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

Objectives: Twin pregnancy implies a higher risk of preterm birth and, consequently, higher neonatal morbidity and mortality. In singleton pregnancies, infections of the lower genital tract (LGTIs) and bacterial vaginosis are associated with preterm labor, and their early detection has been proven effective in reducing complications like the preterm premature rupture of membranes (pPROM) and preterm delivery. The same evidence, however, is lacking for twin pregnancies. This study aimed to evaluate whether the early identification and treatment of LGTIs or bacterial vaginosis in asymptomatic women with twin pregnancy could reduce the rate of miscarriages, pPROM, and preterm birth. Methods: This study performed a retrospective comparison of 285 women with a multiple pregnancy submitted for a cervico-vaginal swab only at 20-22 weeks (Single Test Group, STG), and 199 women who underwent the swab at 12-14 and again at 20-22 weeks (Double Test Group, DTG). All women included in the study had a twin pregnancy and were followed up at Sant\'Anna Hospital, Turin (Italy), between September 2012 and February 2021. Results: In STG, 21.7% of patients had a positive swab; in DTG, 19.9% had an early positive swab that was immediately treated by targeted antibiotics; and 16.7% had a mid-pregnancy positive swab. The DTG showed a significantly lower incidence of pPROM in univariate analysis (14.4% vs. 23.1%, p = 0.021), which was confirmed by multivariate analysis (OR 0.55, CI 0.33-0.93, p = 0.025). Conclusions: Our study suggests that, in asymptomatic women with twin pregnancy, the early screening of LGTIs and bacterial vaginosis by a cervico-vaginal swab at 12-14 weeks of gestational age is effective in reducing the risk of pPROM.

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.

Pregnancies complicated by severe polyhydramnios are associated with a high rate of underlying fetal anomaly. Amnioreduction may be offered to alleviate maternal symptoms. This is a retrospective study of amnioreductions performed on singleton and twin gestations complicated by symptomatic polyhydramnios between 2010 and 2023 at our tertiary referral center. The indications, procedural techniques and pregnancy and neonatal outcomes were retrieved from an archive database and reviewed with the use of the maternal and child medical record chart, the hospital electronic clinical discharge report and telephone recalls. Our study comprised 86 pregnancies, 65 singletons and 21 twin pregnancies. Fetal anomalies were identified in 79% of cases, mainly gastrointestinal obstructive anomalies; 9.3% of cases were idiopathic. The median gestational age at first amnioreduction was 32.5 weeks, and peri-procedural complications were rare (1 case of placental abruption and 2 cases of preterm delivery). The median gestational age at delivery was 36.5 weeks, with a median prolongation of the pregnancy from the time of first drain until birth of 30 days. Preterm labor < 37 weeks occurred in 48.8% of procedures, with 26.7% of patients delivering before 34 weeks and pPROM < 36 weeks recorded in 23.2% of cases. In conclusion, amnioreduction offered to alleviate maternal symptoms is a reasonably safe procedure with a low complication rate. These pregnancies necessitate management in a tertiary referral center because of their need for a multidisciplinary approach both prenatally and postnatally.

OBJECTIVE: Anchoring the fetal membrane to the uterine wall via a novel suture delivery system could reduce the risk of preterm premature rupture of membranes (PPROM) after fetoscopic surgery. This study assesses the feasibility of using a novel device designed for minimally invasive suturing to anchor fetal membranes to the uterine wall and to close surgical defects after fetoscopy.
METHODS: We tested the suturing device both ex vivo and in vivo. In the ex vivo studies, 12-French trocar defects were created with a fetoscope in five specimens of human uterine tissue with fetal membranes attached. Specimens were examined for integrity of the anchoring stitch. For in vivo studies, trocar defects were created in the two uterine horns of three pregnant ewes, each carrying twins at ~79-90 days gestation. One trocar defect in each ewe was repaired using the suture device, and the other was left unrepaired as a control. The repair sites were examined for membrane anchoring integrity when the defect was created and at delivery.
RESULTS: Fetal membranes were successfully anchored to the uterine myometrium using this device in all five trials performed ex vivo. The in vivo trials also revealed successful membrane anchoring compared with controls both at the time of device deployment and five-to-eight weeks after the procedure.
CONCLUSIONS: We successfully anchored amniotic membranes to the underlying myometrium via suturing device both ex vivo and in vivo. Further studies are needed to evaluate the efficacy of the device and to determine whether it can successfully anchor fetal membranes percutaneously in human subjects. This article is protected by copyright. All rights reserved.

