , Mekinian Arsène , Melboucy-Belkhir Sara , Michaud Martin , Michel Marc , Morel Jacques , Moulis Guillaume , Ora Jérémy , Pasquier Elisabeth , Pennaforte Jean-Loup , Perlat Antoinette , Bauer Hélène Petit , Perard Laurent , Pillebout Evangeline , Piot Jean-Maxime , Plu-Bureau Geneviève , Poindron Vincent , Portier Agnès , Pugnet Gregory , Raffray Loïc , Regent Alexis , Richez Christophe , Roriz Mélanie , Sauvetre Gaëtan , Savey Léa , Schleinitz Nicolas , Sellam Jeremy , Seror Raphaele , Sobanski Vincent , Sordet Christelle , Soubrier Martin , Stankovic-Stojanovic Katia , Tieulé Nathalie , Thomas Thierry , Timsit Marie-Agnès , Tsatsaris Vassilis , Urban Maria Letizia , Urbanski Geoffrey , Yelnik Cécile 
Published: January 2022

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://clinicaltrials.gov, NCT02450396.