Premature Rupture Research Articles

Glutamine Attenuates Inflammation and Stimulates Amniotic Cell Proliferation in Premature Rupture of Membranes-related in vitro Models.

Premature rupture of membranes (PROM), with a prevalence of 15.3% in China, frequently results in adverse pregnancy outcomes. In this study, we aimed to identify amino acid metabolites that were differentially expressed in PROM versus healthy controls (HC) using targeted metabolomics and further explored their mechanisms of action with in vitro models.Inclusion and exclusion criteria were established to recruit 50 PROM and 50 HC cases for targeted metabolomics analysis. Twenty-three amino acid metabolites were quantified in the secretions of the posterior vaginal fornix of pregnant women between 31 and 36 weeks of gestation. Glutamine (0.0216 vs. 0.037μg/mg, P = 0.003, AUC = 72.1%) was identified as the most differentially expressed amino acid metabolite between PROM and HC groups, and had a negative correlation with the abundance of Gardnerella (r=-0.3868, P = 0.0055), Megasphaera (r=-0.3130, P = 0.0269), and Prevotella (r=-0.2944, P = 0.0380), respectively.In amniotic epithelial cell and macrophage co-culture model, Glutamine reduced inflammatory cytokines and chemokines expression and suppressed macrophage chemotaxis. In LPS stimulated RAW 264.7 inflammation model, Glutamine inhibited the expression of inflammatory proteins iNOS and COX-2, down-regulated mRNA transcription of TNF, IL-6, and IL-1β, and reduced the production of reactive oxygen species through inhibiting NF-κB signaling pathway, and therefore demonstrated its anti-inflammatory effect. Furthermore, Glutamine protected amniotic epithelial cell from autophagy and stimulated its proliferation, therefore may intensify fetal membrane and prevent PROM in vivo.Our results suggested that low Glutamine level in vaginal secretion can be used as an indicator for PROM, and local Glutamine supplementation is a potential intervention and prevention strategy for PROM.

Artificial Sweetener and the Risk of Adverse Pregnancy Outcomes: A Mendelian Randomization Study.

The relationship between the intake of artificial sweetener (AS) and adverse pregnancy outcomes is under-researched, and existing studies yield inconsistent conclusions. A Mendelian randomization (MR) approach was employed to investigate the causal relationship between the intake of AS and adverse pregnancy outcomes. Instrumental variables related to the exposure phenotype were selected for analysis. The analysis was conducted using genome-wide association study summary data from public datasets. The inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods were used to evaluate the causal relationship between exposure and outcomes. Sensitivity analysis and multivariable Mendelian randomization enrolling body mass index, type 2 diabetes mellitus, and fasting glucose were employed to further validate the consistency and robustness of the results. In univariable MR, the intake of AS added to tea was associated with an increased risk of ectopic pregnancy [OR = 1.821 (1.118-2.967), p = 0.016]. In multivariable MR adjusting for body mass index and type 2 diabetes mellitus, the intake of AS added to cereal was linked to a reduced risk of ectopic pregnancy [OR = 0.361 (0.145-0.895), p = 0.028] and premature rupture of membranes [OR = 0.116 (0.019-0.704), p = 0.019], while the intake of artificial sweetener added to coffee was associated with an increased risk of placenta previa [OR = 1.617 (1.042-2.510), p = 0.032]. No causal relationship was identified between the intake of artificial sweetener and other adverse pregnancy outcomes. The consumption of artificial sweetener during pregnancy warrants careful consideration.

Familial Mediterranean Fever in Pregnancy.

Though the incidence of familial Mediterranean fever (FMF) in pregnancy is rare, understanding the etiology and symptomatology of FMF is essential for obstetric treatment of patients with FMF. Familial Mediterranean fever is a hereditary periodic fever syndrome that has unique obstetric considerations. Familial Mediterranean fever is typically characterized by recurrent episodes of high-grade fevers, pleuritis/pericarditis, and arthritis lasting 1-3 days with complete recovery seen in between episodes. Familial Mediterranean fever is seen worldwide, but particularly in patients of Mediterranean descent. Its incidence varies across ethnicities. This article provides a comprehensive review of existing literature. It is well established that colchicine is safe and effective to use during pregnancy in patients with FMF to control and prevent flares. Although most pregnancies progress without negative outcomes, FMF has been shown in the literature to be associated with preterm birth and premature rupture of membranes. Its impact on increasing the rate of fetal growth restriction and hypertensive disorders is less understood. Additionally, FMF flares may be suppressed in pregnancy, whereas other sources report that flares are similar to those outside of pregnancy in terms of frequency, type of symptoms, and severity. Breastfeeding is safe in patients with FMF who are taking colchicine. Genetic counseling can be offered to patients with FMF, but in utero diagnostic testing is generally not pursued solely for the indication of FMF diagnosis in the fetus. Further investigation of the impact of FMF on pregnancy is needed for advancing our understanding of the condition and optimizing care for pregnant individuals with FMF.

