Association Analysis Between Maternal Neutrophil Ratio and the Risk of Histological Chorioamnionitis in Pregnant Women with Premature Rupture of Membranes in Late Pregnancy.

Background: We aimed to investigate the association between maternal neutrophil ratio and histological chorioamnionitis (HCA) risk in pregnant women with premature rupture of membranes (PROM) in late pregnancy. Methods: A retrospective analysis was conducted on 95 cases of women with PROM in their late pregnancy between March 2018 and August 2021. These women were divided into two groups based on the presence of HCA. General clinical data and laboratory indicators were compared between the two groups. A generalized additive model was used for curve fitting, and a segmented regression model was used to explain further the non-linear relationship between neutrophil ratio and HCA risk. Results: After adjusting for confounding factors, the curve fitting showed a "U"-shaped curve relationship between the neutrophil ratio and the risk of HCA. When the neutrophil ratio was <76.3%, the risk of HCA exhibited a decreasing trend, but the difference was not statistically significant (adjusted OR = 0.884, 95% CI: 0.781-1.001, P = 0.053). However, when the neutrophil ratio was >76.3%, the HCA risk was significantly increased (adjusted OR = 1.339, 95% CI: 1.067-1.680, P = 0.012). Furthermore, we equally divided the neutrophil ratio into three groups. The risk of HCA was significantly increased in the low-ratio group (OR = 4.292, 95% CI: 1.247-14.706, P = 0.021) compared with the middle-ratio group, which was used as the reference group. Similarly, the HCA risk of the high-ratio group (OR = 13.145, 95% CI: 1.796-96.233, P = 0.011) was also significantly enhanced. However, there was no significant difference in HCA risk between the high-ratio and low-ratio groups (OR = 1.182, 95% CI: 0.357-3.909, P = 0.784). Conclusion: There was a significant "U"-shaped relationship between maternal neutrophil ratio and HCA risk in women with PROM in late pregnancy.

Value of fetal echocardiographic examination in pregnancies complicated by preterm premature rupture of membranes.

OBJECTIVES: Cardiopulmonary and infectious complications are more common in preterm newborns after preterm premature rupture of membranes (pPROM). Fetal echocardiography may be helpful in predicting neonatal condition. Our aim was to assess the cardiovascular changes in fetuses from pregnancies complicated by pPROM and possible utility in predicting the intrauterine or neonatal infection, and neonatal heart failure (HF). METHODS: It was a prospective study enrolling 46 women with singleton pregnancies complicated by pPROM between 18+0 and 33+6 weeks of gestation and followed until delivery. 46 women with uncomplicated pregnancies served as a control group. Fetal echocardiographic examinations with the assessment of cardiac structure and function (including pulmonary circulation) were performed in all patients. RESULTS: Mean gestational age of pPROM patients was 26 weeks. Parameters suggesting impaired cardiac function in fetuses from pPROM were: higher right ventricle Tei index (0.48 vs. 0.42 p<0.001), lower blood flow velocity in Ao z-score (0.14 vs. 0.84 p=0.005), lower cardiovascular profile score (CVPS), higher rate of tricuspid regurgitation (18.2 % vs. 4.4 % p=0.04) and pericardial effusion (32.6 vs. 0 %). Intrauterine infection was diagnosed in 18 patients (39 %). 4 (8.7 %) newborns met the criteria of early onset sepsis (EOS). HF was diagnosed in 9 newborns. In fetal echocardiographic examination HF group had shorter mitral valve inflow time and higher left ventricle Tei index (0.58 vs. 0.49 p=0.007). CONCLUSIONS: Worse cardiac function was observed in fetuses from pPROM compared to fetuses from uncomplicated pregnancies.

A Case of Consumptive Coagulopathy Before Cardiopulmonary Failure in Amniotic Fluid Embolism and Review of Literature: A Perspective of the Latent Onset and Progression of Coagulopathy.

