Maternal temperament, stress, and inflammation in preterm birth

母亲的气质、压力和早产炎症

• 批准号: 9070071
• 负责人: CLAIRE A CHOUGNET
• 金额: $ 5.34万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9070071
• 关键词: Acute; Age; Amniotic Fluid; Animals; Bacterial Infections; Behavior; Biological; Biological Models; Biometry; Birth; Blood flow; California; Cancer Biology; Cervical Ripening; Characteristics; Child health care; Chronic stress; Clinical Trials; Confounding Factors (Epidemiology); Data; Discipline of obstetrics; Environment; Exposure to; Family history of; Female; Foundations; Frequencies; Future; Genetic Predisposition to Disease; Goals; Health; High Risk Woman; Hormones; Human; Image; Immune System Diseases; Immunity; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Injection of therapeutic agent; Interleukin-1; Lead; Macaca mulatta; Measures; Messenger RNA; Minority; Modeling; Neonatal Mortality; Neurobiology; Observational Study; Outcome; Partner in relationship; Pathway interactions; Pattern; Physiology; Play; Population; Predisposition; Pregnancy; Pregnancy Outcome; Premature Birth; Premature Labor; Prevention; Primates; Prostaglandins; Proteins; Psychological Stress; Psychology; Public Health; Reproductive Biology; Research; Risk; Sample Size; Sampling; Severities; Stress; Structure; System; Temperament; Testing; Time; United States; Ureaplasma Infections; Uterine Contraction; Woman; Work; adverse outcome; anxious; anxious temperament; biobehavior; coping; cost; cytokine; fetal; high risk; insight; intraamniotic infection; low socioeconomic status; maternal stress; microbial community; microbiome; neonatal morbidity; nonhuman primate; novel; peripheral blood; pregnancy immunology; pregnant; premature; prevent; programs; psychological stressor; reproductive; response

DESCRIPTION (provided by applicant): Preterm birth is a major public health burden that remains the leading cause of neonatal morbidity and mortality worldwide. Our long-term goal is to determine the mechanisms that disrupt the normal timing for parturition and lead to preterm birth. Numerous factors influence the likelihood of preterm birth, such as bacterial infection/colonization, maternal stress, and genetic predisposition. While these factors increase the frequency of preterm birth, the majority of women with these factors in isolation deliver at term. In this proposal, we will test a new hypothesis - similar to insights that have been established in cancer biology - that to manifest a preterm delivery, multiple detrimental "hits" acting together are required. Proving that this is the case is not possible with observational studies in humans, with many uncontrollable variables confounding causal relationships. We will exploit a non-human primate (rhesus) model system, with pregnancy characteristics more similar to humans than typical non-primate systems, to determine whether stress and infection interact to promote early labor and delivery. We propose that individual temperament, inflammation, and stress will each provide an additive "hit", of which two or more will be required to end pregnancy prematurely. We will test the specific hypotheses that: (1) maternal stress and inflammation synergize to induce preterm birth; (2) the individual susceptibility to psychological stressors plays a key role in the induction of preterm birth; and (3) maternal peripheral blood or amniotic fluid hormones and inflammatory responses will differ prior to and following IL-1 � administration during pregnancy depending on underlying temperament and exposure to chronic stress. To test these hypotheses, our Specific Aims will determine: (1) The interactions between maternal stress, inflammation, and the influence of individual susceptibility due to anxious temperament, in preterm birth in rhesus macaques. (2) The interactions of maternal temperament and stress on maternal immunity and hormones before and after an inflammatory challenge. (3) The effects of maternal temperament and chronic stress on amniotic fluid cytokines, prostaglandins and microbial community structure before and after an inflammatory challenge. Our transdisciplinary team will integrate expertise in the physiology of pregnancy, immunology/inflammation, primate behavior/psychology, the neurobiology of stress, biostatistics and the microbiome to more comprehensively investigate the heterogeneous pathways increasing preterm birth risk and yield important new insights into causal mechanisms and avenues for prematurity prevention.

描述（由申请人提供）：早产是一个主要的公共卫生负担，仍然是全世界新生儿发病和死亡的主要原因。我们的长期目标是确定破坏正常分娩时间并导致早产的机制。许多因素影响早产的可能性，如细菌感染/定植，母亲压力和遗传易感性。虽然这些因素增加了早产的频率，但大多数单独存在这些因素的妇女足月分娩。在这个提议中，我们将测试一个新的假设——类似于已经在癌症生物学中建立的见解——要证明早产，需要多种有害的“打击”共同作用。在人类观察性研究中不可能证明这一点，因为许多不可控的变量混淆了因果关系。我们将利用非人类灵长类动物（恒河）模型系统，与典型的非灵长类动物系统相比，其妊娠特征更类似于人类，以确定压力和感染是否相互作用以促进早期分娩。我们认为，个人气质、炎症和压力都将提供一个附加的“打击”，其中两个或两个以上是必需的