Gestational diabetes complicated with preterm birth: a retrospective cohort study

ObjectiveTo delineate the clinical characteristics of preterm birth (PTB) in the context of gestational diabetes mellitus (GDM).MethodsA retrospective cohort study was conducted, including 14,314 pregnant women with GDM who delivered at Fujian Provincial Maternity and Children’s Hospital from January 1, 2018, to December 31, 2021. PTB was stratified into late PTB (34–36 weeks of gestation) and early PTB (< 34 weeks) and pregnancy complications were analyzed.ResultsCompared to the term birth (TB) cohort, a higher prevalence of premature rupture of membranes, hypertensive diseases of pregnancy (HDP), intrahepatic cholestasis of pregnancy (ICP), anemia and cervical insufficiency was observed in the PTB cohort. Notably, early PTB increased the incidence of HDP, ICP, anemia and cervical insufficiency compared to late PTB. In the early stages of pregnancy, early PTB was characterized by elevated triglyceride (TG) levels and decreased high-density lipoprotein cholesterol (HDL-C) levels compared to late PTB. In the late pregnancy stages, early PTB was associated with increased white blood cell (WBC) and neutrophil counts. No disparities were observed in 75 g oral glucose tolerance test (OGTT) between early and late PTB.ConclusionEnhanced surveillance and management of GDM, particularly in the presence of HDP, ICP and anemia, are imperative to mitigate the risk of PTB. The lipid profile may serve as a predictive tool for early PTB in the early stages of pregnancy, warranting further studies.

Laparoscopic Transabdominal Needle-free Emergency Cerclage in the Early Second Trimester of Pregnancy after Failed Transvaginal Cerclage: Two Case Reports and a Review of the Literature.

The aim of the study was to describe the preventive option and safety of laparoscopic transabdominal emergency cerclage in pregnant women with advanced cervical shortening after failed vaginal cerclage or in whom vaginal cerclage is no longer possible. Laparoscopic isthmo-cervical emergency cerclage was carried out in two patients at 13+0 and 15+5 weeks of gestation (GW) respectively. Both patients had cervical shortening and it was no longer possible to expose the cervix after conization or re-conization. The attempts to carry out transvaginal cerclage were unsuccessful. The technical aspects, feasibility, safety, and pregnancy outcomes after laparoscopic transabdominal cerclage are presented here, based on two case reports. The cerclages were placed after blunt dissection of the uterine vessels and careful introduction of a KELLY forceps through the avascular space between the ascending and descending branches of the uterine vessels without using a needle. The operating times were 93 and 134 minutes (min), respectively. The estimated blood loss during the procedure was less than 50ml and neither perioperative nor postoperative complications occurred. The subsequent course of both pregnancies was uneventful and fetal development in both cases was normal. In the first case, the baby was delivered by secondary cesarean section following premature rupture of membranes in week 35+4 of gestation. The baby had a birthweight of 2786g, APGAR scores of 8/9/10 and an umbilical cord arterial pH of 7.36. In the second case, delivery was by primary cesarean section in week 39+5 of gestation. The infant had a birth weight of 4160g, APGAR scores of 5/9/10 and an umbilical cord arterial pH of 7.20. Laparoscopic transabdominal cerclage is a safe and effective treatment option, even early in the second trimester of pregnancy, for patients in whom transvaginal cerclage is no longer possible due to anatomical factors. The method is technically very feasible and is associated with positive obstetric outcomes. The overall risk of perioperative complications is within acceptable limits.

Case study: May human norovirus infection be associated with premature delivery?

Human norovirus (HuNoV) is the leading cause of acute gastroenteritis. The varying severity of chronic infection in patients with underlying immune deficiencies poses additional burdens on public health. However, the potential effects of HuNoV infection during pregnancy, a specific immune perturbed state, have been rarely reported. Recently, four cases of HuNoV-infected patients in the late stages of pregnancy were admitted to the Guangzhou Women and Children's Medical Center, and premature rupture of membranes as primary adverse outcome was observed in these cases. Samples of fetal accessory tissue were collected from two of these cases at delivery to explore the potential pathogenesis. Pathological analysis showed placental malperfusion in both maternal and fetal vascular, while a decrease in vessels was not observed in villi of placenta. There was obvious pathological change in the chorion of fetal membrane, accompanied by a tendency of Th-1 immune bias. Notably, aggregation of M2 macrophages was observed in the chorion of the fetal membrane, potentially recruited for tissue repair. Next-generation sequencing showed minimal changes in immune pathways within placenta tissue. A gene panel associated with immunosuppression was identified in the fetal membrane of HuNoV-infected women compared to those of normal parturient. Taken together, this study provides clues for the association between the HuNoV and premature delivery, which requires the attention of the clinicians.