Amniotic fluid embolism (AFE) induces cardiopulmonary insufficiency with consumptive coagulopathy. Previous studies reported that refractory coagulopathy has already advanced at the onset of maternal cardiovascular and/or respiratory symptoms. However, when the consumption of coagulation factors starts during the clinical course, AFE remains to be elucidated. We report an intrapartum AFE case of consumptive coagulopathy before dyspnea with hypotension developing during urgent cesarean delivery that was revealed by non-reassuring fetal heart rate tracing. The patient, a 42-year-old multiparous parturient, underwent induced labor after a premature rupture of membranes in week 39 of pregnancy. Coagulation screening was initially within the normal range. Fetal heart rate monitoring demonstrated bradycardia coincided with uterine tachysystole after three hours, which required urgent cesarean section with preoperative blood screening. The hemoglobin level was maintained at 129 g/L; however, the fibrinogen value reduced to 1.79 g/L with D-dimer elevation over 60 µg/mL. Ninety minutes later, she developed dyspnea with hypotension at suturing hysterotomy. At the end of surgery, her fibrinogen further decreased to below 0.3 g/L with prolonged prothrombin time. After vigorous intensive care, she was discharged without sequelae. Consumptive coagulopathy may initiate and progress before apparent cardiopulmonary symptoms in some AFE cases. Non-reassuring fetal heart rate tracing concomitant with abrupt uterine tachysystole and/or hypertonus may be an earlier time point for the detection and intervention of AFE-related coagulopathy.

Causal associations between Helicobacter pylori infection and pregnancy and neonatal outcomes: a two-sample Mendelian randomization study.

Background: Observational studies have reported that Helicobacter pylori (H. pylori) infection is associated with a series of pregnancy and neonatal outcomes. However, the results have been inconsistent, and the causal effect is unknown. Methods: A two-sample Mendelian randomization (MR) study was performed using summary-level statistics for anti-H. pylori IgG levels from the Avon Longitudinal Study of Parents and Children Cohort. Outcome data for pregnancy (miscarriage, preeclampsia-eclampsia, gestational diabetes mellitus, placental abruption, premature rupture of membranes, postpartum hemorrhage) and neonates (birthweight, gestational age, and preterm birth) were sourced from genome-wide association meta-analysis as well as the FinnGen and Early Growth Genetics Consortium. Causal estimates were calculated by five methods including inverse variance weighted (IVW). The heterogeneity of instrumental variables was quantified by Cochran's Q test, while sensitivity analyses were performed via MR-Egger, MR-PRESSO, and leave-one-out tests. Results: IVW estimates suggested that genetically predicted anti-H. pylori IgG levels were significantly associated with increased risks of preeclampsia-eclampsia (odds ratio [OR] = 1.12, 95% confidence interval [CI] 1.01-1.24, P = 0.026) and premature rupture of membranes (OR = 1.17, 95% CI 1.05-1.30, P = 0.004). Similar results were obtained for preeclampsia-eclampsia from the MR-Egger method (OR = 1.32, 95% CI 1.06-1.64, P = 0.027) and for premature rupture of membranes from the weighted median method (OR = 1.22, 95% CI 1.06-1.41, P = 0.006). No significant causal effects were found for other outcomes. There was no obvious heterogeneity and horizontal pleiotropy across the MR analysis. Conclusion: Our two-sample MR study demonstrated a causal relationship of H. pylori infection with preeclampsia-eclampsia and premature rupture of membranes. The findings confirm the epidemiological evidence on the adverse impact of H. pylori in pregnancy. Further studies are needed to elucidate the pathophysiological mechanisms and assess the effectiveness of pre-pregnancy screening and preventive eradication.

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.

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.

Rescue Cerclage by McDonald's Technique at 18 Weeks for Cervical Insufficiency With Intravaginal Amniotic Sac: A Case Report.

Recurrent pregnancy loss, premature birth, and associated complications exhibit a multifactorial etiology and persist as substantial challenges during pregnancy, despite the notable advancements in the medical field. Among several factors, cervical insufficiency or incompetence emerges as a prominent causal factor, characterized by painless softening and shortening of the cervix associated with absent contractions. The implementation of emergency cerclage represents a pivotal intervention in mitigating preterm birth among individuals with advanced cervical insufficiency. By extending gestational age, this procedure increases the likelihood of neonatal survival without elevating the risk of chorioamnionitis or preterm rupture of the membranes. In this study, an antenatal woman presented with advanced changes in the cervix along with intravaginal bulging amniotic membranes at 18 weeks and underwent a rescue cervical cerclage, resulting in a successful pregnancy.

Significance of cervical secretion culture in predicting maternal and fetal outcome in pregnant women with premature rupture of membranes: a retrospective cohort study.

