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Streptococcus agalactiae, or Group B Streptococcus (GBS), is a leading cause of neonatal sepsis. Materno-fetal transmission of the microorganisms present in the lower genital tract/perineum is considered to be the most frequent mode for acquisition of infection. It has also been proposed that, in a subset of cases, GBS causes acute chorioamnionitis, intraamniotic infection, and fetal/neonatal sepsis. However, the evidence to support this ascending pathway is derived from microbiologic studies that rely on cultivation methods, which do not have the resolution to determine if the microorganisms causing neonatal sepsis are the same as those found in the amniotic fluid and the vaginal ecosystem. We used whole genome sequencing of the microorganisms isolated from the vagina, amniotic fluid, chorioamniotic membranes, and neonatal blood (four isolates) in a case of early neonatal sepsis. Using hybrid genome assembly, we characterized the genomic features including virulence factors and antimicrobial resistance in four isolates from the same mother, placenta, and newborn. Whole genome sequencing revealed that the microorganisms in the four clinical isolates corresponded to S. agalactiae sequence type 1, clonal complexes 1, and serotype Ib. Comparative genomic analysis illustrated similar DNA sequences of the four genomes. This study presents the first evidence of the genomic similarity of microorganisms in the vaginal ecosystem, the space between the chorioamniotic membranes of the placenta, amniotic fluid, and neonatal blood. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the efficacy of cervical cerclage with spontaneous follow-up strategy on pregnancy duration and neonatal outcomes in women with visible or prolapsed fetal membranes. Patients who were referred to a single tertiary care centre between 1st January 2017 and 31st December 2022 were included in this comparative, retrospective cohort study. Patients were divided into two groups, those undergoing cerclage and those followed with no-cerclage. The range of pregnancy weeks for cerclage is between 18th and 27+6 weeks. A total of 106 cases were reviewed and nine were excluded. Based on shared decision making, cervical cerclage was performed in 76 patients (78.3 %) and 21 patients (21.6 %) were medically treated in no-cerclage group if there was no early rupture of the fetal membranes. The gestational age at delivery was 29.8 ± 6 [median=30 (19–38)] weeks in the cerclage group and 25.8 ± 2.9 [median=25 (19–32)] weeks in the no-cerclage group (p=0.004). Pregnancy prolongation was significantly longer in the cerclage group compared to the no-cerclage group (55 ± 48.6 days [median=28 (3–138)] vs. 12 ± 17.9 days [median=9 (1–52)]; p<0.001). Take home baby rate was 58/76 (76.3 %) in cerclage group vs. 8/21 (38 %) in no-cerclage group. In the post-24 week cerclage group the absolute risk reduction for pregnancy loss was 50 % (95 % CI=21.7–78.2). Cervical cerclage applied before and after 24 weeks (until 27+6 weeks) increased take home baby rate in women with visible or prolapsed fetal membranes without increasing adverse maternal outcome when compared with no-cerclage group. [ABSTRACT FROM AUTHOR]

Among patients with preterm labor and intact membranes (PTL), those with intra-amniotic infection (IAI) present the highest risk of adverse perinatal outcomes. Current identification of IAI, based on microbiological cultures and/or polymerase chain reaction amplification of the 16S ribosomal RNA gene, delay diagnosis and, consequently, antenatal management. The aim to of the study was to assess the performance of a multivariable prediction model for diagnosing IAI in patients with PTL below 34.0 weeks using clinical, sonographic and biochemical biomarkers. From 2019 to 2022, we prospectively included pregnant patients admitted below 34.0 weeks with diagnosis of PTL and had undergone amniocentesis to rule in/out IAI. The main outcome was IAI, defined by a positive culture and/or 16S ribosomal RNA gene in amniotic fluid. Based on the date of admission, the sample (n=98) was divided into a derivation (2019–2020, n=49) and validation cohort (2021–2022, n=49). Logistic regression models were developed for the outcomes evaluated. As predictive variables we explored ultrasound cervical length measurement at admission, maternal C-reactive protein, gestational age, and amniotic fluid glucose and matrix metalloproteinase-8 (MMP-8) levels. The model was developed in the derivation cohort and applied to the validation cohort and diagnostic performance was evaluated. Clinical management was blinded to the model results. During the study period, we included 98 patients admitted with a diagnosis of PTL. Of these, 10 % had IAI. The final model included MMP-8 and amniotic fluid glucose levels and showed an area under the receiver operating characteristic curve to predict the risk of IAI of 0.961 (95 % confidence interval: 0.860–0.995) with a sensitivity of 75 %, specificity of 93.3 %, positive likelihood ratio (LR) of 11.3 and negative LR of 0.27 in the validation cohort. In patients with PTL, a multivariable prediction model including amniotic fluid MMP-8 and glucose levels might help in the clinical management of patients undergoing amniocentesis to rule in/out IAI, providing results within a few minutes. [ABSTRACT FROM AUTHOR]

To evaluate the timing of antenatal corticosteroids (ACS) administration in relation to the delivery timing based on indications and risk factors for preterm delivery. We conducted a retrospective cohort study to understand what factors predict the optimal timing of ACS administration (ACS administration within seven days). We reviewed consecutive charts of adult pregnant women receiving ACS from January 1, 2011, to December 31, 2019. We excluded pregnancies under 23 weeks, incomplete and duplicate records, and patients delivered outside our health system. The timing of ACS administration was categorized as optimal or suboptimal. These groups were analyzed regarding demographics, indications for ACS administration, risk factors for preterm delivery, and signs and symptoms of preterm labor. We identified 25,776 deliveries. ACS were administered to 531 pregnancies, of which 478 met the inclusion criteria. Of the 478 pregnancies included in the study, 266 (55.6 %) were delivered in the optimal timeframe. There was a higher proportion of patients receiving ACS for the indication of threatened preterm labor in the suboptimal group as compared to the optimal group (85.4 % vs. 63.5 %, p<0.001). In addition, patients who delivered in the suboptimal timeframe had a higher proportion of short cervix (33 % vs. 6.4 %, p<0.001) and positive fetal fibronectin (19.8 % vs. 1.1 %, p<0.001) compared to those who delivered in the optimal timeframe. More emphasis should be placed on the judicious use of ACS. Emphasis should be placed on clinical assessment rather than relying solely on imaging and laboratory tests. Re-appraisal of institutional practices and thoughtful ACS administration based on the risk-benefit ratio is warranted. [ABSTRACT FROM AUTHOR]

Early diagnosis and treatment of intra-amniotic infection is crucial. Rapid pathogen identification allows for a definite diagnosis and enables proper management. We determined whether the 16S amplicon sequencing performed by a nanopore sequencing technique make possible rapid bacterial identification at the species level in intra-amniotic infection. Five cases of confirmed intra-amniotic infection, determined by either cultivation or 16S rDNA polymerase chain reaction (PCR) Sanger sequencing, and 10 cases of women who underwent mid-trimester genetic amniocentesis were included. DNA was extracted from amniotic fluid and PCR was performed on the full-length 16S rDNA. Nanopore sequencing was performed. The results derived from nanopore sequencing were compared with those derived from cultivation and Sanger sequencing methods. Bacteria were successfully detected from amniotic fluid using nanopore sequencing in all cases of intra-amniotic infection. Nanopore sequencing identified additional bacterial species and polymicrobial infections. All patients who underwent a mid-trimester amniocentesis had negative cultures, negative 16S PCR Sanger sequencing and nanopore sequencing. Identification of the microorganisms using nanopore sequencing technique at the bacterial species level was achieved within 5–9 h from DNA extraction. This is the first study demonstrating that the nanopore sequencing technique is capable of rapid diagnosis of intra-amniotic infection using fresh amniotic fluid samples. [ABSTRACT FROM AUTHOR]

