Preterm Rupture Of The Membranes Research Articles

Circulating Cell-Free Mitochondrial DNA as a Novel Biomarker for Intra-Amniotic Infection in Obstetrics: A Pilot Trial.

Background/Objectives: Intra-amniotic infection (IAI) is a rare but serious condition with potential complications such as preterm labor and intrauterine fetal death. Diagnosing IAI is challenging due to varied clinical signs. Oxidative stress and mitochondrial dysfunction have been hypothesized to evolve around IAI. This study focused on measuring circulating mtDNA levels, a proposed biomarker for mitochondrial dysfunction, in maternal serum and placenta of women with confirmed IAI and healthy controls. Methods: 12 women with confirmed IAI (IAI group) were enrolled following premature preterm rupture of the membranes (PPROM) and compared to 21 healthy women (control group). Maternal blood was obtained two weeks pre-partum and peripartum; furthermore, postpartum placental blood was taken. In the IAI group, maternal blood was taken once weekly until delivery as well as peripartum, as was placental blood. Circulating cell-free mtDNA was quantified by real-time quantitative PCR. Results: Upon admission, in the IAI group, mean plasma mtDNA levels were 735.8 fg/μL compared to 134.0 fg/μL in the control group (p < 0.05). After delivery, in the IAI group, mean mtDNA levels in the placenta were 3010 fg/μL versus 652.4 fg/μL (p < 0.05). Conclusions: Circulating cell-free mtDNA could serve as a valuable biomarker for IAI prediction and diagnosis. Future research should establish reference values for sensitivity in predicting IAI.

Placental multimodal MRI prior to spontaneous preterm birth

To utilise combined diffusion-relaxation MRI techniques to interrogate antenatal changes in the placenta prior to extreme preterm birth among both women with PPROM and membranes intact, and compare this to a control group who subsequently delivered at term. Observational study. Tertiary Obstetric Unit, London, UK. Cases: pregnant women who subsequently spontaneously delivered a singleton pregnancy prior to 32 weeks' gestation without any other obstetric complications. pregnant women who delivered an uncomplicated pregnancy at term. All women consented to an MRI examination. A combined diffusion-relaxation MRI of the placenta was undertaken and analysed using fractional anisotropy, a combined T2*-apparent diffusion coefficient model and a combined T2*-intravoxel incoherent motion model, in order to provide a detailed placental phenotype associated with preterm birth. Subgroup analyses based on whether women in the case group had PPROM or intact membranes at time of scan, and on latency to delivery were performed. Fractional anisotropy, apparent diffusion coefficients and T2* placental values, from two models including a combined T2*-IVIM model separating fast- and slow-flowing (perfusing and diffusing) compartments. This study included 23 women who delivered preterm and 52 women who delivered at term. Placental T2* was lower in the T2*-apparent diffusion coefficient model (p < 0.001) and in the fast- and slow-flowing compartments (p = 0.001 and p < 0.001) of the T2*-IVIM model. This reached a higher level of significance in the preterm prelabour rupture of the membranes group than in the membranes intact group. There was a reduced perfusion fraction among the cases with impending delivery. Placental diffusion-relaxation reveals significant changes in the placenta prior to preterm birth with greater effect noted in cases of preterm prelabour rupture of the membranes. Application of this technique may allow clinically valuable interrogation of histopathological changes before preterm birth. In turn, this could facilitate more accurate antenatal prediction of preterm chorioamnionitis and so aid decisions around the safest time of delivery. Furthermore, this technique provides a research tool to improve understanding of the pathological mechanisms associated with preterm birth invivo.

Chemokine and cytokine profiles in preterm and term labor, in preterm prelabor rupture of the membranes, and in normal pregnancy