Background: To investigate the clinical value of cervical secretion culture in pregnant women with premature rupture of membranes (PROM) in predicting maternal and fetal outcomes. Methods: We retrospectively reviewed clinical records of pregnant women who underwent obstetric examination and delivered in Fujian Maternal and Child Healthcare from December 2013 to December 2016. Pregnant women with a clear diagnosis of PROM, who underwent cervical secretion culture immediately after hospital admission were selected for the study. The primary outcome was the occurrence of chorioamnionitis. The secondary outcome was neonatal admission to the neonatal intensive care unit (NICU). Correlation between maternal and fetal outcomes and the results of the cervical secretion culture was analyzed by one-way analysis and multifactorial analysis, respectively. The predictive efficacy of cervical secretion culture was evaluated using receiver operating characteristic curve (ROC), area under the curve (AUC) and the integrated discrimination improvement (IDI). Results: A total of 7,727 pregnant women with PROM were included in the study. Of them, 1812 had positive cervical secretion cultures (635 positive for mycoplasma infection, 475 for bacterial, 637 for fungal, and 65 for chlamydial infections). Pregnant women with positive mycoplasma and bacterial cultures had higher rates of developing chorioamnionitis compared to women with negative cervical secretion cultures (9%, 12% vs. 1%, respectively). Similarly, positive mycoplasma and bacterial cultures were associated with higher rate of the preterm (before 34 weeks) labor (3%, 3% vs. 1% in women with negative cultures, respectively), and neonatal admission to the NICU (9%, 11% vs. 7%, respectively). After adjusting for various confounding factors, our analysis demonstrated that a positive cervical secretion culture for mycoplasma or bacterial pathogens remained an independent risk factor for chorioamnionitis. Cervical secretion culture outcome was less effective in predicting chorioamnionitis (AUC 0.569) compared to white blood count (WBC) (AUC 0.626) and C-reactive protein (CRP) levels (AUC 0.605). The IDI of the combined predictive model incorporating WBC, CRP, maternal fever and cervical secretion culture results was 0.0029. Conclusion: Positive cervical secretion cultures, especially for mycoplasma and bacteria, are associated with higher incidence of adverse maternal and fetal outcomes. However, the predictive value of this test is poor, and cannot be efficiently used for predicting chorioamnionitis.

Role of NF-κB p65/TNF-α in Cell Apoptosis in the Fetal Membranes of Pregnant Women with Preterm Premature Rupture of Membranes.

OBJECTIVE: This study aimed to investigate the roles of nuclear factor-kappa B p65 (NF-[Formula: see text]B p65) and tumor necrosis factor-α (TNF-α) in cell apoptosis occurring in the fetal membranes of pregnant women who experience preterm premature rupture of membranes (PPROM). METHODS: This was a case-control study involving 57 pregnant women who delivered in the obstetric department of Affiliated Loudi Hospital, Hengyang Medical School, University of South China, from June 2021 to June 2022. Samples of fetal membrane tissue were collected from pregnant women with PPROM (n=27) and pregnant women who had normal deliveries (control group; n=30). The membrane tissue morphology of both groups was observed, and the expression of NF-[Formula: see text]B p65, p-NF-[Formula: see text]B p65, TNF-α, and caspase-3 was detected. Apoptosis in fetal membranes was examined. RESULTS: Morphological evaluation of the fetal membrane tissues obtained from patients with PPROM revealed an abnormal structure with a thin collagen fiber layer and cells with a largely vacuolar cytoplasm. There was a positive correlation between the expression of p-NF-[Formula: see text]B p65/NF-[Formula: see text]B p65 and cell apoptosis (r1 =0.89, R2 =0.805, P=0.00). Furthermore, TNF-α was positively correlated with fetal membrane cell apoptosis (r2 =0.93, R2=0.881, P=0.00). CONCLUSION: NF-[Formula: see text]B p65 is involved in the occurrence of PPROM by promoting the expression of TNF-α, which upregulates caspase-3 to cause apoptosis of fetal membrane cells.

The relationship between maternal exposure to ambient air pollutants and premature rupture of membranes: A systematic review and meta-analysis.