Preterm birth remains the leading cause of perinatal morbidity and mortality worldwide. Preterm birth is preceded by spontaneous preterm labor, which is commonly associated with sterile intra-amniotic inflammation; yet, no approved treatment exists for this clinical condition. Corticosteroids are the standard of care to improve neonatal outcomes in women at risk of preterm birth. Herein, we first validated our model of alarmin-induced preterm birth. Next, we investigated whether treatment with betamethasone could prevent preterm birth resulting from sterile intra-amniotic inflammation in mice. Under ultrasound guidance, the first cohort of dams received an intra-amniotic injection of the alarmin high-mobility group box-1 (HMGB1, n=10) or phosphate-buffered saline (PBS, n=9) as controls. A second cohort of dams received HMGB1 intra-amniotically and were subcutaneously treated with betamethasone (n=15) or vehicle (n=15). Dams were observed until delivery, and perinatal outcomes were observed. Intra-amniotic HMGB1 reduced gestational length (p=0.04), inducing preterm birth in 40% (4/10) of cases, of which 100% (4/4) were categorized as late preterm births. Importantly, treatment with betamethasone extended the gestational length (p=0.02), thereby reducing the rate of preterm birth by 26.6% (from 33.3% [5/15] to 6.7% [1/15]). Treatment with betamethasone did not worsen the rate of neonatal mortality induced by HMGB1 or alter weight gain in the first three weeks of life. Treatment with betamethasone prevents preterm birth induced by the alarmin HMGB1. This study supports the potential utility of betamethasone for treating women with sterile intra-amniotic inflammation. [ABSTRACT FROM AUTHOR]

The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women's health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women's cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus-dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs. [ABSTRACT FROM AUTHOR]

To evaluate the association between extremely elevated alkaline phosphatase (ALKP) levels (above 1000 U/L) and adverse perinatal outcome. A retrospective case series of all parturients with extremely elevated ALKP levels taken throughout pregnancy at a single university-affiliated medical center (2010–2018). Demographics and medical data were retrieved. Following literature review, previously reported similar cases were added to the cohort. We report perinatal outcome of our cohort as well as literature review. During study period 11 parturients with high ALKP were identified. Ten more cases were retrieved from PubMed search. Overall, median ALKP levels were 1880 (range 1052–4488 U/L). Reasons for evaluation were mostly nonspecific symptoms (pruritus, headache, abdominal pain) or routine obstetrical evaluation. In 10/12 (83%) cases, elevated ALKP levels were of placental origin; the rest had osteal origin. Median gestational age at delivery was 38 (range 35–41); four (19%) women had preterm delivery. Six patients (29%) had gestational diabetes mellitus and six (29%) had hypertensive disorders. Histopathology of the placenta was available in eight cases: three normal histology (38%) and five with different non-specific pathologies. We report the largest case series of extremely elevated levels of ALKP in pregnancy thus far. Our data suggest association with adverse perinatal outcome. [ABSTRACT FROM AUTHOR]

Objectives: Pregnant women are more susceptible to certain infections; however, this increased susceptibility is not fully understood. Herein, systems biology approaches were utilized to elucidate how pregnancy modulates tissue-specific host responses to a bacterial product, endotoxin. Methods: Pregnant and non-pregnant mice were injected with endotoxin or saline on 16.5 days post coitum (n=8–11 per group). The uterus, cervix, liver, adrenal gland, kidney, lung, and brain were collected 12 h after injection and transcriptomes were measured using microarrays. Heatmaps and principal component analysis were used for visualization. Differentially expressed genes between groups were assessed using linear models that included interaction terms to determine whether the effect of infection differed with pregnancy status. Pathway analysis was conducted to interpret gene expression changes. Results: We report herein a multi-organ atlas of the transcript perturbations in pregnant and non-pregnant mice in response to endotoxin. Pregnancy strongly modified the host responses to endotoxin in the uterus, cervix, and liver. In contrast, pregnancy had a milder effect on the host response to endotoxin in the adrenal gland, lung, and kidney. However, pregnancy did not drastically affect the host response to endotoxin in the brain. Conclusions: Pregnancy imprints organ-specific host immune responses upon endotoxin exposure. These findings provide insight into the host-response against microbes during pregnancy. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effects of nifedipine treatment on fetal hemodynamics and cardiac function during preterm labor. This prospective study assessed several quantitative parameters of fetal cardiac circulation and function, and found no significant changes at 48 h after nifedipine treatment. These findings suggest that tocolytic nifedipine may be safe for fetuses. It supports clinicians to use nifedipine treatment for tocolysis without any cardiac effect on the fetus. Methods: A prospective cohort study was conducted at a tertiary hospital between January 2016 and October 2017. A total of 45 pregnant women who required nifedipine for preterm labor were included in this study. Fetal Doppler ultrasound was performed and fetal systolic and diastolic function was measured prior to, and 48 h after, the first nifedipine treatment. Conventional Doppler parameters were used to evaluate fetal heart function and hemodynamic changes. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion and the sphericity index were also evaluated to assess changes in fetal cardiac morphology. Results: No significant changes in fetal Doppler parameters were observed following nifedipine tocolysis. There was no significant difference in the fetal cardiac function parameters of both ventricles before vs. after nifedipine treatment. Tricuspid annular plane systolic excursion, mitral annular plane systolic excursion, and sphericity index values were unchanged following nifedipine treatment. Conclusions: Oral administration of nifedipine did not to alter fetal cardiac function or morphology. Fetal cardiac parameters and various Doppler indices were unchanged following nifedipine treatment. Maternal nifedipine treatment does not appear to have any significant effect on fetal cardiac function. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the leading cause of perinatal morbidity and mortality. Preterm prelabor rupture of membranes (pPROM) occurs in 30% of preterm births; thus, this complication is a major contributor to maternal and neonatal morbidity. However, the cellular immune responses in amniotic fluid of women with pPROM have not been investigated. Methods: Amniotic fluid samples were obtained from women with pPROM and a positive (n = 7) or negative (n = 10) microbiological culture. Flow cytometry was performed to evaluate the phenotype and number of amniotic fluid leukocytes. The correlation between amniotic fluid immune cells and an interleukin-6 (IL-6) concentration or a white blood cell (WBC) count in amniotic fluid was calculated. Results: Women with pPROM and a positive amniotic fluid culture had (1) a greater number of total leukocytes in amniotic fluid, including neutrophils and monocytes/macrophages and (2) an increased number of total T cells in amniotic fluid, namely CD4+ T cells and CD8+ T cells, but not B cells. The numbers of neutrophils and monocytes/macrophages were positively correlated with IL-6 concentrations and WBC counts in amniotic fluid of women with pPROM. Conclusion: Women with pPROM and a positive amniotic fluid culture exhibit a more severe cellular immune response than those with a negative culture, which is associated with well-known markers of intra-amniotic inflammation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of atosiban as a tocolytic agent in patients treated with the fetoscopic endotracheal occlusion (FETO) procedure due to congenital diaphragmatic hernia (CDH). As premature birth after fetoscopy remains a serious concern, an effort to reduce prematurity is required. Methods: A total of 43 patients with severe CDH treated with FETO were enrolled in this study. The study group consisted of 22 patients who received atosiban during the FETO procedure and a control group of 21 patients who did not receive atosiban during the FETO procedure. Demographic data, gestational age (GA) at delivery, cervical length and GA at premature rupture of membranes (PROM) were evaluated. Results: The GA at delivery was significantly different between the two groups studied. The median GA at delivery was 32.6 and 34.5 weeks in the no-atosiban vs. atosiban groups, respectively (P = 0.013). The median cervical length was 29.9 and 31.2 mm for the no-atosiban and atosiban groups, respectively, and was not statistically significant (P = 0.28). There were no significant correlations between groups for the occurrence of PROM, GA at the time of PROM, duration of the procedures, parity, maternal body mass index (BMI) or age. In the univariate linear regression model, the only factor independently associated with GA at delivery was the use of atosiban during FETO procedures (β = 0.375; P < 0.013). Conclusion: In cases of severe CDH treated with FETO, the use of atosiban as a tocolytic agent during the procedure prolonged pregnancy by 2 weeks. Cervical length, duration of FETO or maternal characteristics were not associated with GA at delivery. [ABSTRACT FROM AUTHOR]