Emergency cerclage: Neonatal outcomes and evaluation of prognostic scores − A decade of experience at a tertiary center

ObjectivesEmergency cervical cerclage is a high-risk surgical procedure associated with maternal and fetal risks, including preterm birth. Authors have developed scores to try to predict the probability of success following emergency cerclage, but these tools have yet to be externally validated.Our main objective was to assess the preterm birth rate before 32 weeks following emergency cerclage. Secondary objectives included assessing perinatal outcomes and the predictive validity of two published scores in our setting. We hypothesized that predictive scores, such as Fuchs and Kokia scores, may not perform optimally in our population due to variability in clinical and biological characteristics that influence eligibility for cerclage across different settings. Study designWe conducted a retrospective, monocentric study in a tertiary maternity hospital. All patients who underwent emergency cerclage between January 1st, 2010, and December 31st, 2021, were included. The main outcome was preterm birth rate before 32 weeks. Secondary outcomes were need for maternal hospitalization after initial hospitalization for cerclage, preterm premature rupture of membrane, and perinatal death. The rate of preterm birth before 32 weeks and adverse perinatal outcomes were estimated. To assess the predictive validity of Fuchs’ score in our population, we performed a multivariable logistic regression model including the score’s variables and constructed receiver operating characteristic (ROC) curve. To assess the validity of Kokia’s score in our population, we studied the correlation between the initial score and gestational age at delivery using Pearson’s correlation coefficient. ResultsOur population was composed of 64 women who underwent an emergency cerclage. The median gestational age at delivery was 30.6 weeks (IQR (24.2; 37.6)). The preterm birth rate before 32 weeks was 54.7 %. The rate of perinatal death was 30.7 %. There were no statistical differences between the patients delivered before and after 32 weeks. The multivariable logistic regression model showed that none of the variables of Fuchs’s score were significantly associated with preterm birth risk in our population. The AUC of the ROC curve using Fuchs’ score was 0.63. There was a minor yet significant correlation between Kokia’s score and gestational age at delivery (r = 0.26 – p = 0.04). ConclusionsOur study underscores the persistent risks associated with cervical insufficiency, including very preterm birth. It highlights the variability in performance of predictive scores across different populations, underscoring the need for external validation in diverse clinical settings.

Assessment of five-year data of high-risk pregnancies.

Pregnancy is a natural physiological process, but certain conditions can increase the risk, leading to high-risk pregnancy. Several risk factors may cause high-risk pregnancy. The leading ones are chronic diseases, anemia, multiple pregnancies, premature rupture of membrane, preeclampsia, obesity, frequent pregnancy, and advanced maternal age. A total of 7,230 women with high-risk pregnancies followed up by the Unit of Women's and Reproductive Health of the Directorate of Public Health Services, Kayseri Provincial Directorate of Health between 2016 and 2020 were included in the study. Demographic data, pregnancy outcomes, and risk factors were recorded. The mean age was 27.62±6.55 years. The mean number of pregnancy follow-ups was 3.69±1.36. The mean number of follow-ups for Turkish pregnant women was 3.73±1.34 while it was 1.93±1.1 for foreign pregnant women. Binary logistic regression analysis was used to investigate the effect of risk factors on pregnancy outcomes. Pregnancies that did not result in live birth were associated with preeclampsia (OR=12.677), hypertension (HT) (OR=2.079), and cardiovascular disorders (OR=2.277). It was revealed that the number of follow-ups for high-risk pregnancies was low. In conclusion, we believe that increasing monitoring of high-risk pregnancies and developing follow-up models by health authorities will improve the quality of monitoring for high-risk pregnancies.

Impact of Early Dressing Removal After Cesarean Section on Wound Healing and Complications: A Systematic Review.

The global increase in cesarean section (C-section) births has heightened concerns about surgical site infections (SSIs), a significant risk associated with this common obstetric procedure. This literature review evaluates the impact of early dressing removal after C-sections, drawing from randomized controlled trials and clinical studies to assess potential benefits and risks. The review found no definitive evidence favoring a specific timing for dressing removal to reduce SSIs. However, earlier removal before hospital discharge generally enhances patient comfort. Factors such as high BMI, urgent C-sections, preterm premature rupture of membranes (PPROM), and chorioamnionitis are linked to higher wound healing complications, irrespective of when the dressing is removed. Removing staples before discharge is advised for convenience, with close monitoring recommended for high-risk patients. The findings emphasize the need for further research to optimize wound healing protocols, particularly for high-risk groups, to improve patient outcomes and minimize complications. A personalized approach to postoperative care, tailored to individual risk factors, may offer the best strategy for reducing SSIs and enhancing recovery after C-sections.

