[Analysis of adverse late-term pregnancy outcomes after cervical cold knife conization].

Objective: To investigate the effects of cervical cold knife conization (CKC) on preterm delivery, other pregnancy complications and neonatal outcomes, and explore the relationship between preterm delivery risk and the depth and volume of conization. Methods: The clinical data and pregnancy outcomes of 272 women who underwent CKC in Peking Union Medical College Hospital from January 2002 to March 2018 (conization group) and 1 647 pregnant women who gave birth in Peking Union Medical College Hospital during January to December 2019 (control group) were collected. The preterm delivery, premature rupture of membranes, other pregnancy complications and neonatal outcomes of the two groups were compared, and the relationship between the depth and volume of conization and the risk of preterm delivery in postoperative singleton pregnancy was analyzed. Results: (1) There were no significant differences between the two groups in delivery age, parity, proportion of singleton pregnancy, proportion of assisted reproductive technology (all P>0.05). (2) The rate of preterm delivery in the conization group was significantly higher than that in the control group [14.8% (39/264) vs 5.7% (91/1 589); χ2=28.397, P<0.001]. There were still significant differences in preterm delivery rates between the two groups at <34 weeks and 34-37 weeks (all P<0.01). There was no significant difference in the incidence of premature rupture of membrane between the two groups [23.5% (62/264) vs 23.4% (372/1 589); χ2=0.001, P=0.979], but the incidence of preterm premature rupture of membrane in the conization group was significantly higher than that in the control group [11.4% (30/264) vs 2.2% (35/1 589); χ2=56.132, P<0.001]. (3) The rate of cesarean section in the conization group was higher than that in the control group [59.6% (162/272) vs 38.8% (639/1 647); χ2=41.377, P<0.001]. The birth weight of preterm infants in the conization group was significantly higher than that in the control group [(2 409±680) vs (2 150±684) g; t=2.184, P=0.030]. However, there were no statistically significant differences in the incidence of gestational diabetes mellitus, hypertensive disorders in pregnancy, the birth weight of full-term infants, incidence of small for gestational age infant and neonatal intensive care unit admission rate between the two groups (all P>0.05). (4) The preterm delivery rates of coning depth >15 mm, cone size ≥2 cm3 and cone size <2 cm3 were higher than that in the control group (all P<0.05). When the coning depth ≤15 mm, the preterm delivery rate in the conization group was higher than that in the control group, but there was no significant difference (P=0.620). The rate of preterm delivery of pregnant women with coning depth >15 mm was significantly higher than those with coning depth ≤15 mm (RR=3.084, 95%CI: 1.474-6.453; P=0.001). There was no significant difference in the preterm delivery rate between pregnant women with cone size >2 cm3 and those with cone size ≥2 cm3 (RR=1.700, 95%CI: 0.935-3.092; P=0.077). Conclusion: The risk of preterm delivery and preterm premature rupture of membranes in subsequent pregnancies are increased after cervical CKC, and the risk of preterm delivery is positively correlated with the depth of cervical coning.

The vaginal immunoproteome for the prediction of spontaneous preterm birth: A retrospective longitudinal study.

Background: Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Most cases of preterm birth occur spontaneously and result from preterm labor with intact (spontaneous preterm labor [sPTL]) or ruptured (preterm prelabor rupture of membranes [PPROM]) membranes. The prediction of spontaneous preterm birth (sPTB) remains underpowered due to its syndromic nature and the dearth of independent analyses of the vaginal host immune response. Thus, we conducted the largest longitudinal investigation targeting vaginal immune mediators, referred to herein as the immunoproteome, in a population at high risk for sPTB. Methods: Vaginal swabs were collected across gestation from pregnant women who ultimately underwent term birth, sPTL, or PPROM. Cytokines, chemokines, growth factors, and antimicrobial peptides in the samples were quantified via specific and sensitive immunoassays. Predictive models were constructed from immune mediator concentrations. Results: Throughout uncomplicated gestation, the vaginal immunoproteome harbors a cytokine network with a homeostatic profile. Yet, the vaginal immunoproteome is skewed toward a pro-inflammatory state in pregnant women who ultimately experience sPTL and PPROM. Such an inflammatory profile includes increased monocyte chemoattractants, cytokines indicative of macrophage and T-cell activation, and reduced antimicrobial proteins/peptides. The vaginal immunoproteome has improved predictive value over maternal characteristics alone for identifying women at risk for early (<34 weeks) sPTB. Conclusions: The vaginal immunoproteome undergoes homeostatic changes throughout gestation and deviations from this shift are associated with sPTB. Furthermore, the vaginal immunoproteome can be leveraged as a potential biomarker for early sPTB, a subset of sPTB associated with extremely adverse neonatal outcomes. Funding: This research was conducted by the Perinatology Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS) under contract HHSN275201300006C. ALT, KRT, and NGL were supported by the Wayne State University Perinatal Initiative in Maternal, Perinatal and Child Health.