Background: Monocytes, after neutrophils, are the most abundant white blood cells found in the amniotic cavity of women with intra-amniotic inflammation/infection. However, the origin of such cells has not been fully investigated. Herein, we determined (1) the origin of amniotic fluid monocytes/macrophages from women with intra-amniotic inflammation/infection, (2) the relationship between the origin of amniotic fluid monocytes/macrophages and preterm or term delivery and (3) the localization of monocytes/macrophages in the placental tissues. Methods: Amniotic fluid samples (n = 16) were collected from women with suspected intra-amniotic inflammation or infection. Amniotic fluid monocytes/macrophages were purified by fluorescence-activated cell sorting, and DNA fingerprinting was performed. Blinded placental histopathological evaluations were conducted. Immunohistochemistry was performed to detect CD14+ monocytes/macrophages in the placental tissues. Results: DNA fingerprinting revealed that (1) 56.25% (9/16) of amniotic fluid samples had mostly fetal monocytes/macrophages, (2) 37.5% (6/16) had predominantly maternal monocytes/macrophages and (3) one sample (6.25% [1/16]) had a mixture of fetal and maternal monocytes/macrophages. (4) Most samples with predominantly fetal monocytes/macrophages were from women who delivered early preterm neonates (77.8% [7/9]), whereas all samples with mostly maternal monocytes/macrophages or a mixture of both were from women who delivered term or late preterm neonates (100% [7/7]). (5) Most of the women included in this study presented acute maternal and fetal inflammatory responses in the placenta (85.7% [12/14]). (6) Women who had mostly fetal monocytes/macrophages in amniotic fluid had abundant CD14+ cells in the umbilical cord and chorionic plate, whereas women with mostly maternal amniotic fluid monocytes/macrophages had abundant CD14+ cells in the chorioamniotic membranes. Conclusion: Amniotic fluid monocytes/macrophages can be of either fetal or maternal origin, or a mixture of both, in women with intra-amniotic inflammation or infection. These immune cells could be derived from the fetal and maternal vasculature of the placenta. [ABSTRACT FROM AUTHOR]

Objectives: To determine the relationship between the intensity of the intra-amniotic inflammatory response and the gestational age at the time of diagnosis in cases with preterm premature rupture of membranes (PROM) and intra-amniotic infection caused by Ureaplasma spp. Methods: A retrospective cohort study was conducted which included 71 women with preterm PROM and a positive amniotic fluid culture with Ureaplasma spp. Women with mixed intra-amniotic infections were excluded. The study population was classified into three groups according to gestational age: group 1, <26 weeks (extreme preterm PROM, n = 17); group 2, 26.0–33.9 weeks (moderate preterm PROM, n = 39); group 3, 34.0–36.9 weeks (late preterm PROM, n = 15). The intensity of the intra-amniotic and maternal inflammatory response was compared among the three groups. The intensity of the intra-amniotic inflammatory response was assessed by the concentration of amniotic fluid matrix metalloproteinase-8 (MMP-8) and white blood cell (WBC) count. The maternal inflammatory response was assessed by the concentration of C-reactive protein (CRP) and WBC count in maternal blood at the time of amniocentesis. Results: (1) The median values of amniotic fluid MMP-8 concentration and WBC count were the highest in the extreme preterm PROM group and the lowest in the late preterm PROM group (P < 0.001 and P = 0.01, respectively); (2) the intensity of the maternal inflammatory response measured by maternal blood WBC count and CRP concentration was not significantly associated with gestational age at the time of diagnosis. Conclusion: The earlier the gestational age at the time of PROM, the higher the intensity of the intra-amniotic inflammatory response in women with preterm PROM and intra-amniotic infection caused by Ureaplasma spp. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the risk of intra-amniotic infection/inflammation and spontaneous preterm delivery (SPTD) varies as a function of the concentration of cervical fetal fibronectin (fFN) in patients with preterm labor and intact membranes. Methods: This prospective study included 180 patients with preterm labor and intact membranes who had a sample collected for quantitative fFN measurement and underwent amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and genital mycoplasmas. Intra-amniotic inflammation was defined as an amniotic fluid matrix metalloproteinase-8 concentration >23 ng/mL. Results: (1) The prevalence of intra-amniotic infection/inflammation and SPTD within 7 days was 32.2% (58/180) and 33.9% (61/178), respectively; (2) The higher the fFN concentration, the greater the risk of intra-amniotic infection/inflammation and SPTD within 7 days (P<0.001, respectively); (3) An fFN concentration 150 ng/mL had a better diagnostic performance than an fFN 50 ng/mL in the identification of intra-amniotic infection/inflammation and SPTD within 7 days; (4) Among the patients with an fFN <50 ng/mL, intra-amniotic infection/inflammation was identified in 7.6% (6/79) of patients and 66.7% (4/6) delivered within 7 days. Conclusion: The higher the concentration of fFN, the greater the risk of intra-amniotic infection/inflammation and SPTD in patients with preterm labor and intact membranes. [ABSTRACT FROM AUTHOR]

Background: We investigated the roles of inflammatory cytokines and the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family in the etiopathogenesis of spontaneous preterm delivery by comparing the ADAMTS4, ADAMTS5, interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) levels in second-trimester amniotic fluid between pregnant women with preterm birth and term controls. Methods: All pregnant women who underwent second-trimester amniocentesis for genetic analysis between January 1, 2016, and January 1, 2018, were enrolled in this study. From this cohort, 22 patients who subsequently experienced spontaneous preterm delivery before 34 weeks of pregnancy formed the study group, and 22 age- and body mass index (BMI)-matched patients without preterm birth constituted the control group. Results: No significant differences were observed between the preterm birth and control groups in terms of age, BMI, obstetric history of preterm delivery, gestational age at amniocentesis, or indication for amniocentesis. The mean amniotic fluid levels of ADAMTS4 and ADAMTS5 were significantly increased in the preterm birth group compared to the control group (248.3±22.6 and 182.4±19.8 pg/mL, P=0.012; and 198.6±21.6 and 159.1±21.7 pg/mL, P=0.035, respectively). Significantly increased IL-6 and TNF-α levels were also detected in the amniotic fluid of women who experienced spontaneous preterm delivery, relative to controls (142.1±16.2 and 95.8±16.4 pg/mL, P<0.001; and 139.4±12.5 and 89.6±11.2 pg/mL, P<0.001, respectively). Conclusion: The results of this study imply that increased mid-trimester amniotic fluid levels of ADAMTS4, ADAMTS5, IL-6, and TNF-α play an important role in the pathophysiology of spontaneous preterm delivery. [ABSTRACT FROM AUTHOR]

