Hydroxychloroquine Exposure Intensity During Early Pregnancy and Composite Fetal Adverse Pregnancy Outcomes in Systemic Lupus Erythematosus: A Retrospective Cohort Study

Background: Hydroxychloroquine (HCQ) is commonly recommended during pregnancy in women with systemic lupus erythematosus (SLE), but real-world patterns of early-pregnancy HCQ continuation, reduction, or interruption remain clinically relevant. This study aimed to evaluate the association between HCQ exposure intensity during early pregnancy and composite fetal adverse pregnancy outcomes in pregnancies complicated by SLE. Methods: This retrospective cohort study included 513 pregnancies complicated by SLE. HCQ exposure intensity during early pregnancy, defined as conception to 13 weeks and 6 days of gestation, was classified into three groups: no HCQ exposure, reduced/interrupted HCQ exposure, and full HCQ exposure. The primary outcome was composite fetal adverse pregnancy outcome, defined as fetal loss, preterm birth, or fetal growth restriction. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), with full HCQ exposure as the reference group. Results: Among 513 pregnancies, 96 (18.7%) had no HCQ exposure, 68 (13.3%) had reduced/interrupted HCQ exposure, and 349 (68.0%) had full HCQ exposure during early pregnancy. Composite fetal adverse pregnancy outcomes occurred in 47/96 (49.0%), 48/68 (70.6%), and 136/349 (39.0%) pregnancies, respectively (p < 0.001). After adjustment for maternal age, primiparity, lupus nephritis history, antiphospholipid antibody positivity, chronic hypertension, prednisone dose > 15 mg/day, and baseline immunosuppressant use, reduced/interrupted HCQ exposure was associated with higher odds of composite fetal adverse pregnancy outcome compared with full HCQ exposure (adjusted OR 4.17, 95% CI 2.25–7.75, p < 0.001). No independent association was observed for no HCQ exposure after adjustment (adjusted OR 1.30, 95% CI 0.78–2.16, p = 0.309). Conclusions: In pregnancies complicated by SLE, reduced or interrupted HCQ exposure during early pregnancy was independently associated with an increased risk of composite fetal adverse pregnancy outcomes, while no independent association was observed for no HCQ exposure after adjustment for baseline risk factors. These findings highlight the potential clinical importance of maintaining HCQ treatment continuity during early pregnancy.