Human pregnancies last 40 weeks on average. Preterm births, defined as live births before 37 weeks, occur in about one in ten pregnancies. Being born too early is the main cause of a number of diseases and death in newborn babies. Preterm births are further divided into those that happen early ­ before 34 weeks ­ and those that happen late ­ between 34 and 37 weeks. There are also differences between preterm births in which the amniotic sac ruptures before or after the start of labor. Although several factors can lead to spontaneous preterm birth, bacteria getting into the amniotic fluid around the fetus are a well-known trigger. These bacteria usually come from the vagina. In the past, researchers have studied the number and types of bacteria in the vagina of people who had a normal pregnancy and those that had a preterm birth to predict who is more at risk of preterm birth. However, predictions based only on data about bacteria have been less useful so far. Instead, it might be better to investigate a person's immune response during pregnancy. Shaffer et al. addressed this gap by asking whether measuring the levels of proteins involved in the immune response could help predict preterm births. Shaffer et al. collected vaginal fluids from 739 individuals of predominately African American ethnicity with an average BMI of 28.7 ­ representing a population at high risk for spontaneous preterm birth. The swabs were taken at multiple points during their pregnancy, and 31 different immune-related proteins in those fluids were measured. The researchers further noted whether these individuals had a normal or a preterm birth. The data showed that, compared to normal births, preterm births are associated with higher levels of proteins that attract white blood cells and promote inflammation, such as IL-6 and IL-1ß. Vaginal fluids from individuals who went on to have an early preterm birth where the amniotic sac ruptured before labor, contained lower levels of proteins known as defensins, which defend the body from bacteria. With these new data from vaginal swabs, Shaffer et al. could make better predictions about the likelihood of preterm birth in general and early preterm birth with the amniotic sac ruptured before labor. For the latter scenario, the predictions were not improved when combining immune protein data with other characteristics of the pregnant person, such as age. These findings suggest that clinicians may be able to use measurements of immune-related proteins to help predict preterm births, so that pregnant individuals at high risk can receive extra care. Further research will have to validate the data and determine whether the findings apply more widely.

The impact of premature rupture of membrane on neonatal outcomes in infants born at 34 weeks gestation or later.

BACKGROUND: Premature rupture of membranes (PROMs) is a known risk for adverse neonatal outcomes, often leading to neonatal hospitalization due to suspected perinatal infection or other issues. This study assesses PROM's clinical impact on neonatal outcomes in infants born at 34 weeks of gestation or later. METHODS: We studied hospitalized neonates born between December 2018 and November 2019, with gestational ages of 34 weeks or more and PROM diagnosis. We extracted patient data from clinical records, including demographics, maternal history, medical profiles, and neonatal outcomes. Neonates were categorized based on symptoms, PROM duration, neonatal intensive care unit (NICU) stay, and respiratory support. Data underwent thematic analysis. RESULTS: Of 275 neonates, the average PROM duration was 7.9 ± 8.1 hours, with 247 cases (89.8%) showing symptoms. Among them, 34 (12.4%) had PROM lasting over 18 hours, 48 (17.5%) were born prematurely, and 79 (28.7%) required intensive care. Symptomatic neonates had significantly higher rates of needing intensive care, respiratory support, prolonged antibiotics, and extended hospitalization ( p < 0.05). NICU stays (≥3 days) were significantly associated with prematurity (odds ratio [OR] = 5.49; 95% CI, 2.39-12.60) and an initial pH level <7.25 (OR = 3.35; 95% CI, 1.46-7.68). Extended respiratory support (≥3 days) was significantly correlated with tocolysis ≥7 days (OR = 13.20; 95% CI, 3.94-44.20), Apgar score <7 at 1 minute after birth (OR = 4.28; 95% CI, 1.67-10.97), and inadequate intrapartum antibiotic prophylaxis (IAP) (OR = 2.34; 95% CI, 1.04-5.23). CONCLUSION: Neonates born at or after 34 weeks of gestation with PROM should undergo vigilant monitoring if early symptoms (<24 hours) manifest. Risk factors for requiring NICU care or extended respiratory support (≥3 days) include prematurity, low initial pH (<7.25), prolonged tocolysis requirement (≥7 days), an Apgar score below 7 at 1 minute, and inadequate IAP.

The relationships of inflammatory blood markers with maternal periodontal and dental states and their effects on preterm membrane rupture development.

