CLINICAL PREDICTORS OF PREGNANCY OUTCOMES AND PREMATURE MENOPAUSE IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

Abstract

Background Systemic lupus erythematosus (SLE) is predominantly affects women of child bearing-age. Pregnancies in SLE has still associated with poor maternal and fetal outcomes. Pharmacotherapy for SLE are limited during pregnancy and cyclophosphamide (CYC) increases the risk for premature menopause.

Objectives We investigated the clinical factors predisposing to higher risk, the out-comes and current management during pregnancy in patients with SLE and compared young women with and without prior CYC exposure to affect premature menopause in a Korean population.

Methods The study population was recruited from multicenter lupus cohort. Women with SLE fulfilled the American College of Rheumatology 1997 revised criteria for SLE history (n=377). All patients were required to provide informed consent and completed an initial questionnaire for demographic data, SLE manifestations, and obstetric data. Clinical data included antoantibodies, presence of lupus nephritis, SLICC and treatment.

Results A total of 362 female SLE patients who have not been hysterectomy was recruited. Mean age at the time of study was 36.0 ± 10.9 years and mean disease duration was 4.4 ± 5.2 years. Among the 238 pregnant females identified, spontaneous abortion was 65 (27.3%) and premature birth was 32 (27.5%) women with SLE. In analysis between two groups, patients who were pregnant before SLE onset and after SLE onset, spontaneous abortion (p=2.8 x 10-3) and premature birth (p=2.9 x 10-5) were found higher in patients after SLE onset (Table 1). Interestingly, high SLICC score were significantly associated with spontaneous abortion and premature birth patients (OR=1.96, p=0.014) by multivariable analysis, adjusted autoantibodies (anti-Ro/La, anti-Smith, anti-phospholipid antibody, anti-dsDNA), low complements, high dose steroid treatment (>0.5mg/kg), use of cyclophosphamide, and lupus nephritis. Premature cessation of menstruation was observed in thirty patients after SLE treatment, and mean menopause age was 44.8 years. 21.8% of women who were treated with CYC in patients with less than 40 years old (n=55), developed premature menopause. Among young patients (<40 years), previous CYC treatment increased the risk of irregular menstruation (OR=2.34, p=0.021) and premature menopause (OR=8.09, p=0.0003), adjusted with age, menarche, body mass index, autoantibodies, lupus nephritis, SLICC, and use of high dose steroid. Patients over 30 years old at the time of CYC therapy increased premature menopause compared with younger patients.

Conclusions Pregnancy after SLE onset significantly increases spontaneous abortion and premature birth, in which advanced organ damage (SLICC) is the most important predictor of poor outcome. CYC treatment significantly leads to premature menopause especially in patients over 30 years old.