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.

在大约5个孕妇中，大约有1个被称为GBS（B组链球菌）的虫（B组链球菌）。 GBS已经被认为是一个问题，因为众所周知，患有此虫子的女性可以在出生期间将其传递给婴儿。婴儿感染GB是出生后几天由于感染而死亡的最常见原因。众所周知，母亲可以携带虫子，在分娩过程中给予了抗生素，这降低了婴儿的风险。但是在2019年，我们证明了GB可以在劳动开始之前进入子宫，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素的器官。我们现在有证据表明，GBS通过入侵子宫进入胎盘，当发生这种情况时，婴儿有可能在出生后需要被接纳为新生儿单位的风险。之所以发生这种情况，是因为胎盘中GBS的存在可以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”，这是在严重的Covid-19案件中存在的同一件事。到目前为止，我们的结果表明，GBS在分娩前进入子宫，它过度刺激了婴儿的免疫系统，这可能是为什么某些婴儿出生后病得很重的原因。如果我们能够证明这一点并理解机制，它将增加新疗法以降低新生婴儿并发症发生率的可能性。为了实现这一目标，我们希望在剖腹产开始之前研究大量由剖腹产的妇女。我们选择研究该组的原因有两个。首先，即使众所周知母亲携带GBS，也没有在婴儿出生之前提供全部抗生素的妇女。相比之下，已知携带自然出生的GB的女性接受了抗生素治疗，这将使难以确定哪个胎盘有虫子，哪些没有虫子。其次，我们对虫子首先如何进入子宫特别感兴趣。我们已经知道，作为劳动过程的一部分，虫子可能会进入子宫，因为水已经破裂，子宫的脖子却打开了。研究计划中剖腹产的妇女的样本意味着我们可以确定，我们发现的任何虫子都必须在劳动开始之前入侵子宫。我们想看看胎盘和婴儿如何应对GB的存在。我们还想看看有关GBS的特定类型的任何内容是否决定它是否可以侵入子宫。在进入子宫的情况下，我们可以通过研究GB的遗传组成来做到这一点。我们推测，在劳动开始之前，将其进入子宫的错误可能会在其基因上有所不同，从而有助于他们入侵。如果这项研究产生了积极的结果，则可能会对临床护理产生影响。首先，它可能有助于将抗生素治疗靶向最有可能受益的妊娠。其次，疫苗接种可能是防止这些并发症而无需使用抗生素的一种方法。辉瑞公司（Pfizer）是为Covid-19生产第一批许可疫苗的公司，正在使用抗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其他好处。如果我们确认GB在劳动前正在入侵子宫并损害婴儿，我们将与他们合作，确定母亲对GBS的抗体水平是否保护婴儿免受GBS的这一方面的影响。