The impact of microbial and inflammatory exposures on birth outcomes in rural Zimbabwe

微生物和炎症暴露对津巴布韦农村地区出生结果的影响

• 批准号: MR/T039337/1
• 负责人: Andrew Prendergast
• 金额: $ 149.73万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FT039337%2F1
• 关键词: impact; microbial; inflammatory; exposures; birth

One in seven babies in Africa are born with low birthweight, either because they are born too small (small-for-gestational age; SGA) or born too soon (preterm). Babies born SGA or preterm have a higher risk of dying, and do not grow as well in early life, leading to a higher risk of malnutrition. The most common form of malnutrition (stunting) affects health into adulthood, reduces learning at school, and lowers earning potential. To reduce child deaths and improve health, growth and prosperity throughout life, it is essential to improve birthweight. To do this, we need to understand the processes during pregnancy that lead to SGA and preterm.The fetus depends on a delicate balance of processes to grow properly and be delivered on time. Infections during pregnancy, and activation of the body's defence system to tackle infections (called inflammation) may disturb these processes, leading to SGA and preterm birth. Mothers with sexually transmitted infections, urinary tract infections, gum disease or diarrhoea during pregnancy have a higher risk of SGA and preterm birth. Inflammation can also occur even when a pregnant woman is not sick with an infection. There are trillions of bacteria in the body, called the microbiome, which generally do not cause disease. However, a change in composition of the microbiome can cause inflammation. Unbalanced vaginal, oral and gut microbiomes in pregnant mothers have all been associated with SGA and preterm birth, although most of these studies have been done in high-income countries. It is unclear whether and how disturbed microbiomes cause inflammation, SGA and preterm birth in Africa. We believe that taking antibiotics in pregnancy could improve birth outcomes by reducing harmful infections and inflammation. In order to test this, we will take advantage of an existing trial examining whether a daily antibiotic (called cotrimoxazole) during pregnancy can increase birthweight. We previously found that this antibiotic reduces inflammation as well as preventing infections. During the new study, 1000 women in rural Zimbabwe will receive either cotrimoxazole or placebo from the time they first book their pregnancy at the local clinic up until birth. The treatment will be decided randomly, like the flip of a coin. During pregnancy, oral samples (tongue swabs, dental plaque, saliva), vaginal swabs, stool, urine and blood will be collected from all mothers when they book and at 26, 34 and 36 weeks into pregnancy. Our first aim is to see whether infections and inflammation during pregnancy are associated with SGA and preterm birth. Women will be examined by a dentist to check their oral health and be tested for sexually transmitted infections, urine infections and diarrhoea, with treatment provided if needed. Using the oral, vaginal and stool samples collected from booking and the end of pregnancy, we will study the microbiome and inflammation to see if they are linked to SGA and preterm birth. Our second aim is to compare the microbiome and inflammation in 100 women receiving the antibiotic and 100 women receiving placebo. We will see whether cotrimoxazole reduces inflammation, infections, or changes the microbiome during pregnancy. We will also test whether bacteria become resistant to the antibiotic. Our third aim is to see what effect maternal antibiotics have on the baby. We will collect samples of the placenta, blood and stool at birth, and collect stool and blood again when they are 4 weeks old, to compare infections, microbiome and inflammation in babies whose mothers received antibiotics or placebo in pregnancy.Through this project, we hope to understand whether infections, microbiome disturbances and inflammation during pregnancy cause SGA and preterm birth, and exactly how the antibiotic works (if at all). This is important, because we may be able to design new treatments that can be given during pregnancy to help babies grow better and be born on time.

在非洲，每七个婴儿中就有一个出生时体重过轻，这要么是因为他们出生时太小（小于胎龄; SGA），要么是因为他们出生太早（早产）。SGA或早产儿的死亡风险更高，并且在生命早期发育不良，导致营养不良的风险更高。最常见的营养不良形式（发育迟缓）会影响成年人的健康，减少学校的学习，降低收入潜力。为了减少儿童死亡，改善健康、成长和繁荣，必须改善出生体重。要做到这一点，我们需要了解怀孕期间导致SGA和早产的过程。胎儿依赖于这些过程的微妙平衡来正常生长并按时分娩。怀孕期间的感染以及身体防御系统的激活（称为炎症）可能会扰乱这些过程，导致SGA和早产。怀孕期间患有性传播感染、尿路感染、牙龈疾病或腹泻的母亲患SGA和早产的风险更高。即使孕妇没有感染，炎症也会发生。人体内有数万亿的细菌，称为微生物组，通常不会引起疾病。然而，微生物组组成的变化可能导致炎症。孕妇阴道、口腔和肠道微生物组的不平衡都与SGA和早产有关，尽管这些研究大多数是在高收入国家进行的。目前还不清楚微生物组是否以及如何在非洲引起炎症，SGA和早产。我们认为，在怀孕期间服用抗生素可以通过减少有害的感染和炎症来改善分娩结果。为了测试这一点，我们将利用现有的试验，检查怀孕期间每天使用抗生素（称为复方新诺明）是否会增加出生体重。我们以前发现这种抗生素可以减少炎症并预防感染。在这项新的研究中，津巴布韦农村的1000名妇女将从她们第一次在当地诊所预约怀孕到分娩期间接受复方新诺明或安慰剂。治疗将随机决定，就像抛硬币一样。在妊娠期间，将在所有母亲预约时以及妊娠26、34和36周时采集其口腔样本（舌拭子、牙菌斑、唾液）、阴道拭子、粪便、尿液和血液。我们的第一个目标是了解怀孕期间的感染和炎症是否与SGA和早产有关。妇女将接受牙医检查，以检查其口腔健康，并接受性传播感染，尿液感染和腹泻的检测，并在需要时提供治疗。使用从预订和怀孕结束时收集的口腔，阴道和粪便样本，我们将研究微生物组和炎症，看看它们是否与SGA和早产有关。我们的第二个目标是比较100名接受抗生素的女性和100名接受安慰剂的女性的微生物组和炎症。我们将看到复方新诺明是否会减少炎症，感染或改变怀孕期间的微生物组。我们还将测试细菌是否对抗生素产生耐药性。我们的第三个目标是看看母体抗生素对婴儿有什么影响。我们将在出生时采集胎盘、血液和粪便样本，并在4周龄时再次采集粪便和血液样本，以比较母亲在怀孕期间接受抗生素或安慰剂的婴儿的感染、微生物组和炎症。通过这个项目，我们希望了解怀孕期间的感染、微生物组紊乱和炎症是否会导致SGA和早产，以及抗生素的确切作用（如果有的话）。这很重要，因为我们可以设计出新的治疗方法，在怀孕期间给予，以帮助婴儿更好地成长，按时出生。