A STUDY ON MATERNAL AND FETAL OUTCOME IN OLIGOHYDRAMNIOS

Background: Amniotic fluid provides a protected milieu for growing fetus, cushioning the fetus against mechanical and biological injury. It also supplies nutrients and facilitates growth and movement.Oligohydramnios is defined as Amniotic fluid index (AFI) less than 5 cm, or deep vertical pocket &lt; 21. It occurs in 1–5% pregnancies at term, with the incidence increasing in postdate pregnancies to 11%.2 Maternal conditions associated with decreased AFV ( amniotic fluid volume)include post-dated pregnancy, preterm premature rupture of membranes (PPROM), hypertension, autoimmune disorders and maternal medication like prostaglandin synthetase inhibitors. Fetal factors: Which influence AFV are essentially related to fetal growth (intrauterine growth restriction) and fetal anomalies, particularly of the renal tract. The most commonly associated renal anomalies with oligohydramnios include bilateral renal agenesis, multicystic dysplastic kidneys, bladder outlet obstruction and infantile polycystic kidney disease.The aim of this study is to evaluate the etiological risk factors of oligohydramnios and to know the clinical significance and mode of delivery and maternal and perinatal outcome. Methods: This was a retrospective study conducted on 100 cases in Basaveshwar Medical and Teaching Hospital attached to MahadevappaRampure Medical college, Kalaburagi from 1-8-2023 to 1-6-2024.All cases coming to Basaveshwar medical and teaching hospital with oligohydramnios were included in the study after fulfilling inclusion and exclusion criteria Results: Of the 100 cases in the present study,40 cases were in 25-30 years accounting for 40% of cases with maximum number of cases in this age group.56 cases were primigravida accounting for 56% of cases with majority of cases being primigravida and 44 cases were multigravida accounting for 44% of cases.The number of cases with preterm rupture of membranes were 21 ( 21%), cases with Intra uterine growth restriction were 15 (15%). 6 cases (6%) had congenital anamolies. The number of cases withpost dated pregnancy were 22 (22%), Pregnancy induced hypertension cases were 28 (28%). Cases with autoimmune diseases were 1 (1%) and 7 cases (7%) were idiopathic.The most important cause for oligohydramnios was pregnancy induced hypertension and post-dated pregnancy. 13 of the cases had spontaneous onset of labouri.e 13% cases, 28 cases (28%) were induced and 59 cases underwent cesarean section accounting for 59% of all cases.In the present study, total of 19 cases underwent cesarean section because of fetal distress accounting for 19% of cases with the most common indication for cesarean section.11 cases (11%) underwent LSCS due to IUGR, ,4 cases (4%) underwent cesarean section because of non-progression of labour, 2 cases(2%) underwent LSCS because of malpresentation/malposition, 9 cases (9%) had cephalopelvic disproportion, 2 cases (2%) refused for induction of labour and 12 cases (12%) were previous LSCS.Among the 100 cases studied ,there were 8 cases (8%) with meconium aspiration syndrome, 5 cases (5%) had respiratory distress, 6 cases (6%) had low birth weight, 6 cases (6%) with congenital anomalies, 21 cases (21%)had NICU admissions, 4 cases (4%) were still born and 2 cases(2%) had intrauterine fetal death Conclusion: Oligohydramnios is associated with fetal distress, meconium aspiration syndrome ,respiratory distress syndrome ,increased NICU admissions, low birth weight, perinatal mortality, morbidity and increased maternal morbidity due to increased cesarean section rates.Oligohydramnios requires intense fetal monitoring with proper antenatal and intrapartum care.Hence, AFI can be used as a primary tool in fetal surveillance in antenatal and intrapartum period and can help in categorization of fetus into high risk and low risk .One can have favourable outcome with good antenatal and intrapartum care

Clinical and statistical analysis of the course of preterm birth based on the materials of communal enterprise «Regional Perinatal Center of the Rivne Regional Council» in 2013–2023 years

