Rescue Cerclage in Women With Acute Cervical Insufficiency and Intra-Amniotic Inflammation: A Retrospective Cohort Study.

BACKGROUND: To assess the effectiveness of rescue cerclage concerning pregnancy and neonatal outcomes in women with acute cervical insufficiency (CI) complicated with intra-amniotic inflammation (IAI) compared with those managed expectantly. METHODS: This retrospective cohort study included 87 consecutive singleton pregnant women (17-25 weeks) with acute CI who underwent amniocentesis to assess IAI. Amniotic fluid (AF) samples were assayed for interleukin-6 to define IAI (≥ 2.6 ng/mL). Primary and secondary outcomes were assessed in a subset of CI patients with IAI. The primary outcome measures were spontaneous preterm birth (SPTB) at < 28 and < 34 weeks, and the secondary outcomes were interval from sampling to delivery, neonatal survival, neonatal birth weight, and histologic and clinical chorioamnionitis. Macrolide antibiotics were prescribed depending on the type of microorganism isolated from the AF, clinically suspected IAI, and the discretion of the attending clinician. RESULTS: IAI was identified in 65.5% (57/87) of patients with CI, of whom 73.6% (42/57) were treated with macrolide antibiotics. Among the CI patients with IAI (n = 57), 40 underwent rescue cerclage and 17 were expectantly managed. The rates of SPTBs at < 28 and < 34 weeks were significantly lower and the latency period was significantly longer in the cerclage group than in the group that was managed expectantly. The median birth weight and neonatal survival rate were significantly higher in the cerclage group than in the group that was managed expectantly. However, the rates of histologic and clinical chorioamnionitis did not differ between the groups. Multivariable analyses revealed that rescue cerclage placement and administration of macrolide antibiotics were significantly associated with a decrease in SPTBs at < 28 and < 34 weeks, prolonged gestational latency, and increased likelihood of neonatal survival, after adjusting for possible confounding parameters; however, macrolide antibiotic administration did not reach statistical significance with respect to SPTB at < 34 weeks and neonatal survival (P = 0.076 and 0.063, respectively). CONCLUSION: Rescue cerclage along with macrolide antibiotic treatment may positively impact pregnancy and neonatal outcomes in women with CI complicated by IAI, compared with expectant management. These findings suggest the benefit of cerclage placement even in patients with CI complicated by IAI.

Quantitative Modeling to Characterize Maternal Inflammatory Response of Histologic Chorioamnionitis in Placental Membranes.

PROBLEM: The placental membranes are a key barrier to fetal and uterine infection. Inflammation of the membranes, diagnosed as maternal inflammatory response (MIR) or alternatively as acute chorioamnionitis, is associated with adverse maternal-fetal outcomes. MIR is staged 1-3, with higher stages indicating more hazardous inflammation. However, the diagnosis relies upon subjective evaluation and has not been deeply characterized. The goal of this work is to develop a cell classifier for eight placental membrane cells and quantitatively characterize MIR1-2. METHOD OF STUDY: Hematoxylin and eosin (H&E)-stained placental membrane slides were digitized. A convolutional neural network was trained on a dataset of hand-annotated and machine learning-identified cells. Overall cell class-level metrics were calculated. The model was applied to 20 control, 20 MIR1, and 23 MIR2 placental membrane cases. MIR cell composition and neutrophil distribution were assessed via density and Ripley's cross K-function. Clinical data were compared to neutrophil density and distribution. RESULTS: The classification model achieved a test-set accuracy of 0.845, with high precision and recall for amniocytes, decidual cells, endothelial cells, and trophoblasts. Using this model to classify 53 073 cells from healthy and MIR1-2 placental membranes, we found that (1) MIR1-2 have higher neutrophil density and fewer decidual cells and trophoblasts, (2) Neutrophils colocalize heavily around decidual cells in healthy placental membranes and around trophoblasts in MIR1, (3) Neutrophil density impacts distribution in MIR, and (4) Neutrophil metrics correlate with features of clinical chorioamnionitis. CONCLUSIONS: This paper introduces cell classification into the placental membranes and quantifies cell composition and neutrophil spatial distributions in MIR.