The objective of this study was to investigate the immune mechanisms involved in preterm labor (PTL), preterm prelabor rupture of the membranes (PPROM), and normal pregnancies. The second objective was to explore immune profiles in PTL for association with early ( < 34 gestational weeks (gw)) or instant ( < 48 h) delivery.This prospective observational multi-center study included women with singleton pregnancies with PTL (n = 80) or PPROM (n = 40) before 34 gw, women with normal pregnancies scheduled for antenatal visits (n = 44), and women with normal pregnancies in active labor at term (n = 40). Plasma samples obtained at admission were analyzed for cytokine and chemokine quantification using a multiplex bead assay in order to compare the immune profiles between PTL, PPROM, and normal pregnancies.In PTL, CXCL1 and CCL17 were significantly higher compared to gestational age-matched women at antenatal visits, whereas for PPROM, CXCL1 and IL-6 were increased. Women in term labor had a more pronounced inflammatory pattern with higher levels of CXCL1, CXCL8, and IL-6 compared with PTL (p = 0.007, 0.003, and 0.013, respectively), as well as higher levels of CCL17, CXCL1 and IL-6 (all p < 0.001) compared with the women at antenatal visits. In PTL, CXCL8 was higher in women with delivery before 34 gw, whereas CXCL8, GM-CSF, and IL-6 were significantly higher in women with delivery within 48 h.To conclude, PTL and PPROM were associated with a complex pattern of inflammation, both involving Th17 (CXCL1) responses. Although further studies are needed, CXCL8, GM-CSF, and IL-6 may be potential candidates for predicting preterm birth in PTL.

National registry of thoracoamniotic shunting using a double-basket catheter: A post-marketing surveillance registry of 295 patients with fetal hydrothorax.

We report on the 1-year outcomes of fetuses who underwent thoracoamniotic shunting (TAS) with a double-basket catheter for fetal hydrothorax (FHT) using a national post-marketing surveillance registry. This surveillance study was conducted for cases enrolled between 2011 and 2019. Preoperative, operative, and postoperative findings and outcomes had to be reported through the national surveillance website. Forty-three institutes enrolled 295 patients. In 60 patients, associated abnormalities were diagnosed after birth. Among the 235 patients with isolated hydrothorax, the survival rate at 1year of age was 70.5%. Among these patients, 89% did not require oxygen or other respiratory support. The 1-year survival rate in complicated cases was 27%. Trisomy 21 was the most common associated problem (40%). Catheter associated problems, including dislocation (25%), obstruction (24%), and preterm rupture of the membranes (6%) were observed, but there were no severe maternal complications. TAS before 29.5weeks of gestation (odds ratio [OR] 0.16) and skin edema and ascites (OR 0.06) were risk factors for death at one year, whereas appropriate shunt location for >28days (OR 4.2) was a protective factor. We report a favorable survival rate in fetuses with isolated FHT treated with this double-basket catheter.

New radiofrequency ablation procedure for selective reduction in complicated monochorionic twin or triplet pregnancy using multistep, incremental expansion technique.

Radiofrequency ablation (RFA) is the preferred approach for selective reduction in complex monochorionic (MC) multiple pregnancies owing to the ease of operation and minimal invasiveness. To optimize the RFA technique and reduce the risk of adverse pregnancy outcome resulting from the heat-sink effect of RFA therapy, we used an innovative RFA method, in which an electrode needle was expanded incrementally and stepwise. This study aimed to assess the efficacy and safety profile of this novel multistep incremental expansion RFA method for selective fetal reduction in MC twin and triplet pregnancies. This was a single-center retrospective cohort study of all MC multiple pregnancies undergoing RFA between March 2016 and October 2022 at our center. The multistep RFA technique involved the use of an expandable needle, which was gradually expanded during the RFA procedure until cessation of umbilical cord blood flow was achieved. The needle used for the single-step RFA method was fully extended from the start of treatment. In total, 132 MC multiple pregnancies underwent selective reduction using RFA, including 50 cases undergoing multistep RFA and 82 cases undergoing single-step RFA. The overall survival rates were not significantly different between the multistep and single-step RFA groups (81.1% vs 72.3%; P = 0.234). Similarly, the rates of preterm prelabor rupture of the membranes within 2 weeks after RFA, procedure-related complications, spontaneous preterm delivery and pathological findings on cranial ultrasound, as well as gestational age at delivery and birth weight, did not differ between the two groups. However, there was a trend towards a prolonged procedure-to-delivery interval following multistep RFA compared with single-step RFA (median, 109 vs 99 days; P = 0.377). Moreover, the fetal loss rate within 2 weeks after RFA in the multistep RFA group was significantly lower than that in the single-step RFA group (10.0% vs 24.4%; P = 0.041). The median ablation time was shorter (5.3 vs 7.8 min; P < 0.001) and the median ablation energy was lower (10.2 vs 18.0 kJ; P < 0.001) in multistep compared with single-step RFA. There were no significant differences in neonatal outcomes following multistep vs single-step RFA. Overall survival rates were similar between the two RFA methods. However, the multistep RFA technique was associated with a lower risk of fetal loss within 2 weeks after RFA. The multistep RFA technique required significantly less ablation energy and a shorter ablation time compared with single-step RFA in selective fetal reduction of MC twin and triplet pregnancies. Additionally, there was a trend towards a prolonged procedure-to-delivery interval with the multistep RFA technique. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Feto-Maternal Interface Organ-on-Chip: A New Technology to Study Ascending Infection.

