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Preterm premature rupture of membranes (pPROM) stands as a primary contributor to preterm deliveries worldwide, closely linked to consequential infectious peripartum complications, including chorioamnionitis and early-onset neonatal sepsis. As a prophylactic measure, individuals following pPROM routinely undergo antibiotic treatment. The aim of this study was to evaluate changes in the vaginal microbial colonization after antibiotic treatment following pPROM. Therefore, we retrospectively assessed the impact of antibiotic treatment on the maternal vaginal microbial colonization in 438 post-pPROM patients delivering before 29 gestational weeks. Vaginal samples were collected for microbiological analysis before and after antibiotic administration and analysed for seventeen pre-defined microbial groups. We observed eradication in eleven microbial groups, including beta-hemolytic streptococci group B and Gardnerella vaginalis. No significant reduction was found for the remaining groups, including Escherichia (E.) coli. Moreover, we found a notable increase in resistant bacteria after antibiotic treatment. In conclusion, broad-spectrum antimicrobial treatment exhibited substantial efficacy in eradicating the majority of pathogens in our cohort. However, certain pathogens, notably E. coli, showed resilience. Given E. coli's prominent role in infectious peripartum complications, our findings underline the challenges in antibiotic management post-pPROM and the need to establish international guidelines, particularly regarding emerging concerns about antibiotic resistances. [ABSTRACT FROM AUTHOR]

Background: Pancreatic stone protein (PSP) is a biochemical serum marker that contains levels that are elevated in various inflammatory and infectious diseases. The role of PSP in the diagnosis of these diseases seems to be more important compared to clinically established biochemical serum markers in discriminating the severity of the same diseases. Standard values for PSP in pregnant women in relation to gestational age have been reported recently. Additionally, increased PSP levels have been observed to be associated with renal dysfunction in pregnant women. The aim of this study is to evaluate the diagnostic role of PSP in pregnancy-related diseases, such as pre-eclampsia (PE), hemolysis-elevated liver enzymes, and low platelet (HELLP) syndrome. In addition, the study aims to assess its diagnostic role in inflammation-triggered diseases as preterm premature rupture of membranes (PPROM) or COVID-19-positive pregnant women. Materials and Methods: In this single-centred prospective study performed at a tertiary university hospital between 2013 and 2021, we included 152 pregnant women who were diagnosed with either PE, HELLP syndrome, or PPROM. In December 2020, in the context of the COVID-19 pandemic, the Independent Ethics Committee (IEC) approved an amendment to the study protocol. Depending on the underlying disease, single or serial-serum PSP measurements were assessed. These PSP values were compared to PSP levels of women with normal pregnancies. Results: Pregnant women diagnosed with pre-eclampsia or HELLP syndrome had significantly increased PSP values (mean 9.8 ng/mL, SD 2.6) compared to healthy singleton pregnant women (mean 7.9 ng/mL, SD 2.6, p ≤ 0.001). There was no difference in serum PSP in pregnant women with PPROM compared to women with uncomplicated singleton pregnancies (mean in PPROM: 7.9 ng/mL; SD 2.9 versus mean in healthy pregnancies: 7.9 ng/mL; SD 2.6, p = 0.98). Furthermore, no difference in the PSP values in women with or without intra-amniotic infection was observed (infection: mean 7.9 ng/mL; SD 2.8 versus no infection: mean 7.8 ng/mL; SD 3, p = 0.85). The mean value of PSP in COVID-19-infected women during pregnancy (8.5 ng/mL, SD 2.3) was comparable to healthy singleton pregnancies (mean 7.9 ng/mL, SD 2.6), p = 0.24. Conclusions: The novel serum biomarker PSP is significantly upregulated in pregnant women with pre-eclampsia and HELLP syndrome. Our observations call for the further evaluation of PSP in randomized controlled clinical trials to demonstrate the actual role of PSP in pregnancy-related diseases and whether it may provide new approaches for the management and discrimination of the severity of these gestational conditions. [ABSTRACT FROM AUTHOR]

Preterm premature rupture of membranes, leading to preterm birth, is associated with neonatal and maternal morbidity and mortality. The study aimed to review the existing data on the best predictive value of pregnancy latency for known biomarkers in pregnancies after preterm premature rupture of membranes. The following databases were screened for the purposes of this systematic review: Pubmed/MEDLINE, Web of Science, EMBASE, Scopus, and the Cochrane Library. The study was conducted according to the PRISMA guidelines for systematic reviews. Only a few studies assessed biomarkers predicting pregnancy duration after PPROM. IL-6, IL-8, CRP, IL1RA, s-endoglin, βhCG, AFP, PCT, urea, creatinine, oxygen radical absorbance capacity, MDA, lipocalin-2, endotoxin activity, MMP-8, MMP-9 and S100 A8/A9 were found to have a positive predictive value for delivery timing prediction. Proinflammatory biomarkers, such as IL-6 or CRP, proved to be best correlated with delivery timing, independent of the occurrence of intrauterine infection. [ABSTRACT FROM AUTHOR]