Mode of delivery in chorioamnionitis: impact on neonatal and maternal outcomes.

BACKGROUND: The impact of mode of delivery in chorioamnionitis on neonatal outcomes is unclear. This retrospective cohort study compares the rate of early onset neonatal sepsis between vaginal delivery and cesarean section. METHODS: Singleton pregnancies at greater than 24 + 0 weeks gestation with live birth and clinically-diagnosed chorioamnionitis from January 1, 2019 to December 31, 2021 were included. Cases with multiple gestations, terminations or histological chorioamnionitis alone were excluded. Rates of early onset neonatal sepsis, select secondary neonatal outcomes and a composite outcome of maternal infectious morbidity were compared using propensity score weighting. Subgroup analysis was done by indication for cesarean section. RESULTS: After chart review, 378 cases were included with 197 delivering vaginally and 181 delivering via cesarean section. The groups differed on age, parity, hypertension, renal disease, gestational age, corticosteroid use, magnesium sulfate use, presence of meconium and percentage meeting Gibbs criteria before propensity score weighting. Rate of early onset neonatal sepsis was greater in the cesarean section group (13.8% versus 3.1%, adjusted risk difference 8.3% [3.5-13.1], p < 0.001). Secondary neonatal outcomes were similar between groups. When compared by indication, the rate of early onset neonatal sepsis was greater in the cesarean section for abnormal fetal surveillance group compared to vaginal delivery but not in the cesarean section for other reasons group. Adjusted rates of secondary neonatal outcomes did not differ between groups. The rate of maternal infectious morbidity was greater with cesarean section. (13.8% versus 1.5% [adjusted risk difference 13.0% [7.1-18.9], p < 0.0001). No other difference in maternal secondary outcomes was identified. CONCLUSIONS: The rate of early onset neonatal sepsis was highest in the cesarean section group, particularly in those with abnormal fetal surveillance. Fetuses affected by or vulnerable to sepsis likely have a greater need for cesarean section.

Placental pathology in SARS-CoV-2 infected pregnancies: A single-institution retrospective cohort analysis.

BACKGROUND: Our objectives were to determine 1) the prevalence and description of placental pathologic lesions in pregnancies complicated by SARS-CoV-2 infection compared to healthy controls and 2) whether the prevalence and/ or pattern of placental pathologic lesions differed in the few neonates who tested positive for SARS-CoV-2 in the first 48 hours of life at a busy urban county hospital. METHODS: This study included all pregnant mothers who tested positive for SARS-CoV-2 and delivered at our institution from March 2020 to June 2021, while control placentas were collected from term pregnancies without complications. RESULTS: Approximately 90% (n = 380/425) of placentas from pregnancies complicated by SARS-CoV-2 infections had placental pathologic lesions, compared to 32% (n = 16/50) of controls. The predominant lesions were acute histologic chorioamnionitis with or without fetal response (n = 209/380, 55%), maternal vascular malperfusion (n = 180/380, 47%), and other inflammatory lesions (n = 148/380, 39%). Only 14 (2.5%) infants tested positive for SARS-CoV-2 within the first 48 hours of life. There were no significant differences in placental histopathology between infants who tested positive vs. those that were negative for SARS-CoV-2. Placental lesions in mothers who tested positive for SARS-CoV-2 during the first vs. second vs. third pregnancy trimesters, were significantly different in the incidence of inflammatory placental pathologic lesions (n = 9/19, 53% vs. n = 37/98, 49% vs. n = 102/439, 31%, respectively; p < 0.01). CONCLUSION: A significant proportion of women with SARS-CoV-2 infection during pregnancy at a single county hospital have inflammatory and vascular placental lesions at birth, raising questions regarding their downstream effects and clinical consequences.

The effect of histological and subclinical chorioamnionitis and funisitis on breathing effort in premature infants at birth: a retrospective cohort study.

