mSep：一项前瞻性观察性队列研究方案，旨在研究脓毒症和健康孕妇的生理和免疫代谢生物标志物，以预测胎儿-母体免疫健康。

mSep: investigating physiological and immune-metabolic biomarkers in septic and healthy pregnant women to predict feto-maternal immune health - a prospective observational cohort study protocol.

机构信息

Department of Obstetrics and Gynaecology, University Hospital of Wales, Cardiff, UK

Project Sepsis, Systems Immunity Research Institute, Cardiff University Cardiff Institute of Infection and Immunity, Cardiff, UK.

出版信息

BMJ Open. 2022 Sep 17;12(9):e066382. doi: 10.1136/bmjopen-2022-066382.

DOI:10.1136/bmjopen-2022-066382

PMID:36115679

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9486348/

Abstract

INTRODUCTION

Maternal sepsis remains a leading cause of death in pregnancy. Physiological adaptations to pregnancy obscure early signs of sepsis and can result in delays in recognition and treatment. Identifying biomarkers that can reliably diagnose sepsis will reduce morbidity and mortality and antibiotic overuse. We have previously identified an immune-metabolic biomarker network comprising three pathways with a >99% accuracy for detecting bacterial neonatal sepsis. In this prospective study, we will describe physiological parameters and novel biomarkers in two cohorts-healthy pregnant women and pregnant women with suspected sepsis-with the aim of mapping pathophysiological drivers and evaluating predictive biomarkers for diagnosing maternal sepsis.

METHODS AND ANALYSIS

Women aged over 18 with an ultrasound-confirmed pregnancy will be recruited to a pilot and two main study cohorts. The pilot will involve blood sample collection from 30 pregnant women undergoing an elective caesarean section. Cohort A will follow 100 healthy pregnant women throughout their pregnancy journey, with collection of blood samples from participants at routine time points in their pregnancy: week 12 'booking', week 28 and during labour. Cohort B will follow 100 pregnant women who present with suspected sepsis in pregnancy or labour and will have at least two blood samples taken during their care pathway. Study blood samples will be collected during routine clinical blood sampling. Detailed medical history and physiological parameters at the time of blood sampling will be recorded, along with the results of routine biochemical tests, including C reactive protein, lactate and white blood cell count. In addition, study blood samples will be processed and analysed for transcriptomic, lipidomic and metabolomic analyses and both qualitative and functional immunophenotyping.

ETHICS AND DISSEMINATION

Ethical approval has been obtained from the Wales Research Ethics Committee 2 (SPON1752-19, 30 October 2019).

TRIAL REGISTRATION NUMBER

NCT05023954.

摘要

简介

产妇脓毒症仍然是妊娠死亡的主要原因。妊娠的生理适应性掩盖了脓毒症的早期迹象，可能导致识别和治疗的延迟。确定能够可靠诊断脓毒症的生物标志物将降低发病率和死亡率以及抗生素的过度使用。我们之前已经确定了一个免疫代谢生物标志物网络，该网络由三个途径组成，对检测细菌新生儿脓毒症的准确率超过 99%。在这项前瞻性研究中，我们将在两个队列（健康孕妇和疑似脓毒症孕妇）中描述生理参数和新的生物标志物，目的是绘制病理生理学驱动因素并评估用于诊断产妇脓毒症的预测生物标志物。

方法和分析

将招募年龄在 18 岁以上、超声确认妊娠的妇女参加一个试点和两个主要研究队列。试点将包括从 30 名接受选择性剖宫产的孕妇中采集血样。队列 A 将在整个妊娠过程中跟踪 100 名健康孕妇，在妊娠的常规时间点采集参与者的血样：第 12 周“预约”、第 28 周和分娩期间。队列 B 将跟踪 100 名在妊娠或分娩时出现疑似脓毒症的孕妇，并在其护理过程中至少采集两次血样。研究血样将在常规临床采血时采集。在采血时，将记录详细的病史和生理参数，以及常规生化测试的结果，包括 C 反应蛋白、乳酸和白细胞计数。此外，还将处理和分析研究血样，进行转录组、脂质组和代谢组分析以及定性和功能免疫表型分析。