S.japonicum and pregnancy outcomes: an RCT

描述（由申请人提供）：本研究的主要目的是帮助我们了解血吸虫病感染在介导不良出生结局中的作用。这项研究产生的数据将为血吸虫病流行的发展中国家的卫生保健优先事项提供信息。本建议的具体目的是调查日本血吸虫感染与不良分娩结局之间的关系。此外，本项目将研究在日本血吸虫感染的背景下，胎盘外和胎盘机制介导不良妊娠结局。这项研究的数据应该对我们理解子宫内生长迟缓的发病机制有更广泛的意义，这些发病机制是促进促炎免疫反应的感染性和非感染性疾病的宿主。拟议的研究是一项吡喹酮对菲律宾Leyte流行村庄感染日本血吸虫的妇女的随机对照试验。妇女将在妊娠约12周时接受治疗，并评估治疗对出生体重、子宫内生长、母体血红蛋白、新生儿血红蛋白和铁储量的影响。本项目将解决在日本血吸虫感染反应中产生的促炎细胞因子介导不良出生结果的假设。具体来说，本研究假设这些细胞因子会对全身和胎盘产生不利影响，导致子宫内生长迟缓和出生体重降低。这些细胞因子的全身作用包括炎症性贫血，并伴有母体生物可利用铁的减少，这将在32周时通过血清转铁蛋白受体水平进行评估。母体铁的生物利用度降低会导致铁向发育中的胎儿的转移减少，从而导致子宫内生长迟缓和出生体重降低。脐带血铁蛋白将用于评估新生儿铁储量。血清促炎细胞因子升高也与胎盘中促炎细胞因子水平升高有关。本提案将在分娩时检查胎盘细胞因子，以评估吡喹酮对胎盘炎症和出生体重的影响。滋养层细胞凋亡试验也将用于评估孕32周母体血清对滋养层细胞凋亡的影响。

DESCRIPTION (provided by applicant): The broad objective of this study is to contribute to our understanding of the role of schistosomiasis infection in mediating adverse birth outcomes. Data generated from this study will inform the health care priorities of developing nations in which schistosomiasis is endemic. The specific objective of this proposal is to investigate the relationship between S. japonicum infection and adverse birth outcomes. Further, this project will examine both extra-placental and placental mechanisms mediating adverse pregnancy outcomes in the context of S. japonicum infection. Data from this study should have broader implications for our understanding of the pathogenesis of intra-uterine growth retardation for a host of infectious and non-infectious diseases that promote a pro-inflammatory immune response. The proposed study is a randomized controlled trial of Praziquantel for women infected with S. japonicum in endemic villages in Leyte, The Philippines. Women will be treated at approximately 12 weeks gestation, and the impact of therapy on birth weight, intra-uterine growth, maternal hemoglobin, and newborn hemoglobin and iron stores will be assessed. This project will address the hypothesis that pro-inflammatory cytokines that are made in response to S. japonicum infection mediate adverse birth outcomes. Specifically, this proposal hypothesizes that these cytokines will exert detrimental effects both systemically and at the placenta, causing intra-uterine growth retardation and lower birth weight. Systemic effects of these cytokines include anemia of inflammation, with a concomitant decrease in maternal bio-available iron, which will be assessed at 32 weeks by serum transferrin receptor levels. Decreased maternal iron bio-availability will result in decreased transfer of iron to the developing fetus, contributing to intra-uterine growth retardation and lower birth weight. Cord blood ferritin will be used to assess newborn iron stores. Elevated serum pro-inflammatory cytokines have also been associated with elevated levels in the placenta. This proposal will examine placental cytokines at the time of delivery to assess the effect of Praziquantel on placental inflammation and birth weight. A trophoblast apoptosis assay will also be used to assess the effect of maternal serum from 32 weeks gestation on trophoblast apoptosis.