BACKGROUND: The influence of maternal oral and dental health on the occurrence of Preterm Premature Rupture of Membranes (P-PROM) and its underlying mechanisms remain uncertain. This research seeks to investigate the impact of maternal oral and dental health on the incidence of P-PROM and its association with inflammatory markers in the blood. METHODS: This study adopts a prospective case-control design methodology. The study involved 70 women diagnosed with P-PROM and delivered by an obstetrician and 79 women who had healthy deliveries with no prenatal complications. The values for DMFT (Number of decayed, missing and filled teeth) index, Gingival Index (GI), Plaque index (PI), Pocket depth (PD), Clinical attachment loss (CAL) and medical history were recorded. Mann-Whitney U test and hierarchical binomial logistic regression analysis were applied. It was considered statistically significant at p < 0.05. RESULTS: The case group's DMFT, PI, GI, PD values were statistically significantly higher than the control group (p < 0.001). There was no relationship between DMFT, GI, PD, CAL and inflammatory blood markers (p > 0.05). In the regression analysis for possible risk factors that may be effective in P-PROM, oral and dental health parameters were the most effective. CONCLUSIONS: Oral and dental health of women with P-PROM was found to be worse than that of the control group. Oral and dental health may be a potential risk factor that may contribute to adverse pregnancy outcomes associated with P-PROM.

Relationship between first trimester physical activity and premature rupture of membranes: a birth cohort study in Chinese women.

OBJECTIVE: This study aimed to examine prospective associations of different intensity levels and types of physical activity (PA) in early pregnancy with premature rupture of membranes (PROM) among Chinese pregnant women. METHODS: A total of 6284 pregnant women were included from the Tongji-Shuangliu Birth Cohort. Household/caregiving, occupational, sports/exercise and transportation activities during early pregnancy were investigated by the pregnancy physical activity questionnaire (PPAQ), and the diagnosis of PROM was ascertained during the whole pregnancy. Multivariate logistic regression models were used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the associations between PA and PROM. RESULTS: Among the 6284 pregnant women, 1246 were identified to have PROM (19.8%). Women undertaking the highest level (3 third tertile) of PA during pregnancy appeared to have a lower risk of PROM [OR = 0.68, 95%CI 0.58-0.80) when compared to those at the lowest tertile of PA. Similarly, women with increased levels of light intensity activity, moderate-vigorous intensive, household/caregiving activity and meeting exercise guidelines during pregnancy were associated with reduced risks of PROM (OR = 0.69, 95% CI 0.59-0.81, OR = 0.70, 95% CI 0.60-0.82, OR = 0.62, 95% CI 0.53-0.73 and OR = 0.82, 95% CI 0.70-0.97, respectively). CONCLUSIONS: High levels of PA of different intensities and PA of household/caregiving activities and meeting exercise guidelines during the first trimester were associated with a lower incidence of PROM. TRIAL REGISTRATION: The data of human participants in this study were conducted in accordance with the Helsinki Declaration. This study has been approved by the Ethics Committee of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China ([2017] No. S225). All participants provided written informed consent prior to enrollment. A statement to confirm that all methods were carried out in accordance with relevant guidelines and regulations.

Pregnancy outcomes in pregnant women taking oral probiotic undergoing cerclage compared to placebo: two blinded randomized controlled trial.

AIM: The purpose of this study is to evaluate the oral probiotic effect on pregnancy outcomes in pregnant women undergoing cerclage compared to placebo. METHODS: This study was a double-blind randomized clinical trial undertaken in Yasuj, Iran. 114 eligible participants who have undergone cerclage were randomly divided to either receive probiotic adjuvant or 17α-OHP (250 mg, IM) with placebo from the 16th -37th week of pregnancy by "block" randomization method. Our primary outcomes were preterm labor (PTB) (late and early) and secondary outcomes were other obstetrical and neonatal outcomes included preterm pre-labor rupture of membranes (PPROM), pre-labor rupture of membranes (PROM), mode of delivery, and neonatal outcomes including anthropometric characterize and Apgar score (one and fifth-minute). RESULTS: Results show that there are no statistically significant differences between the two groups in terms of PTB in < 34th (15.51% vs. 17.86%; P = 0.73) and 34-37th weeks of pregnancy (8.7% vs. 16.1%; P = 0.22), and mode of delivery (P = 0.09). PPROM (8.7% vs. 28.5%; P = 0.006) PROM (10.3% vs. 25%; P = 0.04) was significantly lower in patients receiving probiotic adjuvant compared to the control group. After delivery, the findings of the present study showed that there were no significant differences in newborn's weight (3082.46 ± 521.8vs. 2983.89 ± 623.89), head circumstance (36.86 ± 1.53vs. 36.574 ± 1.52), height (45.4 ± 5.34 vs. 47.33 ± 4.92) and Apgar score in one (0.89 ± 0.03 vs. 0.88 ± 0.05) and five minutes (0.99 ± 0.03vs. 0.99 ± 0.03) after birth. CONCLUSION: Our result has shown that the consumption of Lactofem probiotic from the 16th week until 37th of pregnancy can lead to a reduction of complications such as PPROM and PROM.

Maternal Exposure to Environmental Air Pollution and Premature Rupture of Membranes: Evidence from Southern China.