Antenatal inflammation in the form of chorioamnionitis (fetal membranes; HCA) and funisitis (umbilical vessels; FUN) is a major risk factor for preterm birth. Exposure to HCA + FUN affects infants by releasing mediators that may suppress respiratory drive. While the association between clinical chorioamnionitis (CCA) and (depressed) spontaneous breathing has been described, we have investigated the association between breathing and HCA + FUN. Infants born < 30 weeks' gestation with available placental pathology assessments were included. Infants were compared at multiple levels: infants with vs without HCA + FUN (comparison 1) and infants with subclinical HCA + FUN vs infants without any chorioamnionitis (comparison 2). The primary outcome was breathing effort, defined as minute volume (MV) of spontaneous breathing in the first 5 min after birth. We also assessed tidal volume (Vt), respiratory rate (RR), heart rate (HR), oxygen saturation (SpO2) and oxygen requirement (FiO2). Regression analyses were performed to control for confounding factors. One hundred eighty-six infants were included (n = 75 infants with HCA + FUN vs. n = 111 infants without HCA + FUN). Comparison 1: Infants with HCA + FUN had lower gestational ages 26+5 (25+0-28+1; median (IQR) and lower birthweights (mean ± SD; 943 ± 264) compared to infants without HCA + FUN (28+4 (27+0-29+1) weeks, p < 0.001 and 1023 ± 270 g, p = 0.049). Comparison 2: Subclinical HCA + FUN was diagnosed in 46/75 HCA + FUN infants. Infants with subclinical HCA + FUN had lower gestational ages (26+6 (25+1-28+3) vs. 28+4 (27+2-29+1) weeks, p < 0.001) without significant differences for birthweights (987 ± 248 vs. 1027 ± 267 g, p = 0.389) compared to infants without any chorioamnionitis (n = 102 infants). After adjustment, HCA + FUN was associated with lower MV (p = 0.025), but subclinical HCA + FUN was not (p = 0.226). HCA + FUN and subclinical HCA + FUN were associated with lower Vt (p = 0.003; p = 0.014), SpO2 at 5 min (p = 0.021; 0.036) and SpO2/FiO2 ratio (p = 0.028; p = 0.040). CONCLUSION: HCA + FUN and subclinical HCA + FUN are associated with reduced oxygenation and parameters that reflect breathing effort in premature infants at birth. WHAT IS KNOWN: • Acute antenatal inflammation, in the form of chorioamnionitis (fetal membranes) and funisitis (umbilical vessels), affects a large proportion of premature infants. • Clinical chorioamnionitis is associated with reduced breathing effort and oxygenation in premature infants at birth. WHAT IS NEW: • Histological and subclinical chorioamnionitis and funisitis are associated with reduced breathing effort parameters and oxygenation in premature infants at birth.

Changes in Relative Counts of Different Leukocyte Subpopulations in Peripheral and Umbilical Cord Blood of Women With Preterm Prelabor Rupture of Membranes With Respect to Intraamniotic Inflammation and Fetal Inflammatory Response Syndrome.

OBJECTIVE: The aim of this study was to evaluate changes in the relative counts of different leukocyte subsets in peripheral and umbilical cord blood in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of intraamniotic inflammation (IAI) and fetal inflammatory response syndrome (FIRS). METHODS: Fifty-two women with singleton pregnancies complicated by PPROM were included in this study. From samples of peripheral and umbilical cord blood, relative counts of these leukocyte subpopulations were determined using multicolor flow cytometry: granulocytes, monocytes, lymphocytes, T cells and their subpopulations, B cells and their subpopulations, and NK cells and their subpopulations. IAI was defined as increased concentrations of interleukin 6 in the amniotic fluid. Amniotic fluid samples were obtained by transabdominal amniocentesis. RESULTS: Women with IAI had higher relative counts of monocytes (p = 0.04) in peripheral blood. There was an increased relative number of granulocytes (p = 0.003) and a decreased number of lymphocytes (p = 0.0048), helper CD4+ T cells (p = 0.019), NK cells (p = 0.0001) within leukocytes, NK cells within lymphocytes (p = 0.003) and CD16+ NK cells within NK cells (p = 0.005) in umbilical cord blood samples of women with FIRS. However, after adjusting the results for gestational age at sampling, all differences disappeared. CONCLUSIONS: The presence of IAI or FIRS is not accompanied by significant changes in the relative counts of immune cells in peripheral blood or umbilical cord blood in pregnancies complicated by PPROM.

