Predictors of Pregnancy Outcome in Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS) (PROMISSE)

• Otherwise unexplained fetal death occurring after 12 weeks gestation [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  Fetal death occurring after 12 weeks' gestation and not explained by chromosomal abnormalities, anatomic malformations, or congenital infections.
  
  
• Neonatal death prior to hospital discharge and due to complications of prematurity [ Time Frame: Time of neonatal death ] [ Designated as safety issue: No ]
  
• Indicated preterm delivery prior to 36 weeks' gestation because of gestational hypertension, preeclampsia-eclampsia or placental insufficiency [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  
• Small for gestational age (SGA) <5th %ile in the absence of anatomical or chromosomal abnormalities and/or delivery before 36 weeks because of intrauterine growth restriction (IUGR). [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  

• Gestational age [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  
• Birth weight [ Time Frame: End of pregnancy ] [ Designated as safety issue: No ]
  
• Number of days neonate requires positive pressure ventilation [ Time Frame: Neonate discharge from hospital ] [ Designated as safety issue: No ]
  
• Total number of days neonate is hospitalized [ Time Frame: Neonate discharge from hospital ] [ Designated as safety issue: No ]
  

Thrombosis and pregnancy loss are common features of systemic lupus erythematosus (SLE), particularly in the presence of antiphospholipid (aPL) antibodies. The in vivo mechanisms by which aPL antibodies lead to vascular events and, specifically, to recurrent fetal loss are largely unknown. Studies in a mouse model of antiphospholipid antibody syndrome (APS) indicate that in vivo complement activation is necessary for fetal loss caused by aPL antibodies. This study represents an effort to translate these research observations on the potential role of complement activation in the pathogenesis of aPL antibody-mediated pregnancy loss to a clinically relevant human study.

In addition, studies in humans and mice have shown 1) that the balance of circulating angiogenic and antiangiogenic factors predicts preeclampsia and fetal growth restriction in healthy women, 2) circulating antiangiogenic factors cause endothelial dysfunction and abnormal placental development in animal models, and 3) complement activation leads to elevated levels of circulating antiangiogenic factors and complement inhibition prevents increased levels of antiangiogenic factors, placental dysfunction and fetal growth restriction in a mouse model of APS. This study will permit testing the hypothesis that, like in healthy women, the balance of circulating angiogenic and antiangiogenic factors predict complications in women with SLE and APS and to translate the findings in animal models into humans.

The PROMISSE Study is a prospective observational study that will follow 700 pregnant patients who will be grouped and analyzed according to the presence or absence of aPL antibodies and preexisting SLE. The patients are followed regularly during the course of the pregnancy, collecting medical and obstetrical information as well as serial blood specimens for complement and cytokine assays. The data obtained will be analyzed and used to identify mechanisms and predictors of poor fetal outcome. We expect that the insights provided through this study will suggest means to prevent, arrest or modify these conditions.