BACKGROUND Exposure to air pollution (AP) during pregnancy is associated with pre-labor rupture of membranes (PROM). However, there is limited research on this topic, and the sensitive exposure windows remain unclear. The present study assessed the association between AP exposure and the risk of PROM, as well as seeking to identify the sensitive time windows. MATERIAL AND METHODS This retrospective study analyzed 4276 pregnant women's data from Tongling Maternal and Child Health Hospital from 2020 to 2022. We obtained air pollution data, including particulate matter (PM) with an aerodynamic diameter of ≤2.5 µm (PM2․5), particulate matter with an aerodynamic diameter of ≤10 µm (PM10), nitrogen dioxide (NO2), and ozone (O3), from the Tongling Ecology and Environment Bureau. Demographic information was extracted from medical records. We employed a distributed lag model to identify the sensitive exposure windows of prenatal AP affecting the risk of PROM. We conducted a sensitivity analysis based on pre-pregnancy BMI. RESULTS We found a significant association between prenatal exposure to AP and increased PROM risk after adjusting for confounders, and the critical exposure windows of AP were the 6th to 7th months of pregnancy. In the underweight group, an increase of 10 µg/m³ in PM2․5 was associated with a risk of PROM, with an odds ratio (OR) of 1.48 (95% CI: 1.16, 1.89). Similarly, a 10 µg/m³ increase in PM10 was associated with a risk of PROM, with an OR of 1.45 (95% CI: 1.05, 1.77). CONCLUSIONS Prenatal exposure to AP, particularly during months 6-7 of pregnancy, is associated with an increased risk of PROM. This study extends and strengthens the evidence on the association between prenatal exposure to AP and the risk of PROM, specifically identifying the critical exposure windows.

Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis

Background: Premature rupture of membranes (PROM) is defined as the leakage of amniotic fluid before the onset of labor and delivery contractions. Some studies found that women who experienced PROM had significantly lower vitamin C blood levels than those who did not, while others found no significant differences. Previous systematic reviews and meta-analyses on the efficacy of vitamin C in the prevention of PROM had conflicting results. Aims: Conduct a systematic review and meta-analysis to determine if there was a significant difference in vitamin C blood levels in women who had PROM versus the control group who did not and to determine if vitamin C supplements could help prevent it. Study Design: Systematic review and meta-analysis. Methods: We registered our protocol with PROSPERO (CRD42022371644). We searched PubMed/MEDLINE, Web of Science, and Scopus through February 15, 2024. Additionally, backward and forward citation searches were conducted. Studies were selected based on predetermined inclusion and exclusion criteria. Meta-Essentials: Workbooks for Meta-Analysis (version 1.5) was used for analysis. Results: Twenty-five studies (26 reports) met all eligibility criteria, with 18 studies (18 reports) assessing vitamin C levels and seven studies (eight reports) evaluating efficacy. Women with PROM, whether preterm or term, had significantly lower vitamin C levels [Hedges' g, -1.48; 95% confidence interval (CI): -2.82, -0.14; p = 0.020; I2 = 94.08%) and specifically preterm PROM after removing the outlying study [Hedges' g, -1.29; 95% CI: -1.85, -0.73; p < 0.001; I2 = 87.35%). Vitamin C supplementation significantly reduced the risk of preterm or term PROM [risk ratio (RR), 0.57; 95% CI: 0.39, 0.81; p < 0.001; I2 = 12.17%), particularly for preterm PROM (RR, 0.67; 95% CI: 0.45, 0.99; p = 0.001; I2 = 0.00%). There were no significant differences in vitamin C levels between women with term PROM and controls, and there were no differences in the risk of developing term PROM between women taking vitamin C supplements and controls. Results were not robust in all sensitivity analyses. Conclusion: Women with PROM, particularly those who developed it preterm, appear to have significantly lower vitamin C levels, and vitamin C supplementation appears to be effective in reducing the risk of PROM, particularly preterm PROM. More high-quality studies with low risk of bias, more homogenous, and larger samples are needed to confirm these findings.

The adenosine deaminase family acting on RNA 1 can be a useful diagnostic biomarker in chorioamnionitis.

INTRODUCTION: Chorioamnionitis (CAM) involves infection and inflammation of the chorion and amniotic membrane, but there are still no effective diagnostic biomarkers for CAM. METHODS: We investigated the correlation between RNA editing enzyme Adenosine deaminase family acting on RNA 1 (ADAR1) and CAM in chorion and amniotic membrane specimens derived from premature rupture of the membrane (PROM), CAM (pathologically diagnosed), and clinical CAM (clinically diagnosed) patients using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: ADAR1 was upregulated in the chorion and amniotic membrane specimens of CAM and clinical CAM patients (p < 0.001 and p = 0.005). ADAR1 had a significantly higher area under the curve (AUC) (0.735 and 0.828) than markers of inflammation characteristics in diagnosing CAM and clinical CAM patients. ADAR1 also had significantly higher AUC (0.701 and 0.837) than clinical characteristics for CAM and clinical CAM patients. DISCUSSION: ADAR1 can be a useful diagnostic biomarker in CAM patients.