The association of inflammatory changes of the uterus and chorioamniotic membranes with different types of labor activity anomalies.

OBJECTIVE: Aim: To clarify the association between different types of uterine contractility dysfunction and the inflammation of the uterus and chorioamniotic membranes. PATIENTS AND METHODS: Materials and Methods: The association between the inflammation of the uterine layers, chorioamniotic membranes, umbilical cord, and different types of labor activity abnormalities was examined in 382 patients with singleton pregnancies at 28-42 weeks' gestation who underwent Caesarean section (CS) for abnormal uterine contractions and other complications. Statistical analyses included the Mann-Whitney U, Chi-squared test, and logistic regression. RESULTS: Results: In the control group, slight infiltration with polymorphonuclear leukocytes (PMNs) and macrophages of the myometrium and decidua of the lower uterine segment at term pregnancy was found in 59.7% and 73.6% of cases. The main clinical risk factors for placental and decidual membrane inflammation in patients with excessive uterine activity (EUA) were prematurity, multiparity, group B streptococcus (GBS) colonization, and duration of ruptured fetal membranes before the CS. Moderate or marked myometrial inflammation of both uterine segments in the EUA group was diagnosed only in patients with cervical dilation of >6 cm and duration of labor of >8h. In women with hypotonic uterine activity (HUA), decidual and myometrial inflammation was significantly associated with nulliparity and intrapartum factors, such as protracted active first stage of labor, advanced cervical dilation, and number of vaginal examinations. In all cases, inflammation of the myometrium was accompanied by deciduitis. CONCLUSION: Conclusions: Mild inflammation of the decidual membrane and myometrium of the lower segment at term pregnancy is a common physiological phenomenon contributing to labor initiation. Uterine hyperfunction comes as the response of the unaffected myometrium to the release of high concentrations of proinflammatory cytokines produced by the inflamed decidual and chorioamniotic membranes into the bloodstream. Marked myometrial inflammation that occurs in prolonged labor is an additional factor aggravating the hypotonic uterine activity.

Comprehensive morphological study of free radical processes in chronic chorioamnionitis on the background of iron deficiency anemia in pregnancy.

OBJECTIVE: Aim: To establish the features of free radical processes in the endotheliocytes of the chorionic plate of the placenta in chronic chorioamnionitis against the background of iron deficiency anemia of pregnant women using both chemiluminescent and histochemical methods of research. PATIENTS AND METHODS: Materials and Methods: 82 placentas from parturients at 37 - 40 weeks of gestation were studied. Including, for comparison, the placenta during physiological pregnancy and the observation of iron deficiency anemia of pregnant women without inflammation of the placenta. The number of observations in specific study groups is given in the tables. To achieve the objective and solve the tasks set in this study, there were carried out the following histochemical, chemiluminescent, morphometric and statistical methods of material processing. RESULTS: Results: In case of chorionamnionitis against the background of anemia in pregnancy, the R/B ratio (R/B - ratio between amino- (blue) and carboxyl (red) groups of proteins)) in the method with bromophenol blue according to Mikel Calvo was 1.56±0.021, indicators of chemiluminescence of nitroperoxides were 133±4.5, relative optical density units of histochemical staining using the method according to A. Yasuma and T. Ichikawa was - 0.224±0.0015. CONCLUSION: Conclusions: With chronic chorioamnionitis, the intensity of the glow of nitroperoxides, the average indicators of the R/B ratio, and the optical density of histochemical staining for free amino groups of proteins are increased compared to placentas of physiological pregnancy and anemia of pregnant women. Comorbid i anemia of pregnant women causes increasing of the intensity of the glow of nitroperoxides, the average values of the R/B ratio, and the optical density of histochemical staining for free amino groups of proteins comparing to placentas with inflammation without anemia. The key factor in the formation of morphological features of chronic chorioamnionitis with comorbid anemia is the intensification of free radical processes, which is reflected by the increase in the concentration of nitroperoxides in the center of inflammation, with the subsequent intensification of the processes of oxidative modification of proteins, which is followed by the increasing activity of the processes of limited proteolysis.

