To evaluate the potential impact of achieving remission or low disease activity during the preconception period, while maintaining low-dose prednisone (≤5 mg/day in remission and ≤7.5 mg/day in low disease activity), on maternal and fetal outcomes in women with systemic lupus erythematosus (SLE).

We conducted a target trial emulation using data from a single-center retrospective cohort at the Second Xiangya Hospital of Central South University from January 2016 to August 2025. Eligible pregnancies were those in women with SLE who had regular follow-up in rheumatology and obstetric clinics and a clearly documented pregnancy outcome. The 6 months before conception served as the eligibility assessment window, during which at least two disease activity records were required. Conception was defined as time zero. The exposure strategy was sustained achievement of remission or low disease activity for at least 3 consecutive months before conception while maintaining prednisone within the prespecified low-dose thresholds. The comparison strategy was failure to sustain this target. The primary outcome was a composite adverse pregnancy outcome, including fetal loss, preterm birth, preeclampsia/gestational hypertension, small for gestational age infant, and neonatal death. Secondary outcomes included disease flare during pregnancy or within 6 weeks postpartum, severe flare, fetal loss, and medically indicated preterm birth. Inverse probability weighting was used to balance baseline confounders, including age, disease duration, history of lupus nephritis, antiphospholipid antibody status, prior adverse pregnancy history, complement levels, anti-dsDNA antibody status, baseline immunosuppressive therapy, and year of conception. Weighted regression models were applied to estimate effect measures.

A total of 462 pregnancies were included, with 248 in the exposure strategy group and 214 in the comparison group. After weighting, baseline covariates were well balanced. The incidence of composite adverse pregnancy outcomes was 24.7% in the exposure group and 31.5% in the comparison group, corresponding to an adjusted risk ratio (RR) of 0.79 (95% CI, 0.62-1.00) and an absolute risk difference of 6.8 percentage points. The rate of disease flare during pregnancy or early postpartum was 18.5% in the exposure group versus 27.1% in the comparison group, with an adjusted odds ratio (OR) of 0.63 (95% CI, 0.41-0.95). Severe flare occurred in 6.4% versus 10.3% of pregnancies, fetal loss in 7.3% versus 10.7%, and preterm birth in 16.1% versus 21.0%, all showing a favorable trend in the exposure group, although precision was limited. Stratified analyses suggested that this strategy may still be beneficial in subgroups with lupus nephritis or antiphospholipid antibody positivity, although the magnitude of benefit appeared attenuated. Multiple sensitivity analyses showed generally consistent directions of effect.

In real-world clinical practice, achieving remission or low disease activity before conception while maintaining low-dose prednisone may be associated with lower risks of composite adverse pregnancy outcomes and maternal flare in women with SLE. This strategy may represent a feasible pathway for preconception risk reduction, although it does not eliminate risk entirely. More standardized preconception management and prospective studies are needed to confirm these findings.