One of the priority tasks of modern medical science and practice is the preservation of reproductive health and the gene pool of the nation. It is especially difficult to perform this task during the russian war in Ukraine, which has been going on for more than ten years. According to sociologists, the outcomes of a low birth rate for the country will be catastrophic precisely because of the war.One of the reasons for the decline in the quality of health in the future is the increase in the specific weight of premature births, the frequency of which, according to the World Health Organization, has increased in Ukraine already after six months of full-scale war.The objective: to conduct an analysis of the course of premature births in the conditions of war based on the materials of the communal enterprise (CE) “Regional Perinatal Center of the Rivne Regional Council” for 2013–2023.Materials and methods. A retrospective clinical and statistical analysis of 2,742 histories of pregnancy and childbirth of women who were in labor between 22/0–36/6 weeks of gestation in obstetric departments of the communal enterprise “Regional Perinatal Center of the Rivne Regional Council” in 2013–2023 was carried out.Results. According to CE “Regional Perinatal Center of the Rivne Regional Council”, a progressive decrease in the total number of births by 41.9% was observed in the Rivne Region from 2013 to 2023. At the same time, in the general population of women giving birth, the specific rate of premature births did not have a tendency to increase.In the structure of preterm births, early and late preterm births prevailed. The specific gravity of very early preterm births, which are the most unfavorable for perinatal outcomes, did not have a sustained upward trend. At the same time, the frequency of too early premature births among residents of districts and territorial communities of the Rivne region has significantly increased (2013 – 19 (79.2%) cases, 2023 – 17 (100.0%) cases; p&lt;0.05).Every second premature birth occurred within the first day of hospitalization of a pregnant woman, while the specific rate of such too early premature births increased by 3.4 times during the analyzed period, which significantly worsens the chances of survival of newborns and is the reason for their high perinatal morbidity.The number of premature births in pregnant women with multiple pregnancies remains stable. Every third preterm birth took place on the background of early premature rupture of the fetal membranes, while a significant increase in the frequency of this complication was found in women who gave birth at 22/0–27/6 weeks of pregnancy.Traditionally, the specific rate (55.7–57.5%) of surgical delivery by caesarean section of pregnant women and mothers with premature births remains high, which contributed to a reliable reduction of the perinatal mortality rate of premature babies by 13.7% due to the reduction of antenatal losses. Indicators of early neonatal death were formed at the expense of newborns from too early and early premature births in the same ratio.Conclusions. According to thedata of CE “Regional Perinatal Center of the Rivne Regional Council”, there was a progressive decrease in the birth rate in the Rivne Region with a simultaneous stabilization of the number of premature births. The widespread use of a holistic approach during the medical care of pregnant women and the introduction of modern methods of care for premature newborns ensured a significant decrease in the rate of perinatal death of premature infants due to the reduction of antenatal losses.

A Controlled, Retrospective, Single-Center Study to Evaluate the Role of a Probiotic Mixture Administered during Pregnancy in Reducing Streptococcus Agalactiae Swab Positivity and the Frequency of Premature Rupture of Amniochorionic Membranes.

Intrapartum antibiotic prophylaxis, considered able to prevent streptococcal transmission from mother to newborn and its severe negative consequences, leads to microbiota dysbiosis, described as having a negative impact on well-being in both elements of the dyad. Enterococcus faecium L3 is a probiotic strain capable of exerting strong antagonistic activity against most streptococci, including S. agalactiae, due to the production of bacteriocins (known as enterocins A and B). A proprietary probiotic mixture containing the strain L3 demonstrated, in 2016, a significant reduction in episodes of PROM in pregnant women, with a less-than-expected effect on the vaginal-rectal presence of the pathogen S. agalactiae. With the aim of confirming the role exerted by the probiotic mixture in PROM episodes and to better understand the value of its impact on the clinical detection of S. agalactiae, we have retrospectively analyzed the results obtained in 125 L3-treated (over 12 weeks) women versus 125 untreated controls. Despite some limitations, our analysis has confirmed the role exerted by the probiotic in significantly reducing the following: (1) episodes of PROM, (2) vaginal-rectal positivity for S. agalactiae, and (3) the need to administer intrapartum antibiotics for prophylaxis. It likely also suggests operating using a cultural method very specific to S. agalactiae when testing women who were administered an Enterococcus-based probiotic.

Long-term neurodevelopmental outcomes at three years in preterm infants born before 29 Weeks gestation following Preterm Premature Rupture of Membranes (PPROM).

To determine the association between preterm premature rupture of membranes (PPROM) and neurodevelopmental impairment (NDI) at 3 years corrected age (CA) in infants born before 29 weeks of gestational age (GA). Infants born before 29 weeks GA between 2005 and 2017 were included. The primary outcome was a composite of death or NDI (full-scale intelligence quotient<85, cerebral palsy, vision or hearing impairment) at 3 years of CA. Infants were stratified by maternal PPROM status. Associations were explored using multivariate models. Of 1231 participants, 481 were in the PPROM group, and 750 were in the No PPROM group. After adjusting for factors, the odds ratio of death or NDI for PPROM vs. No PPROM was 1.22 (95% Confidence Interval 0.93-1.59). Our study suggests that PPROM was not associated with an increased risk of a composite outcome of death or NDI at 3 years CA.

Markers of epithelial-mesenchymal transformation in placentas from very early preterm births

