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Science (New York, N.Y.) Aug 2014Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by... (Review)
Review
Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment.
Topics: Decidua; Female; Fetus; Humans; Immune Tolerance; Infections; Inflammation; Obstetric Labor, Premature; Placenta; Pregnancy; Syndrome; Vascular Diseases
PubMed: 25124429
DOI: 10.1126/science.1251816 -
Reproduction (Cambridge, England) Jun 2022The syndrome of preterm labor comprises multiple established and novel etiologies. This review summarizes the distinct immune mechanisms implicated in preterm labor and... (Review)
Review
IN BRIEF
The syndrome of preterm labor comprises multiple established and novel etiologies. This review summarizes the distinct immune mechanisms implicated in preterm labor and birth and highlights potential strategies for its prevention.
ABSTRACT
Preterm birth, the leading cause of neonatal morbidity and mortality worldwide, results from preterm labor, a syndrome that includes multiple etiologies. In this review, we have summarized the immune mechanisms implicated in intra-amniotic inflammation, the best-characterized cause of preterm labor and birth, as well as novel etiologies non-associated with intra-amniotic inflammation (i.e. formally known as idiopathic). While the intra-amniotic inflammatory responses driven by microbes (infection) or alarmins (sterile) have some overlap in the participating cellular and molecular processes, the distinct natures of these two conditions necessitate the implementation of specific approaches to prevent adverse pregnancy and neonatal outcomes. Intra-amniotic infection can be treated with the correct antibiotics, whereas sterile intra-amniotic inflammation could potentially be treated by administering a combination of anti-inflammatory drugs (e.g. betamethasone, inflammasome inhibitors, etc.). Recent evidence also supports the role of fetal T-cell activation as a newly described trigger for preterm labor and birth in a subset of cases diagnosed as idiopathic. Moreover, herein we also provide evidence of two maternally-driven immune mechanisms responsible for preterm births formerly considered to be idiopathic. First, the impairment of maternal Tregs can lead to preterm birth, likely due to the loss of immunosuppressive activity resulting in unleashed effector T-cell responses. Secondly, homeostatic macrophages were shown to be essential for maintaining pregnancy and promoting fetal development, and the adoptive transfer of homeostatic M2-polarized macrophages shows great promise for preventing inflammation-induced preterm birth. Collectively, in this review, we discuss the established and novel immune mechanisms responsible for preterm birth and highlight the potential targets for novel strategies aimed at preventing the multi-etiological syndrome of preterm labor leading to preterm birth.
Topics: Female; Homeostasis; Humans; Infant, Newborn; Inflammation; Obstetric Labor, Premature; Parturition; Pregnancy; Premature Birth
PubMed: 35559791
DOI: 10.1530/REP-22-0046 -
Obstetrics and Gynecology Dec 2021
Topics: Humans; Infant, Newborn; Obstetric Labor, Premature; Premature Birth
PubMed: 34794160
DOI: 10.1097/AOG.0000000000004612 -
Cancer Medicine Sep 2019In recent years, the incidence of gynecological malignant tumors during pregnancy has increased, mainly due to the increased number of old age pregnancy. The most common... (Review)
Review
In recent years, the incidence of gynecological malignant tumors during pregnancy has increased, mainly due to the increased number of old age pregnancy. The most common gynecological malignant tumors in pregnancy are cervical cancer, accounting for 71.6%, followed by ovarian malignant tumors, accounting for 7.0%. The incidence of cervical cancer in pregnancy is itself not very high, and the symptoms are easily confused with other diseases in pregnancy. During pregnancy, gynecological examination is limited, and therefore, the rate of misdiagnosis is higher. The treatment of cervical cancer during pregnancy is related to many factors, such as tumor size, pathological type, period of gestation, lymph node involvement, and patients' willingness to maintain pregnancy. As a reason of these factors, it is difficult to determine the optimal treatment. This article reviews the research progress on the diagnosis and treatment principles of cervical cancer in pregnancy, in order to strike a balance between effective treatment of tumors and protection of fetal health, and avoid delays in treatment and preterm delivery.