Quantitative cervicovaginal fluid fetal fibronectin: A liquid biopsy for intra-amniotic inflammation.

INTRODUCTION: Intra-amniotic inflammation is causally linked to spontaneous preterm labor. The gold standard for the diagnosis of intra-amniotic inflammation is the determination of an amniotic fluid profile obtained from transabdominal amniocentesis, which is invasive. Cervicovaginal fluid fetal fibronectin (fFN) is a widely-used predictive biomarker for spontaneous preterm labor. The aims of this study are to determine (1) whether a quantitative cervicovaginal fluid fFN test can be used to identify the presence of intra-amniotic inflammation; and (2) an appropriate cut-off value of a cervicovaginal fluid fFN concentration for the identification of intra-amniotic inflammation. MATERIAL AND METHODS: This prospective cohort study included 78 patients with preterm labor and intact membranes who had a sample collected for quantitative cervicovaginal fluid fFN measurement and underwent transabdominal amniocentesis. Intra-amniotic inflammation was defined as an amniotic fluid interleukin-6 concentration ≥2.6 ng/mL. Clinicians were masked from the results of cervicovaginal fluid fFN and amniotic fluid interleukin-6 concentrations. Logistic regression analysis was used to determine which factors were significant predictors of intra-amniotic inflammation. The diagnostic indices of the cervicovaginal fluid fFN test for the identification of intra-amniotic inflammation were calculated. RESULTS: (1) Frequency of intra-amniotic inflammation was 26.9% (21/78); (2) the higher the cervicovaginal fluid fFN concentration, the greater the risk of intra-amniotic inflammation (p < 0.001); (3) cervicovaginal fluid fFN concentration ≥125 ng/mL had an area under the curve of 0.91 (95% confidence interval: 0.83-0.96) for the identification of intra-amniotic inflammation with 100% sensitivity, 100% negative predictive value, 82.46% specificity and a positive likelihood ratio of 5.7; and (4) cervicovaginal fluid fFN cut-off of 125 ng/mL had a significant higher predictive performance than the traditional cut-off (50 ng/mL) for the identification of intra-amniotic inflammation. CONCLUSIONS: Quantitative cervicovaginal fluid fFN with a cut-off of 125 ng/mL had a high sensitivity and a negative predictive value as well as a positive likelihood ratio for the identification of intra-amniotic inflammation. Its high sensitivity and negative predictive value can be used to decrease an index of suspicion of intra-amniotic inflammation. This test may be useful as an initial assessment test to select appropriate patients for amniocentesis to determine intra-amniotic inflammation.

Novel Biomarkers: Soluble Urokinase-Type Plasminogen Activator Receptor and Procalcitonin- and Histological Chorioamnionitis after Preterm Premature Rupture of Membranes.

Fetal inflammatory response syndrome or infection after preterm premature rupture of membranes (PPROM) increases neonatal morbidity in preterm deliveries. Biochemical markers from the amniotic fluid (AF) have been used to evaluate possible intra-amniotic infection during the asymptomatic phase after PPROM. This study aimed to describe whether soluble urokinase-type plasminogen activator receptor (suPAR) or procalcitonin (PCT) from AF or maternal sera could reveal fetal inflammatory response or infection after PPROM. AF and maternal serum samples were collected weekly after PPROM (23+ 0 - 34+ 6 gestational weeks) until delivery from twenty women and two women with possible chorioamnionitis with intact membranes. Levels of suPAR, PCT, interleukin-6 (IL-6), glucose, lactate dehydrogenase (LDH), and bacterial PCR were determined from AF and suPAR and PCT and IL-6 from maternal sera. Fetal infection or inflammation response were determined by the histology of the placenta after delivery. AF glucose was significantly lower and AF LDH higher in the fetal site histologic chorioamnionitis (HCA) group, while AF suPAR concentrations tended to be higher in this group. AF suPAR correlated significantly with AF glucose and LDH. Based on receiver operating characteristic (ROC) analysis, AF glucose had the best predictability for fetal site histological chorioamnionitis. The findings of AF PCT were insignificant considering HCA. AF glucose had the highest accuracy in predicting fetal site histologic chorioamnionitis. AF suPAR may be a promising marker; however, our findings were limited by a small study population.

