PDF(Pubmed)
Abstract：
UNASSIGNED: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains underpowered due to its syndromic nature and the dearth of independent analyses of the vaginal host immune response. Thus, we conducted the largest longitudinal investigation targeting vaginal immune mediators, referred to herein as the immunoproteome, in a population at high risk for sPTB.
UNASSIGNED: Vaginal swabs were collected across gestation from pregnant women who ultimately underwent term birth, sPTL, or PPROM. Cytokines, chemokines, growth factors, and antimicrobial peptides in the samples were quantified via specific and sensitive immunoassays. Predictive models were constructed from immune mediator concentrations.
UNASSIGNED: Throughout uncomplicated gestation, the vaginal immunoproteome harbors a cytokine network with a homeostatic profile. Yet, the vaginal immunoproteome is skewed toward a pro-inflammatory state in pregnant women who ultimately experience sPTL and PPROM. Such an inflammatory profile includes increased monocyte chemoattractants, cytokines indicative of macrophage and T-cell activation, and reduced antimicrobial proteins/peptides. The vaginal immunoproteome has improved predictive value over maternal characteristics alone for identifying women at risk for early (<34 weeks) sPTB.
UNASSIGNED: The vaginal immunoproteome undergoes homeostatic changes throughout gestation and deviations from this shift are associated with sPTB. Furthermore, the vaginal immunoproteome can be leveraged as a potential biomarker for early sPTB, a subset of sPTB associated with extremely adverse neonatal outcomes.
UNASSIGNED: This research was conducted by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS) under contract HHSN275201300006C. ALT, KRT, and NGL were supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.
Human pregnancies last 40 weeks on average. Preterm births, defined as live births before 37 weeks, occur in about one in ten pregnancies. Being born too early is the main cause of a number of diseases and death in newborn babies. Preterm births are further divided into those that happen early – before 34 weeks – and those that happen late – between 34 and 37 weeks. There are also differences between preterm births in which the amniotic sac ruptures before or after the start of labor. Although several factors can lead to spontaneous preterm birth, bacteria getting into the amniotic fluid around the fetus are a well-known trigger. These bacteria usually come from the vagina. In the past, researchers have studied the number and types of bacteria in the vagina of people who had a normal pregnancy and those that had a preterm birth to predict who is more at risk of preterm birth. However, predictions based only on data about bacteria have been less useful so far. Instead, it might be better to investigate a person’s immune response during pregnancy. Shaffer et al. addressed this gap by asking whether measuring the levels of proteins involved in the immune response could help predict preterm births. Shaffer et al. collected vaginal fluids from 739 individuals of predominately African American ethnicity with an average BMI of 28.7 – representing a population at high risk for spontaneous preterm birth. The swabs were taken at multiple points during their pregnancy, and 31 different immune-related proteins in those fluids were measured. The researchers further noted whether these individuals had a normal or a preterm birth. The data showed that, compared to normal births, preterm births are associated with higher levels of proteins that attract white blood cells and promote inflammation, such as IL-6 and IL-1β. Vaginal fluids from individuals who went on to have an early preterm birth where the amniotic sac ruptured before labor, contained lower levels of proteins known as defensins, which defend the body from bacteria. With these new data from vaginal swabs, Shaffer et al. could make better predictions about the likelihood of preterm birth in general and early preterm birth with the amniotic sac ruptured before labor. For the latter scenario, the predictions were not improved when combining immune protein data with other characteristics of the pregnant person, such as age. These findings suggest that clinicians may be able to use measurements of immune-related proteins to help predict preterm births, so that pregnant individuals at high risk can receive extra care. Further research will have to validate the data and determine whether the findings apply more widely.
UNASSIGNED: Vaginal swabs were collected across gestation from pregnant women who ultimately underwent term birth, sPTL, or PPROM. Cytokines, chemokines, growth factors, and antimicrobial peptides in the samples were quantified via specific and sensitive immunoassays. Predictive models were constructed from immune mediator concentrations.
UNASSIGNED: Throughout uncomplicated gestation, the vaginal immunoproteome harbors a cytokine network with a homeostatic profile. Yet, the vaginal immunoproteome is skewed toward a pro-inflammatory state in pregnant women who ultimately experience sPTL and PPROM. Such an inflammatory profile includes increased monocyte chemoattractants, cytokines indicative of macrophage and T-cell activation, and reduced antimicrobial proteins/peptides. The vaginal immunoproteome has improved predictive value over maternal characteristics alone for identifying women at risk for early (<34 weeks) sPTB.
UNASSIGNED: The vaginal immunoproteome undergoes homeostatic changes throughout gestation and deviations from this shift are associated with sPTB. Furthermore, the vaginal immunoproteome can be leveraged as a potential biomarker for early sPTB, a subset of sPTB associated with extremely adverse neonatal outcomes.