Objective: To determine whether a soft cervix identified by shear-wave elastography between 18 and 24 weeks of gestation is associated with increased frequency of spontaneous preterm delivery (sPTD). Materials and methods: This prospective cohort study included 628 consecutive women with a singleton pregnancy. Cervical length (mm) and softness [shear-wave speed: (SWS) meters per second (m/s)] of the internal cervical os were measured at 18–24 weeks of gestation. Frequency of sPTD <37 (sPTD<37) and <34 (sPTD<34) weeks of gestation was compared among women with and without a short (≤25 mm) and/or a soft cervix (SWS <25th percentile). Results: There were 31/628 (4.9%) sPTD<37 and 12/628 (1.9%) sPTD<34 deliveries. The combination of a soft and a short cervix increased the risk of sPTD<37 by 18-fold [relative risk (RR) 18.0 (95% confidence interval [CI], 7.7–43.9); P<0.0001] and the risk of sPTD<34 by 120-fold [RR 120.0 (95% CI 12.3–1009.9); P<0.0001] compared to women with normal cervical length. A soft-only cervix increased the risk of sPTD<37 by 4.5-fold [RR 4.5 (95% CI 2.1–9.8); P=0.0002] and of sPTD<34 by 21-fold [RR 21.0 (95% CI 2.6–169.3); P=0.0003] compared to a non-soft cervix. Conclusions: A soft cervix at 18–24 weeks of gestation increases the risk of sPTD <37 and <34 weeks of gestation independently of cervical length. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine if the actions of progesterone on preterm labor are accomplished through modulation of the percentage of regulatory T-cells (Treg). Methods: The study was a cohort pilot study made in a single center tertiary obstetrical unit with women in preterm labor arrested with tocolytic treatment. Variation of the number and percentage of Treg cells obtained from peripheral blood samples of women with preterm labor were calculated by flow cytometry, before and after progesterone administration. Results: In the paired samples for each patient, there was a significant difference in the Treg cell pool after progesterone treatment, with an increase in both their percentage (48.9 vs. 53; P=0.07) and absolute number (14.8 vs. 56.5 cells/µL; P=0.046). Conclusions: This research demonstrated a considerable increase in the Treg cell pool after progesterone treatment. This indicates a possible mechanism for progesterone treatment benefits in preterm labor, potentially increasing its more rational use. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association between cervical strain assessed with quasi-static elastography and spontaneous preterm delivery. Methods: Quasi-static elastography was used to estimate cervical strain in 545 pregnant women with singleton pregnancies from 11 weeks to 28 weeks of gestation. Cervical strain was evaluated in one sagittal plane and in the cross-sectional planes of the internal cervical os and external cervical os. The distribution of strain values was categorized into quartiles for each studied region and their association with spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation was evaluated using logistic regression. Results: The prevalence of spontaneous preterm delivery at <37 weeks of gestation was 8.2% (n=45), and that at ≤34 weeks of gestation was 3.8% (n=21). Strain in the internal cervical os was the only elastography value associated with spontaneous preterm delivery. Women with strain values in the 3rd and 4th quartiles had a significantly higher risk of spontaneous preterm delivery at ≤34 weeks and at <37 weeks of gestation when compared to women with strain values in the lowest quartile. When adjusting for a short cervix (<25 mm) and gestational age at examination, women with strain values in the 3rd quartile maintained a significant association with spontaneous preterm delivery at ≤34 weeks (OR 9.0; 95% CI, 1.1-74.0; P=0.02), whereas women with strain values in the highest quartile were marginally more likely than women with lowest quartile strain values to deliver spontaneously at ≤37 weeks of gestation (OR 95% CI: 2.8; [0.9-9.0]; P=0.08). Conclusion: Increased strain in the internal cervical os is associated with higher risk of spontaneous preterm delivery both at ≤34 and <37 weeks of gestation. [ABSTRACT FROM AUTHOR]

Objective: To determine the admission to delivery interval and the rate of immediate delivery in twin versus singleton gestation complicated by spontaneous preterm labor (SPTL). Methods: A retrospective cohort study of pregnant women presenting with advanced cervical dilatation of 3-5 cm and frequent uterine contractions at 24-34 weeks of gestation was performed. The rate of progression to delivery within 12 h and 24 h, as well as rates of prolonged latency, were compared between twins and singletons gestations. Results: Sixty-nine women were included, of which 25 carried twins and 44 singletons. The overall rate of spontaneous delivery within 12 h and 24 h was 47.8% and 59.4%, respectively, and similar between twins and singletons. Nevertheless, prolonged latency of 10 days or more after presentation was more frequent among twins compared with singletons [10/25 (40%) vs. 7/44 (15.9%), respectively; P=0.026]. Moreover, women carrying twins presenting with advanced cervical dilatation had a better chance of completing a full 2-dose antenatal betamethasone course compared with singletons [19/25 (76%) of twins compared with 21/44 (47.7%) of singletons, odds ratio 3.5, 95% confidence interval 1.16-10.34; P=0.022]. Conclusion: Up to 60% of women presenting with advanced cervical dilatation prior to 34 weeks' gestation give birth within 24 h. Nevertheless, women carrying twins have a better chance of completing a betamethasone course and having prolonged latency compared with singletons. [ABSTRACT FROM AUTHOR]

Objective: Our objective is to compare the efficacy of combination regimen (salbutamol and nifedipine) against single regimen (nifedipine alone) in preventing preterm births among women with preterm labor. Results: A total of 76 women with gestational age (GA) ranging from 24+0 to 35+6 weeks, who sought treatment for preterm labor with or without cervical dilatation, were recruited for the prospective cohort study. Of these, 38 (50%) had single tocolytic regimen and 38 (50%) had combination tocolytic regimen. The mean GAs at admission were similar for both groups at 31 weeks (±2.93) for Group 1 and 30.9 weeks (±2.88) for Group 2 (P=0.873). The mean GAs at delivery were 37.8 weeks (±1.98) for the single regimen and 36.2 weeks (±3.26) for the combined regimen (P=0.011). The mean tocolytic to delivery interval for the single regimen was longer at 6.74 weeks (±3.13) as compared with 5.21 weeks (±3.61) for the combination regimen (P<0.05). Those on the combination regimen complained of more adverse effects (P<0.001). Conclusion: Our study results suggested that the use of nifedipine as a single tocolytic regimen is as effective as the combination regimen in the delay of preterm births and has much less side effects. Hence, we recommend the sole use of nifedipine for the management of preterm labor. [ABSTRACT FROM AUTHOR]

Objective: The PartoSure™ time-to-delivery (TTD) test (AmniSure International, Boston, MA, USA) is a newly available bedside test for the prediction of time to spontaneous preterm delivery via the detection of placental alpha microglobulin-1. The objective of this study was to determine the efficacy of the test in predicting imminent delivery in 7 or 14 days from the time of testing. Methods: The study population consisted of 101 consecutively recruited pregnant women with singleton pregnancies between 20+0 and 36+6 weeks of gestation with symptoms of preterm labor, clinically intact amniotic membranes, and minimal cervical dilatation (≤3 cm). The PartoSure™ TTD test was performed on these patients and the test-to-spontaneous-delivery interval was calculated. Results: The PartoSure™ TTD test predicted spontaneous preterm delivery within 7 days with 90.0% sensitivity, 93.8% specificity, 97.4% negative predictive value (NPV), and 78.3% positive predictive value (PPV). The test predicted spontaneous preterm delivery within 14 days with 80% sensitivity, 96.1% specificity, 93.6% NPV, and 87.0% PPV. Conclusion: A positive PartoSure™ TTD test in patients presenting with symptoms of preterm labor, intact membranes, and minimal cervical dilatation (≤3 cm) indicated spontaneous preterm delivery will occur within 7 days with a high degree of accuracy. A negative result indicated that spontaneous preterm delivery within 14 days is highly unlikely. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to determine whether maternal plasma concentrations of soluble α-klotho are different between women with microbial invasion of the intra-amniotic cavity (MIAC) and those without MIAC among preterm labor and intact membranes (PTL) or preterm prelabor rupture of membranes (pPROM). Methods: A cross-sectional study was conducted to include women in the following groups: i) PTL with MIAC (n=14); ii) PTL without MIAC (n=79); iii) pPROM with MIAC (n=30); and iv) pPROM without MIAC (n=33). MIAC was defined as a positive amniotic fluid culture for microorganisms (aerobic/anaerobic bacteria or genital mycoplasmas). Amniotic fluid samples were obtained within 48 h of maternal blood collection. Plasma concentration of soluble α-klotho was determined by ELISA. Results: i) The median plasma concentration (pg/mL) of soluble α-klotho was significantly lower in patients with MIAC than in those without MIAC (787.0 vs. 1117.8; P<0.001). ii) Among patients with PTL, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (787.0 vs. 1138.9; P=0.007). iii) Among patients with pPROM, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (766.4 vs. 1001.6; P=0.045). iv) There was no significant difference in the median plasma concentration of soluble α-klotho between PPROM without MIAC and PTL without MIAC (1001.6 pg/mL vs. 1138.9 pg/mL, respectively; P=0.5). v) After adjustment for potential confounders (maternal age, tobacco use, gestational age at venipuncture), soluble α-klotho remained significantly associated with MIAC (P=0.02); and vi) Among patients without MIAC, smoking was significantly associated with a lower median plasma concentration soluble α-klotho than in non-smokers (794.2 pg/mL vs. 1382.0 pg/mL, respectively; P<0.001); however, this difference was not observed in patients with MIAC. Conclusions: Intra-amniotic infection occurring at preterm gestations (regardless of membrane status) was associated with a decrease in maternal plasma concentrations of soluble α-klotho. Moreover, among patients without infection, the plasma concentration of α-klotho was lower in smokers. [ABSTRACT FROM AUTHOR]