Etiologically Based Functional Taxonomy of the Preterm Birth Syndrome.

Preterm birth (PTB) is a complex syndrome traditionally defined by a single parameter, namely, gestational age at birth (ie, ˂37 weeks). This approach has limitations for clinical usefulness and may explain the lack of progress in identifying cause-specific effective interventions. The authors offer a framework for a functional taxonomy of PTB based on (1) conceptual principles established a priori; (2) known etiologic factors; (3) specific, prospectively identified obstetric and neonatal clinical phenotypes; and (4) postnatal follow-up of growth and development up to 2 years of age. This taxonomy includes maternal, placental, and fetal conditions routinely recorded in data collection systems.

Predicting Preterm Birth Using Cell-Free Ribonucleic Acid.

Spontaneous preterm birth (sPTB) is a complex and clinically heterogeneous condition that remains incompletely understood, leading to insufficient interventions to effectively prevent it from occurring. Cell-free ribonucleic acid signatures in the maternal circulation have the potential to identify biologically relevant subtypes of sPTB. These could one day be used to predict and prevent sPTB in asymptomatic individuals, and to aid in prognosis and management for individuals presenting with threatened preterm labor and preterm prelabor rupture of membranes.

The influence of uterine fibroids on adverse outcomes in pregnant women: a meta-analysis.

OBJECTIVE: The objective of the meta-analysis was to determine the influence of uterine fibroids on adverse outcomes, with specific emphasis on multiple or large (≥ 5 cm in diameter) fibroids. MATERIALS AND METHODS: We searched PubMed, Embase, Web of Science, ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), and SinoMed databases for eligible studies that investigated the influence of uterine fibroids on adverse outcomes in pregnancy. The pooled risk ratio (RR) of the variables was estimated with fixed effect or random effect models. RESULTS: Twenty-four studies with 237 509 participants were included. The pooled results showed that fibroids elevated the risk of adverse outcomes, including preterm birth, cesarean delivery, placenta previa, miscarriage, preterm premature rupture of membranes (PPROM), placental abruption, postpartum hemorrhage (PPH), fetal distress, malposition, intrauterine fetal death, low birth weight, breech presentation, and preeclampsia. However, after adjusting for the potential factors, negative effects were only seen for preterm birth, cesarean delivery, placenta previa, placental abruption, PPH, intrauterine fetal death, breech presentation, and preeclampsia. Subgroup analysis showed an association between larger fibroids and significantly elevated risks of breech presentation, PPH, and placenta previa in comparison with small fibroids. Multiple fibroids did not increase the risk of breech presentation, placental abruption, cesarean delivery, PPH, placenta previa, PPROM, preterm birth, and intrauterine growth restriction. Meta-regression analyses indicated that maternal age only affected the relationship between uterine fibroids and preterm birth, and BMI influenced the relationship between uterine fibroids and intrauterine fetal death. Other potential confounding factors had no impact on malposition, fetal distress, PPROM, miscarriage, placenta previa, placental abruption, and PPH. CONCLUSION: The presence of uterine fibroids poses increased risks of adverse pregnancy and obstetric outcomes. Fibroid size influenced the risk of breech presentation, PPH, and placenta previa, while fibroid numbers had no impact on the risk of these outcomes.

Knowledge, attitude, and practices of midwives on premature rupture of membranes (PROM): A cross-sectional study in Samosir and Toba, Indonesia.

Indonesia has a significantly higher maternal mortality ratio (MMR) than other countries in Southeast Asia, and infection is one of the most common causes of maternal deaths, of which premature rupture of membranes (PROM) can be the consequence of the infections. In primary healthcare settings, midwives play an important role in identifying and managing PROM appropriately; however, studies on their knowledge, attitudes, and practices related to PROM are limited. The aim of this study was to determine the midwives' knowledge, attitude and healthcare practice on PROM in Indonesia. A cross-sectional study was conducted among midwives at primary healthcare facilities in Samosir and Toba Regency, North Sumatra, Indonesia, from July to November 2022. The knowledge, attitude and practice towards PROM were assessed. Results showed that 57.5% of midwives had poor knowledge and 35.1% had poor attitude levels. There were 4.9% of midwives referred the patients immediately to the hospital. Our data indicated that aged 31-40 or 41-50 years, having a lower than bachelor degree and having a higher monthly number of referred PROM patients were significantly associated with poor knowledge compared to younger, having a bachelor degree, and lower monthly referral patient number, respectively. Similarly, younger, having higher degree and a having lower monthly referral number of PROM cases were associated with higher chances of having a sufficient-good attitude towards PROM. This study highlights that a significant percentage of midwives had poor levels of knowledge and attitude, and age, educational level and monthly referral number of PROM cases were associated with the level of knowledge and attitude.

Identification of circRNA Expression Profile and Potential Systemic Immune Imbalance Modulation in Premature Rupture of Membranes.