Modeling human pregnancy is challenging as two subjects, the mother and fetus, must be evaluated in tandem. To understand pregnancy, parturition, and adverse pregnancy outcomes, the two feto-maternal interfaces (FMi) that form during gestation (i.e., the placenta and fetal membrane) need to be investigated to understand their biological roles, and organ dysfunction can lead to adverse outcomes. Adverse pregnancy outcomes such as preterm rupture of the membranes, spontaneous preterm birth, preeclampsia, intra-uterine growth restriction, and gestational diabetes rates are on the rise worldwide, highlighting the need for future studies and a better understanding of molecular and cellular pathways that contribute to disease onset. Current in vivo animal models nor in vitro cell culture systems can answer these questions as they do not model the function or structure of human FMis. Utilizing microfabrication and soft-lithography techniques, microfluidic organ-on-chip (OOC) devices have been adapted by many fields to model the anatomy and biological function of complex organs and organ systems within small in vitro platforms.These techniques have been adapted to recreate the fetal membrane FMi (FMi-OOC) using immortalized cells and collagen derived from patient samples. The FMi-OOC is a four-cell culture chamber, concentric circle system, that contains both fetal (amniochorion) and maternal (decidua) cellular layers and has been validated to model physiological and pathological states of pregnancy (i.e., ascending infection, systemic oxidative stress, and maternal toxicant exposure). This platform is fully compatible with various analytical methods such as microscopy and biochemical analysis. This protocol will outline this device's fabrication, cell loading, and utility to model ascending infection-related adverse pregnancy outcomes.

Spatial transcriptomics of fetal membrane-Decidual interface reveals unique contributions by cell types in term and preterm births.

During pregnancy, two fetomaternal interfaces, the placenta-decidua basalis and the fetal membrane-decidua parietals, allow for fetal growth and maturation and fetal-maternal crosstalk, and protect the fetus from infectious and inflammatory signaling that could lead to adverse pregnancy outcomes. While the placenta has been studied extensively, the fetal membranes have been understudied, even though they play critical roles in pregnancy maintenance and the initiation of term or preterm parturition. Fetal membrane dysfunction has been associated with spontaneous preterm birth (PTB, < 37 weeks gestation) and preterm prelabor rupture of the membranes (PPROM), which is a disease of the fetal membranes. However, it is unknown how the individual layers of the fetal membrane decidual interface (the amnion epithelium [AEC], the amnion mesenchyme [AMC], the chorion [CTC], and the decidua [DEC]) contribute to these pregnancy outcomes. In this study, we used a single-cell transcriptomics approach to unravel the transcriptomics network at spatial levels to discern the contributions of each layer of the fetal membranes and the adjoining maternal decidua during the following conditions: scheduled caesarian section (term not in labor [TNIL]; n = 4), vaginal term in labor (TIL; n = 3), preterm labor with and without rupture of membranes (PPROM; n = 3; and PTB; n = 3). The data included 18,815 genes from 13 patients (including TIL, PTB, PPROM, and TNIL) expressed across the four layers. After quality control, there were 11,921 genes and 44 samples. The data were processed by two pipelines: one by hierarchical clustering the combined cases and the other to evaluate heterogeneity within the cases. Our visual analytical approach revealed spatially recognized differentially expressed genes that aligned with four gene clusters. Cluster 1 genes were present predominantly in DECs and Cluster 3 centered around CTC genes in all labor phenotypes. Cluster 2 genes were predominantly found in AECs in PPROM and PTB, while Cluster 4 contained AMC and CTC genes identified in term labor cases. We identified the top 10 differentially expressed genes and their connected pathways (kinase activation, NF-κB, inflammation, cytoskeletal remodeling, and hormone regulation) per cluster in each tissue layer. An in-depth understanding of the involvement of each system and cell layer may help provide targeted and tailored interventions to reduce the risk of PTB.