If maternal atopy and environmental exposure affect prenatal Th cell development, the maternal and fetal immune systems should display common Th1/Th2 phenotypes. To test this hypothesis, we studied maternal and neonatal blood samples from mothers with total serum IgE <300 IU/mL. Basal levels of IFN-γ, IL-4, and eotaxin in paired maternal and fetal sera were tightly correlated. Polyclonal T cell activation in vitro by Staphylococcal exotoxin B induced co-ordinate IFN-γ production from paired maternal and fetal mononuclear cells, accompanied by co-ordinate increases in activated CD4+CD69+ cells that display the CCR4+Th2 and CXCR3+ Th1 phenotypes. Maternal and fetal CD4+CXCR3+ T cells were subsequently identified as the major producers of IFN-γ. The data established that a transplacental nexus exists during normal pregnancy and that fetal Th cell responses may be biased by the maternal immune system. [ABSTRACT FROM AUTHOR]

Objective: The fetal inflammatory response syndrome (FIRS) is associated with impending onset of preterm labor/delivery, microbial invasion of the amniotic cavity and increased perinatal morbidity. FIRS has been defined by an elevated fetal plasma interleukin (IL)-6, a cytokine with potent effects on the differentiation and proliferation of hematopoietic precursors. The objective of this study was to characterize the hematologic profile of fetuses with FIRS. Study design: Fetal blood sampling was performed in patients with preterm prelabor rupture of membranes and preterm labor with intact membranes (n=152). A fetal plasma IL-6 concentration ≥11 pg/mL was used to define FIRS. Hemoglobin concentration, platelet count, total white blood cell (WBC) count, differential count, and nucleated red blood cell (NRBC) count were obtained. Since blood cell count varies with gestational age, the observed values were corrected for fetal age by calculating a ratio between the observed and expected mean value for gestational age. Results: 1) The prevalence of FIRS was 28.9% (44/152); 2) fetuses with FIRS had a higher median corrected WBC and corrected neutrophil count than those without FIRS (WBC: median 1.4, range 0.3-5.6, vs. median 1.1, range 0.4-2.9, P=0.001; neutrophils: median 3.6, range 0.1-57.5, vs. median 1.8, range 0.2-13.9, P<0.001); 3) neutrophilia (defined as a neutrophil count >95th centile of gestational age) was significantly more common in fetuses with FIRS than in those without FIRS (71%, 30/42, vs. 35%, 37/105; P<0.001); 4) more than two-thirds of fetuses with FIRS had neutrophilia, whereas neutropenia was present in only 4.8% (2/42); 5) FIRS was not associated with detectable changes in hemoglobin concentration, platelet, lymphocyte, monocyte, basophil or eosinophil counts; and 6) fetuses with FIRS had a median corrected NRBC count higher than those without FIRS. However, the difference did not reach statistical significance (NRBC median 0.07, range 0-1.3, vs. median 0.04, range 0-2.3, P=0.06). Conclusion: The hematologic profile of the human fetus with FIRS is characterized by significant changes in the total WBC and neutrophil counts. The NRBC count in fetuses with FIRS tends to be higher than fetuses without FIRS. [ABSTRACT FROM AUTHOR]

Objectives: Fetal neutrophilia is present in two-thirds of cases with the fetal inflammatory response syndrome (FIRS). The mechanisms responsible for this finding have not been elucidated. Granulocyte colony-stimulating factor (G-CSF) is the primary physiologic regulator of neutrophil production and plays a key role in the rapid generation and release of neutrophils in stressful conditions (i.e., infection). The objective of this study was to determine: 1) whether FIRS was associated with changes in fetal plasma G-CSF concentrations; and 2) if fetal plasma G-CSF concentrations correlated with fetal neutrophil counts, chorioamnionitis, neonatal morbidity/mortality and cordocentesis-to-delivery interval. Study design: Percutaneous umbilical cord blood sampling was performed in a population of patients with preterm labor (n=107). A fetal plasma interleukin-6 (IL-6) concentration >11 pg/mL was used to define FIRS. Cord blood G-CSF was measured by a sensitive and specific immunoassay. An absolute neutrophil count was determined and corrected for gestational age. Receiver operating characteristic (ROC) curve, survival analysis and Cox proportional hazard model were employed. Results: 1) G-CSF was detected in all fetal blood samples; 2) fetuses with FIRS had a higher median fetal plasma G-CSF concentration than those without FIRS (P<0.001); 3) a fetal plasma G-CSF concentration ≥134 pg/mL (derived from an ROC curve) was associated with a shorter cordocentesis-to-delivery interval, a higher frequency of chorioamnionitis (clinical and histological), intra-amniotic infection, and composite neonatal morbidity/mortality than a fetal plasma concentration below this cut-off; and 4) a fetal plasma G-CSF concentration ≥134 pg/mL was associated with a shorter cordocentesis-to-delivery interval (hazard ratio 3.2; 95% confidence interval 1.8-5.8) after adjusting for confounders. Conclusions: 1) G-CSF concentrations are higher in the peripheral blood of fetuses with FIRS than in fetuses without FIRS; and 2) a subset of fetuses with FIRS with elevated fetal plasma G-CSF concentrations are associated with neutrophilia, a shorter procedure-to-delivery interval, chorio-amnionitis and increased perinatal morbidity and mortality. [ABSTRACT FROM AUTHOR]

Aim: The association between infection and inflammatory response in preterm labor (PTL) is well established. Our aim was to elucidate the roles of utero-placental perfusion and fetal component, in PTL. Methods: Histopathologic findings in placentas from pregnancies complicated by preterm birth with or without premature rupture of membranes (ROM) (study group) were compared to placentas from pregnancies with delivery >34 weeks, with or without spontaneous ROM (control group). Placental lesions were classified as those consistent with maternal circulation abnormalities, maternal underperfusion, vascular or villous changes, and those consistent with fetal thrombo-occlusive disease, vascular or villous changes. Lesions were analyzed by maternal or fetal origin of inflammatory response. Results: The study group of 68 women, had a higher rate of vascular lesions than controls (136 women, 26.5% vs. 11%, P=0.005) and of inflammatory lesions of maternal and fetal origin (P<0.001). Within the study group, inflammatory lesions were more common in those with ruptured membrane than in those without (P<0.001). Conclusions: Placentas from preterm birth demonstrate vascular lesions of maternal origin, in addition to the known inflammatory process. Preterm premature membrane rupture is associated with an increased rate of inflammatory lesions relative to spontaneous intact membranes-preterm birth, suggesting a different underlying mechanism. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency and clinical significance of oligohydramnios in patients with preterm labor and intact membranes. Study design: An amniotic fluid index (AFI) was determined before amniocentesis (<24 h) in 272 patients with preterm labor and intact membranes (<35 weeks of gestation). Amniotic fluid (AF) was cultured for aerobic and anaerobic bacteria and genital mycoplasmas, and assayed for matrix metalloproteinase-8 (MMP-8). Non-parametric statistical techniques and survival analysis were used. Results: 1) The overall prevalence of oligohydramnios (AFI of ≤5 cm) in patients with preterm labor and intact membranes was 2.6% (7/272); 2) patients with oligohydramnios had a higher frequency of AF infection and/or inflammation than those without oligohydramnios [85.7% (6/7) vs. 32.8% (87/265); P<0.01]; 3) patients with oligohydramnios had a higher median AF MMP-8 concentration than those without oligohydramnios [median 664.2 (range 16.6-3424.7) ng/mL vs. median 2.3 (range <0.3-6142.6) ng/mL; P<0.01]; 4) women with preterm labor and oligohydramnios had a shorter interval to delivery than those without oligohydramnios [median 18 h (range 0-74 h) vs. median 311 h (range 0-3228 h); P<0.01], and this difference remained significant after adjusting for gestational age and the presence or absence of AF infection/inflammation. Conclusion: Patients with preterm labor and oligohydramnios are at increased risk for impending preterm delivery and intra-amniotic inflammation and, therefore, may benefit from careful surveillance. [ABSTRACT FROM AUTHOR]