Impact of Extreme Prematurity, Chorioamnionitis, and Sepsis on Neonatal Monocyte Characteristics and Functions.

INTRODUCTION: The innate branch of the immune system is important in early life, in particular for infants born preterm. METHODS: We performed a longitudinal analysis of the peripheral monocyte compartment in extremely preterm children from a randomized, placebo-controlled study of probiotic supplementation. PBMCs and fecal samples were collected at several timepoints during the first months of life. Monocyte characteristics were analyzed by flow cytometry, and LPS-stimulated PBMC culture supernatants were analyzed by Luminex or ELISA. Plasma cytokines and gut microbiota composition were analyzed by ELISA and 16S rRNA-sequencing, respectively. RESULTS: The extremely preterm infants had persistent alterations in their monocyte characteristics that were further aggravated in chorioamnionitis cases. They showed a markedly reduced TLR4 expression and hampered LPS-stimulated cytokine responses 14 days after birth. Notably, at later timepoints, TLR4 expression and LPS responses no longer correlated. Sepsis during the first weeks of life strongly associated with increased pro-inflammatory, and reduced IL-10, responses also at postmenstrual week 36. Further, we report a correlation between gut microbiota features and monocyte phenotype and responses, but also that probiotic supplementation associated with distinct monocyte phenotypic characteristics, without significantly influencing their responsiveness. CONCLUSION: Extremely preterm infants have monocyte characteristics and functional features that deviate from infants born full-term. Some of these differences persist until they reach an age corresponding to full-term, potentially making them more vulnerable to microbial exposures during the first months of life.

Plasma proteomic signature of neonates in the context of placental histological chorioamnionitis.

BACKGROUND: Placental histological chorioamnionitis (HCA) is recognised as a significant risk factor for various adverse neonatal outcomes. This study aims to explore if the inflammatory protein levels in neonates were associated with HCA. METHODS: All women with singleton births from February 2020 to November 2022 were selected and divided into three groups based on maternal placental pathology results: the HCA-stage 1 group (n=24), the HCA-stage 2 group (n=16) and the control group (n=17). Olink Target 96 Inflammation Panel was used to detect the levels of 92 inflammation-related proteins in the plasma of newborns from all three groups within 24 hours after birth. We compared the protein profiles through differential protein expression analysis. RESULTS: A total of six inflammation-related proteins exhibited significant differences between the HCA-stage 1 and the control group. Specifically, TRANCE and CST5 were significantly upregulated (p=0.006, p=0.025, respectively), whereas the expression of IFN-gamma, CXCL9, CXCL10 and CCL19 was significantly downregulated (p=0.040, p=0.046, p=0.007, p=0.006, respectively). HCA-stage 2 newborns had significantly elevated levels of CD5 and CD6 and decreased IFN-gamma, CXCL10 and CCL19 in comparison to controls. These differential proteins were significantly enriched in positive regulation of cytokine activity, leucocyte chemotaxis and positive regulation of T-cell activation pathway-related Gene Ontology terms. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that viral protein interaction with cytokine and cytokine receptor, interleukin-17/NF-kappa B/toll-like receptor/chemokine signalling pathway, and cytokine-cytokine receptor interaction exhibited significant differences. Spearman analysis demonstrated a significant positive connection between the levels of CD6 and CD5 proteins, not only in neonatal leucocytes but also in maternal leucocytes. Additionally, CD6 was found to be associated with neonatal birth weight. CONCLUSIONS: In conclusion, placental histological changes associated with chorioamnionitis appear to influence the expression of inflammatory proteins in offspring. Notably, CD6 and CD5 proteins may potentially contribute to the pathogenesis of HCA-related neonatal diseases.