Premature rupture of membrane (PROM) refers to the rupture of membranes before the onset of labor which increases the risk of perinatal morbidity and mortality. Recently, circular RNAs (circRNAs) have emerged as promising regulators of diverse diseases. However, the circRNA expression profiles and potential circRNA-miRNA-mRNA regulatory mechanisms in PROM remain enigmatic. In this study, we displayed the expression profiles of circRNAs and mRNAs in plasma and fetal membranes of PROM and normal control (NC) groups based on circRNA microarray, the Gene Expression Omnibus database, and NCBI's Sequence Read Archive. A total of 1,459 differentially expressed circRNAs (DECs) in PROM were identified, with 406 upregulated and 1,053 downregulated. Then, we constructed the circRNA-miRNA-mRNA network in PROM, encompassing 22 circRNA-miRNA pairs and 128 miRNA-mRNA pairs. Based on the analysis of gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and gene set enrichment analysis (GSEA), DECs were implicated in immune-related pathways, with certain alterations persisting even postpartum. Notably, 11 host genes shared by DECs of fetal membrane tissue and prenatal plasma in PROM were significantly implicated in inflammatory processes and extracellular matrix regulation. Our results suggest that structurally stable circRNAs may predispose to PROM by mediating systemic immune imbalances, including peripheral leukocyte disorganization, local immune imbalance at the maternal-fetal interface, and local collagen disruption. This is the first time to decipher a landscape on circRNAs of PROM, reveals the pathogenic cause of PROM from the perspective of circRNA, and opens up a new direction for the diagnosis and treatment of PROM.

Outcome of prelabor rupture of membranes before or at the limit of viability: systematic review and meta-analysis.

OBJECTIVE: Counseling of pregnancies complicated by pre- and periviable premature rupture of membranes to reach shared decision-making is challenging, and the current limited evidence hampers the robustness of the information provided. This study aimed to elucidate the rate of obstetrical and neonatal outcomes after expectant management for premature rupture of membranes occurring before or at the limit of viability. DATA SOURCES: Medline, Embase, CINAHL, and Web of Science databases were searched electronically up to September 2023. STUDY ELIGIBILITY CRITERIA: Our study included both prospective and retrospective studies of singleton pregnancies with premature rupture of membranes before and at the limit of viability (ie, occurring between 14 0/7 and 24 6/7 weeks of gestation). METHODS: Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Moreover, our study used meta-analyses of proportions to combine data and reported pooled proportions. Given the clinical heterogeneity, a random-effects model was used to compute the pooled data analyses. This study was registered with the International Prospective Register of Systematic Reviews database (registration number: CRD42022368029). RESULTS: The pooled proportion of termination of pregnancy was 32.3%. After the exclusion of cases of termination of pregnancy, the rate of spontaneous miscarriage or fetal demise was 20.1%, whereas the rate of live birth was 65.9%. The mean gestational age at delivery among the live-born cases was 27.3 weeks, and the mean latency between premature rupture of membranes and delivery was 39.4 days. The pooled proportion of cesarean deliveries was 47.9% of the live-born cases. Oligohydramnios occurred in 47.1% of cases. Chorioamnionitis occurred in 33.4% of cases, endometritis in 7.0%, placental abruption in 9.2%, and postpartum hemorrhage in 5.3%. Hysterectomy was necessary in 1.2% of cases. Maternal sepsis occurred in 1.5% of cases, whereas no maternal death was reported in the included studies. When focusing on neonatal outcomes, the mean birthweight was 1022.8 g in live-born cases. The neonatal intensive care unit admission rate was 86.3%, respiratory distress syndrome was diagnosed in 66.5% of cases, pulmonary hypoplasia or dysplasia was diagnosed in 24.0% of cases, and persistent pulmonary hypertension was diagnosed in 40.9% of cases. Of the surviving neonates, the other neonatal complications included necrotizing enterocolitis in 11.1%, retinopathy of prematurity in 27.1%, and intraventricular hemorrhage in 17.5%. Neonatal sepsis occurred in 30.2% of cases, and the overall neonatal mortality was 23.9%. The long-term follow-up at 2 to 4 years was normal in 74.1% of the available cases. CONCLUSION: Premature rupture of membranes before or at the limit of viability was associated with a great burden of both obstetrical and neonatal complications, with an impaired long-term follow-up at 2 to 4 years in almost 30% of cases, representing a clinical challenge for both counseling and management. Our data are useful when initially approaching such patients to offer the most comprehensive possible scenario on short- and long-term outcomes of this condition and to help parents in shared decision-making. El resumen está disponible en Español al final del artículo.

Semi-quantitative metalloproteinase-8 rapid test for the prediction of adverse pregnancy outcomes in patients with preterm premature rupture of membranes.

