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Journal ArticleDOI

Preterm labor: One syndrome, many causes

15 Aug 2014-Science (American Association for the Advancement of Science)-Vol. 345, Iss: 6198, pp 760-765
TL;DR: The current understanding of the mechanisms of disease implicated in preterm labor are summarized and advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance are reviewed.
Abstract: 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.

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Citations
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Journal ArticleDOI
TL;DR: It is suggested that pregnancy outcomes might be predicted by features of the microbiota early in gestation, as well as the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.
Abstract: Despite the critical role of the human microbiota in health, our understanding of microbiota compositional dynamics during and after pregnancy is incomplete. We conducted a case-control study of 49 pregnant women, 15 of whom delivered preterm. From 40 of these women, we analyzed bacterial taxonomic composition of 3,767 specimens collected prospectively and weekly during gestation and monthly after delivery from the vagina, distal gut, saliva, and tooth/gum. Linear mixed-effects modeling, medoid-based clustering, and Markov chain modeling were used to analyze community temporal trends, community structure, and vaginal community state transitions. Microbiota community taxonomic composition and diversity remained remarkably stable at all four body sites during pregnancy (P > 0.05 for trends over time). Prevalence of a Lactobacillus-poor vaginal community state type (CST 4) was inversely correlated with gestational age at delivery (P = 0.0039). Risk for preterm birth was more pronounced for subjects with CST 4 accompanied by elevated Gardnerella or Ureaplasma abundances. This finding was validated with a set of 246 vaginal specimens from nine women (four of whom delivered preterm). Most women experienced a postdelivery disturbance in the vaginal community characterized by a decrease in Lactobacillus species and an increase in diverse anaerobes such as Peptoniphilus, Prevotella, and Anaerococcus species. This disturbance was unrelated to gestational age at delivery and persisted for up to 1 y. These findings have important implications for predicting premature labor, a major global health problem, and for understanding the potential impact of a persistent, altered postpartum microbiota on maternal health, including outcomes of pregnancies following short interpregnancy intervals.

801 citations


Cites background from "Preterm labor: One syndrome, many c..."

  • ...Approximately 25% of preterm births are associated with occult microbial invasion of the amniotic cavity (5)....

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  • ...J Allergy Clin Immunol 129(5):1204–1208....

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Journal ArticleDOI
TL;DR: How prenatal and postnatal factors shape the development of both the microbiome and the immune system are described and the prospects of microbiome-mediated therapeutics and the need for more effective approaches that can reconfigure bacterial communities from pathogenic to homeostatic configurations are discussed.
Abstract: Recent studies have characterized how host genetics, prenatal environment and delivery mode can shape the newborn microbiome at birth. Following this, postnatal factors, such as antibiotic treatment, diet or environmental exposure, further modulate the development of the infant's microbiome and immune system, and exposure to a variety of microbial organisms during early life has long been hypothesized to exert a protective effect in the newborn. Furthermore, epidemiological studies have shown that factors that alter bacterial communities in infants during childhood increase the risk for several diseases, highlighting the importance of understanding early-life microbiome composition. In this review, we describe how prenatal and postnatal factors shape the development of both the microbiome and the immune system. We also discuss the prospects of microbiome-mediated therapeutics and the need for more effective approaches that can reconfigure bacterial communities from pathogenic to homeostatic configurations.

766 citations

Journal ArticleDOI
01 May 2019-Nature
TL;DR: Over ten years, the Human Microbiome Project has provided resources for studying the microbiome and its relationship to disease; this Perspective summarizes the key achievements and findings of the project and its relation to the broader field.
Abstract: The NIH Human Microbiome Project (HMP) has been carried out over ten years and two phases to provide resources, methods, and discoveries that link interactions between humans and their microbiomes to health-related outcomes. The recently completed second phase, the Integrative Human Microbiome Project, comprised studies of dynamic changes in the microbiome and host under three conditions: pregnancy and preterm birth; inflammatory bowel diseases; and stressors that affect individuals with prediabetes. The associated research begins to elucidate mechanisms of host–microbiome interactions under these conditions, provides unique data resources (at the HMP Data Coordination Center), and represents a paradigm for future multi-omic studies of the human microbiome. Over ten years, the Human Microbiome Project has provided resources for studying the microbiome and its relationship to disease; this Perspective summarizes the key achievements and findings of the project and its relationship to the broader field.

679 citations

Journal ArticleDOI
TL;DR: The definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental disease are reviewed and diagrams of the mechanisms of disease are provided.

612 citations

Journal ArticleDOI
TL;DR: These data illustrate how multiple pathways may lead to clinically similar psychosis manifestations, and they provide explanations for the marked heterogeneity observed across laboratories on the same biomarker variables when DSM diagnoses are used as the gold standard.
Abstract: Objective:Clinical phenomenology remains the primary means for classifying psychoses despite considerable evidence that this method incompletely captures biologically meaningful differentiations. Rather than relying on clinical diagnoses as the gold standard, this project drew on neurobiological heterogeneity among psychosis cases to delineate subgroups independent of their phenomenological manifestations.Method:A large biomarker panel (neuropsychological, stop signal, saccadic control, and auditory stimulation paradigms) characterizing diverse aspects of brain function was collected on individuals with schizophrenia, schizoaffective disorder, and bipolar disorder with psychosis (N=711), their first-degree relatives (N=883), and demographically comparable healthy subjects (N=278). Biomarker variance across paradigms was exploited to create nine integrated variables that were used to capture neurobiological variance among the psychosis cases. Data on external validating measures (social functioning, struct...

505 citations

References
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Journal Article
TL;DR: In this article, a comprehensive update of disease burden worldwide incorporating a systematic reassessment of disease and injury-specific epidemiology has been done since the 1990 study, and the authors aimed to calculate disease burden globally and for 21 regions for 1990, 2005, and 2010 with methods to enable meaningful comparisons over time.

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Journal ArticleDOI
Christopher J L Murray1, Theo Vos2, Rafael Lozano1, Mohsen Naghavi1  +366 moreInstitutions (141)
TL;DR: The results for 1990 and 2010 supersede all previously published Global Burden of Disease results and highlight the importance of understanding local burden of disease and setting goals and targets for the post-2015 agenda taking such patterns into account.

6,861 citations

Journal ArticleDOI
TL;DR: A short cervical length and a raised cervical-vaginal fetal fibronectin concentration are the strongest predictors of spontaneous preterm birth.

6,275 citations

Journal ArticleDOI
TL;DR: Worldwide, regional, and national estimates of preterm birth rates for 184 countries in 2010 with time trends for selected countries are reported, and a quantitative assessment of the uncertainty surrounding these estimates is provided.

3,742 citations

Journal ArticleDOI
TL;DR: The latest estimates of causes of child mortality in 2010 with time trends since 2000 show that only tetanus, measles, AIDS, and malaria (in Africa) decreased at an annual rate sufficient to attain the Millennium Development Goal 4.

3,441 citations