UNASSIGNED: This research was conducted by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS) under contract HHSN275201300006C. ALT, KRT, and NGL were supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.
Human pregnancies last 40 weeks on average. Preterm births, defined as live births before 37 weeks, occur in about one in ten pregnancies. Being born too early is the main cause of a number of diseases and death in newborn babies. Preterm births are further divided into those that happen early – before 34 weeks – and those that happen late – between 34 and 37 weeks. There are also differences between preterm births in which the amniotic sac ruptures before or after the start of labor. Although several factors can lead to spontaneous preterm birth, bacteria getting into the amniotic fluid around the fetus are a well-known trigger. These bacteria usually come from the vagina. In the past, researchers have studied the number and types of bacteria in the vagina of people who had a normal pregnancy and those that had a preterm birth to predict who is more at risk of preterm birth. However, predictions based only on data about bacteria have been less useful so far. Instead, it might be better to investigate a person’s immune response during pregnancy. Shaffer et al. addressed this gap by asking whether measuring the levels of proteins involved in the immune response could help predict preterm births. Shaffer et al. collected vaginal fluids from 739 individuals of predominately African American ethnicity with an average BMI of 28.7 – representing a population at high risk for spontaneous preterm birth. The swabs were taken at multiple points during their pregnancy, and 31 different immune-related proteins in those fluids were measured. The researchers further noted whether these individuals had a normal or a preterm birth. The data showed that, compared to normal births, preterm births are associated with higher levels of proteins that attract white blood cells and promote inflammation, such as IL-6 and IL-1β. Vaginal fluids from individuals who went on to have an early preterm birth where the amniotic sac ruptured before labor, contained lower levels of proteins known as defensins, which defend the body from bacteria. With these new data from vaginal swabs, Shaffer et al. could make better predictions about the likelihood of preterm birth in general and early preterm birth with the amniotic sac ruptured before labor. For the latter scenario, the predictions were not improved when combining immune protein data with other characteristics of the pregnant person, such as age. These findings suggest that clinicians may be able to use measurements of immune-related proteins to help predict preterm births, so that pregnant individuals at high risk can receive extra care. Further research will have to validate the data and determine whether the findings apply more widely.
