Preterm labor Romero, Roberto; Dey, Sudhansu K.; Fisher, Susan J.
Science (American Association for the Advancement of Science),
08/2014, Letnik:
345, Številka:
6198
Journal Article
Recenzirano
Odprti dostop
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.
Problem
Inflammation and infection play a major role in preterm birth. The purpose of this study was to (i) determine the prevalence and clinical significance of sterile intra‐amniotic inflammation ...and (ii) examine the relationship between amniotic fluid (AF) concentrations of high mobility group box‐1 (HMGB1) and the interval from amniocentesis to delivery in patients with sterile intra‐amniotic inflammation.
Method of study
AF samples obtained from 135 women with preterm labor and intact membranes were analyzed using cultivation techniques as well as broad‐range PCR and mass spectrometry (PCR/ESI‐MS). Sterile intra‐amniotic inflammation was defined when patients with negative AF cultures and without evidence of microbial footprints had intra‐amniotic inflammation (AF interleukin‐6 ≥ 2.6 ng/mL).
Results
(i) The frequency of sterile intra‐amniotic inflammation was significantly greater than that of microbial‐associated intra‐amniotic inflammation 26% (35/135) versus 11% (15/135); (P = 0.005), (ii) patients with sterile intra‐amniotic inflammation delivered at comparable gestational ages had similar rates of acute placental inflammation and adverse neonatal outcomes as patients with microbial‐associated intra‐amniotic inflammation, and (iii) patients with sterile intra‐amniotic inflammation and high AF concentrations of HMGB1 (≥8.55 ng/mL) delivered earlier than those with low AF concentrations of HMGB1 (P = 0.02).
Conclusion
(i) Sterile intra‐amniotic inflammation is more frequent than microbial‐associated intra‐amniotic inflammation, and (ii) we propose that danger signals participate in sterile intra‐amniotic inflammation in the setting of preterm labor.
Despite considerable effort aimed at decreasing the incidence of spontaneous preterm birth, it remains the leading cause of perinatal morbidity and mortality. Screening strategies are imperfect. ...Approaches used to identify women considered by historical factors to be low risk for preterm delivery (generally considered to be women with singleton pregnancies without a history of a previous preterm birth) as well as those at high risk for preterm birth (those with a previous preterm birth, short cervix, or multiple gestation) continue to evolve. Herein, we review the current evidence and approaches to screening women for preterm birth, and examine future directions for clinical practice. Further research is necessary to better identify at-risk women and provide evidence-based management.
•Women with 25(OH)D ≥40ng/mL had 59% lower risk of preterm birth than those ≤20.•Gestation week at birth initially rises steadily with increasing 25(OH)D then plateaus at ∼40ng/mL.•46% lower preterm ...birth rate among women with 25(OH)D ≥40ng/mL compared to CC-MOD reference group.•Findings most robust in Hispanic and Black women.
Two vitamin D pregnancy supplementation trials were recently undertaken in South Carolina: The NICHD (n=346) and Thrasher Research Fund (TRF, n=163) studies. The findings suggest increased dosages of supplemental vitamin D were associated with improved health outcomes of both mother and newborn, including risk of preterm birth (<37 weeks gestation). How that risk was associated with 25(OH)D serum concentration, a better indicator of vitamin D status than dosage, by race/ethnic group and the potential impact in the community was not previously explored. While a recent IOM report suggested a concentration of 20ng/mL should be targeted, more recent work suggests optimal conversion of 25(OH)D–1,25(OH)2D takes place at 40ng/mL in pregnant women.
Post-hoc analysis of the relationship between 25(OH)D concentration and preterm birth rates in the NICHD and TRF studies with comparison to Charleston County, South Carolina March of Dimes (CC-MOD) published rates of preterm birth to assess potential risk reduction in the community.
Using the combined cohort datasets (n=509), preterm birth rates both for the overall population and for the subpopulations achieving 25(OH)D concentrations of ≤20ng/mL, >20 to <40ng/mL, and ≥40ng/mL were calculated; subpopulations broken down by race/ethnicity were also examined. Log-binomial regression was used to test if an association between 25(OH)D serum concentration and preterm birth was present when adjusted for covariates; locally weighted regression (LOESS) was used to explore the relationship between 25(OH)D concentration and gestational age (weeks) at delivery in more detail. These rates were compared with 2009–2011 CC-MOD data to assess potential risk reductions in preterm birth.
Women with serum 25(OH)D concentrations ≥40ng/mL (n=233) had a 57% lower risk of preterm birth compared to those with concentrations ≤20ng/mL n=82; RR=0.43, 95% confidence interval (CI)=0.22,0.83; this lower risk was essentially unchanged after adjusting for covariates (RR=0.41, 95% CI=0.20,0.86). The fitted LOESS curve shows gestation week at birth initially rising steadily with increasing 25(OH)D and then plateauing at ∼40ng/mL. Broken down by race/ethnicity, there was a 79% lower risk of preterm birth among Hispanic women with 25(OH)D concentrations ≥40ng/mL (n=92) compared to those with 25(OH)D concentrations ≤20ng/mL (n=29; RR=0.21, 95% CI=0.06,0.69) and a 45% lower risk among Black women (n=52 and n=50; RR=0.55, 95% CI=0.17,1.76). There were too few white women with low 25(OH)D concentrations for assessment (n=3). Differences by race/ethnicity were not statistically significant with 25(OH)D included as a covariate.