Air pollution is an environmental stimulus that may predispose pregnant women to preterm rapture of membrane (PROM). However, the relationship of maternal exposure to air pollutants and PROM is still unclear. To investigate the relationship between the long-term and short-term maternal exposure to air pollution and PROM. We searched all studies published in PubMed, Embase and Web of Science up to February 2024. The studies provided quantitative effect estimates with 95% confidence intervals, for the impact of short-term (<30 days) or long-term (≥30 days) maternal exposure to air pollutants on PROM, preterm PROM (PPROM) or term PROM (TPROM). The odds ratio (OR), risk ratio (RR), or hazard ratio (HR), with 95% confidence intervals was extracted, and RR or HR were deemed as OR because of the low prevalence of PROM. Fixed- or random-effects meta-analyses performed. In total, 17 relevant studies were included. Maternal exposure to PM2.5 in the second trimester increases the risk of PROM (pooled OR = 1.15, 95%CI: 1.05-1.26). Maternal exposure to PM10, NO2, NO, CO and SO2 during pregnancy and short-term maternal exposure to PM2.5, NO2, SO2 and O3 also associate with PROM occurrence. The results of the study show that both long-term maternal exposure in the second or third trimester and short-term maternal exposure to ambient air pollution can increase the risk of PROM.

In premature rupture of membranes, maternal serum delta neutrophil index may be a predictive factor for histological chorioamnionitis and affect fetal inflammatory markers: A retrospective cross-sectional study.

PROBLEM: We aimed to investigate the predictive value of delta neutrophil index (DNI) for histological choriomanionitis (HCAM) and the effect of maternal inflammatory markers on neonatal outcomes and fetal inflammatory parameters. METHOD OF STUDY: In this retrospective cross-sectional study, 68 pregnant women without HCAM (group 1) and 46 pregnant women diagnosed with HCAM (group 2) were divided into two groups. Demographic stories of the groups; maternal hematological parameters; maternal DNI and systemic inflammatory index (SII) values; outcomes of newborns; fetal inflammatory markers were recorded and compared between groups. RESULTS: Maternal DNI, and SII levels were significantly higher in group 2 (p value < .05 for all). Admission to the neonatal unit (NICU) was higher in group 2 than in group 1 (p = .0001). We found that fetal inflammatory markers were significantly higher in group 2 (p values .001 for CRP, .0001 for DNI, and .002 for leukocyte). Maternal DNI was determined to be significantly diagnostic at a value of ≥1.3 in HCAM (p = .001). We observed that SII had a significant predictive value of 953036.6 (p = .019) for NICU admission. There is also a positive correlation between fetal inflammatory markers and maternal inflammatory markers. CONCLUSIONS: We found that maternal inflammatory markers are high in HCAM, maternal DNI can predict patients who will develop HCAM, maternal SII value can predict NICU admission, fetal inflammatory markers are high in HCAM, and these markers are affected by maternal inflammatory markers.

Prenatal exposure to intra-amniotic infection with Ureaplasma species increases the prevalence of bronchopulmonary dysplasia.

OBJECTIVES: The present study investigated the relationship between bronchopulmonary dysplasia (BPD) and intra-amniotic infection with Ureaplasma species. METHODS: This was a single-center, retrospective cohort study. Patients with singleton pregnancies who underwent inpatient management at our department for preterm premature rupture of membranes (PPROM), preterm labor, cervical insufficiency, and asymptomatic cervical shortening at 22-33 gestational weeks were included. Amniocentesis was indicated for patients with PPROM or an elevated maternal C-reactive protein level (≥0.58 mg/dL). Patients with an amniotic fluid IL-6 concentration ≥3.0 ng/mL were diagnosed with intra-amniotic inflammation, while those with positive aerobic, anaerobic, M. hominis, and Ureaplasma spp. cultures were diagnosed with microbial invasion of the amniotic cavity (MIAC). Patients who tested positive for both intra-amniotic inflammation and MIAC were considered to have intra-amniotic infection. An umbilical vein blood IL-6 concentration >11.0 pg/mL indicated fetal inflammatory response syndrome (FIRS). The maternal inflammatory response (MIR) and fetal inflammatory response (FIR) were staged using the Amsterdam Placental Workshop Group Consensus Statement. RESULTS: Intra-amniotic infection with Ureaplasma spp. was diagnosed in 37 patients, intra-amniotic infection without Ureaplasma spp. in 28, intra-amniotic inflammation without MIAC in 58, and preterm birth without MIR/FIR and FIRS in 86 as controls. Following an adjustment for gestational age at birth, the risk of BPD was increased in patients with intra-amniotic infection with Ureaplasma spp. (adjusted odds ratio: 10.5; 95% confidence interval: 1.55-71.2), but not in those with intra-amniotic infection without Ureaplasma spp. or intra-amniotic inflammation without MIAC. CONCLUSION: BPD was only associated with intra-amniotic infection with Ureaplasma species.