Topics: Clinical Decision-Making; Disease Management; Female; Humans; Obstetric Labor, Premature; Practice Guidelines as Topic; Pregnancy; Pregnancy Complications, Neoplastic; Risk Assessment; Uterine Cervical Neoplasms
PubMed: 31385452
DOI: 10.1002/cam4.2435 -
Seminars in Immunopathology Aug 2020Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes... (Review)
Review
Almost half of all preterm births are caused or triggered by an inflammatory process at the feto-maternal interface resulting in preterm labor or rupture of membranes with or without chorioamnionitis ("first inflammatory hit"). Preterm babies have highly vulnerable body surfaces and immature organ systems. They are postnatally confronted with a drastically altered antigen exposure including hospital-specific microbes, artificial devices, drugs, nutritional antigens, and hypoxia or hyperoxia ("second inflammatory hit"). This is of particular importance to extremely preterm infants born before 28 weeks, as they have not experienced important "third-trimester" adaptation processes to tolerate maternal and self-antigens. Instead of a balanced adaptation to extrauterine life, the delicate co-regulation between immune defense mechanisms and immunosuppression (tolerance) to allow microbiome establishment is therefore often disturbed. Hence, preterm infants are predisposed to sepsis but also to several injurious conditions that can contribute to the onset or perpetuation of sustained inflammation (SI). This is a continuing challenge to clinicians involved in the care of preterm infants, as SI is regarded as a crucial mediator for mortality and the development of morbidities in preterm infants. This review will outline the (i) role of inflammation for short-term consequences of preterm birth and (ii) the effect of SI on organ development and long-term outcome.
Topics: Chorioamnionitis; Female; Humans; Infant; Infant, Newborn; Infant, Premature; Inflammation; Obstetric Labor, Premature; Pregnancy; Premature Birth
PubMed: 32661735
DOI: 10.1007/s00281-020-00803-2 -
Cell Reports Jan 2023Preterm birth, the leading cause of perinatal morbidity and mortality worldwide, frequently results from the syndrome of preterm labor. The best-established causal link...
Preterm birth, the leading cause of perinatal morbidity and mortality worldwide, frequently results from the syndrome of preterm labor. The best-established causal link to preterm labor is intra-amniotic infection, which involves premature activation of the parturition cascade in the reproductive tissues. Herein, we utilize single-cell RNA sequencing (scRNA-seq) to generate a single-cell atlas of the murine uterus, decidua, and cervix in a model of infection-induced preterm labor. We show that preterm labor affects the transcriptomic profiles of specific immune and non-immune cell subsets. Shared and tissue-specific gene expression signatures are identified among affected cells. Determination of intercellular communications implicates specific cell types in preterm labor-associated signaling pathways across tissues. In silico comparison of murine and human uterine cell-cell interactions reveals conserved signaling pathways implicated in labor. Thus, our scRNA-seq data provide insights into the preterm labor-driven cellular landscape and communications in reproductive tissues.
Topics: Pregnancy; Female; Infant, Newborn; Mice; Animals; Humans; Premature Birth; Obstetric Labor, Premature; Parturition; Labor, Obstetric; Uterus
PubMed: 36599348
DOI: 10.1016/j.celrep.2022.111846 -
JCI Insight Aug 2022Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. One of every 4 preterm neonates is born to a mother with intra-amniotic inflammation...
Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. One of every 4 preterm neonates is born to a mother with intra-amniotic inflammation driven by invading bacteria. However, the molecular mechanisms underlying this hostile immune response remain unclear. Here, we used a translationally relevant model of preterm birth in Nlrp3-deficient and -sufficient pregnant mice to identify what we believe is a previously unknown dual role for the NLRP3 pathway in the fetal and maternal signaling required for the premature onset of the labor cascade leading to fetal injury and neonatal death. Specifically, the NLRP3 sensor molecule and/or inflammasome is essential for triggering intra-amniotic and decidual inflammation, fetal membrane activation, uterine contractility, and cervical dilation. NLRP3 also regulates the functional status of neutrophils and macrophages in the uterus and decidua, without altering their influx, as well as maternal systemic inflammation. Finally, both embryo transfer experimentation and heterozygous mating systems provided mechanistic evidence showing that NLRP3 signaling in both the fetus and the mother is required for the premature activation of the labor cascade. These data provide insights into the mechanisms of fetal-maternal dialog in the syndrome of preterm labor and indicate that targeting the NLRP3 pathway could prevent adverse perinatal outcomes.
