Pentraxin 3 in maternal circulation: an association with preterm labor and preterm PROM, but not with intra-amniotic infection/inflammation.

Objective: Pentraxin 3 (PTX3) is an acute-phase protein that has an important role in the regulation of the innate immune response. The aim of this study was to determine if maternal plasma PTX3 concentration changes in the presence of intra-amniotic infection and/or inflammation (IAI) in women with preterm labor (PTL) and intact membranes, as well as those with preterm prelabor rupture of membranes (preterm PROM).

Study Design: This cross-sectional study included women in the following groups: (1) nonpregnant (n=40); (2) uncomplicated pregnancies in the first (n=22), second (n=22) or third trimester (n=71, including 50 women at term not in labor); (3) uncomplicated pregnancies at term with spontaneous labor (n=49); (4) PTL and intact membranes who delivered at term (n=49); (5) PTL without IAI who delivered preterm (n=26); (6) PTL with IAI (n=65); (7) preterm PROM without IAI (n=25); and (8) preterm PROM with IAI (n=77).

Maternal and neonatal circulating visfatin concentrations in patients with pre-eclampsia and a small-for-gestational age neonate.

Objective: Maternal circulating visfatin concentrations are higher in patients with a small-for-gestational-age (SGA) neonate than in those who delivered an appropriate-for-gestational age (AGA) neonate or in those with pre-eclampsia. It has been proposed that enhanced transfer of visfatin from the foetal to maternal circulation may account for the high concentrations of maternal visfatin observed in patients with an SGA neonate. The aims of this study were: (1) to determine whether cord blood visfatin concentrations differ between normal neonates, SGA neonates and newborns of pre-eclamptic mothers; and (2) to assess the relationship between maternal and foetal circulating visfatin concentrations in patients with an SGA neonate and those with pre-eclampsia.

Maternal plasma concentration of the pro-inflammatory adipokine pre-B-cell-enhancing factor (PBEF)/visfatin is elevated in pregnant patients with acute pyelonephritis.

Problem: Visfatin/pre-B-cell-enhancing factor (PBEF) has been implicated in the regulation of the innate immune system, as well as in glucose metabolism. Specifically, visfatin plays a requisite role in delayed neutrophil apoptosis in patients with sepsis. The aim of this study was to determine whether pyelonephritis during pregnancy is associated with changes in maternal plasma visfatin concentration in normal weight and overweight/obese patients.

Universal cervical length screening and treatment with vaginal progesterone to prevent preterm birth: a decision and economic analysis.

Objective: The purpose of this study was to estimate which strategy is the most cost-effective for the prevention of preterm birth and associated morbidity.

Study Design: We used decision-analytic and cost-effectiveness analyses to estimate which of 4 strategies was superior based on quality-adjusted life-years, cost in US dollars, and number of preterm births prevented.

Results: Universal sonographic screening for cervical length and treatment with vaginal progesterone was the most cost-effective strategy and was the dominant choice over the 3 alternatives: cervical length screening for women at increased risk for preterm birth and treatment with vaginal progesterone; risk-based treatment with 17 alpha-hydroxyprogesterone caproate (17-OHP-C) without screening; no screening or treatment.

Leukocytes of pregnant women with small-for-gestational age neonates have a different phenotypic and metabolic activity from those of women with preeclampsia.

Objective: Preeclampsia and pregnancies complicated by small-for-gestational age (SGA) neonates share several underlying mechanisms of disease. However, while an exaggerated systemic maternal inflammatory response is regarded as one of the hallmarks of the pathogenesis of preeclampsia, the presence of a similar systemic intra-vascular inflammation in mothers of SGA neonates without hypertension is controversial. The aim of this study was to determine phenotypic and metabolic changes in granulocytes and monocytes of women who develop preeclampsia and those who deliver an SGA neonate, compared to normal pregnant women.

Fetal membranes as an interface between inflammation and metabolism: increased aquaporin 9 expression in the presence of spontaneous labor at term and chorioamnionitis.

