-
Lancet (London, England) Jan 2008This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born... (Review)
Review
This paper is the first in a three-part series on preterm birth, which is the leading cause of perinatal morbidity and mortality in developed countries. Infants are born preterm at less than 37 weeks' gestational age after: (1) spontaneous labour with intact membranes, (2) preterm premature rupture of the membranes (PPROM), and (3) labour induction or caesarean delivery for maternal or fetal indications. The frequency of preterm births is about 12-13% in the USA and 5-9% in many other developed countries; however, the rate of preterm birth has increased in many locations, predominantly because of increasing indicated preterm births and preterm delivery of artificially conceived multiple pregnancies. Common reasons for indicated preterm births include pre-eclampsia or eclampsia, and intrauterine growth restriction. Births that follow spontaneous preterm labour and PPROM-together called spontaneous preterm births-are regarded as a syndrome resulting from multiple causes, including infection or inflammation, vascular disease, and uterine overdistension. Risk factors for spontaneous preterm births include a previous preterm birth, black race, periodontal disease, and low maternal body-mass index. A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.
Topics: Body Mass Index; Female; Fetal Membranes, Premature Rupture; Humans; Infant, Newborn; Obstetric Labor, Premature; Pre-Eclampsia; Pregnancy; Premature Birth; Racial Groups; Risk Factors
PubMed: 18177778
DOI: 10.1016/S0140-6736(08)60074-4 -
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 -
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 -
Deutsches Arzteblatt International Mar 2013The percentage of preterm births in Germany is high at 9%, but stable. 77% of cases of perinatal death are in prematurely born infants. Intensive research efforts are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The percentage of preterm births in Germany is high at 9%, but stable. 77% of cases of perinatal death are in prematurely born infants. Intensive research efforts are being directed toward the development of new means of primary and secondary prevention, diagnostic assessment, and pharmacotherapy of premature labor.
METHODS
We review pertinent publications that were retrieved by a selective search of the literature from 1966 to 2012, including current meta-analyses from the Cochrane database and the guidelines of German and foreign obstetric societies.
RESULTS
Preterm labor is a multifactorial problem. The current treatment options are symptomatic, rather than causally directed. Preventive treatment with progesterone can lower the rate of preterm birth in high-risk groups by more than 30%. Transporting the pregnant women to an appropriately qualified perinatal care center and induction of fetal lung maturation lowers perinatal mortality. A variety of tocolytic drugs with different mechanisms of action (betamimetics, oxytocin antagonists, calcium-channel blockers, NO donors, and inhibitors of prostaglandin synthesis) can be used for individualized tocolytic treatment. Premature rupture of the membranes is an indication for antibiotics.
CONCLUSION
The goal of all attempts to prevent and treat preterm labor is to improve preterm infants' chances of surviving with as few complications as possible. The methods discussed here can be used to prolong pregnancies at risk for preterm labor and so to reduce perinatal morbidity and mortality.
Topics: Comorbidity; Female; Humans; Infant Mortality; Infant, Newborn; Maternal Age; Obstetric Labor, Premature; Pregnancy; Prevalence; Risk Assessment; Smoking; Social Class; Survival Analysis; Survival Rate
PubMed: 23596503
DOI: 10.3238/arztebl.2013.0227 -
American Family Physician Feb 1999Preterm labor is the leading cause of perinatal morbidity and mortality in the United States. It is characterized by cervical effacement and/or dilatation and increased... (Review)
Review
Preterm labor is the leading cause of perinatal morbidity and mortality in the United States. It is characterized by cervical effacement and/or dilatation and increased uterine irritability before 37 weeks of gestation. Women with a history of preterm labor are at greatest risk. Strategies for reducing the incidence of preterm labor and delivery have focused on educating both physicians and patients about the risks for preterm labor and methods of detecting preterm cervical dilatation. Methods used to predict preterm labor include weekly cervical assessment, transvaginal ultrasonography, detection of fetal fibronectin and home uterine activity monitoring. As yet, it is unclear if any of these strategies should be routinely employed. At present, management of preterm labor may include the use of tocolytic agents, corticosteroids and antibiotics.
Topics: Female; Humans; Obstetric Labor, Premature; Pregnancy; Risk; Risk Factors; Tocolytic Agents; Ultrasonography, Prenatal
PubMed: 10029786
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 -
American Family Physician Feb 2010Preventing preterm delivery remains one of the great challenges in modern medicine. Preterm birth rates continue to increase and accounted for 12.7 percent of all U.S.... (Review)
Review
Preventing preterm delivery remains one of the great challenges in modern medicine. Preterm birth rates continue to increase and accounted for 12.7 percent of all U.S. births in 2005. The etiology of preterm delivery is unclear, but is likely to be complex and influenced by genetics and environmental factors. Women with previous preterm birth are at increased risk of subsequent preterm delivery and may be candidates for treatment with antenatal progesterone. Fetal fibronectin testing and endovaginal ultrasonography for cervical length are useful for triage. For the patient in preterm labor, only antenatal corticosteroids and delivery in a facility with a level III neonatal intensive care unit have been shown to improve outcomes consistently. Tocolytic agents may delay delivery for up to 48 hours, enabling the administration of antenatal corticosteroids or maternal transfer. Routine use of antibiotics in preterm labor is not indicated except for group B streptococcus prophylaxis or treatment of chorioamnionitis.
Topics: Adrenal Cortex Hormones; Antihypertensive Agents; Calcium Channel Blockers; Female; Humans; Obstetric Labor, Premature; Pregnancy; Risk Factors; Tocolytic Agents; Ultrasonography, Prenatal; United States
PubMed: 20148502
DOI: No ID Found