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。本建议的具体目标是研究S。日本血吸虫感染和不良出生结果。此外，本项目将研究在S。日本血吸虫感染这项研究的数据应该有更广泛的影响，我们的理解的发病机制，子宫内生长迟缓的感染性和非感染性疾病，促进促炎性免疫反应的主机。本研究是一项吡喹酮治疗女性链球菌感染的随机对照试验。在菲律宾的莱特的地方病村庄中发现了一种日本血吸虫。女性将在妊娠约12周时接受治疗，并将评估治疗对出生体重、子宫内生长、母体血红蛋白和新生儿血红蛋白和铁储备的影响。这个项目将解决这一假设，即促炎细胞因子是在响应S。日本血吸虫感染介导不良出生结局。具体而言，该提议假设这些细胞因子将在全身和胎盘处产生有害作用，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效应包括炎症性贫血，伴随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。母体铁生物利用率降低将导致铁转移到发育中的胎儿减少，导致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备。血清促炎细胞因子升高也与胎盘中水平升高相关。该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。还将使用滋养层细胞凋亡测定来评估妊娠32周的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.