Objective <p>Given the persistent challenges in managing systemic lupus erythematosus (SLE) pregnancies despite therapeutic advancements, this study aimed to identify modifiable predictive biomarkers and clinical risk factors for adverse pregnancy outcomes (APOs) in SLE patients through comprehensive analysis of maternal–fetal parameters.</p> Methods <p>This retrospective cohort study analyzed 420 consecutive pregnant SLE patients admitted to Qilu Hospital between 2011 and 2022. Multivariable logistic regression models assessed associations between clinical/laboratory parameters and APOs, including miscarriage, preterm birth, low birth weight (LBW), and cesarean delivery.</p> Results <p>APOs were observed in the following descending order of incidence: cesarean delivery (78.6%), preterm birth (30.7%), miscarriage (26.4%), and LBW (24.9%). Urinary protein positivity emerged as a pan-predictor of APOs—specifically, in multivariate analyses, proteinuria ≥ 1 + was associated with a 3.506-fold increased risk of preterm birth and a 4.136-fold elevated risk of cesarean delivery, while in univariate analyses, it was associated with a 3.907-fold increased risk of LBW. Elevated blood urea nitrogen (BUN) served as a universal predictor of LBW, preterm birth, and cesarean delivery in univariate analyses (OR = 1.214–1.515, <i>P</i> ≤ 0.033), with the association between elevated BUN and LBW remaining statistically significant in multivariate models (OR = 1.475, <i>P</i> = 0.001). A higher Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score was associated with increased risks of LBW (OR = 1.502, <i>P</i> &lt; 0.001), preterm birth (OR = 1.440, <i>P</i> &lt; 0.001), and cesarean delivery (OR = 1.224, <i>P</i> = 0.021) in univariate analysis, and served as an independent predictor of LBW in multivariate analysis (OR = 1.239, <i>P</i> = 0.017). Non-use of thromboprophylaxis (aspirin or low-molecular-weight heparin [LMWH])—particularly non-use of LMWH (multivariate OR = 2.690, <i>P</i> = 0.035)—was associated with a significant increase in miscarriage risk.</p> Conclusion <p>Standardized monitoring of renal dysfunction (proteinuria, BUN), strict control of disease activity, and protocolized thromboprophylaxis (LDA/LMWH) should be prioritized to mitigate APOs risks in SLE pregnancies.<Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="justify" colname="c1" colnum="1" /> <colspec align="justify" colname="c2" colnum="2" /> <tbody> <row> <entry nameend="c2" namest="c1"> <p><b>Key Points</b></p> <p>• <i>Urinary protein positivity is a pan-predictor of adverse pregnancy outcomes (APOs); multivariate analyses show proteinuria ≥ 1 + correlates with higher risks of preterm birth and cesarean delivery.</i></p> <p>• <i>Elevated blood urea nitrogen (BUN) universally predicts low birth weight (LBW), preterm birth, and cesarean delivery in univariate analyses.</i></p> <p>• <i>A higher SLEDAI-2K score links to increased risks of LBW, preterm birth, and cesarean delivery (univariate analysis) and independently predicts LBW (multivariate analysis).</i></p> <p>• <i>Non-use of thromboprophylaxis—especially LMWH—significantly raises miscarriage risk.</i></p> </entry> </row> </tbody> </tgroup> </Table></p>