Microbiological investigation of pregnancies following vaginal radical trachelectomy using 16S rRNA sequencing of FFPE placental specimens.

This study examined the risk of intrauterine infection associated with radical trachelectomy (RT) in early-stage cervical cancer patients. This procedure preserves fertility but is linked to increased risk of intrauterine infection due to cervical defects during pregnancy. DNA was extracted from the formalin-fixed paraffin-embedded (FFPE) placental specimens of 23 pregnant post-RT patients and 16S rRNA gene sequencing was used for bacterial identification. The prevalence of Lactobacillus crispatus and Burkholderia stabilis was significantly higher in the non-chorioamnionitis group. In contrast, alpha diversity analysis using the PD index showed significantly higher diversity in the chorioamnionitis group (P = 0.04). The demonstrated relationship between chorioamnionitis and microbial diversity affirms the importance of controlling the genital bacterial flora in pregnancies following RT.

Association between asymptomatic bacteriuria in pregnancy and adverse pregnancy- and births outcomes. A systematic review.

BACKGROUND: Existing guidelines for screening and treatment of asymptomatic bacteriuria (ASB) in pregnancy are based on studies completed more than 30 years ago. This evidence is characterized by a lack of consensus on the association between ASB and adverse pregnancy- and birth outcomes. AIM: This systematic review aimed to investigate the association between untreated/treated ASB (≥105 colony-forming units (cfu) of the same bacteria per ml urine in two consecutive voided cultures without any symptoms) and pregnancy outcomes (pyelonephritis, chorioamnionitis, prelabour rupture of membranes (PROM)), and birth outcomes (preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA)). The impact of the most serious pathogens E. coli and Group B streptococci (GBS) on these outcomes was also examined. METHODS: A systematic literature search was prepared according to the guideline Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). The search was conducted in the databases Medline, Embase, and Cochrane Library, with a systematic strategy based on the PICO acronym (Population, Intervention, Comparison, Outcome). Covidence was used as a screening- and data extraction tool. Randomized trials and observational studies published between, January 01, 2005-February 10, 2023, were identified. The Cochrane Collaboration risk of bias tool 2 and the Newcastle-Ottawa Quality Assessment Scale were applied to assess the quality of the included studies. A protocol was published prior to this review, at the international prospective register of systematic reviews (PROSPERO). RESULTS: The database search yielded 3029 records. Fourteen studies were included. Untreated pregnant women with ASB had significantly increased odds of pyelonephritis. Most of the studies showed no significant association between treated ASB and pyelonephritis. In treated ASB, an increased risk of both chorioamnionitis and PROM was found. Divergent results were found in the association between ASB and PTB, as well as in the association between untreated ASB and LBW. Most of the studies showed no significant association between treated ASB and LBW. One study found no significant association between untreated/treated ASB and SGA. No studies were identified that addressed the association between ASB with E. coli/GBS and the outcomes examined. CONCLUSION: There is a need for more recent high-quality studies to investigate the association between untreated/treated ASB and pregnancy- and birth outcomes, and to assess the impact of E. coli/GBS on these outcomes.

Maternal chorioamnionitis and the risk for necrotizing enterocolitis in the United States: A national cohort study.

