MICA: The role of placental infection in adverse pregnancy outcome.

MICA：胎盘感染在不良妊娠结局中的作用。

基本信息

批准号：
MR/K021133/1
负责人：
Gordon Smith
金额：
$ 201.73万
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FK021133%2F1
关键词：
MICA role placental infection adverse

项目摘要

The context for this study is that there are >5 million births in the EU and >4 million births in the USA and severe adverse outcome of pregnancy is relatively common. For example, in the UK alone, >4000 infants are stillborn per year. The majority of adverse outcomes occur to women who lack known risk factors. Poor placental function is thought to be responsible for the majority of stillbirths (the placenta is the "afterbirth" and is critically important for normal pregnancy). The complications which lead to stillbirth are also associated with infant mortality, disability and, through a poor prenatal environment, ill health in later life. However, the underlying cause of placental dysfunction leading to these complications remains obscure. Infection is clearly one of the major possible explanations when considering possible causes of dysfunction of an organ. Multiple studies have reported high rates of placental inflammation in pregnancies with adverse outcome. Others have reported associations between the presence of antibodies to infectious agents in the mother's blood during pregnancy and the risk of outcomes such as pre-eclampsia (high blood pressure and abnormal kidney function during pregnancy). Others have shown that infection of placental cells in culture with certain bacteria or viruses impairs their function. However, the quality of the evidence around both placental inflammation and placental infection is generally poor. Furthermore, recent developments in the analysis of genetic material have generated powerful new tools to identify the presence of infectious agents in tissue and these have not previously been applied to studying the possible role of placental infection in causing pre-eclampsia and poor fetal growth.We have been conducting a study since January 2008 (funded by the NIHR Cambridge Comprehensive Biomedical Research Centre). We have recruited women having first pregnancies at the time of their first scan. We obtain blood samples at around 12, 20, 28 and 36 weeks of pregnancy. We also obtain samples of the placenta following birth. We perform extra research scans so that we have detailed information on both the women experiencing complications and the controls with whom they will be compared. By the start of this project, we will have data and samples from more than 4,000 women who have completed the study and this provides a unique and powerful resource to identify whether infection of the placenta is a determinant of common pregnancy complications (pre-eclampsia and poor growth of the baby). Our approach is (1) to detect the presence of genetic material (DNA or RNA) for infectious agents in the placenta, (2) to measure markers of infection and inflammation in the stored blood samples, and (3) to determine whether inflammation in the placenta is more common in complicated pregnancies. Critically, we have also enlisted internationally recognised experts (from the renowned Wellcome Trust Sanger Institute) in the technology of detecting infectious agents (bacteria, viruses etc) in tissue samples. This project could uncover such a role for a currently recognised infectious agent, or it could even identify if these complications are being caused by some currently unrecognised bacterium or virus. Identification of previously unrecognised infectious causes of disease has been critical in medicine in the last 30 years. Recognition of the role of a bacterium (Helicobacter pylori) transformed the management of peptic ulcer disease and recognition of the role of a virus (human papilloma virus) in cervical cancer has led to vaccination as a preventative approach. If the mystery of adverse pregnancy outcome is partly explained by infection, this could lead to similarly dramatic changes in understanding and generate new approaches to improving the health of mothers and babies.

这项研究的背景是，欧盟有500万个出生，在美国有400万个出生，而怀孕的严重不良后果相对普遍。例如，仅在英国，> 4000名婴儿每年死产。缺乏已知危险因素的妇女发生了大多数不良结果。胎盘功能不佳被认为是大多数死产的原因（胎盘是“生育后”，对于正常妊娠至关重要）。导致死产的并发症也与婴儿死亡率，残疾以及通过贫困的产前环境相关，后来的健康状况不佳。但是，导致这些并发症的胎盘功能障碍的根本原因仍然晦涩难懂。当考虑器官功能障碍的可能原因时，感染显然是可能的解释之一。多项研究报告了妊娠不良预后的胎盘炎症率高。其他人则报告了抗体在怀孕期间与母亲血液中传染剂的抗体之间存在关联，以及诸如先兆子痫之前的结局风险（高血压和怀孕期间的肾功能异常）。其他人则表明，用某些细菌或病毒培养胎盘细胞的感染会损害其功能。但是，围绕胎盘炎症和胎盘感染的证据质量通常很差。此外，遗传材料分析的最新发展产生了强大的新工具，以识别组织中传染剂的存在，这些工具以前尚未用于研究胎盘感染在引起胎儿前的胎儿和胎儿不良生长中的可能作用。我们在第一次扫描时招募了第一次怀孕的妇女。我们在怀孕的12、20、28和36周左右获得血液样本。我们还获得出生后胎盘的样品。我们进行了额外的研究扫描，以便我们详细介绍了遇到并发症的妇女和与之比较的控制。到该项目开始时，我们将获得已完成研究的4,000多名妇女的数据和样本，这提供了一种独特而有力的资源，可以确定胎盘感染是否是常见妊娠并发症的决定因素（前宾夕法尼亚前体和婴儿的成长较差）。我们的方法是（1）检测胎盘中传染剂的遗传物质（DNA或RNA）的存在，（2）测量储存的血液样本中感染和炎症标志物的存在，（3）确定胎盘中的炎症在复杂的妊娠中是否更常见。至关重要的是，我们还参与了国际认可的专家（来自著名的Wellcome Trust Sanger Institute），以检测组织样品中传染病（细菌，病毒等）的技术。该项目可能会发现当前公认的传染病剂的作用，或者甚至可以确定这些并发症是否是由一些目前未识别的细菌或病毒引起的。在过去的30年中，先前未知的疾病感染原因在医学中至关重要。认识到细菌（幽门螺杆菌）的作用，改变了消化性溃疡疾病的治疗，并认识了病毒（人乳头瘤病毒）在宫颈癌中的作用，导致了作为预防方法的疫苗接种。如果不良怀孕结局的奥秘部分通过感染来解释，这可能会导致理解的巨大变化，并为改善母亲和婴儿的健康而产生新的方法。

项目成果

期刊论文数量（10）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction.

DOI：
10.1038/ng.3699
发表时间：
2016-12
期刊：
Nature genetics
影响因子：
30.8
作者：
Cleaton MA;Dent CL;Howard M;Corish JA;Gutteridge I;Sovio U;Gaccioli F;Takahashi N;Bauer SR;Charnock-Jones DS;Powell TL;Smith GC;Ferguson-Smith AC;Charalambous M
通讯作者：
Charalambous M

Evolutionary History of Endogenous Human Herpesvirus 6 Reflects Human Migration out of Africa.

DOI：
10.1093/molbev/msaa190
发表时间：
2021-01-04
期刊：
Molecular biology and evolution
影响因子：
10.7
作者：
Aswad A;Aimola G;Wight D;Roychoudhury P;Zimmermann C;Hill J;Lassner D;Xie H;Huang ML;Parrish NF;Schultheiss HP;Venturini C;Lager S;Smith GCS;Charnock-Jones DS;Breuer J;Greninger AL;Kaufer BB
通讯作者：
Kaufer BB

IFPA meeting 2018 workshop report II: Abnormally invasive placenta; inflammation and infection; preeclampsia; gestational trophoblastic disease and drug delivery