Topics: Animals; Female; Fetus; Humans; Infant, Newborn; Inflammation; Mice; NLR Family, Pyrin Domain-Containing 3 Protein; Obstetric Labor, Premature; Pregnancy; Premature Birth
PubMed: 35993366
DOI: 10.1172/jci.insight.158238 -
Minerva Ginecologica Feb 2015The study of preterm labor and prematurity has undergone a major transformation in its approach from an inevitable part of obstetrics with few answers to one in which... (Review)
Review
The study of preterm labor and prematurity has undergone a major transformation in its approach from an inevitable part of obstetrics with few answers to one in which science has led to knowledge and clinical intervention. Despite these advancements, understanding of preterm labor and prevention of prematurity is still limited. In the current review, we begin the discussion with fetal viability, first from a historical perspective and then from the understanding of this issue from a prospective of various professional organizations. We then present the scope of the problem of preterm birth from various countries including the discrepancy between the US and Europe. We continue with updates on extreme prematurity and outcomes with two longitudinal studies from the past 2 years. We further review available interventions for prematurity and discuss the use of antenatal corticosteroids. First, we examine their use in the context of professional recommendations and then examine the trajectory of their continued use in the late preterm period. We focus on a European-based trial with preliminary results and an ongoing American counterpart. The current knowledge of molecular mechanisms behind preterm labor is presented with a focus on the multiple etiologies of preterm labor, both known and presumed, with updates in the basic science realm. Furthermore, we present up-to-date studies on prediction of preterm birth and prematurity-related morbidity.
Topics: Adrenal Cortex Hormones; Animals; Female; Fetal Viability; Humans; Infant, Extremely Premature; Infant, Newborn; Infant, Premature; Obstetric Labor, Premature; Pregnancy; Pregnancy Complications
PubMed: 25300768
DOI: No ID Found -
Seminars in Perinatology Dec 2017In the United States, the generally accepted indication for tocolytic therapy centers on suppression of preterm labor. This may be in the form of preventative therapy... (Review)
Review
In the United States, the generally accepted indication for tocolytic therapy centers on suppression of preterm labor. This may be in the form of preventative therapy with progesterone in women with prior spontaneous preterm birth or as an acute intervention to suppress established uterine contractions associated with cervical change occurring at less than 37 weeks gestation. This article seeks to apply this perspective to tocolytic therapy. Here, we provide a review of current tocolytic options and what the last decade of discovery has revealed about the regulation of myometrial excitability and quiescence. Moving forward, we must incorporate the emerging molecular data that is amassing in order to develop novel and effective tocolytic therapeutic options to prevent preterm labor and spontaneous preterm birth (sPTB).
Topics: Adult; Female; Humans; Obstetric Labor, Premature; Pregnancy; Premature Birth; Randomized Controlled Trials as Topic; Tocolysis; Tocolytic Agents; Treatment Outcome
PubMed: 29191291
DOI: 10.1053/j.semperi.2017.08.008 -
Seminars in Immunopathology Aug 2020Preterm birth is the leading cause of mortality in children under the age of five worldwide. Despite major efforts, we still lack the ability to accurately predict and... (Review)
Review
Preterm birth is the leading cause of mortality in children under the age of five worldwide. Despite major efforts, we still lack the ability to accurately predict and effectively prevent preterm birth. While multiple factors contribute to preterm labor, dysregulations of immunological adaptations required for the maintenance of a healthy pregnancy is at its pathophysiological core. Consequently, a precise understanding of these chronologically paced immune adaptations and of the biological pacemakers that synchronize the pregnancy "immune clock" is a critical first step towards identifying deviations that are hallmarks of peterm birth. Here, we will review key elements of the fetal, placental, and maternal pacemakers that program the immune clock of pregnancy. We will then emphasize multiomic studies that enable a more integrated view of pregnancy-related immune adaptations. Such multiomic assessments can strengthen the biological plausibility of immunological findings and increase the power of biological signatures predictive of preterm birth.
Topics: Child; Female; Fetus; Humans; Infant, Newborn; Obstetric Labor, Premature; Placenta; Pregnancy; Premature Birth
PubMed: 32020337
DOI: 10.1007/s00281-019-00772-1