Abstract:
BACKGROUND:Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. OBJECTIVE:The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. STUDY DESIGN:We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. RESULTS:Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P<.05). A total of 609 probe sets were expressed differentially (>1.5-fold change, P<.05) in the fetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included several with known functions in cardiac injury, morphogenesis, angiogenesis, and tissue remodeling (eg, angiotensin I converting enzyme 2, STEAP family member 4, natriuretic peptide A, and secreted frizzled-related protein 4; all P<.05). Multiple gene sets and pathways that are involved in cardiac morphogenesis and vasculogenesis were downregulated significantly by gene set and Ingenuity Pathway Analysis (hallmark transforming growth factor beta signaling, cellular morphogenesis during differentiation, morphology of cardiovascular system; all P<.05). CONCLUSION:Disruption of gene networks for cardiac morphogenesis and vasculogenesis occurred in the preterm fetal heart of nonhuman primates with preterm labor, intraamniotic infection, and severe fetal inflammation. Inflammatory injury to the fetal heart in utero may contribute to the development of heart disease later in life. Development of preterm labor therapeutics must also target fetal inflammation to lessen organ injury and potential long-term effects on cardiac function.
journal_name
Am J Obstet Gynecoljournal_title
American journal of obstetrics and gynecologyauthors
Mitchell T,MacDonald JW,Srinouanpranchanh S,Bammler TK,Merillat S,Boldenow E,Coleman M,Agnew K,Baldessari A,Stencel-Baerenwald JE,Tisoncik-Go J,Green RR,Gale MJ Jr,Rajagopal L,Adams Waldorf KMdoi
10.1016/j.ajog.2018.01.009subject
Has Abstractpub_date
2018-04-01 00:00:00pages
438.e1-438.e16issue
4eissn
0002-9378issn
1097-6868pii
S0002-9378(18)30009-7journal_volume
218pub_type
杂志文章abstract:OBJECTIVE:Our goal was to evaluate whether active management of labor lowers cesarean section rates, shortens the length of labor, and overcomes any negative effects of epidural analgesia on nulliparous labor. STUDY DESIGN:We randomly assigned 405 low-risk term nulliparous patients to either an active management of la...
journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0002-9378(97)70152-2
更新日期:1997-09-01 00:00:00
abstract::Descriptive teratology has developed several fundamental precepts, two of which can now be challenged on the basis of experimental evidence. The first is that prior to implantation the developing embryo is not susceptible to survivable defects from chemical injury. The second is that developmental defects cannot be du...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章,评审
doi:10.1016/s0002-9378(87)80198-9
更新日期:1987-08-01 00:00:00
abstract:OBJECTIVE:This study was undertaken to evaluate whether it was possible to abstain from performing an endometrial biopsy when endometrial thickness according to transvaginal ultrasonography was =4 mm in women with postmenopausal bleeding or irregular bleeding during hormone replacement therapy. STUDY DESIGN:Transvag...
journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章
doi:10.1067/mob.2000.103092
更新日期:2000-03-01 00:00:00
abstract::In 1970 Morgan described an operation designed to meet the problem created by scarring and fibrosis resulting from previous operative procedures to the urethra and bladder neck. In the method, a 2 cm wide polypropylene (Marlex) mesh is placed as a broad hammock to elevate and support the urethrovesical junction with l...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(79)90681-1
更新日期:1979-02-01 00:00:00
abstract::Value-based care, best clinical outcome relative to cost, is a priority in correcting the high costs for average clinical outcomes of health care delivery in the United States. Hysterectomy represents the most common and identifiable nonobstetric major surgical procedure among women. Surgical approaches to hysterectom...
journal_title:American journal of obstetrics and gynecology
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doi:10.1016/j.ajog.2018.11.124
更新日期:2019-03-01 00:00:00
abstract::Diabetic ketoacidosis may occur in women treated with intravenous beta-sympathomimetic agents for tocolysis. We describe diabetic ketoacidosis and transient severe insulin resistance in a woman with diabetes who was treated with subcutaneous terbutaline infusion. Subcutaneous terbutaline infusion may precipitate trans...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(90)91185-f
更新日期:1990-08-01 00:00:00
abstract::A case is described in which a leiomyoma of the ovary was accompanied by hydrothorax. There was no reaccumulation of fluid after oophorectomy. ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(89)90260-3
更新日期:1989-07-01 00:00:00
abstract:OBJECTIVE:The objective of the study was to assess whether implementation of a statewide initiative was associated with changes in perinatal human immunodeficiency virus (HIV) testing practices. STUDY DESIGN:This was an observational cohort study of all 1,141,799 women who delivered in Illinois birthing hospitals over...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2012.08.006
更新日期:2012-11-01 00:00:00
abstract::Women with Stage I epithelial carcinoma of the ovary were initially treated by an extirpative operation and were subsequently randomized to either no further treatment, radiotherapy, or chemotherapy. Only two patients (6%) treated with chemotherapy developed recurrence, compared to five (17%) and seven (30%) patients ...
journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0002-9378(80)90024-1
更新日期:1980-09-15 00:00:00
abstract:OBJECTIVE:We sought to establish the lowest dose of 3-keto-desogestrel, when added to a copper-releasing intrauterine contraceptive device, that is needed to reduce menstrual blood loss to a very low level and to treat (essential) menorrhagia successfully. STUDY DESIGN:A double-blind group comparative study was design...
journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2000-03-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章,多中心研究
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更新日期:2019-02-01 00:00:00
abstract::Maternal sepsis is a significant cause of maternal morbidity and mortality and is a preventable cause of maternal death. The purpose of this guideline is to summarize what is known about sepsis and to provide guidance for the management of sepsis in pregnancy and the postpartum period. The following are SMFM recommend...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
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更新日期:2019-04-01 00:00:00
abstract::Forty-five of 49 patients were aborted successfully with 15(S)-15-Me-PGF2alpha after previous techniques to induce abortion had met with failure in 39. Nine patients had spontaneous premature rupture of membranes without onset of labor. The majority of patients aborted within 7 hours following initiation of this metho...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(79)90465-4
更新日期:1979-01-15 00:00:00
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journal_title:American journal of obstetrics and gynecology
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更新日期:1991-09-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(87)90299-7
更新日期:1987-02-01 00:00:00
abstract::Pelvic blood flow was serially determined in 19 pregnant ewes before and after the induction of one-kidney renal hypertension. The six twin gestations and 13 singleton gestations behaved similarly for all parameters, except renal blood flow. After the renal preparatory surgical procedure, there was a 19% increase in m...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(16)32681-3
更新日期:1981-12-15 00:00:00
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
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更新日期:1990-09-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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更新日期:1987-07-01 00:00:00
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更新日期:1997-11-01 00:00:00
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更新日期:2004-03-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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doi:10.1016/j.ajog.2007.11.043
更新日期:2008-06-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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更新日期:2012-10-01 00:00:00
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更新日期:2011-06-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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journal_title:American journal of obstetrics and gynecology
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更新日期:2009-05-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
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更新日期:2003-09-01 00:00:00
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journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2008.03.034
更新日期:2008-06-01 00:00:00
abstract::Vaginitis is one of the most common causes of patient visits to gynecologists, primary care providers, and urgent care centers. However, many women leave without a clear diagnosis or experience recurrent symptoms despite treatment. The 3 most common etiologies of vaginitis are trichomonas, bacterial vaginosis, and vul...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章,评审
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更新日期:2020-02-01 00:00:00