Preterm labor (PTL) and preterm premature rupture of membranes (PPROM) lead to high perinatal morbidity/mortality rates worldwide. Small extracellular vesicles (sEV) act in cell communication and contain microRNAs that may contribute to the pathogenesis of these complications. We aimed to compare the expression, in sEV from peripheral blood, of miRNAs between term and preterm pregnancies. This cross-sectional study included women who underwent PTL, PPROM, and term pregnancies, examined at the Botucatu Medical School Hospital, SP, Brazil. sEV were isolated from plasma. Western blot used to detect exosomal protein CD63 and nanoparticle tracking analysis were performed. The expression of 800 miRNAs was assessed by the nCounter Humanv3 miRNA Assay (NanoString). The miRNA expression and relative risk were determined. Samples from 31 women—15 preterm and 16 term—were included. miR-612 expression was increased in the preterm groups. miR-612 has been shown to increase apoptosis in tumor cells and to regulate the nuclear factor κB inflammatory pathway, processes involved in PTL/PPROM pathogenesis. miR-1253, miR-1283, miR378e, and miR-579-3p, all associated with cellular senescence, were downregulated in PPROM compared with term pregnancies. We conclude that miRNAs from circulating sEV are differentially expressed between term and preterm pregnancies and modulate genes in pathways that are relevant to PTL/PPROM pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the effect of gestational age (GA) at the time of fetoscopic laser photocoagulation (FLP) for severe twin–twin transfusion syndrome (TTTS) on perinatal outcomes in a single center in Taiwan. Materials and methods: Severe TTTS was defined as a diagnosis of TTTS before a GA of 26 weeks. Consecutive cases of severe TTTS treated at our hospital with FLP between October 2005 and September 2022 were included. The evaluated perinatal outcomes were preterm premature rupture of membranes (PPROM) within 21 days of FLP, survival 28 days after delivery, GA at delivery, and neonatal brain sonographic imaging findings within 1 month of delivery. Results: We included 197 severe TTTS cases; the mean GA at the time of FLP was 20.6 weeks. After the cases were divided into cases of FLP at early (below 20 weeks) and late GAs (more than 20 weeks), the early-GA group was discovered to be associated with a deeper maximum vertical pocket in the recipient twin, a higher rate of PPROM development within 21 days of FLP, and lower rates of survival of one or both twins. In the cases of stage I TTTS, the rate of PPROM within 21 days of FLP was higher in the group that underwent FLP at an early GA than in the group that underwent FLP at a late GA (50% (3/6) vs. 0% (0/24), respectively, p = 0.005). Logistic regression analysis revealed that the GA at the time of FLP and the cervical length before FLP is implemented are significantly associated with the survival of one twin and the incidence of PPROM development within 21 days of FLP. The GA at the time of FLP, the cervical length before FLP, and TTTS being stage III TTTS were associated with the survival of both twins after FLP. Neonatal brain image anomalies were associated with GA at delivery. Conclusions: FLP being performed at an earlier GA is a risk factor for lower fetal survival and PPROM development within 21 days of FLP in cases of severe TTTS. Delaying FLP for cases involving stage I TTTS diagnosed at an early GA without risk factors, such as maternal symptoms, cardiac overload in the recipient twin, or a short cervical length, may be considered, but whether delaying FLP would improve surgical outcomes and, if so, how long the delay should be may need further trials to answer. [ABSTRACT FROM AUTHOR]

Background: The classic mid-trimester preterm premature rupture of membranes (PPROM) is defined as a rupture of the fetal membranes prior to 28 weeks of gestation (WG) with oligo/anhydramnion; it complicates approximately 0.4–0.7% of all pregnancies and is associated with very high neonatal mortality and morbidity. Antibiotics have limited success to prevent bacterial growth, chorioamnionitis and fetal inflammation. The repetitive amnioinfusion does not work because fluid is lost immediately after the intervention. The continuous amnioinfusion through the transabdominal port system or catheter in patients with classic PPROM shows promise by flushing out the bacteria and inflammatory components from the amniotic cavity, replacing amniotic fluid and thus prolonging the PPROM-to-delivery interval. Objective: This multicenter trial aims to test the effect of continuous amnioinfusion on the neonatal survival without the typical major morbidities, such as severe bronchopulmonary dysplasia, intraventricular hemorrhage, cystic periventricular leukomalacia and necrotizing enterocolitis one year after the delivery. Study Design: We plan to conduct a randomized multicenter trial with a two-arm parallel design. Randomization will be between 22/0 and 26/0 SSW. The control group: PPROM patients between 20/0 and 26/0 WG who will be treated with antibiotics and corticosteroids (from 22/0 SSW) in accordance with the guidelines of German Society of Obstetrics and Gynecology (standard PPROM therapy). In the interventional group, the standard PPROM therapy will be complemented with the Amnion Flush Method, with the amnioinfusion of Amnion Flush Solution through the intra-amnial catheter (up to 100 mL/h, 2400 mL/day). Subjects: The study will include 68 patients with classic PPROM between 20/0 and 26/0 WG. TRIAL-registration: ClinicalTrials.gov ID: NCT04696003. German Clinical Trials Register: DRKS00024503, January 2021. [ABSTRACT FROM AUTHOR]

