Characterizing retained placenta : epidemiology and pathophysiology of a critical obstetric disorder

Abstract: Background: Retained placenta is associated with severe postpartum hemorrhage but its etiology and pathophysiology are largely unknown. Certain studies have suggested that retained placenta is associated to defective placentation disorders- pregnancy disorders with an initial defective placentation resulting in increased oxidative stress. The aim of this thesis was to investigate risk factors for and consequences of retained placenta, determine whether retained placenta and defective placentation disorders are epidemiologically associated and to assess if this association is supported at the molecular and histological level. Methods and Main Results: Study I was a case-control study comparing pregnancy and deliveryrelated variables in women with retained placenta and controls (n=408 in each group) after singleton vaginal birth. The study found that retained placenta was associated with severe postpartum hemorrhage and that a history of abortion or recurrent miscarriage, pre-eclampsia, preterm delivery and prolonged oxytocin use in the current pregnancy were independent risk factors for retained placenta. Study II was a population based cohort study investigating the association between retained placenta and defective placentation disorders (pre-eclampsia, preterm birth, small-for-gestational-age birth and stillbirth) in primiparous women giving vaginal birth at 32-41 gestational weeks between 1997 and 2009 in Sweden (n=386 607). The study found that retained placenta was associated to pre-eclampsia, spontaneous preterm birth, small-for-gestational-age birth and stillbirth. The risk was further increased for women with these disorders among preterm deliveries. Study III was a cross-sectional pilot study investigating the antioxidative enzyme Glutathione Peroxidase 1 (GPX1) and the transcription factor Nuclear Factor Kappa-light-chain-enhancer of activated β-cells (NFκB), as markers of antioxidative defence capacity and inflammation, in 29 retained and 31 non-retained placentas. The study found that retained placentas showed a tendency of lower median concentrations GPX1 and were significantly more likely to have a low level of GPX1 protein concentration. There were no differences in expression ofNFκB. Study IV was a case-control study comparing histological signs of maternal underperfusion and inflammation in retained (n=49) and non-retained (n=47) placentas. The study found that retained placentas had a significantly smaller surface area, were more oblong in shape and showed overall more signs of maternal placental underperfusion compared to non-retained placentas. Conclusions: Retained placenta is epidemiologically associated to defective placentation disorders, a finding which is supported in part by signs of decreased antioxidative capacity in the placenta and increased histological signs of maternal placental underperfusion. Prolonged oxytocin use may exacerbate the risk of retained placenta. Risk awareness of retained placenta should guide preparedness during the third stage of labor given the high risk of severe postpartum hemorrhage that the disorder entails.