OBJECTIVE: We aimed to determine whether the semi-quantitative metalloproteinase-8 (MMP-8) bedside test is a worthwhile indicator in reflecting the severity of of intra-amniotic inflammation (IAI) and in predicting adverse pregnancy outcomes. STUDY DESIGN: This retrospective cohort study comprised 76 singleton-pregnant women admitted to the Seoul National University Bundang Hospital with a diagnosis of preterm premature rupture of membranes (preterm PROM) between 20 weeks 0 days and 33 weeks 6 days of gestation who underwent trans-abdominal amniocentesis to confirm intra-amniotic infection by positive results for aerobic/anaerobic bacteria, fungi, and genital mycoplasma and evaluate lung maturity. The semi-quantitative MMP-8 rapid test kit employs a colourimetric assay to quantify MMP-8 levels in amniotic fluid (AF), expressing results from 0 to 100 percent. Participants were divided into three groups: group 1, including negative MMP-8 test with colour scale of 0 % (negative, n = 17); group 2, including positive MMP-8 test with colour scale < 51 % (weak positive, n = 21); and group 3, including positive MMP-8 test with colour scale of 51 %-100 % (strong positive, n = 38). RESULTS: Approximately 78 % (59/76) of the participants showed a positive MMP-8 test result; all culture-proven AF samples (33.3 % [25/75]) yielded positive MMP-8 test, categorizing these patients into either group 2 or group 3. A significant trend was observed where the rate of positive culture-proven samples increased with the progression from group 1 (negative) to group 3 (strong positive). Both white blood cell counts in AF and maternal serum C-reactive protein levels were found to escalate with the progression of test results from negative to strong positive. This progression was associated with an increased risk of spontaneous preterm birth within 48 h, 7 days, and 14 days from amniocentesis and within 34 weeks of gestation. CONCLUSION: The more the test results progress from negative to strong positive, the shorter the interval from amniocentesis to delivery becomes, and the higher the risk of intra-amniotic infection, spontaneous preterm delivery, and other perinatal complications. This relationship highlights the critical value of the semi-quantitative MMP-8 rapid test in predicting adverse pregnancy outcomes in patients with preterm PROM.

Anti-infectious and anti-inflammatory effect of amniopatch in the treatment of spontaneous previable rupture of membranes.

Spontaneous previable rupture of membranes complicates approximately 0.4-0.7% of pregnancies and is associated with severe maternal and neonatal morbidity and mortality. Intra-amniotic inflammation is present in up to 94.4% of cases, most often caused by a bacterial infection. In comparison, the effectiveness of antibiotic therapy in its eradication reaches less than 17%. Inflammatory activity in the amniotic cavity disrupts the physiological development of the fetus with an increase in maternal, fetal, and neonatal inflammatory morbidity through the development of fetal inflammatory response syndrome, maternal chorioamnionitis, and neonatal sepsis. Amniopatch is an invasive therapeutic technique based on intra-amniotic administration of maternal hemoderivates in the form of thromboconcentrate and plasma cryoprecipitate to provide the temporary closure of the fetal membranes defect and secondary restitution of normohydramnios with correction of pressure-volume ratios. The supposed basis of this physical-mechanical action is the aggregation of coagulant components of amniopatch in the area of the defect with the formation of a valve cap. The background for the formulation of the hypothesis on the potential anti-infectious and anti-inflammatory action of non-coagulant components of amniopatch involved: i) clinical-academic and publishing outputs of the authors based on their many years' experience with amniopatch application in the treatment of spontaneous previable rupture of membranes (2008-2019), ii) the documented absence of clinically manifested chorioamnionitis in patients treated this way with a simultaneously reduced incidence of neonatal respiratory distress syndrome compared to expectant management (tocolysis, corticotherapy, antibiotic therapy). The non-coagulant components of plasma cryoprecipitate include mainly naturally occurring isohemagglutinins, albumin, and soluble plasma fibrinogen. Although these components of the amniopatch have not been attributed a significant therapeutic role, the authors assume that due to their opsonizing and aggregative properties, they can significantly participate in optimizing the intrauterine environment through the reduction in bacterial and cytokine charge in the amniotic fluid. The authors think these facts constitute a vital stimulus to future research-academic activity and, at the same time, an idea for reconsidering the therapeutic role of amniopatch as a tool for improving perinatal results of spontaneous previable ruptures of membranes.

Analysis of perinatal outcomes for emergency cervical cerclage in singleton pregnancies at 24-28 weeks of gestation.