Autophagy Determines Distinct Cell Fates in Human Amnion and Chorion Cells.

Human fetal membranes (amniochorion) that line the intrauterine cavity consist of two distinct cell layers; single-layer amnion epithelial cells (AEC) and multilayer chorion trophoblast cells (CTC). These layers are connected through a collagen-rich extracellular matrix. Cellular remodeling helps support membrane growth and integrity during gestation and helps to maintain pregnancy. Preterm prelabor rupture of the human amniochorionic (fetal) membrane (pPROM) is antecedent to 40% of all spontaneous preterm birth. Oxidative stress (OS) induced activation of the p38 MAPK due to various maternal risk exposures and the amniochorion cells' senescence are reported pathological features of pPROM. Our transcriptomics analysis implicated dysregulated autophagy and epithelial-mesenchymal transition (EMT) in fetal membranes from pPROM. The molecular interplay between OS-induced p38 MAPK activation, autophagy, and EMT was investigated in AECs and CTCs to better understand the involvement of autophagy and EMT. We report the differential impact of OS on the autophagic machinery in AECs and CTCs, resulting in distinct cell fates. In AECs, OS-induced p38 MAPK activation causes autophagosome accumulation and reduced autophagic flux mediated by decreased ULK1 activity and kinase activity, leading to senescence. In CTCs, induction of autophagy has a limited effect; however, inhibition of autophagy led to SQSTM1-mediated EMT of trophoblast cells. Autophagy, EMT, and senescence were associated with proinflammatory changes. Thus, AECs and CTCs respond differently to OS via differential autophagy response, partly mediated via p38 MAPK. Besides senescence, OS-induced autophagy dysregulation in amniochorion cells may play a mechanistic role in pPROM pathophysiology.

FPR1 Antagonist (BOC-MLF) Inhibits Amniotic Epithelial-mesenchymal Transition.

OBJECTIVE: Premature rupture of membranes (PROM) is a common pregnancy disorder that is closely associated with structural weakening of fetal membranes. Studies have found that formyl peptide receptor 1 (FPR1) activates inflammatory pathways and amniotic epithelialmesenchymal transition (EMT), stimulates collagen degradation, and leads to membrane weakening and membrane rupture. The purpose of this study was to investigate the anti-inflammatory and EMT inhibitory effects of FPR1 antagonist (BOC-MLF) to provide a basis for clinical prevention of PROM. METHODS: The relationship between PROM, FPR1, and EMT was analyzed in human fetal membrane tissue and plasma samples using Western blotting, PCR, Masson staining, and ELISA assays. Lipopolysaccharide (LPS) was used to establish a fetal membrane inflammation model in pregnant rats, and BOC-MLF was used to treat the LPS rat model. We detected interleukin (IL)-6 in blood from the rat hearts to determine whether the inflammatory model was successful and whether the anti-inflammatory treatment was effective. We used electron microscopy to analyze the structure and collagen expression of rat fetal membrane. RESULTS: Western blotting, PCR and Masson staining indicated that the expression of FPR1 was significantly increased, the expression of collagen was decreased, and EMT appeared in PROM. The rat model indicated that LPS caused the collapse of fetal membrane epithelial cells, increased intercellular gaps, and decreased collagen. BOC-MLF promoted an increase in fetal membrane collagen, inhibited EMT, and reduced the weakening of fetal membranes. CONCLUSION: The expression of FPR1 in the fetal membrane of PROM was significantly increased, and EMT of the amniotic membrane was obvious. BOC-MLF can treat inflammation and inhibit amniotic EMT.

Maternal biomarkers in predicting neonatal sepsis after preterm premature rupture of membranes in preterm infants.

