Pregnancy Outcomes in Women with Primary Sjögren's Syndrome: an Analysis of Data from the Multicentre, Prospective, GR2 Study

Background Adverse pregnancy outcomes in women with primary Sjogren's syndrome have only been evaluated retrospectively using heterogeneous methods and with contradictory results. We aimed to describe adverse pregnancy, delivery, and birth outcome risks in pregnant women with primary Sjogren's syndrome compared with those of a matched general population in France, and to identify factors predictive of disease flares or adverse pregnancy outcomes. Methods We conducted a multicentre, prospective, cohort study in France using the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) registry. Women from the GR2 study were eligible if they had conceived before March, 2021, had primary Sjogren's syndrome according to the American College of Rheumatology and European Alliance of Associations for Rheumatology (EULAR) 2016 classification criteria, and had an ongoing pregnancy at 12 weeks of gestation. In women who entered in the registry with pregnancies before 18 weeks of gestation, we sought to identify factors associated with primary Sjogren's syndrome flare (=3-point increase in EULAR Sjogren's Syndrome Disease Activity Index [ESSDAI] score) or adverse pregnancy outcomes (fetal or neonatal death, placental insufficiency leading to a preterm delivery [<37 weeks of gestation], or small-for-gestational-age birthweight). A matched controlled study compared adverse pregnancy, delivery, and birth outcome rates between pregnant women with primary Sjogren's syndrome from the GR2 registry and matched controls from the general population included in the last French perinatal survey (Enquete Nationale Perinatale 2016). Findings 1944 pregnancies were identified in the GR2 cohort, of which 106 pregnancies in 96 women with primary Sjogren's syndrome were included in this analysis. The median age at pregnancy onset was 33 years (IQR 31-36). 87 (83%) of 105 pregnancies (with ethnicity data) were in White women, 18 (17%) were in Black women; 92 (90%) of 102 had previous systemic activity (ESSDAI score of =1; data missing in four pregnancies), and 48 (45%) of 106 had systemic activity at inclusion. Of 93 pregnancies included at week 18 of gestation or earlier, primary Sjogren's syndrome flares occurred in 12 (13%). No baseline parameters were associated with primary Sjogren's syndrome flare. Four twin pregnancies and one medical termination were excluded from the adverse pregnancy outcome analysis; of the remaining 88, adverse pregnancy outcomes occurred in six (7%). Among pregnancies in women with data for antiphospholipid antibodies (n=55), antiphospholipid antibody positivity was more frequent among pregnancies with adverse outcomes (two [50%] of four pregnancies) compared with those without adverse outcomes (two [ 4%] of 51 pregnancies; p=0 center dot 023). Anti-RNP antibody positivity was also more frequent among pregnancies with adverse outcomes than those without, although this was not statistically significant. In the matched controlled study, adverse pregnancy outcomes occurred in nine (9%) of 105 pregnancies in women with primary Sjogren's syndrome and 28 (7%) of the 420 matched control pregnancies; adverse pregnancy outcomes were not significantly associated with primary Sjogren's syndrome (odds ratio 1 center dot 31, 95% CI 0 center dot 53-2 center dot 98; p=0 center dot 52). Interpretation Pregnancies in women with primary Sjogren's syndrome had very good prognoses for mothers and fetuses, with no overall increase in adverse pregnancy outcome risk compared with the general population. Women with antiphospholipid antibodies or anti-RNP antibodies require close monitoring, because these factors might be associated with a higher risk of adverse pregnancy outcomes. Funding Lupus France, Association des Sclerodermiques de France, Association Gougerot Sjogren, Association Francophone Contre la Polychondrite Chronique Atrophiante, AFM-Telethon, Societe Nationale Francaise de Medecine Interne, Societe Francaise de Rhumatologie, Cochin Hospital, French Health Ministry, Fondation for Research in Rheumatology, Association Prix Veronique Roualet, Union Chimique Belge. Copyright (c) 2023 Elsevier Ltd. All rights reserved.