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Objectives OBJECTIVE: Delivery of a small for gestational age (SGA) infant is a common pregnancy complication among women with systemic lupus erythematosus (SLE). Although disease activity and autoantibodies such as anti-Smith and anti-RNP associate with SGA, underlying pathological mechanisms remain unclear and reliable predictors are lacking. To address this, we applied a proteomic approach to identify proteins associated with SGA in SLE.Methods METHODS Plasma samples were collected repeatedly during pregnancy, at delivery, and from placental intervillous blood in women with SLE (n=83) and healthy controls (n=67) enrolled in the prospective SLE-Placenta study. Postpartum samples (6 months after delivery) from a subset of women with SLE (n=19) served as non-pregnant controls. Mass spectrometry was performed on a discovery cohort comprising six healthy uncomplicated pregnancies, eight uncomplicated SLE pregnancies, and eight SLE pregnancies complicated by SGA (SLE-SGA). Differential protein abundance analysis was performed in R. Candidate proteins were quantified by ELISA in the full cohort.Results RESULTS Discovery proteomics identified four proteins with increased abundance in SLE-SGA compared to uncomplicated SLE pregnancies: endostatin (Padj=0.0003), angiogenin (Padj=0.03), insulin-like growth factor-binding protein 5 (Padj=0.03) and complement factor H-related protein 5 (Padj=0.004). In the full cohort, ELISA quantification did not confirm increased levels of these proteins in SLE-SGA but suggested elevated levels of the angiogenesis-related proteins endostatin and angiogenin in women with SLE who later developed preeclampsia. Endostatin levels were consistently higher in SLE compared to controls across all trimesters (p=0.0001). Endostatin, but not angiogenin, was enriched in placental intervillous blood.Conclusions CONCLUSION Our study did not validate the differentially abundant proteins as markers for SLE-SGA but suggested a link between the anti- and pro-angiogenic proteins, endostatin and angiogenin, respectively, and preeclampsia in SLE. Given the consistent elevation of endostatin throughout pregnancy in SLE compared to controls, its potential effects on placental development in SLE warrant further investigation.