Objective: To investigate the severity of histologic chorioamnionitis /funisitis according to the indication for preterm delivery and their corresponding neonatal outcomes. Method: This study included 411 singleton women who delivered between 21+0 and 31+6 week of gestation due to preterm labor (PTL, n = 165), preterm premature rupture of membranes (PPROM, n = 202), or incompetent internal os of the cervix (IIOC, n = 44). The primary outcome measure was the rate of severe histological chorioamnionitis/funisitis. Secondary outcome measure was neonatal outcomes including neonatal and infant death, and neonatal composite morbidity. Results: The PPROM group demonstrated a higher rate of severe histological chorioamnionitis/funisitis compared to the PTL group (severe histological chorioamnionitis; PPROM, 66.3% vs. PTL, 49.1%, p = 0.001, severe funisitis; PPROM, 44.1% vs. PTL, 23.6%, p < 0.001) and this remained significant after multivariable analysis (severe histologic chorioamnionitis, OR 2.367, 95% CI 1.517–3.693; severe funisitis, OR 2.668, 95% CI 1.684–4.226). For neonatal outcomes only, a higher rate of patent ductus arteriosus was observed in the IIOC group compared to the PTL and PPROM groups (IIOC, 77.3% vs. PTL, 54.0% vs. PPROM, 54.0%, p = 0.043) and this remained significant after multivariable analysis. Conclusion: Indication of spontaneous preterm delivery might affect the placental inflammatory pathology and neonatal morbidity. [ABSTRACT FROM AUTHOR]

Preterm premature rupture of membranes (PPROM) interrupts normal lung development, resulting in neonatal respiratory morbidity. Although post-PPROM risks have been researched, only a few studies have investigated noninvasively obtained amniotic fluid (AF) to predict neonatal outcomes. In this study, we aimed to determine whether epidermal growth factor (EGF) in vaginally-collected AF is a significant predictor of neonatal respiratory outcomes after PPROM. We analyzed EGF in vaginally-obtained AF from 145 women with PPROM at 22–34 weeks of gestation. The following neonatal outcomes were included: respiratory distress syndrome, surfactant need, duration and type of respiratory support, and bronchopulmonary dysplasia. We found that EGF concentration was associated with gestational age, and its medians were lower in neonates with respiratory morbidities than unaffected ones. EGF concentrations gradually declined, the lowest being in the most clinically ill patients. EGF < 35 pg/mL significantly predicted the odds of severe respiratory outcomes. EGF in noninvasively collected AF may be a reliable predictor for respiratory outcomes of preterm neonates with PPROM before 34 weeks of gestation. The results of our study may have implications for further research both in noninvasive amniotic fluid analysis and the management of patients after PPROM. [ABSTRACT FROM AUTHOR]

Citrobacter koseri is a facultative anaerobic, motile, non-spore-forming Gram-negative bacillus, which belongs to the family of Enterobacteriaceae. Severe infections due to Citrobacter spp. have been reported in the urinary tract, respiratory airways, intra-abdominal organs, skin and soft tissue, eye, bone, bloodstream, and central nervous system. In newborns, C. koseri is a well-known cause of meningitis, cerebral abscesses, brain adhesions, encephalitis, and pneumocephalus. Infection can be acquired through vertical maternal transmission or horizontal hospital settings; however, in many cases, the source is unknown. Preterm premature rupture of membranes (PPROM), caused by C. koseri, has rarely been described. Herein, we describe a case of PPROM at 16 weeks and 3 days of gestation, leading to anhydramnios. The parents opted for legal termination of the pregnancy, as the prognosis was very poor. C. koseri was isolated postmortem from a placental subamniotic swab and parenchymal sample, as well as fetal blood and lung. To the best of our knowledge, this is the first case of early second-trimester PPROM in which C. koseri infection was demonstrated. [ABSTRACT FROM AUTHOR]