Objectives: To assess the relationship between maternal and umbilical serum concentrations of matrix metalloproteinases (MMP)-2,8,9, the soluble receptor for advanced glycation end products (sRAGE) and IL-10 and premature delivery and fetal inflammation. Methods: Maternal serum levels of MMPs, sRAGE, IL-10 and C-reactive protein (CRP) were determined in 67 women with preterm labor and in 38 healthy pregnant women of similar gestational age (GA). In the group with preterm labor we also determined umbilical concentrations of MMPs, IL-6 and sRAGE. The group with preterm labor was additionally divided based on the presence of funisitis and elevations of fetal umbilical IL-6 concentrations. Results: Maternal serum levels of MMP-2 and sRAGE were significantly lower in women with preterm labor compared to women with normal pregnancy. Additionally, within the group of women with preterm labor, maternal serum MMP-2 concentrations were significantly lower in the subgroup with funisitis and in the subgroup with elevated umbilical concentration of IL-6. Conclusion: Our results demonstrate significantly different serum concentrations of MMP-2 and sRAGE in women with preterm labor compared to healthy pregnant patients of the same GA. [ABSTRACT FROM AUTHOR]

Objective: Idiopathic vaginal bleeding, a common complication of pregnancy, increases the risk of small-for-gestational age (SGA) neonate, preeclampsia and preterm delivery and can be the only clinical manifestation of intra-amniotic infection and/or inflammation (IAI). Placenta previa is thought to be protective against ascending intrauterine infection, yet an excess of histologic chorioamnionitis has been reported in this condition. The aim of this study was to determine the frequency and clinical significance of IAI in women with placenta previa and vaginal bleeding in the absence of preterm labor. Study design: A retrospective cohort study including 35 women with placenta previa and vaginal bleeding <37 weeks of gestation who underwent amniocentesis was undertaken. Patients with multiple gestations were excluded. Intra-amniotic infection was defined as a positive culture for microorganisms, and intra-amniotic inflammation as an elevated amniotic fluid interleukin (IL)-6 concentration. IL-6 concentrations were determined by ELISA in 28 amniotic fluid samples available. Non-parametric statistics were used for analysis. Results: 1) The prevalence of intra-amniotic infection was 5.7% (2/35), and that of IAI was 17.9% (5/28); 2) the gestational age at delivery was lower in patients with IAI than in those without IAI [29.4 weeks, interquartile range (IQR): 23.1–34.7 vs. 35.4 weeks, IQR: 33.9–36.9; P=0.028]; and 3) patients with placenta previa and IAI had a higher rate of delivery within 48 h (80% (4/5) vs. 19% (4/21); P=0.008) than those without IAI. Conclusions: Patients with placenta previa presenting with vaginal bleeding have intra-amniotic infection in 5.7% of the cases, and IAI in 17.9%. IAI in patients with placenta previa and vaginal bleeding is a risk factor for preterm delivery within 48 h. [ABSTRACT FROM AUTHOR]

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. The cohort consisted of 12,297 pregnancies, of which 196 had an IUD. Only singleton pregnancies were included. Logistic regression analysis was used to adjust for potential confounders between the groups. Results: 1) Pregnancies with an IUD were associated with a higher rate of late miscarriage, preterm delivery, vaginal bleeding, clinical chorioamnionitis, and placental abruption than those without an IUD; 2) among patients with available histologic examination of the placenta, the rate of histologic chorioamnionitis and/or funisitis was higher in patients with an IUD than in those without an IUD (54.2% vs. 14.7%; P<0.001). Similarly, among patients who underwent an amniocentesis, the prevalence of microbial invasion of the amniotic cavity (MIAC) was also higher in pregnant women with an IUD than in those without an IUD (45.9% vs. 8.8%; P<0.001); and 3) intra-amniotic infection caused by Candida species was more frequently present in pregnancies with an IUD than in those without an IUD (31.1% vs. 6.3%; P<0.001). Conclusion: Pregnant women with an IUD are at a very high risk for adverse pregnancy outcomes. This finding can be attributed, at least in part, to the high prevalence of intra-amniotic infection and placental inflammatory lesions observed in pregnancies with an IUD. [ABSTRACT FROM AUTHOR]

Objective: Recent observations have revealed an interaction between inflammation and angiogenesis, which may be mediated by angiopoietins and chemokines. Given the importance of inflammation in parturition, we sought to determine whether angiopoietin-2 (Ang-2) is present in amniotic fluid (AF) and if its concentration changes with gestational age, labor, and in intra-amniotic infection/inflammation (IAI) in patients with spontaneous preterm labor and intact membranes. Study design: This cross-sectional study included 486 patients in the following groups: 1) women in the mid-trimester of pregnancy (14–18 weeks) who underwent amniocentesis for genetic indications and delivered a normal neonate at term (n=52); 2) normal pregnant women at term with (n=48) and without (n=45) spontaneous labor; 3) patients with an episode of spontaneous preterm labor (PTL) and intact membranes who were classified into: a) PTL without IAI who delivered at term (n=152); b) PTL without IAI who delivered preterm (<37 weeks gestation; n=107); and c) PTL with IAI (n=82). Ang-2 concentration in AF was determined by enzyme-linked immunoassay. Non-parametric statistics were used for analysis. Results: 1) Ang-2 was detected in all AF samples; 2) the median AF Ang-2 concentration at term was significantly lower than that in the mid-trimester (1877.4 pg/mL vs. 3525.2 pg/mL; P<0.001); 3) among patients with PTL, the median AF Ang-2 concentration was significantly higher in patients with IAI than in those without IAI (4031.3 pg/mL vs. 2599.4 pg/mL; P<0.001) and those with PTL without IAI who delivered at term (4031.3 pg/mL vs. 2707.3 pg/mL; P<0.001); and 4) no significant differences were observed in the median AF Ang-2 concentration between patients with spontaneous labor at term and those at term not in labor (1722.9 pg/mL vs. 1877.4 pg/mL; P=0.6). Conclusions: 1) Ang-2, a protein involved in the process of vascular remodeling, is a physiologic constituent of the amniotic fluid and its concentration decreased with advancing gestation; 2) the median Ang-2 concentration in amniotic fluid is higher in patients with IAI than in those without; and 3) spontaneous parturition at term is not associated with changes in the AF concentration of Ang-2. These findings support the view of a link between angiopoietins and inflammation. [ABSTRACT FROM AUTHOR]

Aims: To identify risk factors for a short interval to birth in women with preterm labor, and to construct a statistical model to predict birth within seven days from the diagnosis of preterm labor at 22–35 weeks of gestation. Methods: Vaginal flora was obtained from 126 singleton pregnant women hospitalized for preterm labor at 22–35 weeks' gestation. The amount of vaginal large Gram-positive rods (GPR) was counted in a bright field under ×400 magnification and classified semiquantitively as loss of GPRs, decreased GPRs (<10), and normal flora (10 or more). The effects of vaginal GPRs, cervical dilatation, and previous history of preterm birth on the subsequent occurrence of birth were analyzed using proportional hazards model, and the effects on birth within seven days from the diagnosis of preterm labor were analyzed using multivariate logistic regression. Results: Fifty-four women (42.9%) delivered preterm. Both loss of GPRs and decreased GPRs were independent risk factors for a short interval from threatened preterm labor to birth, after adjusting the effect of cervical dilatation and past history of preterm birth (hazard ratio 3.4 [95% CI 2.0–5.5] and 2.0 [95% CI 1.1–3.6], respectively). Cervical dilatation of <4.0 cm and 2.0–3.9 cm, and past history of preterm birth were also independent risk factors for a short interval to birth. Loss of GPRs and decreased GPRs, and cervical dilatation of <4.0 cm and 2.0–3.9 cm were independently associated with birth within seven days from the diagnosis of preterm labor (OR 26 [95% CI 5.3–130], 11 [1.9–69], 76 [8.0–720], and 6.4 [1.5–27], respectively). Conclusions: Loss of GPRs and decreased GPRs may be independently important for developing birth in women with preterm labor. [ABSTRACT FROM AUTHOR]