OBJECTIVE: This study aimed to determine the occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta, marked by elevated levels of interferon gamma-induced protein 10 (IP-10) (≥2200 pg/mL) in the amniotic fluid of women with preterm prelabor rupture of membranes (PPROM). Specifically, the study investigated whether these intra-amniotic inflammatory changes were more common in women with microbial invasion of amniotic cavity (MIAC) and intra-amniotic inflammation (IAI), as indicated by increased amniotic fluid interleukin (IL)-6 concentration (≥3000 pg/mL).
METHODS: A cohort of 114 women with singleton pregnancies complicated by PPROM between 24+0 and 36+6 weeks of gestation were included. Amniotic fluid samples were obtained via amniocentesis upon admission. MIAC diagnosis involved aerobic and anaerobic cultures, as well as polymerase chain reaction (PCR) analysis of the amniotic fluid. Immunoassay tests and enzyme-linked immunosorbent assay (ELISA) were used to determine IL-6 and IP-10 concentrations, respectively.
RESULTS: Among the participants, 19.3 % and 15.8 % had MIAC and IAI, respectively. The occurrence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was similar between women with and without MIAC (25 % vs. 40.9 %, p = 0.136, adjusted p = 0.213). The rate of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta was significantly higher in women with IAI compared to those without, after adjusting for gestational age at sampling (55.6 % vs. 22.9 %, p = 0.005, adjusted p = 0.011).
CONCLUSIONS: This study revealed comparable rates of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with and without MIAC, but a higher prevalence of intra-amniotic inflammatory changes associated with chronic inflammation in the placenta in women with IAI. These findings suggest involvement of chronic inflammation even in women with PPROM with acute intra-amniotic inflammation.

Preterm Premature Rupture of Membranes (PPROM) is defined as the rupture of fetal membranes prior to the onset of labor, before 37 weeks gestation and remains a significant obstetric complication of pregnancy with high rates of perinatal morbidity and mortality worldwide. The aim of our study was to establish the determinants of PPROM <34 weeks at this GJG MRH hospital which has a high incidence of PPROM. It was a descriptive , retrospective chart review of women diagnosed with PPROM over a 1 year period from 1st of January 2018 to 31st of December 2018. Detailed clinical and demographic information was recorded. Statistical analysis was carried out using SPSS (Version 28.0 IBM, Armonk, New York, USA) of 7071 singleton deliveries, 428 were diagnosed with PPROM. Majority (69%) were between the age groups of 21 to 30 years. Women belonging to age groups of <20 years and >=30 years, including women who attend antenatal clinics >=4 times were less likely to experience PPROM. History of abortions, previous preterm delivery, previous PPROM and women who had infectious components were determinants of PPROM. Among the neonates delivered by women who had PPROM, 56.3% had an unfavorable outcome.
La rupture prématurée des membranes (PPROM) est définie comme la rupture des membranes fœtales avant le début du travail, avant 37 semaines de gestation et reste une complication obstétricale importante de la grossesse avec des taux élevés de morbidité et de mortalité périnatales dans le monde. Le but de notre étude était d\'établir les déterminants de la PPROM <34 semaines dans cet hôpital GJG MRH qui a une incidence élevée de PPROM. Il s\'agissait d\'un examen descriptif et rétrospectif des dossiers de femmes diagnostiquées avec PPROM sur une période d\'un an allant du 1er janvier 2018 au 31 décembre 2018. Des informations cliniques et démographiques détaillées ont été enregistrées. L\'analyse statistique a été réalisée à l\'aide de SPSS (version 28.0 IBM, Armonk, New York, USA) sur 7 071 accouchements uniques, 428 ont été diagnostiqués avec PPROM. La majorité (69 %) appartenait au groupe d\'âge de 21 à 30 ans. Les femmes appartenant aux groupes d\'âge <20 ans et >=30 ans, y compris les femmes qui fréquentent les cliniques prénatales >=4 fois, étaient moins susceptibles de souffrir de PPROM. Les antécédents d\'avortements, les accouchements prématurés antérieurs, les antécédents de PPROM et les femmes présentant des composantes infectieuses étaient des déterminants de la PPROM. Parmi les nouveau-nés accouchés par des femmes atteintes de PPROM, 56,3 % ont eu une évolution défavorable.