Premature birth complicates one in ten births in the world, two-thirds of which are caused by spontaneous labor and premature rupture of membranes (PROM). The opinion about the inflammatory origin of preterm birth is generally accepted, more and more attention is devoted to the phenomena of epithelial-mesenchymal transformation (EMT).The objective: to study markers of cell proliferation and EMT in samples of placentas from very early preterm, early preterm and term births.Materials and methods. Placenta samples were examined from 101 women who had labour at 22–27 weeks of gestation on the background of PROM (I group), 102 women who had labour at 22–27 weeks on the background of intact fetal membranes (II group), 100 women who had labour at 28-34 weeks on the background of PROM (III group) and 102 women in labour – at 28-34 weeks on the background of intact membranes (IV group). Samples of 60 placentas from timely normal births were included in the control group.The presence of proliferation factor Ki-67 was determined in placenta samples by immunohistochemical method, cytokeratin-18 content was determined in 10 placentas of each group, and vimentin – in 10 amniotic membrane samples. Regarding the proliferation antigen Ki-67, the placentas were divided according to the detection of the sign in the distal, proximal and basal villi. The expression of cytokeratin and vimentin in syncytium and amnion cells was measured in conventional units and compared between groups.The statistical evaluation of the obtained differences was carried out using the Student’s test.Results. Proliferation antigen Ki-67 was detected in 61.9% of all placentas, including term births. In the groups of very early preterm birth (PB), they were detected mainly in villi of distal localization – in 44.6% in the group of PROM and in 51.0% – in the group of labour on the background of intact membranes. In the case of deliveries on the background of intact membranes in extremely premature terms, only 22.5% of the samples had a positive antigen in the basal villi, on the background of PROM in these terms – in 36.7%, in the groups of early PB – in 79.4% and 74.0% respectively.Distal Ki-67 expression in such placentas was a rare finding – 10.0% in the III group, 11.8% – in the IV group, and 8.3% – in placentas from term deliveries.In all gestational periods, the expression of cytokeratin in amniotic membranes in placentas from births on the background of PROM is statistically lower than in placentas from births on the background of intact membranes.In the case of very early PB, the greater expression of vimentin in the distal villi (0.324±0.001 units in the I group and 0.356±0.007 units in the II group) than in the intermediate villi (0.234±0.004 units and 0.248±0.002 units, respectively) and basal ones (0.178±0.002 units and 0.189±0.006 units, respectively). This once again confirms that the inflammatory reaction and the associated EMT at birth before 28 weeks are mainly of fetal origin.In placentas from early PB, the pattern is the opposite – from 0.345±0.007 units and 0.369±0.009 units in III and IV groups, respectively, in basal villi to 0.257±0.004 units and 0.239±0.005 – in intermediate villi and 0.178±0.009 units and 0.165±0.005 units – in the distal ones.Conclusions. 1. The expression of the inflammatory proliferation marker Ki-67 was detected in two thirds of the studied placentas regardless of the term of delivery, but very early PBs are characterized by the predominant localization of the marker in the distal villi, while in early PBs – in the basal and proximal villi. 2. The expression of EMT markers indicates the fetal origin of the inflammatory response in very early PB – less cytokeratin in syncytial cells and more vimentin in distal chorionic villi. In placentas from early PB and term deliveries, a more pronounced expression of vimentin in the basal vessels of the chorion dominates.

Effect of basic periodontal treatment on CRP in elderly pregnant women with periodontal disease

Periodontal disease is a chronic infectious disease, which is common and frequent disease in pregnant women. It is an infectious disease caused by a variety of microorganisms, and the physiological changes in pregnant women after pregnancy can promote the occurrence and development of periodontal disease. Women no less than 35 years old are at an increased risk of maternal and fetal complications in pregnancy, older pregnant women with periodontal disease are prone to preterm birth, fetal growth retardation, premature rupture of membranes, and the incidence of neonatal low birth weight is significantly higher than that in older women with healthy oral health, i.e., these risks are increased with age. CRP is an acute-phase protein produced by liver organs, which is produced by hepatocytes under the promotion of inflammatory factors, and serves as the most direct and sensitive marker of inflammatory response. Studies have shown that basic periodontal treatment relieve periodontal tissue inflammation in pregnant women with periodontitis, while significantly reducing their serum CRP concentration, thereby decreasing the occurrence of adverse pregnancy outcomes. The objective of this study is to investigate the effect of basic periodontal treatment on CRP in elderly pregnant women with periodontal disease.

Prenatal Surgery for Open Fetal Spina Bifida in Patients with Obesity: A Review of Current Evidence and Future Directions.

Background: Obesity rates have significantly increased globally, affecting up to 40% of women of childbearing age in the United States. While prenatal repair of open fetal spina bifida has shown improved outcomes, most fetal surgery centers exclude patients with a body mass index (BMI) ≥ 35 kg/m2 based on criteria from the Management of Myelomeningocele Study (MOMS) trial. This exclusion raises concerns about healthcare equity and highlights a significant knowledge gap regarding the safety and efficacy of fetal spina bifida repair in patients with obesity. Objective: To review the current state of knowledge regarding open fetal surgery for fetal spina bifida in patients with obesity, focusing on safety, efficacy, and clinical considerations. Methods: A comprehensive literature search was conducted using the PubMed and EMBASE databases, covering articles from the inception of the databases to April 2024. Studies discussing fetal surgery for neural tube defects and documenting BMI measurements and their impact on surgical outcomes, published in peer-reviewed journals, and available in English were included. Quantitative data were extracted into an Excel sheet, and data synthesis was conducted using the R programming language (version 4.3.3). Results: Three retrospective studies examining outcomes of prenatal open spina bifida repair in a total of 43 patients with a BMI ≥ 35 kg/m2 were identified. These studies did not report significant adverse maternal or fetal outcomes compared to patients with lower BMIs. Our pooled analysis revealed a perinatal mortality rate of 6.1% (95% CI: 1.76-18.92%), with 28.0% (95% CI: 14.0-48.2%) experiencing the premature rupture of membranes and 82.0% (95% CI: 29.2-98.0%) delivering preterm (<37 weeks). Membrane separation was reported in 10.3% of cases (95% CI: 3.3-27.7%), the mean gestational age at birth was 34.3 weeks (95% CI: 32.3-36.3), and the average birth weight was 2651.5 g (95% CI: 2473.7-2829.4). Additionally, 40.1% (95% CI: 23.1-60.0%) required a ventriculoperitoneal shunt. Conclusion: While current evidence suggests that fetal spina bifida repair may be feasible in patients with obesity, significant limitations in the existing body of research were identified. These include small sample sizes, retrospective designs, and a lack of long-term follow-up data. There is an urgent need for large-scale, prospective, multicenter studies to definitively establish the safety and efficacy of fetal spina bifida repair in patients with obesity. Such research is crucial for developing evidence-based guidelines, improving clinical outcomes, and addressing healthcare disparities in this growing patient population with obesity.