Aims: To determine whether sonographic measurement of cervical length predicts intra-amniotic infection and impending preterm delivery (within 7 days of amniocentesis) in women with preterm labor and intact membranes, and to compare the predictability with that of amniotic fluid (AF) white blood cell (WBC) count. Methods: Transvaginal ultrasonographic assessment of cervical length was performed immediately after amniocentesis in 67 consecutive women with preterm labor. AF obtained by amniocentesis was cultured for aerobic and anaerobic bacteria and for Mycoplasmas, and WBC count was determined. Results: Patients with a positive AF culture had a significantly shorter median cervical length, higher median AF WBC count, and lower median gestational age at delivery than did those with a negative AF culture. Multivariate analysis indicated that only the AF WBC count bears a significant relationship with the presence of intra-amniotic infection, whereas only cervical length correlates with impending preterm delivery. Conclusions: Transvaginal sonographic measurements of cervical length are a valuable method for predicting intra-amniotic infection as well as impending preterm delivery in women with preterm labor. However, in comparison with AF WBC, cervical length is less predictive for intra-amniotic infection, whereas cervical length demonstrates better predictability of impending preterm delivery. [ABSTRACT FROM AUTHOR]

Objective: Visfatin, a novel adipokine originally discovered as a pre-B-cell colony enhancing factor, is expressed by amniotic epithelium, cytotrophoblast, and decidua and is over-expressed when fetal membranes are exposed to mechanical stress and/or pro-inflammatory stimuli. Visfatin expression by fetal membranes is dramatically up-regulated after normal spontaneous labor. The aims of this study were to determine if visfatin is detectable in amniotic fluid (AF) and whether its concentration changes with gestational age, spontaneous labor, preterm prelabor rupture of membranes (preterm PROM) and in the presence of microbial invasion of the amniotic cavity (MIAC). Methods: In this cross-sectional study, visfatin concentration in AF was determined in patients in the following groups: 1) mid-trimester (n=75); 2) term not in labor (n=27); 3) term in spontaneous labor (n=51); 4) patients with preterm labor with intact membranes (PTL) without MIAC who delivered at term (n=35); 5) patients with PTL without MIAC who delivered preterm (n=52); 6) patients with PTL with MIAC (n=25); 7) women with preterm PROM without MIAC (n=26); and 8) women with preterm PROM with MIAC (n=26). Non-parametric statistics were used for analysis. Results: 1) The median AF concentration of visfatin was significantly higher in patients at term than in mid-trimester; 2) Among women with PTL who delivered preterm, the median visfatin concentration was significantly higher in patients with MIAC than those without MIAC; 3) Similarly, patients with PTL and MIAC had a higher median AF visfatin concentration than those with PTL who delivered at term; 4) Among women with preterm PROM, the median AF visfatin concentration was significantly higher in patients with MIAC than those without MIAC. Conclusions: 1) Visfatin is a physiologic constituent of AF; 2) The concentration of AF visfatin increases with advancing gestational age; 3) AF visfatin concentration is elevated in patients with MIAC, regardless of the membrane status, suggesting that visfatin participates in the host response against infection. [ABSTRACT FROM AUTHOR]

Objective: The receptor for advanced glycation end products (RAGE) has been proposed to participate in the innate and adaptive immune responses. RAGE can induce production of pro-inflammatory cytokines and chemokines, as well as neutrophil chemotaxis in a manner that may be suppressed or stimulated by soluble, truncated forms of RAGE including the soluble form of RAGE (sRAGE) and endogenous secretory RAGE (esRAGE). The objective of this study was to determine whether intra-amniotic infection/inflammation (IAI) is associated with changes in the amniotic fluid concentration of sRAGE and esRAGE. Study design: Amniotic fluid (AF) was retrieved from patients in the following groups: 1) mid-trimester (14–18 weeks of gestation; n=68); 2) term not in labor (n=24); 3) term in labor (n=51); 4) preterm labor and intact membranes (n=124); and 5) preterm PROM (n=80). Intra-amniotic infection and inflammation were defined as the presence of a positive amniotic fluid culture for microorganisms and an AF interleukin-6 concentration ≥2.6 ng/mL, respectively. The AF concentration of sRAGE and esRAGE were determined using specific and sensitive ELISAs which measured total immunoreactive sRAGE and esRAGE, respectively. Patients were matched for gestational age at amniocentesis to compare the AF concentration of sRAGE and esRAGE in patients with and without IAI. Non-parametric statistics were used for analysis and a P<0.05 was considered significant. Results: 1) Patients at term not in labor had higher median AF concentrations of sRAGE and esRAGE than those in the mid-trimester (P<0.001 for both comparisons) and those at term in labor (P=0.03 and P=0.04, respectively); 2) patients with preterm labor and intact membranes with intra-amniotic infection/inflammation (IAI) had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.02 and P=0.005, respectively); 3) similarly, patients with preterm PROM with IAI had higher median AF concentrations of sRAGE and esRAGE than those without IAI (P=0.03 and P=0.02, respectively). Conclusion: Intra-amniotic infection/inflammation is associated with increased amniotic fluid concentrations of sRAGE and esRAGE. Changes in the amniotic fluid concentration of sRAGE and esRAGE may represent part of the immune response to intra-amniotic infection/inflammation. [ABSTRACT FROM AUTHOR]

Objective: The receptor for advanced glycation end products, RAGE, plays an important role in the pathogenesis of several diseases. sRAGE, soluble receptor for advanced glycation end products, is an inhibitor of the pathological effect mediated via RAGE. The aim of this study was to assess the usefulness of measuring sRAGE concentration in pregnant women with threatening preterm labor. Methods: Serum levels of sRAGE, interleukin-6 (IL-6) and routine markers of inflammation were determined in 46 pregnant women with threatening preterm labor, 35 healthy pregnant women and 15 non-pregnant controls. Results: Serum levels of sRAGE in healthy pregnant women were significantly lower than in non-pregnant controls (669±296 vs. 1929±727 pg/mL, P<0.05). Women with threatening preterm birth had a significantly higher concentration of serum sRAGE in comparison with healthy pregnant women (819±329 pg/mL vs. 669±296 pg/mL, P<0.05). Conversely, patients with PPROM had significantly lower levels of sRAGE compared with patients with threatening premature labor (600±324 pg/mL, P<0.05). sRAGE correlated negatively with leukocyte counts (r=−0.325, P<0.05). Conclusions: sRAGE might be a new and promising marker of premature labor, especially with the symptoms of PPROM. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of atosiban with usual management of threatened preterm labor. Methods: In this prospective, open-label, randomized controlled trial, women admitted to the hospital in threatened preterm labor (between 24 and 34 weeks' gestation) were randomized to receive atosiban or usual care (β-agonists, calcium channel blockers, magnesium sulphate, or any other tocolytic, alone or in combination, and/or bed rest). Results: In women randomized to receive atosiban (n=295) or usual care (n=290), significantly more women receiving atosiban remained undelivered at 48 h with no alternative tocolytic compared with usual care (77.6% vs. 56.6%; P<0.001). The proportion of women remaining undelivered after 48 h was comparable between the treatment groups. However, more women in the atosiban group required no additional tocolytics (85.1% vs. 62.8%; P<0.001). Maternal and fetal safety was significantly superior with atosiban. Neonatal safety was comparable. Conclusions: These findings support the use of atosiban to delay preterm birth and are consistent with previously conducted, randomized, controlled trials. Atosiban was associated with fewer maternal and fetal adverse events compared with other tocolytics, and presented no safety concerns for either the mother or the unborn baby. [ABSTRACT FROM AUTHOR]