SFM Fetal Therapy Practice Guidelines: Fetoscopic Laser Photocoagulation in Monochorionic Twins

AbstractFetoscopic laser coagulation is offered as a method of treatment for twin-to-twin transfusion syndrome or twin anemia polycythemia sequence. It involves laser ablation of intercommunicating superficial blood vessels on the surface of the placenta, under sono-endoscopic control. Preterm labor and preterm prelabor rupture of the membranes are known complications. The results depend on the expertise of the surgeon, location of the placenta, indication for treatment, severity of disease, and growth of babies. The chances of both babies surviving are around 65% and one baby surviving is 85%.

Ambulation for latency during expectant management of preterm prelabor rupture of membranes: a randomized controlled trial (AMBLE)

BackgroundIndividuals hospitalized with preterm prelabor rupture of the membranes (PPROM) are often advised to limit their activity or adhere to bedrest. Some evidence suggests that greater activity is associated with longer latency and improved outcomes, but no high-quality evidence from a randomized-controlled trial exists. ObjectiveTo evaluate whether encouragement to ambulate at least 2,000 steps daily impacts latency among individuals with PPROM compared with usual care. Study DesignMultisite unblinded, two-arm randomized trial of individuals at 23 0/7 to 35 0/7 weeks gestation undergoing inpatient expectant management of PPROM with planned delivery at least 7 days away. Each participant wore a Fitbit InspireTM that tracked steps. The intervention arm was encouraged (verbal and Fitbit-based reminders) to reach a goal of 2,000 steps per day. The usual care arm was allowed ad lib activity with no step goal or reminders. The primary outcome was latency (days) from randomization to delivery. Secondary analyses included composite neonatal and maternal clinical outcomes and maternal mental health survey results. Statistical analyses were intent-to-treat under a Bayesian framework using neutral priors (a priori assumed 50:50 likelihood of longer latency in either arm). 100 participants were required to have 80% power to demonstrate a 4-day difference in latency with 75% certainty (Bayesian probability). ResultsAmong 163 eligible individuals, 100 (61%) were randomized, and after loss to follow-up, 95 were analyzed. Gestational age at randomization was 29 3/7 weeks (interquartile range [IQR] 26 2/7, 31 5/7) in the intervention arm and 27 4/7 weeks (IQR 25 4/7, 29 6/7) in the usual care arm. Median step counts were 1,690/day in the intervention arm (IQR 1,031-2,641) and 1,338/day in the usual care arm (IQR 784-1,913). Median days of latency were 9 days in the intervention arm (IQR 4-17) and 6 days in the usual care arm (IQR 2-14). The primary analysis indicated a 65% posterior probability that the intervention increased latency versus usual care (posterior relative risk [RR] 1.09; 95% credible interval [CrI], 0.70-1.71). The RR for composite neonatal adverse outcome was 0.55 (95% CrI 0.32-0.82) with 99% posterior probability of intervention benefit and for composite maternal adverse outcome was 0.94 (95% CrI 0.72-1.20), with 70% posterior probability of intervention benefit. There was a 94% posterior probability of the intervention arm having a greater decrease in maternal stress score from baseline to before delivery compared with the usual care arm (mean arm difference 3.24 points [95% CrI -7.23-0.79]). Adjustment for gestational age at randomization had minimal impact on secondary outcome results. ConclusionsIndividuals with PPROM randomized to encouragement to ambulate had a longer latency to delivery and improved neonatal and mental health outcomes with similar maternal clinical outcomes compared to usual care.

Cx43 regulates mechanotransduction mechanisms in human preterm amniotic membrane defects.

The effects of mechanical stimulation in preterm amniotic membrane (AM) defects were explored. Preterm AM was collected from women undergoing planned preterm caesarean section (CS) due to fetal growth restriction or emergency CS after spontaneous preterm prelabour rupture of the membranes (sPPROM). AM explants near the cervix or placenta were subjected to trauma and/or mechanical stimulation with the Cx43 antisense. Markers for nuclear morphology (DAPI), myofibroblasts (αSMA), migration (Cx43), inflammation (PGE2 ) and repair (collagen, elastin and transforming growth factor β [TGFβ1 ]) were examined by confocal microscopy, second harmonic generation, qPCR and biochemical assays. In preterm AM defects, myofibroblast nuclei were highly deformed and contractile and expressed αSMA and Cx43. Mechanical stimulation increased collagen fibre polarisation and the effects on matrix markers were dependent on tissue region, disease state, gestational age and the number of fetuses. PGE2 levels were broadly similar but reduced after co-treatment with Cx43 antisense in late sPPROM AM defects. TGFβ1 and Cx43 gene expression were significantly increased after trauma and mechanical stimulation but this response dependent on gestational age. Mechanical stimulation affects Cx43 signalling and cell/collagen mechanics in preterm AM defects. Establishing how Cx43 regulates mechanosignalling could be an approach to repair tissue integrity after trauma.

