91 research outputs found

    The Extended Use of Eculizumab in Pregnancy and Complement Activation-Associated Diseases Affecting Maternal, Fetal and Neonatal Kidneys-The Future Is Now?

    Get PDF
    Excessive complement activation is involved in the pathogenesis of many diseases and the kidney is an organ with particular susceptibility to complement-mediated injury. Apart from paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), there are several other diseases with clear evidence of complement activation affecting both maternal and fetal kidneys during pregnancy and causing long-term adverse outcomes. Several novel drugs have been recently developed for blocking the complement cascade, including purified plasma proteins, new monoclonal antibodies, recombinant proteins, small molecules, and small interfering RNA agents. Eculizumab, the humanized monoclonal IgG2/4-antibody targeting C5 was approved by the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for treatment of two rare diseases: PNH in 2007 and aHUS in 2011. There is an increasing number of publications of successful use of eculizumab for off-label indications, e.g., in pregnant women with antiphospholipid syndrome, sickle-cell anemia, and HELLP syndrome. These severe diseases are associated with both high maternal and fetal morbidity and mortality rate and substantial prematurity. Eculizumab has considerably improved overall outcome of patients with PNH and aHUS, enabling safe pregnancy for many women. Prolongation of pregnancy and the use of eculizumab, even for only a few weeks, may protect not only maternal renal function, but also alleviate acute and long-term renal consequences of prematurity in offspring.Peer reviewe

    Oxidative stress - Related spontaneous preterm delivery challenges in causality determination, prevention and novel strategies in reduction of the sequelae

    Get PDF
    Spontaneous preterm birth (PTB) is one of the major complications of pregnancy and the main cause of neonatal mortality and morbidity. Despite the efforts devoted to the understanding of this obstetrical syndrome and improved medical care, there has been a tendency for the PTB rate to increase in the last decades globally. The costs of the screening for spontaneous PTB, its management, and treatment of the sequelae represent a major burden to the health service economy of high-income countries. In this scenario, it has been widely acknowledged that oxidative stress (OS) plays an important role in the pathogenicity of human disease in wide range of areas of medicine. There is an emerging evidence that an imbalance between pro-and-antioxidants may be associated with spontaneous PTB. However, there are still many controversies on the mechanisms by which OS are involved in the pathogenesis of prematurity. Moreover, the crucial question whether the OS is the cause or consequence of the disease is yet to be answered. The purpose of this article is to briefly summarize the current knowledge and controversies on oxidative stress-related spontaneous PTB and to give a critical approach on future perspectives on this topic as a classical example of translational medicine. Placenta-mediated pregnancy adverse outcome associated with OS leading to iatrogenic PTB (e.g. pre-eclampsia, intrauterine growth restriction, gestational diabetes) will not be discussed.Peer reviewe

    Cost of providing cell-free DNA screening for Down syndrome in Finland using different strategies

    Get PDF
    Introduction A financial analysis is carried out to assess costs and benefits of providing cell-free DNA screening in Finland, using different strategies. Materials and methods Three cell-free DNA screening strategies are considered: Primary, all women; Secondary, those with positive Combined test; and Contingent, the 10-30% with the highest Combined test risks. Three costs are estimated: additional cost for 10,000 pregnancies compared with the Combined test; 'marginal' cost of avoiding a Down syndrome birth which occurs in a pregnancy that would have been false-negative using the Combined test; and marginal cost of preventing the iatrogenic loss of a non-Down syndrome birth which occurs in a pregnancy that would have been false-positive. Results Primary cell-free DNA will require additional funds of euro250,000. The marginal cost per Down syndrome birth avoided is considerably less than the lifetime medical and indirect cost; the marginal cost per unaffected iatrogenic fetal loss prevented is higher than one benefit measure but lower than another. If the ultrasound component of the Combined test is retained, as would be in Finland, the additional funds required rise to euro992,000. Secondary cell-free DNA is cost-saving as is a Contingent strategy with 10% selected but whilst when 20-30% costs rise they are much less than for the Primary strategy and are cost-beneficial. Conclusions When considering the place of cell-free DNA screening it is important to make explicit the additional and marginal costs of different screening strategies and the associated benefits. Under most assumptions the balance is favorable for Contingent screening.Peer reviewe

    Busy day effect on intrapartum adverse maternal outcomes – A population-based study of 601 247 singleton deliveries