Background: Culture-proven sepsis is the gold standard in early-onset neonatal sepsis diagnosis. Infants born ≤29 weeks gestation after preterm rupture of membranes in the years 2009–2015 were included in a retrospective cohort study performed at a level III fetal-maternal unit. The study aimed to compare culture-proven sepsis, clinical sepsis and positive laboratory biomarkers ≤72 h as predictors of mortality before discharge and the combined outcome of mortality or severe short-term morbidity (severe cerebral morbidity, bronchopulmonary dysplasia and retinopathy). Results: Of the 354 patients included, culture-proven sepsis, clinical sepsis and laboratory biomarkers were positive in 2.3%, 8.5% and 9.6%, respectively. The mortality rate was 37.5% for patients with culture-proven sepsis (3/8), 33.3% for patients with clinical sepsis (10/30) and 8.8% for patients with positive laboratory biomarkers (3/34), respectively. Mortality or severe morbidity occurred in 75.0% of patients with culture-proven sepsis (6/8), 80.0% of patients with clinical sepsis (24/30) and 44.1% of patients with positive laboratory biomarkers (15/34), respectively. Conclusion: In preterm infants after preterm rupture of membranes, clinical sepsis was almost four times more common and at least equally valuable in predicting mortality and mortality or severe morbidity compared to culture-proven sepsis. [ABSTRACT FROM AUTHOR]

Despite the progress of medicine in the last decades, recurrent pregnancy loss, premature birth, and related complications are still a vast problem. The reasons for recurrent pregnancy loss and preterm delivery are diverse and multifactorial. One of the main reasons for these complications is cervical insufficiency, which means that the cervix is weak and unable to remain closed until the date of delivery. It manifests as painless softening and shortening of the cervix without contractions. The aim of the study was to review the available literature on rescue sutures, which are an emergency treatment in pregnancies with premature cervical dilatation and protrusion of the fetal membranes in the second trimester of pregnancy. This review confirms that emergency cerclage reduces the rate of preterm birth in patients with advanced cervical insufficiency. This procedure prolongs gestational age and improves the chances of survival of the newborn without increasing the risk of chorioamnionitis and preterm premature rupture of membranes. [ABSTRACT FROM AUTHOR]

Background: Preterm premature rupture of membranes (PPROM) is a complication responsible for a third of preterm births. Clinical management is initially hospital based, but homecare management is possible if patients are clinically stable 48 h after PPROM. This study set out to determine factors that are predictive of short latency (delivery ≤ 7 days) exceeding 48 h after PPROM, enabling estimation of the prevalence of maternal and neonatal complications and comparison of maternal and fetal outcomes between inpatient and outpatient management. Method: This was a monocentric retrospective study conducted between 1 January 2010 and 28 February 2017 on all patients experiencing PPROM at 24 to 34 weeks + 6 days and who gave birth after 48 h. Maternal, obstetric, fetal, and neonatal variables were included in the data collected. The primary endpoint was latency, defined as the number of days between rupture of membranes and delivery. Results: 170 consecutive patients were analyzed. Short latency could be predicted by the need for tocolysis, a cervical length less than 25 mm at admission and the existence of anamnios. Outpatient follow-up was not found to lead to increased maternal morbidity or neonatal mortality. Conclusion: Our study highlights predictive factors of short latency exceeding 48 h after PPROM. Knowledge of these factors may provide justification for outpatient monitoring of patients presenting with a long cervix, absence of need for tocolysis and persistence of amniotic fluid and, thus, no risk factors after 48 h of admission. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the association between uterine myomas and preterm birth (PTB), preterm premature rupture of membranes (pPROM), and intrauterine infection (II). The study was based on data from the Japan Environment and Children's Study, a nationwide birth-cohort study. Data of 86,370 women with singleton births after 22 weeks of gestation (with uterine myomas, n = 5354) were retrospectively analyzed. Using logistic regression, adjusted odds ratios (aORs) for PTB, pPROM, and II were calculated considering women without uterine myomas as the reference. Additionally, the effects of II on the incidence of PTB and pPROM were evaluated. In women with uterine myomas, the aORs for PTB before 37 and 34 weeks, pPROM, and II were 1.37 (95% confidence interval, 1.22-1.54), 1.61 (1.27-2.05), 1.65 (1.33-2.04), and 1.05 (0.75-1.46), respectively. The aORs for PTB and pPROM in women with II and uterine myomas were not significantly increased. Uterine myomas during pregnancy were associated with an increased incidence of PTB and pPROM. However, II in women with uterine myomas was not associated with an increased incidence of PTB or pPROM. These findings suggest a potential risk of occult PTB in pregnant women with uterine myomas., Competing Interests: The authors declare no conflicts of interest.