Systemic inflammatory responsiveness was studied in normal human pregnancy and its specific inflammatory disorder, pre-eclampsia. Compared with nonpregnancy, monocytes were primed to produce more TNF-α throughout normal pregnancy, more IL-12p70 in the first and second trimesters, and more IL-18 in the first trimester only. Intracellular cytokine measurements (TNF-α and IL12p70) showed little change by comparison. IFN-γ production was suppressed in all three trimesters. In pre-eclampsia, IL-18 secretion was increased. Secreted but not intracellular measures of TNF-α and IL-12p70 were also further enhanced compared with normal pregnancy. Inhibition of IFN-γ production was lost and involved both CD56+ NK and CD56− lymphocyte subsets. We determined whether circulating syncytiotrophoblast microparticles (STBM) could contribute to these inflammatory changes. Unbound STBM could be detected in normal pregnancy by the second trimester and increased significantly in the third. They were also bound in vivo to circulating monocytes. Women with pre-eclampsia had significantly more circulating free but not cell-bound STBMs. STBMs prepared by perfusion of normal placental lobules stimulated production of inflammatory cytokines (TNF-α, IL12p70, and IL-18 but not IFN-γ) when cultured with PBMCs from healthy nonpregnant women. Inflammatory priming of PBMCs during pregnancy is confirmed and is established by the first trimester. It is associated with early inhibition of IFN-γ production. The inflammatory response is enhanced in pre-eclampsia with loss of the IFN-γ suppression. Circulating STBMs bind to monocytes and stimulate the production of inflammatory cytokines. It is concluded that they are potential contributors to altered systemic inflammatory responsiveness in pregnancy and pre-eclampsia.
Women with antiphospholipid syndrome (APS) may have diverse pregnancy outcomes. The objective of this study was to evaluate pregnancy outcome in women with APS according to their clinical phenotype, i.e. thrombotic and obstetric APS. Eighty-three pregnancies in 67 women with APS were included in the study, including 21 with recurrent miscarriage (Group 1), 21 with late fetal loss or early delivery due to placental dysfunction (Group 2) and 41 with thrombotic APS (Group 3). Group 3 had higher rates of preterm delivery (26.8% versus 4.7%, p = 0.05) than Group 1 and more small for gestational age (SGA) babies than Group 2 (39.5% versus 4.8%, p = 0.003). Group 2 had significantly longer gestations compared with their pretreatment pregnancies (38.4 [28.4-41.4] versus 24.0 [18-35] weeks, p < 0.0001) and 100% live birth rate after treatment with aspirin and low-molecular-weight heparin (LMWH). In conclusion, women with thrombotic APS (Group 3) have higher rates of pregnancy complications than those with obstetric APS (Groups 1 and 2). Treatment with aspirin and LMWH is associated with improved outcomes for women with previous late fetal loss or early delivery due to placental dysfunction (Group 2).
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