Intrauterine infection is a significant cause of neonatal morbidity and mortality. Ureaplasma parvum is a microorganism commonly isolated from cases of preterm birth and preterm premature rupture of membranes (pPROM). However, the mechanisms of early stage ascending reproductive tract infection remain poorly understood. To examine inflammation in fetal (chorioamnionic) membranes we utilized a non-human primate (NHP) model of choriodecidual U. parvum infection. Eight chronically catheterized pregnant rhesus macaques underwent maternal-fetal catheterization surgery at ~105-112 days gestation and choriodecidual inoculation with U. parvum (105 CFU/mL, n =4) or sterile media (controls; n = 4) starting at 115-119 days, repeated at 5-day intervals until C-section at 136-140 days (term=167 days). The average inoculation to delivery interval was 21 days, and Ureaplasma infection of the amniotic fluid (AF) was undetectable in all animals. Choriodecidual Ureaplasma infection resulted in increased fetal membrane expression of MMP-9 and PTGS2, but did not result in preterm labor or increased concentrations of AF pro-inflammatory cytokines. However, membrane expression of inflammasome sensors, NLRP3, NLRC4, AIM2, and NOD2, and adaptor ASC (PYCARD) gene expression were significantly increased. Gene expression of IL-1β, IL-18, IL-18R1  , CASPASE-1, and pro-CASPASE-1 protein increased with Ureaplasma infection. Downstream inflammatory genes MYD88 and NFκB (Nuclear factor kappa-light-chain-enhancer of activated B cells) were also significantly upregulated. These results demonstrate that choriodecidual Ureaplasma infection, can cause activation of inflammasome complexes and pathways associated with pPROM and preterm labor prior to microbes being detectable in the AF.

Preterm, prelabor rupture of the human fetal membranes (pPROM) is involved in 40% of spontaneous preterm births worldwide. Cellular-level disturbances and inflammation are effectors of membrane degradation, weakening, and rupture. Maternal risk factors induce oxidative stress (OS), senescence, and senescence-associated inflammation of the fetal membranes as reported mechanisms related to pPROM. Inflammation can also arise in fetal membrane cells (amnion/chorion) due to OS-induced autophagy and epithelial-mesenchymal transition (EMT). Autophagy, EMT, and their correlation in pPROM, along with OS-induced autophagy-related changes in amnion and chorion cells in vitro, were investigated. Immunocytochemistry staining of cytokeratin-18 (epithelial marker)/vimentin (mesenchymal marker) and proautophagy-inducing factor LC3B were performed in fetal membranes from pPROM, term not in labor, and term labor. Ultrastructural changes associated with autophagy were verified by transmission electron microscopy of the fetal membranes and in cells exposed to cigarette smoke extract (an OS inducer). EMT and LC3B staining was compared in the chorion from pPROM versus term not in labor. Transmission electron microscopy confirmed autophagosome formation in pPROM amnion and chorion. In cell culture, autophagosomes were formed in the amnion with OS treatment, while autophagosomes were accumulated in both cell types with autophagy inhibition. This study documents the association between pPROMs and amniochorion autophagy and EMT, and supports a role for OS in inducing dysfunctional cells that increase inflammation, predisposing membranes to rupture.

OBJECTIVE: The objective of our study was to evaluate serum CX3CL1/Fractalkine, a monocyte/macrophage chemoattractant expressed in cytotrophoblasts and decidual cells, as a predictive biomarker for the occurrence of preterm premature rupture of membranes (PPROM).
METHODS: A case-control study of 438 pregnancies including 82 PPROM cases and 64 preterm labor with intact membranes cases with blood samples collected at first trimester, second trimester and delivery was conducted. The predictive ability of CX3CL1 and maternal risk factors for the occurrence of PPROM was assessed by receiver operating characteristic curve analysis. A second, independent cohort was prospectively constituted to confirm the case-control study results.
RESULTS: First trimester CX3CL1 was significantly increased in PPROM cases when compared to matched controls. Multivariate regression analysis highlighted a significant difference for CX3CL1 measured during the first trimester (p<0.001). Alone, CX3CL1 predicts PPROM with a 90 % sensitivity and a specificity around 40 %. The area under the receiver operating characteristic curve for PPROM prediction were 0.64 (95% confidence interval: 0.57-0.71) for first trimester CX3CL1, and 0.61 (95% confidence interval: 0.54-0.68) for maternal risk factors (body mass index<18.5 kg/m2, nulliparity, tobacco use and the absence of high school diploma). The combination of CX3CL1 and maternal risk factors significantly improved the area under the curve: 0.72 (95% confidence interval: 0.66-0.79) (p<0.001). The results were confirmed on a second independent cohort.
CONCLUSIONS: CX3CL1 is a promising blood biomarker in the early (first trimester) prediction of PPROM.