Objective: Aquaporin 9 (AQP9) is a water channel protein characterized by its high permeability to nutrients such as lactate and glycerol, as well as urea and other small solutes. These unique properties of AQP9 suggest that this molecule may play a role in the modulation of nutrient flux through the fetal membranes in conditions associated with increased metabolic demand, such as spontaneous labor and inflammation. The objective of this study was to determine the expression of AQP9 in the chorioamniotic membranes from women with and without term labor, as well as those with preterm prelabor rupture of membranes (PPROM) with and without histologic chorioamnionitis.

Amniotic fluid soluble human leukocyte antigen-G in term and preterm parturition, and intra-amniotic infection/inflammation.

Objective: Circulating soluble human leukocyte antigen-G (sHLA-G) has been associated with pregnancy complications, and determination of sHLA-G concentrations in amniotic fluid (AF) has been reported in normal pregnancies. Our aim was to determine if the AF concentrations of sHLA-G change with advancing gestation, spontaneous labor at term, and in patients with spontaneous preterm labor (PTL) with intact membranes, as well as in those with preterm prelabor rupture of membranes (PROM), in the presence or absence of intra-amniotic infection/inflammation (IAI).

Study Design: This cross-sectional study included the following groups: (1) mid-trimester (n = 55); (2) normal pregnancy at term with (n = 50) and without (n = 50) labor; (3) spontaneous PTL with intact membranes divided into: (a) PTL who delivered at term (n = 153); (b) PTL who delivered preterm without IAI (n = 108); and (c) PTL with IAI (n = 84); and (4) preterm PROM with (n = 46) and without (n = 44) IAI.

A subset of patients destined to develop spontaneous preterm labor has an abnormal angiogenic/anti-angiogenic profile in maternal plasma: evidence in support of pathophysiologic heterogeneity of preterm labor derived from a longitudinal study.

Objective: An imbalance between angiogenic and anti-angiogenic factors in maternal blood has been observed in several obstetrical syndromes including preeclampsia, pregnancies with fetal growth restriction and fetal death. Vascular lesions have been identified in a subset of patients with spontaneous preterm labor (PTL). It is possible that PTL may be one of the manifestations of an anti-angiogenic state.

A prospective cohort study of the value of maternal plasma concentrations of angiogenic and anti-angiogenic factors in early pregnancy and midtrimester in the identification of patients destined to develop preeclampsia.

Objective: Changes in the maternal plasma concentrations of angiogenic (placental growth factor (PlGF) and vascular endothelial growth factor (VEGF)) and anti-angiogenic factors (sEng and vascular endothelial growth factor receptor-1 (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 1622 consecutive singleton pregnant women.

Changes in amniotic fluid concentration of thrombin-antithrombin III complexes in patients with preterm labor: evidence of an increased thrombin generation.

Objective: Preterm labor is associated with excessive maternal thrombin generation, as evidenced by increased circulating thrombin-antithrombin (TAT) III complexes concentration. In addition to its hemostatic functions, thrombin has uterotonic properties that may participate in the mechanism leading to preterm birth in cases of intrauterine bleeding. Thrombin also has a proinflammatory role, and inflammation is associated with increased thrombin generation.

The clinical significance of eosinophils in the amniotic fluid in preterm labor.

Objective: White blood cells are not traditionally considered to be normally present in amniotic fluid. This study was conducted after the observation that a patient with preterm labor and intact membranes had eosinophils as a predominant cell in the amniotic fluid, and had an episode of asthma during the index pregnancy. The goal of this study was to determine whether women presenting with preterm labor with eosinophils in the amniotic fluid had a different outcome than those without eosinophils as the predominant white blood cell in the amniotic cavity.

Could alterations in maternal plasma visfatin concentration participate in the phenotype definition of preeclampsia and SGA?

Objective: Women with preeclampsia and those who delivered a small-for-gestational-age (SGA) neonate share several mechanisms of disease, including chronic uteroplacental ischemia and failure of physiologic transformation of the spiral arteries. However, the clinical manifestation of these obstetrical syndromes is remarkably different. It has been proposed that an altered maternal metabolic state, as well as a unique circulating cytokines milieu, predispose women to develop either preeclampsia or SGA.