Cervical cerclage for prevention of preterm birth and adverse perinatal outcome in twin pregnancies with short cervical length or cervical dilatation: A systematic review and meta-analysis.

The optimal approach to prevent preterm birth (PTB) in twins has not been fully established yet. Recent evidence suggests that placement of cervical cerclage in twin pregnancies with short cervical length at ultrasound or cervical dilatation at physical examination might be associated with a reduced risk of PTB. However, such evidence is based mainly on small studies thus questioning the robustness of these findings. The aim of this systematic review was to determine the role of cervical cerclage in preventing PTB and adverse maternal or perinatal outcomes in twin pregnancies. Key databases searched and date of last search: MEDLINE, Embase, and CINAHL were searched electronically on 20 April 2023. Eligibility criteria: Inclusion criteria were observational studies assessing the risk of PTB among twin pregnancies undergoing cerclage versus no cerclage and randomized trials in which twin pregnancies were allocated to cerclage for the prevention of PTB or to a control group (e.g., placebo or treatment as usual). The primary outcome was PTB <34 weeks of gestation. The secondary outcomes were PTB <37, 32, 28, 24 weeks of gestation, gestational age at birth, the interval between diagnosis and birth, preterm prelabor rupture of the membranes (pPROM), chorioamnionitis, perinatal loss, and perinatal morbidity. Subgroup analyses according to the indication for cerclage (short cervical length or cervical dilatation) were also performed. Risk of bias assessment: The risk of bias of the included randomized controlled trials (RCTs) was assessed using the Revised Cochrane risk-of-bias tool for randomized trials, while that of the observational studies using the Newcastle-Ottawa scale (NOS). Statistical analysis: Summary risk ratios (RRs) of the likelihood of detecting each categorical outcome in exposed versus unexposed women, and (b) summary mean differences (MDs) between exposed and unexposed women (for each continuous outcome), with their 95% confidence intervals (CIs) were computed using head-to-head meta-analyses. Synthesis of the results: Eighteen studies (1,465 twin pregnancies) were included. Placement of cervical cerclage in women with a twin pregnancy with a short cervix at ultrasound or cervical dilatation at physical examination was associated with a reduced risk of PTB <34 weeks of gestation (RR: 0.73, 95% CI [0.59, 0.91], p = 0.005 corresponding to a 16% difference in the absolute risk, AR), <32 (RR: 0.69, 95% CI [0.57, 0.84], p < 0.001; AR: 16.92%), <28 (RR: 0.54, 95% [CI 0.43, 0.67], 0.001; AR: 18.29%), and <24 (RR: 0.48, 95% CI [0.23, 0.97], p = 0.04; AR: 15.57%) weeks of gestation and a prolonged gestational age at birth (MD: 2.32 weeks, 95% [CI 0.99, 3.66], p < 0.001). Cerclage in twin pregnancy with short cervical length or cervical dilatation was also associated with a reduced risk of perinatal loss (RR: 0.38, 95% CI [0.25, 0.60], p < 0.001; AR: 19.62%) and composite adverse outcome (RR: 0.69, 95% CI [0.53, 0.90], p = 0.007; AR: 11.75%). Cervical cerclage was associated with a reduced risk of PTB <34 weeks both in women with cervical length <15 mm (RR: 0.74, 95% CI [0.58, 0.95], p = 0.02; AR: 29.17%) and in those with cervical dilatation (RR: 0.68, 95% CI [0.57, 0.80], p < 0.001; AR: 35.02%). The association between cerclage and prevention of PTB and adverse perinatal outcomes was exclusively due to the inclusion of observational studies. The quality of retrieved evidence at GRADE assessment was low. Emergency cerclage for cervical dilation or short cervical length <15 mm may be potentially associated with a reduction in PTB and improved perinatal outcomes. However, these findings are mainly based upon observational studies and require confirmation in large and adequately powered RCTs.

Googling preterm prelabour rupture of the membranes: A systematic review of patient information available on the internet.