Compared to the CC-MOD reference group, women with serum concentrations ≥40ng/mL in the combined cohort had a 46% lower rate of preterm birth overall (n=233, p=0.004) with a 66% lower rate among Hispanic women (n=92, p=0.01) and a 58% lower rate among black women (n=52, p=0.04).
In this post-hoc analysis, achieving a 25(OH)D serum concentration ≥40ng/mL significantly decreased the risk of preterm birth compared to ≤20ng/mL. These findings suggest the importance of raising 25(OH)D levels substantially above 20ng/mL; reaching 40ng/mL during pregnancy would reduce the risk of preterm birth and achieve the maximal production of the active hormone.
Progress in our understanding of the role of the maternal immune system during healthy pregnancy will help us better understand the role of the immune system in adverse pregnancy outcomes. In this ...review, we discuss our present understanding of the ‘immunity of pregnancy’ in the context of the response to cervical and placental infections and how these responses affect both the mother and the fetus. We discuss novel and challenging concepts that help explain the immunological aspects of pregnancy and how the mother and fetus respond to infection.
Preterm birth is the leading cause of neonatal mortality and the most common reason for antenatal hospitalization . In the United States, approximately 12% of all live births occur before term, and ...preterm labor preceded approximately 50% of these preterm births . Although the causes of preterm labor are not well understood, the burden of preterm births is clear-preterm births account for approximately 70% of neonatal deaths and 36% of infant deaths as well as 25-50% of cases of long-term neurologic impairment in children . A 2006 report from the Institute of Medicine estimated the annual cost of preterm birth in the United States to be $26.2 billion or more than $51,000 per premature infant . However, identifying women who will give birth preterm is an inexact process. The purpose of this document is to present the various methods proposed to manage preterm labor and to review the evidence for the roles of these methods in clinical practice. Identification and management of risk factors for preterm labor are not addressed in this document.
Toll‐like receptors (TLRs) form the major family of pattern recognition receptors (PRRs) that are involved in innate immunity. Innate immune responses against microorganisms at the maternal‐fetal ...interface may have a significant impact on the success of pregnancy, as intrauterine infections have been shown to be strongly associated with certain complications of pregnancy. At the maternal‐fetal interface, TLRs are expressed not only in the immune cells but also in non‐immune cells such as trophoblasts and decidual cells; moreover, their expression patterns vary according to the stage of pregnancy. Here, we will update potential functions of TLRs in these cells, their recognition and response to microorganisms, and their involvement in the innate immunity. The impact of TLR‐mediated innate immune response will be discussed via animal model studies, as well as clinical observations.
Epidemiologists have grouped the multiple disorders that lead to preterm delivery before the 28th week of gestation in a variety of ways. The authors sought to identify characteristics that would ...help guide how to classify disorders that lead to such preterm delivery. They enrolled 1,006 women who delivered a liveborn singleton infant of less than 28 weeks' gestation at 14 centers in the United States between 2002 and 2004. Each delivery was classified by presentation: preterm labor (40%), prelabor premature rupture of membranes (23%), preeclampsia (18%), placental abruption (11%), cervical incompetence (5%), and fetal indication/intrauterine growth restriction (3%). Using factor analysis (eigenvalue = 1.73) to compare characteristics identified by standardized interview, chart review, placental histology, and placental microbiology among the presentation groups, the authors found 2 broad patterns. One pattern, characterized by histologic chorioamnionitis and placental microbe recovery, was associated with preterm labor, prelabor premature rupture of membranes, placental abruption, and cervical insufficiency. The other, characterized by a paucity of organisms and inflammation but the presence of histologic features of dysfunctional placentation, was associated with preeclampsia and fetal indication/intrauterine growth restriction. Disorders leading to preterm delivery may be separated into two groups: those associated with intrauterine inflammation and those associated with aberrations of placentation.
Aims: This study aimed to identify the different expression of circular RNAs (circRNAs) in the placental tissues of pregnant women with preeclampsia (PE) and to provide a new avenue of research ...regarding the pathological mechanisms of PE. Methods: In this study, we collected 40 placental tissues from PE patients and 35 placental tissues from gestational age-matched patients who gave premature birth. Arraystar circRNA Microarray Technology (KANGCHEN, Shanghai, China) was used to analyze the differential expression of circRNAs. According to the basic content of circRNAs in the two groups and their fold changes and due to the practicability of the designed divergent primers of each candidate circRNA, we selected three up-regulated circRNAs, hsa_circRNA_100782, hsa_circRNA_102682 and hsa_circRNA_104820, to validate the data. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was utilized to estimate the Ct values in both groups. We further evaluated the differences with a paired t-test and a receiver operating characteristic (ROC) curve. Results: Many circRNAs were found to be differentially expressed in PE placental tissues versus their controls; of these, 143 circRNAs were up-regulated and 158 were down-regulated. The expression levels of hsa_circRNA_100782 (p < 0.05), hsa_circRNA_102682 (p < 0.05), and hsa_circRNA_104820 (p < 0.0001) were validated as significantly up-regulated in the experimental group compared with the controls. Finally, we performed a literature comparison to forecast the possible mechanisms of circRNA function during PE. Conclusion: circRNA expression significantly differed in placental PE tissues compared with controls. According to the circRNA microarray results and the existing papers, circRNAs may contribute to the pathogenesis of PE by acting as miRNA sponges; this possibility requires additional investigation in future studies.
This article summarises the most recent recommendations on the prevention, diagnosis, and management of preterm labour from the National Institute for Health and Care Excellence (NICE).
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