    Get PDF
    BackgroundThis was a retrospective population-based study, utilizing the data of 601 247 singleton hospital deliveries collected from the Finnish Medical Birth Register (MBR) in 2006-2016. The aim of this study was to analyse the busy day effect on intrapartum adverse maternal outcomes.MethodsTo implement the study design, daily delivery frequencies and ranges (min-max) for each delivery unit (n=26) were stratified to the daily delivery volume distributions by the delivery unit's annual delivery volume and profile: Category (C)1= 3000 and C5 the profile of university hospitals. To study the busy day effect, the quiet, optimal and busy days were defined by calculating the number of days (%) with the lowest and highest daily delivery frequencies and summed to the nearest 10% in each hospital category. Optimal days were determined by calculating approximately 80% of deliveries occurring between the lowest 10%, and highest 10% in each hospital category. Crude and adjusted odd ratios (ORs) with 99% confidence intervals (CIs) were used to analyze the busy day effect on adverse maternal outcomes, blood transfusions, manual removal of the placenta and obstetric anal sphincter injuries, separately in each hospital category.ResultsThe busy day effect was associated with the 28% (99% CI 8-52%) and 25% (99% CI 11-40%) increased need for blood transfusions in C2 and university hospitals (C5), respectively, whereas 22% (99% CI 10-31%) less blood transfusions were needed at university hospitals during quiet days. In C3 hospitals, 83% (99% CI 65-92%) less blood transfusions were needed during busy days. Obstetric and anal sphincter injury rates declined during quiet days by 22% (99% CI 3-38%) only in university hospitals.ConclusionsThe findings of this study identify no specific pattern to the busy day effect for adverse maternal outcomes defined as manual removal of the placenta or obstetric and anal sphincter injuries. However, both quiet and busy days seem to be associated with increased or decreased need for blood transfusions in different sized delivery units. Findings also suggest that quiet days are associated with a decreased number of obstetric and anal sphincter injuries.Peer reviewe

    Major or minor placenta previa : Does it make a difference?

    Get PDF
    Introduction: Placenta previa is a severe pregnancy complication with considerable maternal and neonatal morbidity. Placenta previa can be defined as major or minor by location. Major placenta previa is associated with higher complication rates. Management of women with minor placenta previa has not been well defined. The primary goal of the study was to evaluate the accuracy of our existing screening protocol for placenta previa. Secondly, we wanted to compare pregnancy and delivery outcomes by the type of placenta previa. Methods: The study was conducted at the Helsinki University Hospital between June 2010 and September 2014. The study population consisted of all women with the antenatal ultrasound diagnosis of placenta previa during delivery. Data were retrospectively collected and analysed. Results: Altogether 176 women had placenta previa at delivery (major 129, minor 47). Placenta previa remained undiagnosed at second trimester screening ultrasound in 32 women (18.2%). Twenty (62.5%) of these cases had minor placenta previa and 12 (37.5%) had major placenta previa. Five (15.6%) of the undiagnosed cases developed life-threatening hemorrhage (>= 2500 ml) during the delivery and two had abnormally invasive placenta followed by hysterectomy. Women with major placenta previa had significantly more blood loss and delivered earlier than women with minor placenta previa. The groups were otherwise similar, including the rate of abnormally invasive placenta. Discussion: The existing protocol for placenta previa missed almost one fifth of cases. Both major and minor placenta previa are risk factors for abnormally invasive placenta and should be treated as severe conditions.Peer reviewe

    Is there an association between postpartum hemorrhage, interventional radiology procedures, and psychological sequelae?

    Get PDF
    Background: Postpartum hemorrhage (PPH) may cause post-traumatic psychological sequelae. Interventional radiology procedures (IRP) have been established in the management of PPH when conventional management fails. IRP is also used prophylactically in women who are at high risk for PPH in pregnancies with abnormally invasive placentation. We sought to determine if there is an association between PPH, IRP, and psychological sequelae. Objectives: Seventy-three women who underwent IRP due to PPH or were at high risk for PPH. Method: A structured questionnaire was sent to all women. Results: Overall 49 women returned the questionnaire. Two-thirds of the women developed psychological sequelae and one-third reported a lack of professional support. Nine women had symptoms of post-traumatic stress disorder. Psychological sequelae were not associated with a volume of bleeding, whether or not hysterectomy was performed, or whether the IRP was performed as an emergency procedure or prophylactically. However, women who had elective IRP and no hysterectomy performed had significantly less fear of death compared to the rest of the study population. Conclusions: We observed a high rate of psychological sequelae associated with IRP. Lack of proper professional support may have contributed to the development of post-traumatic psychological sequelae suggesting a need for debriefing in such women.Peer reviewe

    Thrombotic microangiopathies during pregnancy : The obstetrical and neonatal perspective

    Get PDF
    Thrombotic Microangiopathies during pregnancy and puerperium are very rare and, if undiagnosed, can be lifethreating. Pregnancy and postpartum can represent a trigger in predisposed patients. Therefore, obstetricians are usually the first to observe clinical symptoms and laboratory abnormalities suggestive of Thrombotic Microangiopathies. The aim of this review is to briefly describe the obstetrical and perinatal outcome of these entities and highlight the clues for a correct diagnosis of pregnancy-related Thrombotic Microangiopathies. (C) 2019 Elsevier B.V. All rights reserved.Peer reviewe
    • …
    corecore