Preterm prelabour rupture of the membranes (PPROM) complicates 3% of pregnancies and is associated with an increased risk of maternal and perinatal morbidity and mortality. In an attempt to better understand this diagnosis, patients routinely resort to the internet for medical information. The lack of governance online leaves patients at risk of relying on low-quality websites. To assess systematically the accuracy, quality, readability and credibility of World Wide Web pages on PPROM. Five search engines (Google, AOL, Yahoo, Ask and Bing) were searched with location services and browser history disabled. Websites from the first page of all searches were included. Websites were included if they provided at least 300 words of health information aimed at patients relating to PPROM. Validated assessments of health information readability, credibility and quality were undertaken, as was an accuracy assessment. Pertinent facts for accuracy assessment were based on feedback from healthcare professionals and patients through a survey. Characteristics were tabulated. In all, 39 websites were included, with 31 different texts. No pages were written with a reading age of 11 years or less, none were considered credible, and only three were high quality. An accuracy score of 50% or more was obtained by 45% of websites. Information that patients considered pertinent was not consistently reported. Search engines produce information on PPROM that is low quality, low accuracy and not credible. It is also difficult to read. This risks disempowerment. Healthcare professionals and researchers must consider how to ensure patients have access to information that they can recognise as high quality.

Bayesian post-hoc analysis of cerclage retention versus removal in preterm prelabor rupture of the membranes

To estimate the probability of benefit/harm for cerclage retention compared to removal on prolongation of pregnancy and chorioamnionitis in the presence of a cervical cerclage and subsequent preterm prelabor rupture of the membranes (PPROM) using a Bayesian framework.

Epithelial to mesenchymal transition (EMT) of feto-maternal reproductive tissues generates inflammation: a detrimental factor for preterm birth

Human pregnancy is a delicate and complex process where multiorgan interactions between two independent systems, the mother, and her fetus, maintain pregnancy. Intercellular interactions that can define homeostasis at the various cellular level between the two systems allow uninterrupted fetal growth and development until delivery. Interactions are needed for tissue remodeling during pregnancy at both fetal and maternal tissue layers. One of the mechanisms that help tissue remodeling is via cellular transitions where epithelial cells undergo a cyclic transition from epithelial to mesenchymal (EMT) and back from mesenchymal to epithelial (MET). Two major pregnancy-associated tissue systems that use EMT, and MET are the fetal membrane (amniochorion) amnion epithelial layer and cervical epithelial cells and will be reviewed here. EMT is often associated with localized inflammation, and it is a well-balanced process to facilitate tissue remodeling. Cyclic transition processes are important because a terminal state or the static state of EMT can cause accumulation of proinflammatory mesenchymal cells in the matrix regions of these tissues and increase localized inflammation that can cause tissue damage. Interactions that determine homeostasis are often controlled by both endocrine and paracrine mediators. Pregnancy maintenance hormone progesterone and its receptors are critical for maintaining the balance between EMT and MET. Increased intrauterine oxidative stress at term can force a static (terminal) EMT and increase inflammation that are physiologic processes that destabilize homeostasis that maintain pregnancy to promote labor and delivery of the fetus. However, conditions that can produce an untimely increase in EMT and inflammation can be pathologic. These tissue damages are often associated with adverse pregnancy complications such as preterm prelabor rupture of the membranes (pPROM) and spontaneous preterm birth (PTB). Therefore, an understanding of the biomolecular processes that maintain cyclic EMT-MET is critical to reducing the risk of pPROM and PTB. Extracellular vesicles (exosomes of 40-160 nm) that can carry various cargo are involved in cellular transitions as paracrine mediators. Exosomes can carry a variety of biomolecules as cargo. Studies specifically using exosomes from cells undergone EMT can carry a pro-inflammatory cargo and in a paracrine fashion can modify the neighboring tissue environment to cause enhancement of uterine inflammation.

