Hydroxychloroquine Use, Preeclampsia, and Preterm Delivery Complications in Systemic Lupus Erythematosus Pregnancies: Is There a Protective Effect?

Abstract

Systemic lupus erythematosus (SLE) increases the risk of adverse pregnancy outcomes, including preeclampsia and preterm delivery. Hydroxychloroquine (HCQ), widely used to manage SLE, has shown mixed associations with pregnancy outcomes. We investigated the association between HCQ use and risks of preeclampsia/eclampsia and preterm delivery, accounting for maternal covariates in a population-based cohort of SLE pregnancies. We studied 847 singleton pregnancies among 597 publicly insured women with SLE in the British Columbia Perinatal Data Registry (mean ± SD maternal age 33.1 ± 4.6 years; 43% nulliparous). SLE was identified before pregnancy, and HCQ exposure during pregnancy was defined using multiple approaches, including ≥2 fills or ≥60 days' supply during the 20 weeks of pregnancy. Modified Poisson regression estimated risk ratios (RRs) and 95% confidence intervals (CIs) using propensity scores to address confounding. Stratified analyses examined effect modification. For preterm delivery, we conducted a time-to-event analysis using a Cox proportional hazards model. Multiple sensitivity analyses explored definitions of SLE, HCQ exposures, and outcomes. Pregnancies with ≥2 fills or ≥60 days' supply compared to no fills had an adjusted RR of 0.92 (95% CI 0.47-1.80). Results were similar when expanding the exposure window to include three months preconception. We found no association across different definitions for preterm delivery. The stratified analyses results showed no appreciable differences. Early pregnancy HCQ use in patients with SLE was not significantly associated with reduced risk of preeclampsia or preterm delivery. Further studies with larger cohorts are needed to clarify these associations.