Pre-labour invasion of the human uterus by Streptococcus agalactiae

无乳链球菌在产前侵入人类子宫

• 批准号: MR/W025620/1
• 负责人: Gordon Smith
• 金额: $ 140.14万
• 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: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FW025620%2F1
• 关键词: Pre; labour; invasion; human; uterus

A bug (bacterium) known as GBS (Group B Streptococcus) is present in the birth canal in about 1 in 5 pregnant women. GBS is already recognised as a problem, because it is known that women who have this bug can pass it on to their baby during the birth. Infection of the baby with GBS is the most common reason why babies die due to infection in the days after birth. Where the mother is known to carry the bug, she is given antibiotics during labour and this reduces the risks to the baby. But in 2019 we demonstrated that GBS can get into the womb before labour starts and we can find it in the placenta, the organ which supplies the fetus with all the nutrients needed for healthy development. We now have evidence that GBS gets into the placenta by invading the womb and that when this happens the baby is at increased risk of needing to be admitted to the neonatal unit following the birth. This happens because the presence of GBS in the placenta can hyperstimulate the baby's immune system. This hyperstimulation is sometimes referred to as a "cytokine storm", and it's the same thing that is present in severe cases of COVID-19. Our results so far indicate that GBS gets into the womb before labour, that it hyperstimulates the baby's immune system, and that this could be an unrecognised cause of why some babies get very sick after they are born. If we can prove this and understand the mechanisms, it raises the possibility of new treatments to reduce rates of complications in new born infants. To try and achieve this, we want to study a large number of women being delivered by caesarean section before their labour starts. We are choosing to study this group for two reasons. First, women being delivered by a planned caesarean are not given a full course of antibiotics before the baby is born, even if the mother is known to carry GBS. In contrast, women known to carry GBS who are giving birth naturally are treated with antibiotics and this would make it difficult to be sure which placentas had the bug and which did not. Second, we are particularly interested in how the bug can get into the womb in the first place. We already know that bugs can get into the womb as part of the process of labour, because the waters have broken and the neck of the womb opens up. Studying samples from women being delivered by planned caesarean section means we can be sure that any bugs we find must have invaded the womb before labour started. We want to see how the placenta and the baby respond to the presence of GBS. We also want to see whether anything about the specific type of GBS determines whether or not it can invade the womb. We can do this by studying the genetic make-up of GBS in cases where it gets into the womb. We speculate that the bugs that make it into the womb before the onset of labour might have differences in their genes which help them to invade. If this study yields a positive result, it could impact on clinical care. First, it might help target antibiotic treatment to the pregnancies which are most likely to benefit. Second, it is possible that vaccination might be a way to prevent these complications without using antibiotics at all. Pfizer, the company who produced the first licensed vaccine for COVID-19, are working on an anti-GBS vaccine. They are very interested in the proposed study as it could point to additional benefits of vaccination. If we confirm that GBS is invading the uterus before labour and compromising the baby, we will work with them to determine whether the mother's levels of antibodies against GBS protect the baby from this aspect of GBS.

一种被称为GBS （B族链球菌）的细菌（细菌）在大约五分之一的孕妇中存在于产道中。GBS已经被认为是一个问题，因为众所周知，患有这种细菌的妇女可以在分娩时将其传染给婴儿。婴儿感染GBS是婴儿在出生后几天因感染而死亡的最常见原因。在已知母亲携带病菌的情况下，在分娩期间给她服用抗生素，这样可以降低婴儿的风险。但在2019年，我们证明了GBS可以在分娩开始前进入子宫，我们可以在胎盘中找到它，胎盘是为胎儿提供健康发育所需的所有营养的器官。我们现在有证据表明，GBS通过侵入子宫进入胎盘，当这种情况发生时，婴儿出生后需要住进新生儿病房的风险就会增加。这是因为胎盘中GBS的存在会过度刺激婴儿的免疫系统。这种过度刺激有时被称为“细胞因子风暴”，这与COVID-19严重病例中的情况相同。到目前为止，我们的研究结果表明，GBS在分娩前就进入了子宫，它会过度刺激婴儿的免疫系统，这可能是一些婴儿出生后病得很重的一个未被发现的原因。如果我们能够证明这一点并了解其机制，就有可能找到新的治疗方法来降低新生儿并发症的发生率。为了实现这一目标，我们想研究大量在分娩前剖腹产的妇女。我们选择研究这个群体有两个原因。首先，通过计划剖腹产分娩的妇女在婴儿出生前没有接受完整疗程的抗生素治疗，即使已知母亲携带GBS。相比之下，已知携带GBS的自然分娩妇女使用抗生素治疗，这将使确定哪些胎盘携带细菌而哪些没有变得困难。其次，我们特别感兴趣的是细菌是如何首先进入子宫的。我们已经知道，作为分娩过程的一部分，细菌可以进入子宫，因为羊水破裂，子宫颈部张开。研究计划剖腹产妇女的样本意味着我们可以确定，我们发现的任何细菌都必须在分娩开始前侵入子宫。我们想看看胎盘和婴儿对GBS的反应。我们还想知道，是否有某种特定类型的GBS决定了它是否会侵入子宫。我们可以通过研究GBS进入子宫的基因组成来做到这一点。我们推测，在分娩前进入子宫的细菌可能在基因上存在差异，这有助于它们入侵。如果这项研究取得积极的结果，可能会对临床护理产生影响。首先，它可能有助于针对最有可能受益的妊娠期进行抗生素治疗。其次，接种疫苗可能是一种不使用抗生素就能预防这些并发症的方法。首次获得许可生产新冠病毒疫苗的辉瑞公司正在开发抗gbs疫苗。他们对拟议的研究非常感兴趣，因为它可以指出疫苗接种的额外好处。如果我们确认GBS在分娩前侵入子宫并危及婴儿，我们将与他们一起确定母亲的抗GBS抗体水平是否能保护婴儿免受这方面的GBS。