BACKGROUND: Cervical cerclage is the only effective treatment for cervical insufficiency, effectively preventing late miscarriage and preterm birth. The effectiveness and safety of emergency cervical cerclage (ECC) as an emergency treatment when the cervix is already dilated or when there is protrusion of the fetal membranes into the vagina remain controversial, especially in pregnancies at 24-28 weeks when the fetus is viable. There is still no consensus on whether emergency cervical cerclage should be performed in such cases. PURPOSE: To investigate the effectiveness and safety of emergency cervical cerclage in singleton pregnant women at 24-28 weeks of gestation. METHODS: This study employed a single-center prospective cohort design, enrolling singleton pregnant women at 24-28 weeks of gestation with ultrasound or physical examination indicating cervical dilation or even membrane protrusion. Emergency cervical cerclage was compared with conservative treatment. The primary endpoints included a comprehensive assessment of perinatal pregnancy loss, significant neonatal morbidity, and adverse neonatal outcomes. Secondary endpoints included prolonged gestational age, preterm birth, neonatal hospitalization rate, premature rupture of membranes, and intrauterine infection/chorioamnionitis. RESULTS: From June 2021 to March 2023, a total of 133 pregnant women participated in this study, with 125 completing the trial, and were allocated to either the Emergency Cervical Cerclage (ECC) group (72 cases) or the conservative treatment group (53 cases) based on informed consent from the pregnant women. The rate of adverse neonatal outcomes was 8.33% in the ECC group and 26.42% in the conservative treatment (CT) group, with a statistically significant difference (P = 0.06). There were no significant differences between the two groups in terms of perinatal pregnancy loss and significant neonatal morbidity. The conservative treatment group had a mean prolonged gestational age of 63.0 (23.0, 79.5) days, while the ECC group had 84.0 (72.5, 89.0) days, with a statistically significant difference between the two groups (P < 0.001). Compared with CT group, the ECC group showed a significantly reduced incidence of preterm birth before 28 weeks, 32 weeks, and 34 weeks, with statistical significance (P = 0.046, 0.007, 0.001), as well as a significantly decreased neonatal hospitalization rate (P = 0.013, 0.031). Additionally, ECC treatment did not increase the risk of preterm premature rupture of membranes or intrauterine infection/chorioamnionitis, with no statistically significant differences (P = 0.406, 0.397). CONCLUSION: In singleton pregnant women with cervical insufficiency at 24-28 weeks of gestation, emergency cervical cerclage can reduce adverse neonatal pregnancy outcomes, effectively prolong gestational age, decrease preterm births before 28 weeks, 32 weeks, and 34 weeks, lower neonatal hospitalization rates, and does not increase the risk of preterm premature rupture of membranes or intrauterine infection/chorioamnionitis.

Changes in serum inflammatory factors in group B streptococcal infection and their predictive value for premature rupture of membranes complicated by chorioamnionitis.

Objective: The aim of this study as to unveil changes in serum inflammatory factors in pregnant women with genital tract group B Streptococcus (GBS) infection and their predictive value for premature rupture of membranes (PROM) complicated by chorioamnionitis (CS) and adverse pregnancy outcomes. Methods: The value of serum inflammatory factor levels in predicting PROM complicating CS and adverse pregnancy outcomes in GBS-infected pregnant women was evaluated by ELISA. Results: Serum IL-6, TNF-α, PCT and hs-CRP levels were higher in pregnant women with GBS infection. The combined diagnosis of these factors had excellent diagnostic value in PROM complicating CS and adverse pregnancy outcomes. Conclusion: Joint prediction of IL-6, TNF-α, PCT and hs-CRP has the best predictive value for PROM complicating CS and adverse pregnancy outcomes.

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Analysis of cases of premature rupture of membranes and preterm births to identify effective management measures to prevent them.

OBJECTIVE: Aim: Based on retrospective analysis recognize the key factors of development of premature childbirth and elaborate highly specific criteria for individual prognosis to improve perinatal outcomes. PATIENTS AND METHODS: Materials and Methods: A retrospective analysis of the birth histories of 250 women and their newborns with spontaneous preterm births at 22-36 weeks was conducted using archival data from the department for pregnant women with obstetric pathology of the State Institution "Institute of Pediatrics, Obstetrics and Gynecology named by academician OM Lukianova of the National Academy of Medical Sciences of Ukraine". RESULTS: Results: Important risk factors for premature rupture of membranes (PROM) in preterm pregnancy include the presence of sexually transmitted diseases (χ2=31.188, p=0.001), bacterial vaginosis (χ2=30.913, p=0.0001), a history of abortion and/or preterm birth (χ2=16.62, p=0.0002), SARS during pregnancy (χ2=16.444, p=0.0002), chronic adnexitis in anamnesis (χ2=11.522, p=0.0031), inflammatory cervical disease (χ2=11.437, p=0.0032), anaemia (χ2=10.815, p=0.0044), isthmic-cervical insufficiency (ІСІ) (χ2=10.345, p=0.0057), chronic pyelonephritis with exacerbation (χ2=9.16, p=0.01), smoking during pregnancy (χ2=10.815, p=0.0044). CONCLUSION: Conclusions: The results of a retrospective analysis of 250 cases of preterm birth at 22 to 36 weeks allowed us to identify ways to effectively use existing diagnostic measures to determine readiness for pregnancy and the possibility of prolonging pregnancy to the viability of the newborn. Ways to improve the prevention of preterm birth and the design of further research were identified.