Preeclampsia and pregnancies with small-for-gestational age neonates have different profiles of complement split products.

Objective: The activation of the complement system results in the generation of split products with pro-inflammatory properties. The objective of this study was to determine whether preeclampsia and small-for-gestational age (SGA) are associated with changes in the maternal plasma concentrations of anaphylatoxins C3a, C4a and C5a.

Methods: A cross-sectional study was conducted in the following groups: (a) normal pregnant women (n = 134); (b) women who delivered an SGA neonate (n = 53); (c) preeclampsia with (n = 52) and without SGA (n = 54).

Retinol binding protein 4: an adipokine associated with intra-amniotic infection/inflammation.

Objective: Retinol binding protein 4 (RBP4), a specific carrier for retinol in the blood, is a novel adipokine that has been implicated in the pathophysiology of insulin resistance, and its gene expression has been associated with adipose tissue inflammation. Recently, proteomic profiling of amniotic fluid (AF) from women with preterm labor (PTL) revealed over-expression of RBP4 in those who delivered preterm. The aim of this study was to determine whether RBP4 is present in AF, and if its concentrations change with gestational age, in the presence of labor, and intra-amniotic infection/inflammation (IAI) in patients with spontaneous PTL.

MicroRNA expression profiling of the human uterine cervix after term labor and delivery.

Objective: MicroRNAs (miRNAs) are noncoding RNAs involved in posttranscriptional regulation of target genes. The objective of this study was to determine the miRNA expression profile of the human uterine cervix after spontaneous term labor (TL).

Study Design: The miRNA expression pattern of cervical tissue was characterized using microarrays.

The transcriptome of cervical ripening in human pregnancy before the onset of labor at term: identification of novel molecular functions involved in this process.

Objective: The aim of this study was to identify changes in the cervical transcriptome in the human uterine cervix as a function of ripening before the onset of labor.

Study Design: Human cervical tissue was obtained from women at term not in labor with ripe (n = 11) and unripe (n = 11) cervices and profiled using Affymetrix GeneChip HGU133Plus2.0 arrays.

High tissue factor activity and low tissue factor pathway inhibitor concentrations in patients with preterm labor.

Objective: Preterm labor (PTL) has been associated with an increased thrombin generation in the maternal circulation and amniotic fluid. Tissue factor (TF) is a potent initiator of the coagulation cascade, which can trigger the hemostatic system to generate thrombin. The aims of this study were to determine whether spontaneous PTL with intact membranes is associated with changes in the maternal plasma concentrations and activity of TF as well as tissue factor pathway inhibitor (TFPI).

Pentraxin 3 in amniotic fluid: a novel association with intra-amniotic infection and inflammation.

Objective: Pentraxin 3 (PTX3) is a soluble pattern recognition receptor (PRR) that has an important role in immunoregulation and vascular integrity. The aim of this study was to determine if PTX3 is present in amniotic fluid (AF) and whether its concentration changes with gestational age (GA), in the presence of preterm or term labor, and in cases of intra-amniotic infection/inflammation (IAI) associated with spontaneous preterm labor (PTL) or preterm prelabor rupture of membranes (PROM).

Study Design: This cross-sectional study included the following groups: 1) mid-trimester (n=45); 2) uncomplicated pregnancies at term with (n=48) and without (n=40) spontaneous labor; 3) women with PTL and intact membranes who: a) delivered at term (n=44); b) delivered preterm without IAI (n=40); or c) delivered preterm with IAI (n=62); 4) women with preterm PROM with (n=63) and without (n=36) IAI.

Repeatability and reproducibility of fetal cardiac ventricular volume calculations using spatiotemporal image correlation and virtual organ computer-aided analysis.

