Objective: To assess the strength of the association of systemic lupus erythematosus (SLE) with feto-maternal outcomes compared to those without SLE (healthy controls) beyond 20 weeks of gestation, and to determine the factors associated with a flare during pregnancy and postpartum among those with SLE.

Methods: This matched-observational study was conducted between 2011 and 2020 in a tertiary referral center in southeastern India, comparing feto-maternal outcomes such as preterm birth, hypertensive disorders of pregnancy (HDP), small for gestational age (SGA), among pregnancies that crossed 20 weeks, with and without SLE (ratio of 1:1). Rates of lupus flare among cases were studied. Conditional logistic regression assessed the association between SLE and fetal-maternal outcomes matched for age, whereas factors associated with lupus flare were assessed by multivariate logistic regression, expressed as adjusted odds ratios (OR) with a 95% confidence interval (95% CI).

Results: During the study period, there were 144 cases of SLE, and 27 (18.8%) were diagnosed for the first time during pregnancy. Those with SLE had higher odds for HDP (OR: 5.10, 95% CI: 2.39-10.88), SGA (OR: 2.21, 95% CI: 1.24-3.91), preterm birth (< 37 weeks) (OR: 2.61, 95% CI: 1.36-5.02), and perinatal loss (OR: 13.92, 95% CI: 1.79-108.45), than those without SLE (n = 144). The most common neonatal lupus presentation was complete heart block. Among those with SLE, HDP (OR: 9.99, 95% CI: 2.42-41.26) and lupus nephritis (OR: 4.62, 95% CI: 1.21-17.63) increased the risk of perinatal loss. Flares occurred in 27 (18.8%) cases, with six having multiple flares, and hydroxychloroquine was associated with its reduction (OR: 0.15, 95% CI: 0.03-0.71).

Conclusions: Pregnant women with SLE had a higher risk of adverse feto-maternal outcomes than those without SLE, beyond 20 weeks of gestation. Lupus nephritis and HDP increase the risk of perinatal loss, whereas hydroxychloroquine usage reduces lupus flare.