Non-invasive prognostic markers of the risk of preterm rupture of the membranes in premature pregnancy

The objective: to study the prognostic significance of non-invasive markers of endogenous intoxication for determining the risk of premature rupture of membranes (PROM) at the gestation period of 26–34 weeks.Materials and methods. During the study the patients were divided into two groups: the 1st (main) group – 80 women with PROM at 26–34 weeks of pregnancy, and the 2nd (control) group – 50 women with a physiological course of pregnancy and term delivery without complications. The mean age of the examined women was 29.60±6.30 years. To determine the diagnostic value of the level of hematological indicators (concentration of leukocytes (WBC), granulocytes (GRAN), lymphocytes (LYM) in peripheral blood) and indices of endogenous intoxication (EI) as predictors of PROM and the initiation of preterm labor at a gestation period of 26–34 weeks, ROC-analysis was performed and the average quality of these prognostic factors was established (p&lt;0.001).Results. The optimal cut-off point (cut-off value) for predicting PROM in preterm pregnancy according to the criterion of the maximum balance between sensitivity and specificity corresponded to WBC was more than 12.39/l, LYM – less than 19 %, GRAN – more than 76 %, NLR – more than 3.87, Kalf-Kalif’s leukocyte intoxication index (LII) is more than 3.42, Ostrovsky’s LII – more than 2.76. It was established that the area under the curve (AUROC) was 0.786 for WBC, 0.863 for LYM, 0.847 for GRAN, 0.866 for NLR, 0.753 for LII Ostrovsky, which testifies to the significant prognostic value of the studied predictors. Conclusions. The main non-invasive markers of the degree of activity of the inflammatory process and the severity of endogenous intoxication in premature birth with PRPO in pregnant women are: the total number of leukocytes, the level of granulocytes and lymphocytes, Kalf-Kalif LII and the neutrophil-lymphocyte ratio. In order to detect infectious markers of intra-amniotic infection and the further development of PROM and premature birth, it is recommended to calculate the level of endogenous intoxication in the second half of pregnancy using general blood analysis data on a hemolytic analyzer (WBC, GRAN, LYM, NLR).

Pregnancy and perinatal outcomes of COVID-19 (SARS-CoV-2)

This article presents current data on the impact of COVID-19 (SARS-CoV-2) on pregnancy and perinatal consequences. The working theories of the pathogenesis of obstetric and fetal complications due to infection during pregnancy, already proven to date, are considered.Symptoms of COVID-19 disease, the risk of their development, and frequency of severe disease in non-pregnant and pregnant women of reproductive age do not differ significantly. However, there are powerful studies that have shown that this infection in pregnant women leads to a high probability of a dramatically severe and fulminant course. Pregnant women with SARS-CoV-2 infection have an increased risk of preeclampsia, incl. severe, hemolysis, thrombocytopenia and increased levels of liver enzymes compared with pregnant women without infection. Women who have COVID-19 are twice as likely to have preterm rupture of the membranes and three times as likely to have a preterm birth compared to the not infected pregnant women.Vertical transmission of the virus from mother to fetus is likely, but data are insufficient to be certain. There is also insufficient evidence of an increased miscarriage rate and teratogenic effects of the COVID-19 virus. However, antenatal fetal death is statistically significantly more common in infected pregnant women than in uninfected pregnant women. Morphological and functional disorders in the chorion/placenta are the main pathogenetic factor in the development of preeclampsia, intrauterine growth retardation, antenatal fetal death and impaired state of the fetus and children born by women with COVID-19.Many studies report that mothers with confirmed COVID-19 infection has asymptomatic babies. At the same time, some studies indicate adverse complications in newborns from infected mothers. The most common neonatal disorders in babies from pregnant women with COVID-19 are tachypnea, hyperthermia, and gastrointestinal disorders, in particular vomiting and flatulence.

Outcome of Active versus Expectant Management in Preterm Premature Rupture of Membranes between 34 weeks to 36 weeks Six days: A Retrospective Study