Objective: The objective of this study was to quantify the repeatability and reproducibility of fetal cardiac ventricular volumes obtained using spatiotemporal image correlation (STIC) and Virtual Organ Computer-Aided Analysis (VOCAL; GE Healthcare, Kretztechnik, Zipf, Austria).

Methods: A technique was developed to compute ventricular volumes using the subfeature Contour Finder: Trace. Twenty-five normal pregnancies were evaluated for the following: (1) to compare the coefficient of variation (CV) of ventricular volumes obtained using 15 degrees and 30 degrees rotation; (2) to compare the CV between 3 methods of quantifying ventricular volumes: (a) Manual Trace, (b) Inversion Mode, and (c) Contour Finder: Trace; and (3) to determine repeatability by calculating agreement and reliability of ventricular volumes when each STIC was measured twice by 3 observers.

Evidence of maternal platelet activation, excessive thrombin generation, and high amniotic fluid tissue factor immunoreactivity and functional activity in patients with fetal death.

Objective: Fetal death can lead to disseminated intravascular coagulation or fetal death syndrome. However, currently it is not clear what are the changes in the coagulation system in patients with a fetal death without the fetal death syndrome. This study was undertaken to determine: (1) whether fetal death in the absence of fetal death syndrome is associated with changes in hemostatic markers in maternal plasma and amniotic fluid; and (2) whether maternal hypertension or placental abruption are associated with further changes in the hemostatic profile of these patients.

Retinol binding protein 4--a novel association with early-onset preeclampsia.

Objective: Dysregulation of maternal circulating adipokines has been implicated in several "great obstetrical syndromes" including preeclampsia (PE), small-for-gestational age (SGA) neonate and fetal death (FD). It has been suggested that adipokines provide a molecular link between metabolic derangements and inflammatory response in complicated pregnancies. Retinol binding protein 4 (RBP4), a novel adipokine, plays a role in obesity-related disorders, as well as in the regulation of the immune response.

Isobaric labeling and tandem mass spectrometry: a novel approach for profiling and quantifying proteins differentially expressed in amniotic fluid in preterm labor with and without intra-amniotic infection/inflammation.

Objective: Examination of the amniotic fluid (AF) proteome has been previously attempted to identify useful biomarkers in predicting the outcome of preterm labor (PTL). Isobaric Tag for Relative and Absolute Quantitation (iTRAQ) labeling allows direct ratiometric comparison of relative abundance of identified protein species among multiplexed samples. The purpose of this study was to apply, for the first time, the combination of iTRAQ and tandem mass spectrometry to identify proteins differentially regulated in AF samples of women with spontaneous PTL and intact membranes with and without intra-amniotic infection/inflammation (IAI).

Low circulating maternal adiponectin in patients with pyelonephritis: adiponectin at the crossroads of pregnancy and infection.

Objective: An emerging theme in modern biology is that adipose tissue can respond to metabolic stress, and to inflammatory stimuli, by regulating the secretion of a complex network of soluble mediators, termed adipokines. Adiponectin, the most prevalent circulating adipokine in human, has profound insulin-sensitizing and anti-inflammatory properties. Indeed, the notion that adiponectin plays an important role in the interactions between the metabolic and the immune systems has been strongly suggested.

The prognosis of pregnancy conceived despite the presence of an intrauterine device (IUD).

Objective: Intrauterine devices (IUDs) are used for contraception worldwide; however, the management of pregnancies with an IUD poses a clinical challenge. The purpose of this study was to determine the outcome of pregnancy in patients with an IUD.

Study Design: A retrospective cohort study (December 1997-June 2007) was conducted.

Discordant placental echogenicity: a novel sign of impaired placental perfusion in twin-twin transfusion syndrome?

Twin-twin transfusion syndrome (TTTS) is present in approximately 5-15% of monochorionic-diamniotic twin pregnancies. A chronic blood flow imbalance through placental vascular anastomoses from the donor to the recipient twin is considered the pathophysiologic mechanism responsible for the development of TTTS. Discordant echogenicity between the donor and recipient placenta has been proposed in a previous case report as an additional sonographic sign of TTTS.