A prospective cohort for the investigation of alteration in temporal transcriptional and microbiome trajectories preceding preterm birth: a study protocol
A prospective cohort for the investigation of alteration in temporal transcriptional and microbiome trajectories preceding preterm birth: a study protocol
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DOI：
10.1136/bmjopen-2018-023417
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发表时间：
2019-06-01
期刊：
影响因子：
2.9
通讯作者：
Chaussabel, Damien
中科院分区：
文献类型：
--
作者：
Brummaier, Tobias;Kabeer, Basirudeen Syed Ahamed;Chaussabel, Damien
引言 早产 (PTB) 是由异质性影响造成的，是新生儿死亡率和发病率的一个主要原因，并且在新生儿期之后继续对婴儿产生不利影响。该方案描述了通过在怀孕期间、分娩时和产后期进行高频采样来确定预测 PTB 的分子特征的程序。 方法和分析 来自缅甸或泰国的克伦族或缅族族裔的 400 名妊娠早期孕妇，她们具有可行的单胎妊娠将被纳入这项非干预性、前瞻性妊娠出生队列研究，并将跟踪至产后期。每两周手指刺破毛细血管血液采样将能够监测全血中全基因组转录丰度。每个三个月、分娩时和产后收集粪便样本和阴道拭子将有助于监测肠道和阴道微生物组成。在巢式病例对照分析中，将比较产下早产儿的母亲和产下足月新生儿的匹配病例之间毛细血管血液中转录本丰度的扰动以及肠道、阴道和口腔微生物组的纵向变化。早产儿和足月新生儿的胎盘组织将用于确定细菌定植以及建立编码和非编码 RNA 谱。此外，脐带血血清中循环非编码 RNA 的 RNA 谱将与分娩时母体外周血清的 RNA 谱进行比较。 伦理与传播 本研究方案旨在检测不良妊娠结局之前分子轨迹的扰动，并获得泰国曼谷玛希隆大学热带医学院伦理委员会（伦理参考号：TMEC 15-062）、牛津热带研究伦理委员会（伦理参考号： OxTREC：33-15）和当地来兴府社区道德咨询委员会。该合作项目的成果将在国际同行评审科学期刊上陆续发表的多种出版物中传播。
Introduction Preterm birth (PTB) results from heterogeneous influences and is a major contributor to neonatal mortality and morbidity that continues to have adverse effects on infants beyond the neonatal period. This protocol describes the procedures to determine molecular signatures predictive of PTB through high-frequency sampling during pregnancy, at delivery and the postpartum period.Methods and analysis Four hundred first trimester pregnant women from either Myanmar or Thailand of either Karen or Burman ethnicity, with a viable, singleton pregnancy will be enrolled in this non-interventional, prospective pregnancy birth cohort study and will be followed through to the postpartum period. Fortnightly finger prick capillary blood sampling will allow the monitoring of genome-wide transcript abundance in whole blood. Collection of stool samples and vaginal swabs each trimester, at delivery and postpartum will allow monitoring of intestinal and vaginal microbial composition. In a nested case-control analysis, perturbations of transcript abundance in capillary blood as well as longitudinal changes of the gut, vaginal and oral microbiome will be compared between mothers giving birth to preterm and matched cases giving birth to term neonates. Placenta tissue of preterm and term neonates will be used to determine bacterial colonisation as well as for the establishment of coding and non-coding RNA profiles. In addition, RNA profiles of circulating, non-coding RNA in cord blood serum will be compared with those of maternal peripheral blood serum at time of delivery.Ethics and dissemination This research protocol that aims to detect perturbations in molecular trajectories preceding adverse pregnancy outcomes was approved by the ethics committee of the Faculty of Tropical Medicine, Mahidol University in Bangkok, Thailand (Ethics Reference: TMEC 15-062), the Oxford Tropical Research Ethics Committee (Ethics Reference: OxTREC: 33-15) and the local Tak Province Community Ethics Advisory Board. The results of this cooperative project will be disseminated in multiple publications staggered over time in international peer-reviewed scientific journals.