Introduction: An important cause of neonatal morbidity and mortality is the prelabour Preterm Rupture of the Membranes (PPROM) which refers to, the rupture of the membranes before 37 weeks. There are two modes of managing PPROM, active management (immediate delivery) and expectant management (therapy directed toward extending the pregnancy to improve neonatal outcome). Aim: To compare neonatal outcomes following active and expectant (conservative) management in PPROM cases from 34 weeks to 36 weeks six days. Materials and methods: This retrospective study was conducted in the Department of Obstetrics and Gynaecology at Government Medical College (tertiary care teaching hospital), Thiruvananthapuram Kerala, India, from February 2021 to July 2021. The data collection period was from January 2013 to December 2014. PPROM cases between 34 weeks and 36 weeks and six days were retrospectively studied. A total of 62 patients among the Active Management (AM) group and 62 patients among the Expected Management (EM) group were selected. The neonatal outcomes (respiratory distress syndrome, hypoglycaemia, neonatal sepsis) and maternal outcomes (caesarean section, chorioamnionitis) were compared. The latency period in conservative management and in active management was also compared. The data was analysed using the Chi-square test. Results: In the AM group, 13 (21%) babies had respiratory distress syndrome, whereas, in the EM group it was 4 (6.5%) (p-value=0.019). In the AM group, 13 (21%) babies had hypoglycaemia, whereas, in the EM group, it was 5 (8.1%) (p-value=0.041). In the AM group, 3 (4.8%) women had signs and symptoms of chorioamnionitis, whereas, in the EM group, it was 7 (11.3%) (p-value=0.187). In the AM group, 16 (25.8%) of women had Caesarean section, whereas, in EM it was 9 (14.5%) (p-value=0.117). In AM group, 1 (1.6%) has neonatal sepsis and in EM it was 3 (4.8%) p-value=0.309. The latency period in conservative management was 119.5±31 hours and in active management, it was 51.5±13.2 hours. Conclusion: The present study indicated that expectant management of PROM between 34 weeks to 36 weeks and six days leads to a statistically significant reduction of neonatal respiratory distress syndrome and hypoglycaemia.

Expectant Management of PPROM Improves Neonatal Outcome-A Retrospective Study of 562 Patients.

Prelabor preterm rupture of the membranes (PPROM) refers to the rupture of the membranes before 37 weeks, but also before the onset of labor. Approximately 3% of pregnancies are complicated by PPROM, which is an important cause of neonatal morbidity and mortality. The aim of the study is to demonstrate the benefit of expectant management in PPROM, compared to immediate birth, defined in our study as birth in the first 48 h. We analyzed 562 pregnancies with PPROM by gestational age groups and short-term morbidities. Material and methods: We conducted a retrospective observational analytical study, which included women with PPROM between 24 + 0 and 36 + 6 weeks. We divided the cohort into gestational age groups: group 1 gestational age (GA) between 24 and 27, group 2 GA between 28 and 31, group 3 GA between 32 and 34, group 4 GA > 35 weeks. In each group, we analyzed the benefit of the latency period (established in our study as delivery after 48 h of hospitalization) in terms of short-term neonatal complications. Result: The latency period brought a significant benefit starting with GA greater than 28 weeks; therefore, in the group with GA between 28–31, the complications were significantly statistically lower, mentioning respiratory distress syndrome (no latency 100% vs. latency 85.1%) and admission to the neonatal intensive care unit (no latency 89.7% vs. latency 70.2%). In group 3, with GA between 32–34, we reached statistical significance in terms of respiratory distress syndrome (no latency 61.8% vs. latency 39%), hypoxia (no latency 50% vs. latency 31.7%) and admission to the neonatal intensive care unit (no latency 70.2% vs. latency 47.4%). Conclusion: Expectant management of pregnancies with PPROM can bring a real benefit in terms of the incidence of complications in premature infants, but this benefit depends most on the gestational age at which the membranes ruptured and the medical conduct put into practice during the latency period.

Proteomic profiling of human amnion for preterm birth biomarker discovery

Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.

Transcriptome changes in maternal peripheral blood during term parturition mimic perturbations preceding spontaneous preterm birth†.

The complex physiologic process of parturition includes the onset of labor, which requires the orchestrated stimulation of a common pathway involving uterine contractility, cervical ripening, and chorioamniotic membrane activation. However, the labor-specific processes taking place in these tissues have limited use as predictive biomarkers unless they can be probed in non-invasive samples, such as the peripheral blood. Herein, we utilized a transcriptomic dataset to assess labor-specific changes in the peripheral blood of women who delivered at term. We identified a set of genes that were differentially expressed with labor and enriched for immunological processes, and these gene expression changes were strongly correlated with results from prior studies, providing in silico validation of our findings. We then identified significant correlations between labor-specific transcriptomic changes in the maternal circulation and those detected in the chorioamniotic membranes, myometrium, and cervix of women at term, demonstrating that tissue-specific labor signatures are partly mirrored in the peripheral blood. Finally, we demonstrated a significant overlap between the peripheral blood transcriptomic changes in term parturition and those observed in asymptomatic women, prior to the diagnosis of preterm prelabor rupture of the membranes, who ultimately delivered preterm. Collectively, we provide evidence that the normal process of labor at term is characterized by a unique immunological expression signature, which may serve as a useful tool for assessing labor status and for potentially identifying women at risk for preterm birth.