AIM: This retrospective cohort study aimed to assess the utility of maternal C-reactive protein (CRP) and leukocyte levels in predicting neonatal sepsis after preterm premature rupture of membranes (pPROM). METHODS: We conducted a retrospective cohort study (2009-2021), encompassing preterm infants born ≤29 + 6 weeks of gestation following pPROM. The primary outcome was early-onset neonatal sepsis within the initial 72 h of life. RESULTS: We analysed data from 706 patients with a median gestational age at pPROM of 25.1 weeks and a median gestational age at birth of 26.4 weeks. Overall survival rate was 86.1%, with 65.7% survival without severe morbidities. These rates were significantly worse in preterm infants with sepsis. Maternal CRP and leukocyte levels correlated significantly with neonatal infection markers and sepsis. However, their predictive values, correlation coefficients, and area under the curve values were generally low. Using maternal CRP ≥2 mg/dL to predict neonatal sepsis yielded a positive predictive value of 18.5%, negative predictive value of 91.5%, AUC of 0.589, 45.5% sensitivity, and 74.5% specificity. CONCLUSION: Maternal CRP and leukocyte levels were ineffective as a tool for predicting early-onset neonatal sepsis following early pPROM. Consequently, these biomarkers lack the reliability required for clinical decision-making in this context.

Soluble urokinase plasminogen activator receptor in vaginally collected amniotic fluid predicting fetal inflammatory response syndrome: a prospective cohort study.

BACKGROUND: Improving noninvasive antenatal diagnosis of fetal inflammatory response syndrome (FIRS) can assist in the evaluation of prenatal risk and reduce perinatal outcomes. This study aimed to determine whether soluble urokinase-type plasminogen activator receptor (suPAR) in vaginally collected amniotic fluid is significant in identifying FIRS after preterm premature rupture of membranes before 34 weeks of gestation. METHODS: This was a prospective cohort study of 114 pregnant women and their newborns after preterm premature rupture of membranes at 22-34+6 weeks of gestation. SuPAR was evaluated using an enzyme-linked immunosorbent assay in vaginally collected amniotic fluid. Patients were classified according to the presence or absence of FIRS. FIRS was defined by umbilical cord blood interleukin-6 level > 11 pg/mL or histological funisitis. The data were analyzed using the R package (R-4.0.5). RESULTS: SuPAR was detected in all amniotic fluid samples with a median of 26.23 ng/mL (interquartile range (IQR), 15.19-51.14). The median level of suPAR was higher in the FIRS group than in the non-FIRS group, 32.36 ng/mL (IQR, 17.27-84.16) vs. 20.46 ng/mL (IQR, 11.49-36.63) (P = 0.01), respectively. The presence of histological chorioamnionitis significantly increased the suPAR concentration in the FIRS group (P < 0.001). The areas under the curve for FIRS and FIRS with histological chorioamnionitis were 0.65 and 0.74, respectively, with an optimum cutoff value of 27.60 ng/mL. Controlling for gestational age, the cutoff of suPAR more than 27.60 ng/mL predicted threefold higher odds for FIRS and sixfold higher odds for FIRS with histologic chorioamnionitis. CONCLUSION: Soluble urokinase-type plasminogen activator receptor in vaginally obtained amniotic fluid may assist in evaluating prenatal risk of FIRS in patients after preterm premature rupture of membranes before 34 weeks of gestation.

Statement of the Obstetrics and Prenatal Medicine Working Group (AGG - Preterm Birth Section) on "Outpatient Management for Pregnant Women with Preterm Premature Rupture of Membranes (PPROM)".

Preterm premature rupture of membranes (PPROM) is one of the leading causes of perinatal morbidity and mortality. After a PPROM, more than 50% of pregnant women are delivered within 7 days. Fetal and maternal risks are primarily due to infection and inflammation, placental abruption, umbilical cord complications and preterm birth. Standard care usually consists of an expectant approach. Management includes the administration of antenatal steroids and antibiotic therapy. Patients with PPROM require close monitoring. The management of pregnant women with PPROM (inpatient vs. outpatient) is still the subject of controversial debate. The international guidelines also do not offer a clear stance. The statement presented here discusses the current state of knowledge.

Development and Validation of a Multivariable Predictive Model for the Risk of Histologic Chorioamnionitis in Patients with Premature Rupture of Membranes in the Late Preterm and Term.

