The Effect of Inflammation on Preterm Birth

Rey, Grazzia; Pereyra, Silvana; Velazquez, Tatiana; Grasso, Daniel; Alonso, Justo; Bertoni, Bernardo; Sapiro, Rossana

doi:10.5772/26586

Cited by 2 publications

(1 citation statement)

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“…7 Considering the breadth of microparticle protein markers described here that span coagulation, inflammation, and immunomodulatory pathways, while recalling the important role of intrauterine inflammation in SPTB, 7, 30,34 it is not surprising that we are observing evidence of microparticle mediated dysfunction as early as the end of the first trimester. Contemporary theory suggests that, if not all, at least a high proportion of adverse pregnancy outcomes have their pathophysiologic origins in early pregnancy.…”

Section: Discussionmentioning

confidence: 87%

Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth

Cantonwine

Zhang

Rosenblatt

et al. 2016

American Journal of Obstetrics and Gynecology

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Background The analysis of circulating microparticles in pregnancy is of revolutionary potential as it represents an in vivo ‘biopsy’ of active gestational tissues. Objectives We hypothesize that circulating microparticle signaling will differ in pregnancies that experience spontaneous preterm birth from those delivering at term and that these differences will be evident many weeks in advance of clinical presentation. Study Design Utilizing plasma specimens obtained between 10–12 weeks gestation as part of a prospectively collected birth cohort where pregnancy outcomes are independently validated by two board certified Maternal Fetal Medicine physicians, 25 singleton cases of spontaneous preterm birth ≤34 weeks were matched by maternal age, race, and gestational age of sampling (+/− 2 weeks) to 50 uncomplicated term deliveries. Circulating microparticles s from these first trimester specimens were isolated and analyzed by multiple reaction monitoring mass spectrometry for potential protein biomarkers following from previous studies. Markers with robust univariate performance in correlating spontaneous preterm birth were further evaluated for their biological relevance via a combined functional profiling/pathway analysis, and for multivariate performance. Results Among the 132 proteins evaluated, 62 demonstrated robust power of detecting spontaneous preterm birth in bootstrap receiver-operating characteristic curve analysis at a false discovery rate of < 20% estimated via label permutation. Differential dependency network analysis identified spontaneous preterm birth -associated co-expression patterns linked to biological processes of inflammation, wound healing, and the coagulation cascade. Linear modeling of spontaneous preterm birth using a multiplex of the candidate biomarkers with a fixed sensitivity of 80% exhibited a specificity of 83% with median area under the curve of 0.89. These result indicate strong potential of multivariate model development for informative risk stratification. Conclusion This project has identified functional proteomic factors with associated biological processes that are already unique in their expression profiles at 10–12 weeks among women who go on to deliver spontaneously ≤34 weeks. These changes, with further validation, will allow the stratification of patients at risk of spontaneous preterm birth before clinical presentation.

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Section: Discussionmentioning

confidence: 87%

Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth

Cantonwine

Zhang

Rosenblatt

et al. 2016

American Journal of Obstetrics and Gynecology

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Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth

et al. 2019

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Background Preterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results from the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proven challenging because of the multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact to facilitate parturition. The transcriptome of the chorioamnion membranes at the site of rupture in PTB and term fetuses may reflect the molecular pathways of preterm labor. Methods In this work, chorioamnion membranes from severe preterm and term fetuses were analyzed using RNA sequencing. Functional annotations and pathway analysis of differentially expressed genes were performed with the GAGE and GOSeq packages. A subset of differentially expressed genes in PTB was validated in a larger cohort using qRT-PCR and by comparing our results with genes and pathways previously reported in the literature. Results A total of 270 genes were differentially expressed (DE): 252 were upregulated and 18 were down-regulated in severe preterm births relative to term births. Inflammatory and immunological pathways were upregulated in PTB. Both types of pathways were previously suggested to lead to PTB. Pathways that were not previously reported in PTB, such as the hemopoietic pathway, appeared upregulated in preterm membranes. A group of 18 downregulated genes discriminated between term and severe preterm cases. These genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate genes for understanding the syndrome. Some of the downregulated genes are involved in the nervous system, morphogenesis ( WNT1, DLX5, PAPPA2 ) and ion channel complexes ( KCNJ16, KCNB1 ), making them good candidates as biomarkers of PTB. Conclusions The identification of this DE gene pattern will help with the development of a multi-gene disease classifier. These markers were generated in an admixed South American population in which PTB has a high incidence. Since the genetic background may differentially impact different populations, it is necessary to include populations such as those from South America and Africa, which are usually excluded from high-throughput approaches. These classifiers should be compared to those in other populations to obtain a global landscape of PTB. Electronic supplementary material The online version of this article (10.1186/s12920-019-0498-3) contains supplementary material, which is available to authorized users.

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The Effect of Inflammation on Preterm Birth

Cited by 2 publications

References 94 publications

Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth

Evaluation of proteomic biomarkers associated with circulating microparticles as an effective means to stratify the risk of spontaneous preterm birth

Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth

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