Placental malperfusion and angiogenesis‐related proteins are associated with small‐for‐gestational‐age in systemic lupus erythematosus

BACKGROUND: Although systemic lupus erythematosus (SLE) pregnancy frequently results in small for gestational age (SGA) infants, the understanding of underlying mechanisms is limited. We aimed to identify specific histological patterns of placental injury in SGA in SLE and to explore whether an altered balance of angiogenesis-related proteins precedes this outcome. METHODS: We prospectively followed 83 SLE and 67 control pregnancies. Placental histological patterns were determined according to the Amsterdam consensus in 63 women with SLE (76%), of whom 10 developed SGA. Soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) in plasma were quantified using LEGENDplex in the first, second and third trimesters. RESULTS: SLE patients remain at risk of having an SGA infant, and their placentas and infants had lower weight compared to controls. In placentas from women with SLE and SGA, maternal vascular malperfusion lesions were common (80% vs. 30% in controls; p = 0.010), but inflammatory lesions were not observed. Women with maternal vascular malperfusion gave birth to infants with lower birth weight compared to women without these lesions. The ratio of sFlt-1:PlGF in the third trimester was elevated in women with SLE with an SGA infant. CONCLUSION: In a prospective cohort of well-controlled SLE patients with low disease activity delivering mostly at term, SGA and small placentas remain common. The increased prevalence of placental malperfusion lesions together with an altered balance of pro- and anti-angiogenic proteins suggests that the role of vascular and angiogenesis-related factors should be further explored in relation to SGA in SLE pregnancy.