Aims: Nifedipine is believed to be a superior tocolytic agent on the basis of efficacy and side-effect profile, but was never prospectively evaluated in a placebo-controlled randomized clinical trial (RCT). In our study, we sought to identify limitations in participation for a would-be RCT comparing nifedipine to placebo. Methods: A prospective feasibility study was conducted at Ste-Justine Hospital, a tertiary care center, on women between 24 and 34 weeks' gestation, presenting to the labor and delivery room with obstetrical complaints. Patient information was collected and would-be participants were identified on the basis of pre-established clinical and ultrasound criteria as well as on willingness to participate, as determined by the study research nurse. Results: During a 6-month period, 483 women presenting with signs and symptoms of preterm labor (PTL) were eligible for further evaluation. A total of 321 (66.5%) women were excluded for obstetrical and medical reasons whereas 125 (25.9%) did not meet strict inclusion criteria (cervical length <25 mm or positive fetal fibronectin). When using strict criteria, only 37 women (7.6%) were found to be eligible for study participation. Subject willingness to participate as assessed by the research nurse was 50%. Conclusions: If adhering to strict inclusion/exclusion criteria, the feasibility of an appropriately sampled RCT testing tocolytic therapy against a placebo would require a large concerted multicenter effort to meet sample size demands. [ABSTRACT FROM AUTHOR]

The major burden of preterm birth is in the developing world, where much of the death and morbidity is secondary to infectious diseases such as malaria, HIV, tuberculosis and intestinal parasites. There is some evidence to support the concept that normal gestational length varies with ethnic group; babies of black African ancestry tend to be born earlier, more commonly pass meconium in labor, but have less respiratory distress than white European babies of matched gestational age. However, ethnic differences are tiny compared with the effects of infectious disease and malnutrition. Interventions to prevent preterm birth should predominantly be aimed at the prevention and treatment of infectious disease, and the improvement of maternal nutrition. Without this, medical intervention tends to increase the rate of preterm birth without corresponding improvement in outcomes. [ABSTRACT FROM AUTHOR]

Objective: The complement system plays a central role in the first line of defense against invading pathogens, and its activation involves the release of potent pro-inflammatory mediators such as anaphylatoxins C3a, C4a and C5a. The aim of this study was to determine whether differences existed in maternal plasma anaphylatoxin concentrations between patients with term and preterm parturition. Study design: A cross-sectional study was designed to determine the plasma anaphylatoxin concentrations in 296 pregnant women in the following groups: 1) normal pregnancy between 20-36 6/7 weeks (n=64); 2) term not in labor (n=70); 3) term in labor (n=60); and 4) preterm labor with intact membranes (n=102). Women with preterm labor were classified into: a) term delivery (n=24); b) preterm delivery without intra-amniotic infection (IAI) (n=62); and c) preterm delivery with IAI (n=16). Concentrations of C3a, C4a and C5a were determined by ELISAs. Statistical analysis was conducted with nonparametric methods. Results: 1) The median plasma C5a concentration was lower in women at term in labor than in those not in labor (P<0.001). In contrast, there were no differences in plasma C3a and C4a concentrations between the two groups (P>0.05). 2) Among patients with preterm labor, those with IAI had a higher median plasma C5a concentration than those without IAI and those who delivered at term (post-hoc tests P<0.001 and P=0.01, respectively). When comparing the preterm labor subgroups with normal pregnancy, only women with preterm delivery and IAI had a median plasma C5a concentration higher than that of normal pregnant women (Kruskal-Wallis P<0.001, post hoc test P<0.001). There was no difference in the plasma C4a concentration among patients with preterm labor. The median plasma C3a concentration in patients with preterm labor with IAI was higher than in those without IAI (Kruskal-Wallis P=0.01, and post-hoc test P=0.005). There was no difference in the plasma C3a concentrations between women with preterm labor who delivered at term and those with preterm delivery, with or without IAI. In addition, no differences were observed in the median plasma C3a concentration between women with normal pregnancy and those in each of the preterm labor subgroups. Conclusions: The maternal plasma concentration of anaphylatoxin C5a is increased in women with preterm labor and IAI, but not in spontaneous labor at term. [ABSTRACT FROM AUTHOR]

Functional genomics (transcriptomics and proteomics) is a global, systematic and comprehensive approach to the identification and description of the processes and pathways involved in normal and abnormal physiological states. The functional genomics methods most applied today are DNA microarrays and proteomics methods, primarily two-dimensional gel electrophoresis coupled with mass spectrometry. To date, interesting research has been carried out, representing milestones for future implementation of functional genomics/proteomics in perinatal medicine. For instance, possible biomarkers of pre-eclampsia, preterm labor and gestational trophoblastic diseases have been discovered. Further systematic examination of differentially regulated genes and proteins in maternal and fetal tissues and fluids will be required. However, high-throughput technologies reflect biological fluctuations and methodological errors. Large amounts of such different data challenge the performance and capacity of the statistical tools and software available at present. Further major developments in this field are pending and the intellectual investment will certainly result in clinical advances. [ABSTRACT FROM AUTHOR]

Inflammatory cytokines are involved in both preterm labor and preterm premature of the membranes pathways; however, the interaction between TNF-α and its receptors may dictate the clinical outcome of pregnancy. [ABSTRACT FROM AUTHOR]

Aim: Premature birth is the single largest cause of perinatal mortality and morbidity in non-anomalous infants in all developed nations. The aim of this study is to survey the role of glucocorticoid therapy in decreasing early neonatal complications in preterm delivery. Methods: A case control study was carried out on 300 preterm labors. Half the women received one to four 6 mg doses of dexamethasone every 6 hours, depending on the interval between admission and delivery. Neonatal complications were compared between the two groups. Results: Corticosteroid therapy was observed to have the greatest effect in preventing respiratory distress and neonatal mortality between 29-34 gestational weeks. There was a significant relationship between antenatal corticosteroid therapy interval and mortality of preterm neonates. Complications such as respiratory distress, sepsis, pneumonia, and hyperbilirubinemia were significantly lower in the case group than in the control. Conclusion: It is recommended that all women at high risk for preterm labor before 35 gestational weeks be given glucocorticoid at least 24 hours before delivery in order to markedly reduce neonatal mortality and morbidity. [ABSTRACT FROM AUTHOR]

Objectives: The maternal-fetal genotypes (MFG) interaction influences on intrauterine development, phenotype formation of the offspring and their diseases risk in the postnatal period. GSTT1, GSTM1, GSTP1 genes of glutation-S-transferases (GSTs) family were analyzed only in the case of neonanal pathologies and premature birth risk in neonates or pregnant. GSTs genes expressions affect the antioxidant defense and metabolism of various toxins in many pathways. The presence of GSTT1(deletion), GSTM1(deletion), GSTP1(313A/G or 313G/G) variants and their combinations reduces the antioxidant defense at any ontogenesis stage since intrauterine development, but their interaction has not been studied for preterm labour. The aim of the study was to determine the influence of MFG interaction on the risk of preterm labor. Methods: Inclusion criteria study were preterm labor at 24-32 weeks in pregnant without extragenital diseases and uncomplicated pregnancy course. Exclusion criteria were the presence of malformations and neonatal pathologies in offspring. Mother-neonate pairs were divided into groups depending of gestational age: group 1- 24-27 weeks (13 cases); and group 2 - 28-32 weeks (10 cases). GSTT1(deletion/allele), GSTM1(deletion/allele), GSTP1(313A/G) polymorphic variants tested using multiplex PCR and PCR-RFLP methods. Statistical analysis of genotypes frequencies (xisquare test) and MFG interaction (MDR program version 3.0.2) between comparative groups was done. Results: The frequencies of investigated genotypes did not differ between groups among mothers and neonates and population spreads. Only 2 reliable predictive models were identified using MDR method of MFG interaction in preterm labor risk. A model with better prognostic value demonstrated that the fetal genotype of all investigated genes had significant effect on preterm labor at 24-27 weeks (Figure 1). MFG genotypes combinations in pairs showed increased frequencies of GSTT1(deletion), GSTM1(deletion), GSTP1(313A/G or 313G/G) variants among the pairs of group 1compared to group 2 (77% and 53%, respectively). Conclusion: Further studies are needed to confirm these results. It is possible to predict preterm labor based on information about parents' genotypes and the possible results of non-invasive diagnostics. The use of nutrients with antioxidant protection in pregnant women will help reduce preterm labor. [ABSTRACT FROM AUTHOR]