Investigation of Aquaporin Molecules in the Placentas of Pregnant Women with Premature Rupture of Membranes

Aim: This study aimed to investigate the immunohistochemical expression of Aquaporin 3 (AQP3) in placentas of pregnant women with premature rupture of membrane (PROM) and to explore AQP3-related interactors and signaling pathways using in silico approaches. Material and Method: Placental samples from 21 healthy (control) pregnant women and 21 pregnant women diagnosed with PROM were processed for routine histological tissue preparation. Sections were immunostained with AQP3 and analyzed under light microscope via ImageJ software. Protein-protein interaction (PPI) network of AQP3 was constructed with Cytoscape (version 3.10.2). Nodal centrality indexes (degree, closeness and betweenness) were computed through CentiScaPe plugin. The Enrichr tool was utilized to perform pathway enrichment analysis for 15 central genes. Results: AQP3 immune activity was significantly decreased in the plasma membrane of the trophoblastic cell layer of the PROM group compared to control group. According to network centrality analysis, AQP subfamily proteins predominantly play central roles in the AQP3 network; Major Intrinsic Protein of Lens Fiber (MIP), Glycerol-3-Phosphate Dehydrogenase 2 (GPD2), Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH), Glycerol Kinase 2 (GK2), GK, and Actin Beta (ACTB) with additional central interactors including proteins. Peroxisome proliferator-activated receptors (PPAR) signaling pathway was obtained as the most significantly enriched pathway. Conclusion: Alterations in AQP3 expression level in the PROM group compared with the control group may contribute to disturbances in water transport and cellular homeostasis in placental tissues and in silico potential interaction between AQP3 expression and PPAR signaling suggest the role of AQP3 in cell metabolism in PROM.

Prenatal Ultrasonographic Features Associated With ARSL and X-Linked Chondrodysplasia Punctata 1 (CDPX1): Literature Review and Case Series.

Chondrodysplasia punctata 1 (CDPX1) is an X-linked recessive disorder of cartilage and bone development characterized by stippling on the cartilage and bone, flattened nasal bridge, and brachydactyly, or short fingers. CDPX1 has been associated with variants in the ARSL gene and is known to manifest prenatally, however, there has been no systematic literature review on this evidence. Here, we reviewed the current literature on prenatal manifestations of CDPX1, and additionally introduce previously unpublished cases. A systematic review of the literature was performed. Additionally, a GeneMatcher submission was created and a call for cases was presented at the Fetal Sequencing Consortium meetings to find previously unpublished cases. For the 22 fetuses reported here, we found that 55% had nasal hypoplasia, 41% had bony stippling or calcifications, 32% had polyhydramnios, 5% had oligohydramnios, 23% had shortened long bones, 23% had spinal canal stenosis, 18% had ventriculomegaly, 9% had brachydactyly/brachytelephalangy, 9% had clubbed feet, 9% had premature rupture of membranes, and 9% had intraventricular hemorrhage detected through sonography or radiography. We also found 17 unique variants in ARSL for these 22 fetuses. A previously unpublished association of ARSL variants with intrauterine fetal death or stillbirth has been noted in this study. It is also possible that intracranial hemorrhage is an underrecognized feature associated with CDPX1 variation. However, there have been challenges in applying ACMG criteria to ARSL, a gene without an associated Variant Curation Expert Panel. This literature review and case series highlights which features of CDPX1 manifest prenatally, as well as introduces new phenotypes that have not been previously identified.