Background: This study aimed to develop and validate a model to predict histologic chorioamnionitis (HCA) risk in late preterm and term premature rupture of membranes (PROM) patients using clinical and laboratory parameters. Methods: We conducted a retrospective study on 116 late preterm and term PROM cases, divided into a training (n=81) and a validation set (n=35). A multivariable logistic regression model was developed using the training set. Performance was assessed via the area under the receiver operating characteristic curve (AUC) and net reclassification index (NRI). Decision curve analysis (DCA) evaluated the model's clinical utility. Additionally, nomograms and a web version of the model were developed. Results: In the training set, the combined model constructed using maternal BMI, gravidity, amniotic fluid characteristics, and prenatal white blood cell (WBC) count showed significantly higher AUC than WBC alone (0.859 vs 0.710, P=0.010), with improved accuracy and sensitivity. In the validation set, the AUC of the combined model remained higher than that of WBC, but the difference was not statistically significant (0.728 vs 0.584, P=0.173). NRI analysis indicated that the combined model improved the correct classification of HCA by 25.0% (P=0.012) compared to that of WBC alone. DCA demonstrated that the combined model had a higher net benefit than WBC in most cases. The nomograms and web version of the model provided convenient tools for clinicians to predict the risk of HCA. Conclusion: This study successfully developed and validated a clinically feasible multivariable model to predict the risk of HCA in women with late preterm and term PROM.

Potential of plasma inflammatory and angiogenic mediators for predicting spontaneous preterm delivery, intraamniotic infection/inflammation, and composite neonatal morbidity/mortality in women with early preterm premature rupture of membranes.

PROBLEM: To assess the potential of five inflammatory and six angiogenic/antiangiogenic plasma proteins for predicting imminent spontaneous preterm delivery (SPTD; ≤14 days of sampling), microbial invasion of the amniotic cavity and/or intraamniotic inflammation (MIAC/IAI), and composite neonatal morbidity and mortality (CNMM) in women with early preterm premature rupture of membranes (PPROM). METHODS OF STUDY: This retrospective cohort study included 76 singleton pregnant women with early PPROM (23-30 weeks). Amniotic fluid obtained via amniocentesis was cultured for microorganism detection and assayed for interleukin-6 to define IAI (≥2.6 ng/mL). Plasma C4a, endoglin, endostatin, IGFBP-1, IGFBP-2, MMP-9, PlGF, S100A8, S100A9, S100 A8/A9, and VEGFR-1 levels were determined using ELISA. RESULTS: Multivariate logistic regression analyses revealed significant associations between (i) high levels of plasma S100A8/A9, SPTD ≤14 days after sampling, and shorter sampling-to-delivery intervals; (ii) elevated plasma MMP-9, S100A9, and S100A8/A9 levels and MIAC/IAI, and (iii) decreased plasma endoglin levels and increased CNMM risk, while adjusting for gestational age at sampling (or delivery) and tocolytic use. The area under the curves of the aforementioned proteins ranged from 0.655 to 0.731 for each outcome. Notably, the SPTD risk increased significantly with increasing plasma S100A8/A9 levels (P for trend < .05). CONCLUSIONS: Plasma S100A8/A9, MMP-9, S100A9, and endoglin may represent valuable biomarkers associated with SPTD, MIAC/IAI, and CNMM in women with early PPROM. Owing to their less invasive nature, repeatability, and fair-to-moderate diagnostic accuracy, these biomarkers may contribute to risk stratification of PPROM-related complications in the clinical setting.

The Importance of Tissue Doppler Imaging and M-Mode Ultrasonography in Fetuses With Preterm Premature Rupture of Membranes: A Case-Control Study.

OBJECTIVE: To compare the cardiac functions of fetuses with preterm premature rupture of membranes (PPROM) between their control groups and investigate its relationship with perinatal outcomes. METHODS: This prospective study was conducted with 102 pregnant women. Pregnant women with PPROM were divided into two subgroups Group A, between 26 and 30 weeks, and Group B, between 30 and 34 weeks. A control group was formed by randomly including one healthy pregnant woman for each study patient. Sociodemographic, obstetric data, tissue Doppler imaging, and M-mode imaging results were compared. The relationship between echocardiographic parameters and perinatal outcomes was also investigated. RESULTS: Tricuspid annular plane systolic excursion (TAPSE), S', and ET' of systolic cardiac parameters were shortened in both groups compared with their controls. Diastolic function indicator E'/A', and global function indicator myocardial performance index' increased in both groups. Isovolumetric contraction time' did not change between groups. A correlation was found between myocardial performance index', and the length of neonatal intensive care unit stay in Group A and TAPSE and duration of respiratory support and length of neonatal intensive care unit stay in Group B. CONCLUSIONS: The fetal cardiac function seems to be affected by PPROM, and these changes are associated with neonatal outcomes. Therefore, administering fetal cardiac function evaluation in pregnancies complicated by PPROM may help physicians establish more appropriate clinical management protocols in this special population.