SPIA was implemented as an R package available at http://vortex.cs.wayne.edu/ontoexpress/

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The change in concentrations of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters in risk assessment for the subsequent development of preeclampsia and small-for-gestational age, The Journal of Maternal-Fetal & Neonatal Medicine, 21:5, 279-287, DOI: 10.1080 AbstractIntroduction. An imbalance between angiogenic and anti-angiogenic factors has been proposed as central to the pathophysiology of preeclampsia (PE). Indeed, patients with PE and those delivering small-for-gestational age (SGA) neonates have higher plasma concentrations of soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and the soluble form of endoglin (s-Eng), as well as lower plasma concentrations of vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) than do patients with normal pregnancies. Of note, this imbalance has been observed before the clinical presentation of PE or the delivery of an SGA neonate. The objective of this study was to determine if changes in the profile of angiogenic and anti-angiogenic factors in maternal plasma between the first and second trimesters are associated with a high risk for the subsequent development of PE and/or delivery of an SGA neonate. Methods. This longitudinal case-control study included 402 singleton pregnancies in the following groups: (1) normal pregnancies with appropriate for gestational age (AGA) neonates (n ¼ 201); (2) patients who delivered an SGA neonate (n ¼ 145); and (3) patients who developed PE (n ¼ 56). Maternal plasma samples were obtained at the time of each prenatal visit, scheduled at 4-week intervals from the first or early second trimester until delivery. In this study, we included two samples per patient: (1) first sample obtained between 6 and 15 weeks of gestation ('first trimester' sample), and (2) second sample obtained between 20 and 25 weeks of gestation ('second trimester' sample). Plasma concentrations of s-Eng, sVEGFR-1, and PlGF were determined by specific and sensitive immunoassays. Changes in the maternal plasma concentrations of these angiogenesis-related factors were compared among normal patients and those destined to develop PE or deliver an SGA neonate while adjusting for maternal age, nulliparity, and body mass index. General linear models and polytomous logistic regression models were used to relate the analyte concentrations, ratios, and product to the subsequent development of PE and SGA. Results.(1) An increase in the maternal plasma concentration of s-Eng between the first and second trimesters conferred risk for the development of preterm PE and SGA (OR 14.9, 95% CI 4.9-45.0 and OR 2.9, 95% CI 1.5-5.6, respectively).(2) An increase in the maternal plasma concentration of sVEGFR-1 between the first and second trimester conferred risk for the development of preterm PE (OR 3.9, 95% CI 1.2-12.6). (3) A subnormal increase in maternal plasma PlGF concentration between the first and the second trimester was a risk factor for the subsequent development of preterm and term PE (OR 4....

OBJECTIVE Changes in the maternal plasma concentrations of angiogenic (such as PlGF and VEGF) and anti-angiogenic factors (such as sEng and sVEGFR-1) precede the clinical presentation of preeclampsia. This study was conducted to examine the role of maternal plasma PlGF, sEng and sVEGFR-1 concentrations in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia. METHODS This longitudinal cohort study included 1,622 consecutive singleton pregnant women. Plasma samples were obtained in early pregnancy (6–15 weeks) and midtrimester (20–25 weeks). Maternal plasma PlGF, sEng and sVEGFR-1 concentrations were determined using sensitive and specific immunoassays. The primary outcome was the development of preeclampsia. Secondary outcomes included term, preterm and early-onset preeclampsia. Receiving operating characteristic (ROC) curves, sensitivity, specificity, positive and negative likelihood ratios, and multivariable logistic regression were used for statistical analyses. A p-value of <0.05 was considered significant. RESULTS 1) The prevalence of preeclampsia, term, preterm (<37 weeks) and early-onset preeclampsia (<34 weeks) was 3.8% (62/1,622), 2.5% (40/1,622), 1.4% (22/1,622) and 0.6% (9/1,622), respectively; 2) Higher likelihood ratios were provided by ratios of midtrimester plasma concentrations of PlGF, sEng, and sVEGFR-1 than single analytes; 3) Individual angiogenic and anti-angiogenic factors did not perform well in the identification of preeclampsia as a whole; in particular, they perform poorly in the prediction of term preeclampsia; 4) In contrast, a combination of these analytes such as the PlGF/sEng ratio, its delta and slope had the best predictive performance with a sensitivity of 100%, a specificity of 98%–99%, and likelihood ratios for a positive test of 57.6, 55.6 and 89.6, respectively, for predicting early-onset preeclampsia. CONCLUSIONS 1) The PlGF/sEng ratio and its delta and slope had an excellent predictive performance for the prediction of early-onset preeclampsia, with very high likelihood ratios for a positive test result and very low likelihood ratios for a negative test result; and 2) Although the positive likelihood ratios are high and the positive predictive values low, the number of patients needed to be closely followed is 4:1 for the PlGF/sEng ratio and 3:1 for the slope of PlF/sEng.

Aims: To characterize the transcriptome of human myometrium during spontaneous labor at term. Methods: Myometrium was obtained from women with (ns19) and without labor (ns20). Illumina ᭨ HumanHT-12 microarrays were utilized. Moderated t-tests and false discovery rate adjustment of P-values were applied. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed for a select set of differentially expressed genes in a separate set of samples. Enzyme-linked immunosorbent assay and Western blot were utilized to confirm differential protein production in a third sample set. Results: 1) Four hundred and seventy-one genes were differentially expressed; 2) gene ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using signaling pathway impact analysis indicated six significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-STAT signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) systemic lupus erythematosus; and f) chemokine signaling pathway; 4) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2, heparin binding epidermal growth factor (EGF)-like growth factor, chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5, interleukin (IL)-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta, suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 and aldehyde dehydrogenase in labor; 5) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group. Conclusions: Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with qRT-PCR using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics.

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K E Y W O R D S:amniotic fluid 'sludge'; chorioamnionitis; funisitis; microbial invasion of the amniotic cavity; preterm labor; preterm premature rupture of membranes; short cervix; spontaneous preterm delivery; transvaginal ultrasound ABSTRACT Objectives