Adverse pregnancy outcome associations among women prior to a diagnosis of systemic lupus erythematosus.

Background: Immune dysregulation years prior to a clinical diagnosis of systemic lupus erythematosus (SLE) may include a range of asymptomatic autoantibody positivity to clinically evident disease. The effect of this spectrum of immune dysregulation on pregnancy outcomes, including pregnancies in women prior to a diagnosis of SLE, is poorly understood. We sought to identify associations of adverse pregnancy outcomes across groups along this spectrum. Methods: Utilizing a large longitudinal cohort at a single center, we evaluated pregnancy outcomes among the following four groups: antinuclear antibody (ANA) negative controls, ANA-positive controls, pregnancies before a diagnosis of SLE, and pregnancies after a diagnosis of SLE. The pregnancy outcomes considered were live birth rate, preeclampsia, low birth weight, premature birth, spontaneous abortion, and stillbirth. Generalized estimating equation models were used to evaluate key associations and confounders. Results: We included 811 participants and 2,209 pregnancies. Of these, 198 participants were ANA-positive controls and 369 were diagnosed with SLE, with their first pregnancy occurring before diagnosis. Overall, 81.5% self-identified as Black and 31% had resided in areas with high social vulnerability. The median number of pregnancies between the groups was similar, with the majority of participants having at least one live birth. The lowest median number of pregnancies occurred in the pregnancy after SLE diagnosis group. The adverse outcome rate did not differ between the ANA-positive and ANA-negative controls. The risk of any adverse outcome was greatest in those with pregnancies after an SLE diagnosis [OR (95% CI): 3.33 (2.35, 4.71)], but was also increased in those with pregnancies before a diagnosis of SLE as compared to the ANA-positive controls [OR (95% CI): 1.78 (1.28, 2.47)]. When grouped by time prior to diagnosis, the risk of any adverse outcome remained increased in pregnancies occurring both 2-5 years or greater than 5 years prior to SLE diagnosis as compared to the ANA-positive controls [OR (95% CI): 1.64 (1.01, 2.67) and OR (95% CI): 1.65 (1.17, 2.32), respectively]. Conclusion: The risk of adverse pregnancy outcomes appears to increase along the SLE spectrum, with the highest risk occurring after diagnosis. ANA positivity alone is not sufficient to impact pregnancy outcomes.