摘要：
早产是全球新生儿发病和死亡的主要原因。大多数早产病例是自发发生的，是由于早产的胎膜完整（自发性早产[sPTL]）或破裂（早产胎膜破裂[PPROM]）。自发性早产（sPTB）的预测由于其综合征性质和缺乏对阴道宿主免疫反应的独立分析，仍然不足。因此，我们针对阴道免疫介质进行了最大的纵向调查，本文称为免疫蛋白质组，在sPTB高危人群中。
■阴道拭子是在妊娠期间从最终接受足月分娩的孕妇中收集的，sPTL,或PPROM。细胞因子,趋化因子,生长因子，样品中的抗菌肽通过特异性和敏感性免疫测定进行定量。从免疫介质浓度构建预测模型。
■在整个简单的妊娠过程中，阴道免疫蛋白质组拥有一个具有稳态谱的细胞因子网络。然而，在最终经历sPTL和PPROM的孕妇中,阴道免疫蛋白质组向促炎状态倾斜.这样的炎症特征包括增加的单核细胞化学引诱物,指示巨噬细胞和T细胞活化的细胞因子，和减少抗微生物蛋白/肽。阴道免疫蛋白质组比单独的母体特征具有改善的预测价值，用于识别处于早期（<34周）sPTB风险的女性。
■阴道免疫蛋白质组在整个妊娠过程中经历稳态变化，并且这种变化的偏差与sPTB有关。此外，阴道免疫蛋白质组可以作为早期sPTB的潜在生物标志物，sPTB的一个子集与极其不良的新生儿结局相关。
■这项研究是由围产学研究处进行的，产科和母胎医学部，校内研究司，尤尼斯·肯尼迪·施莱弗国家儿童健康与人类发展研究所，美国国立卫生研究院,美国卫生与人类服务部（NICHD/NIH/DHHS）根据合同HHSN275201300006C。ALT,KRT,和NGL得到了韦恩州立大学孕产妇围产期倡议的支持，围产期和儿童健康。
人类怀孕平均持续40周。早产,定义为37周前的活产，发生在大约十分之一的怀孕中。过早出生是许多疾病和新生儿死亡的主要原因。早产进一步分为早期-在34周之前-和晚期-在34至37周之间。早产在分娩开始之前或之后羊膜囊破裂之间也存在差异。尽管有几个因素可以导致自发性早产，细菌进入胎儿周围的羊水是众所周知的触发因素。这些细菌通常来自阴道。在过去,研究人员研究了正常怀孕和早产的人阴道中细菌的数量和类型，以预测谁更容易早产。然而,到目前为止，仅基于细菌数据的预测不太有用。相反，最好调查一个人在怀孕期间的免疫反应。Shaffer等人。通过询问测量参与免疫反应的蛋白质水平是否有助于预测早产来解决这一差距。Shaffer等人。从739名主要为非洲裔美国人的个体中收集阴道液,平均BMI为28.7-代表自发性早产高危人群.棉签是在怀孕期间多次采集的，并测量了这些液体中31种不同的免疫相关蛋白。研究人员进一步指出，这些人是正常出生还是早产。数据显示,与正常出生相比，早产与高水平的蛋白质相关，这些蛋白质吸引白细胞并促进炎症，如IL-6和IL-1β。在分娩前羊膜囊破裂的早期早产患者的阴道液，含有较低水平的蛋白质，称为防御素，保护身体免受细菌侵害。有了这些来自阴道拭子的新数据，Shaffer等人。可以更好地预测一般早产和羊膜囊在分娩前破裂的早期早产的可能性。对于后一种情况，当将免疫蛋白数据与孕妇的其他特征相结合时，预测没有得到改善，比如年龄。这些发现表明，临床医生可能能够使用免疫相关蛋白质的测量来帮助预测早产，以便高危孕妇可以得到额外的护理。进一步的研究将必须验证数据并确定研究结果是否更广泛地适用。
■阴道拭子是在妊娠期间从最终接受足月分娩的孕妇中收集的，sPTL,或PPROM。细胞因子,趋化因子,生长因子，样品中的抗菌肽通过特异性和敏感性免疫测定进行定量。从免疫介质浓度构建预测模型。
■在整个简单的妊娠过程中，阴道免疫蛋白质组拥有一个具有稳态谱的细胞因子网络。然而，在最终经历sPTL和PPROM的孕妇中,阴道免疫蛋白质组向促炎状态倾斜.这样的炎症特征包括增加的单核细胞化学引诱物,指示巨噬细胞和T细胞活化的细胞因子，和减少抗微生物蛋白/肽。阴道免疫蛋白质组比单独的母体特征具有改善的预测价值，用于识别处于早期（<34周）sPTB风险的女性。
■阴道免疫蛋白质组在整个妊娠过程中经历稳态变化，并且这种变化的偏差与sPTB有关。此外，阴道免疫蛋白质组可以作为早期sPTB的潜在生物标志物，sPTB的一个子集与极其不良的新生儿结局相关。
■这项研究是由围产学研究处进行的，产科和母胎医学部，校内研究司，尤尼斯·肯尼迪·施莱弗国家儿童健康与人类发展研究所，美国国立卫生研究院,美国卫生与人类服务部（NICHD/NIH/DHHS）根据合同HHSN275201300006C。ALT,KRT,和NGL得到了韦恩州立大学孕产妇围产期倡议的支持，围产期和儿童健康。
人类怀孕平均持续40周。早产,定义为37周前的活产，发生在大约十分之一的怀孕中。过早出生是许多疾病和新生儿死亡的主要原因。早产进一步分为早期-在34周之前-和晚期-在34至37周之间。早产在分娩开始之前或之后羊膜囊破裂之间也存在差异。尽管有几个因素可以导致自发性早产，细菌进入胎儿周围的羊水是众所周知的触发因素。这些细菌通常来自阴道。在过去,研究人员研究了正常怀孕和早产的人阴道中细菌的数量和类型，以预测谁更容易早产。然而,到目前为止，仅基于细菌数据的预测不太有用。相反，最好调查一个人在怀孕期间的免疫反应。Shaffer等人。通过询问测量参与免疫反应的蛋白质水平是否有助于预测早产来解决这一差距。Shaffer等人。从739名主要为非洲裔美国人的个体中收集阴道液,平均BMI为28.7-代表自发性早产高危人群.棉签是在怀孕期间多次采集的，并测量了这些液体中31种不同的免疫相关蛋白。研究人员进一步指出，这些人是正常出生还是早产。数据显示,与正常出生相比，早产与高水平的蛋白质相关，这些蛋白质吸引白细胞并促进炎症，如IL-6和IL-1β。在分娩前羊膜囊破裂的早期早产患者的阴道液，含有较低水平的蛋白质，称为防御素，保护身体免受细菌侵害。有了这些来自阴道拭子的新数据，Shaffer等人。可以更好地预测一般早产和羊膜囊在分娩前破裂的早期早产的可能性。对于后一种情况，当将免疫蛋白数据与孕妇的其他特征相结合时，预测没有得到改善，比如年龄。这些发现表明，临床医生可能能够使用免疫相关蛋白质的测量来帮助预测早产，以便高危孕妇可以得到额外的护理。进一步的研究将必须验证数据并确定研究结果是否更广泛地适用。
