CO:10:6 | Impact of pregnancy on organ damage in systemic lupus erythematosus: a prospective multicenter study

Giancarlo Cascarano¹, Greta Hulej², Dina Zucchi¹, Antonia Calligaro², Elena Elefante¹, Luca Iaccarino², Sabrina Gori¹, Margherita Zen², Chiara Tani¹, Andrea Doria², Marta Mosca¹. | ¹Università degli Studi di Pisa; ²Università degli Studi di Padova, Italy

Background. Pregnancy in systemic lupus erythematosus (SLE) is associated with increased risk of fetal and maternal complications, as well as a higher risk of disease flares. Data on pregnancy’s impact on damage accrual in SLE are limited. We aimed to assess the role of pregnancy and related factors in damage increase in SLE patients.

Methods. Consecutive patients fulfilling the 2019-ACR/EULAR SLE criteria were prospectively enrolled at pregnancy detection and monitored every 4 weeks at two referral centers. At baseline, demographic, clinical, and treatment data were collected. Disease activity was assessed by SLE Disease Activity Index-2k score(SLEDAI-2k); flares during pregnancy by the modified SELENA-SLEDAI flare index. Remission was defined by DORIS-criteria, and low disease activity state (LLDAS) by the Asian Pacific definition. Disease was defined as active if SLEDAI-2K>4. Pregnancy outcomes included preeclampsia, premature membrane rupture <37 gestational-weeks, small for gestational-age, intrauterine growth restriction, intrauterine fetal death and birthweight <2500 gr. Damage accumulation was assessed using the SLICC Damage Index score over two years pre-pregnancy, one year pre- and one year post-pregnancy. Factors influencing damage accrual during pregnancy were analyzed by logistic regression. To assess the effect of pregnancy per se on damage accrual, we examined this relationship using a cross-over design. The year before pregnancy was compared with the year post-pregnancy in terms of damage accrual; results are expressed as delta damage.

Results. We analyzed 165 pregnancies in 122 patients. Figure1 shows demographic, clinical, and serological features; Figure2 reports obstetric outcomes and first pregnancy visit data. At conception, 26 pregnancies(15.8%) had pre-existing damage(mean 1.1, SD±0.32). In the year after pregnancy, 29 cases (17.6%) had a SLICC score of 1 or higher(mean 1.24, SD ±0.51), including 3 new damage cases in previously unaffected patients. 7 patients (4.4%) presented increased damage post-pregnancy, consisting of osteoporotic fracture, malignancy, cerebrovascular event, scarring alopecia, cognitive impairment, and diabetes mellitus. Only 1 new damage event(cataract) occurred in the year before pregnancy. At logistic regression of the cross-over analysis, pregnancy per se was not significantly associated with SLICC increase (OR 3.61, 95% CI). Exploring variables potentially associated with damage accrual, with a multivariate logistic regression analysis we found that pre-existing organ damage (OR 8.24, 95% CI) and disease activity at the beginning of pregnancy (OR 6.65, 95% CI) were independently associated with post-pregnancy damage accrual. No associations emerged with age, disease duration, overlap syndromes, or ongoing therapies during pregnancy.

Conclusions. In SLE patients followed at tertiary centers, pregnancy per se was not linked to damage accrual. However, in patients with pre-existing damage and active disease at conception, damage accrual should be considered in the pre-conceptional counselling. These results highlight the need for organ damage prevention strategies and pregnancy planning during disease control