Safety of the Seasonal Influenza Vaccine in 2 Successive Pregnancies

ImportanceAlthough influenza vaccination has been found to be safe in pregnancy, few studies have assessed repeated influenza vaccination over successive pregnancies, including 2 vaccinations in a year, in terms of adverse perinatal outcomes.ObjectiveTo examine the association of seasonal influenza vaccination across successive pregnancies with adverse perinatal outcomes and whether the association varies by interpregnancy interval (IPI) and vaccine type (quadrivalent or trivalent).Design, Setting, and ParticipantsThis retrospective cohort study included individuals with at least 2 successive singleton live-birth pregnancies between January 1, 2004, and December 31, 2018. Data were collected from the Vaccine Safety Datalink, a collaboration between the Centers for Disease Control and Prevention and integrated health care organizations. Data analysis was performed between January 8, 2021, and July 17, 2024.ExposuresInfluenza vaccination was identified using vaccine administration codes. The vaccinated cohort consisted of people who received influenza vaccines during the influenza season (August 1 through April 30) in 2 successive pregnancies. The comparator cohort consisted of people identified as unvaccinated during both pregnancies.Main Outcomes and MeasuresMain outcomes were risk of preeclampsia or eclampsia, placental abruption, fever, preterm birth, preterm premature rupture of membranes, chorioamnionitis, and small for gestational age among individuals with and without vaccination in both pregnancies. Adjusted relative risks (RRs) from Poisson regression were used to assess the magnitude of associations. The associations with adverse outcomes by IPI and vaccine type were evaluated.ResultsOf 82 055 people with 2 singleton pregnancies between 2004 and 2018, 44 879 (54.7%) had influenza vaccination in successive pregnancies. Mean (SD) age at the start of the second pregnancy was 32.2 (4.6) years for vaccinated individuals and 31.2 (5.0) years for unvaccinated individuals. Compared with individuals not vaccinated in both pregnancies, vaccination in successive pregnancies was not associated with increased risk of preeclampsia or eclampsia (adjusted RR, 1.10; 95% CI, 0.99-1.21), placental abruption (adjusted RR, 1.01; 95% CI, 0.84-1.21), fever (adjusted RR, 0.87; 95% CI, 0.47-1.59), preterm birth (adjusted RR, 0.83; 95% CI, 0.78-0.89), preterm premature rupture of membranes (RR, 1.00; 95% CI, 0.94-1.06), chorioamnionitis (adjusted RR, 1.03; 95% CI, 0.90-1.18), or small for gestational age birth (adjusted RR, 0.99; 95% CI, 0.93-1.05). IPI and vaccine type did not modify the observed associations.Conclusions and RelevanceIn this large cohort study of successive pregnancies, influenza vaccination was not associated with increased risk of adverse perinatal outcomes, irrespective of IPI and vaccine type. Findings support recommendations to vaccinate pregnant people or those who might be pregnant during the influenza season.

Placental lesions in patients with antiphospholipid antibody syndrome: experience of a single tertiary-care Italian reference center

IntroductionAbnormal placentation contributes to obstetric morbidity in antiphospholipid antibodies syndrome (APS). The placenta is the main target of antiphospholipid antibodies (aPL) in obstetric APS and is the site of dysfunctional inflammatory responses and thrombosis. Standard treatment for APS during pregnancy includes low-dose aspirin (LDA) plus low molecular weight heparin (LMWH) and, in refractory cases, hydroxychloroquine (HCQ). Recently, a systematic review of the literature identified five main pathological placental lesions in APS patients: placental infarction, decidual vasculopathy, decidual inflammation, increase of syncytial knots due to syncytiotrophoblast death, and decrease in vasculosyncytial membranes. The aims of this study were to investigate whether placental lesions associate with obstetrical outcomes in a cohort of APS patients.Methods130 pregnant APS patients evaluated between 2009 and 2023 at the High-Risk Obstetrics Outpatient Clinic of San Raffaele Hospital, Milan, were enrolled. Placental samples from 25 spontaneously conceived pregnancies in APS patients were collected from January 2017 to May 2023 and analyzed.ResultsAll (n = 130) patients were on LDA and 110/130 (85%) on both LDA and LMWH. Twenty-six patients (20%) also received HCQ. In these patients, signs of placental inflammation (preterm birth and preterm premature rupture of membranes) were less frequently observed. Of the 25 placental samples analyzed, 19 (76%) patients had primary APS, while 6 patients had APS secondary to SLE. All patients were treated with LDA and LMWH. In patients with concomitant systemic lupus erythematosus (SLE) or in refractory APS, HCQ was added. Histological analysis of placental tissue revealed increased syncytial knots in 17/25 (68%) placentas, decreased vasculosyncytial membranes in 11/25 (44%), infarction in 8/25 (32%), presence of macrophages and decidual inflammation in 2/25 (8%), and atherosis or reduction of spiral artery remodeling in 3/25 (12%). We also observed at least two coexisting placental lesions in 12/25 (48%) placentas. In the placenta of patients treated with HCQ we did not observe any decidual inflammation at histology.ConclusionPlacental anomalies have occurred in patients with APS despite close and optimal obstetric monitoring. It is thus tempting to speculate that HCQ may have beneficial effects on pregnancy by decreasing the risk of deciduitis in patients with APS.