BACKGROUND: Necrotizing enterocolitis (NEC) is a major cause for morbidity and mortality among newborn infants. Chorioamnionitis is a perinatal complication that is associated with preterm delivery. Few reports have studied chorioamnionitis as a possible risk factor for NEC. Further investigation is needed to fully understand this association. OBJECTIVE: To examine the association of chorioamnionitis with NEC in newborn infants. METHODS: We used National Inpatient Sample (NIS) datasets produced by the federal Healthcare Cost and Utilization Project (HCUP). We identified infants born to mothers diagnosed with chorioamnionitis and infants born to mothers who did not have chorioamnionitis. The odds ratios (OR) to develop NEC in infants born to mothers affected by chorioamnionitis were calculated using chi square and Fisher Exact tests in the overall sample and in subgroups of different birthweight (BW) categories. The association was re-evaluated using logistic regression models to control for confounding variables. RESULTS: The study identified 18,973,800 newborn infants admitted during the years 2016-2020. Among infants born to mothers with chorioamnionitis, NEC occurred in 0.9 % compared to 0.1 % in infants born to mothers without chorioamnionitis, (adjusted OR = 1.12, CI:1.02-1.15, p = 0.01). The prevalence of NEC in infants born to mothers with chorioamnionitis varied by the birth weight category, mainly for BW category 2500-4499 g (aOR = 1.61, CI:1.44-1.80, p < 0.001). CONCLUSION: Maternal chorioamnionitis is associated with increased incidence of NEC, particularly in the BW category 2500-4499 g. Further studies are needed to examine the pathophysiological factors underlying this association.

"Investigation of the potential cellular changes induced by magnesium sulfate and salubrinal in a lipopolysaccharide-induced chorioamnionitis model".

Chorioamnionitis is closely associated with preterm labor and poses a significant public health concern. In this pathological process where inflammation plays a key role, intracellular mechanisms such as endoplasmic reticulum stress are crucial. In this study, we aimed to explore the potential positive outcomes of the combined use of salubrinal (SLB) with magnesium (Mg) treatment in chorioamnionitis. Thirty pregnant rats were divided into 5 groups as: Control, LPS (1 mg/kg), LPS + SLB (1 mg/kg), LPS + Mg (Dhaka protocol), LPS + SLB + Mg. Rats were sacrificed 4 h after LPS administration, then placental and fetal brain tissues were collected. LPS administration enhanced the levels of tumor necrosis factor-alpha, vascular endothelial growth factor, caspase-3 immunoexpressions, BAX, eukaryotic initiation factor 2-alpha, s100, and glial fibrillary acidic protein expressions and lowered BCL2 expressions in the placenta or fetal brains. SLB and Mg treatments were observed to reverse all these findings, and the most significant positive effect was in the LPS + SLB + Mg group. The known anti-inflammatory activity of Mg, when used with SLB, preventing the transition to apoptosis and increasing antioxidant enzyme activity, as identified in this study, can contribute significantly to the literature. However, these results need to be supported by additional molecular studies.

Chorioamnionitis and respiratory outcomes in prematurely born children: a systematic review and meta analysis.

INTRODUCTION: To conduct a systematic review and meta-analysis of the association between chorioamnionitis and respiratory outcomes of prematurely born children. CONTENT: Pubmed, Medline and Embase were searched for relevant studies. Studies were included if they assessed prematurely born children, who had been exposed to chorioamnionitis and had either lung function testing or assessment of wheeze or asthma following NICU discharge. Two reviewers independently screened the search results, applied inclusion criteria and assessed methodological quality. One reviewer extracted the data and these were checked by a second reviewer. SUMMARY: A total of 1,237 studies were identified, but only eight which included 35,000 infants, fulfilled the inclusion criteria. One study looked at both lung function results and wheeze or asthma in childhood. Four of five studies found an association between wheeze/asthma in childhood and exposure to chorioamnionitis: the overall Odds Ratio (OR) for developing wheeze/asthma in childhood was OR 1.71 (95 % CI: 1.55-1.89). Four studies looked at lung function in childhood, three of which showed no statistically significant association between chorioamnionitis exposure and altered lung function. One study found lower lung function in those exposed to chorioamnionitis and lower expiratory flows with increasing levels of chorioamnionitis (forced expiratory flow at 50 % of exhaled forced vital capacity (=FEF50) p=0.012, forced expiratory flow at 25-75 % of the forced vital capacity is exhaled (=FEF25-75) p=0.014). OUTLOOK: There was a significant association between chorioamnionitis and the development of wheeze or asthma in childhood, but overall not in impairment of lung function.

Absolute counts of leukocyte subsets in peripheral blood in pregnancies complicated by preterm prelabour rupture of membranes.

BACKGROUND: This study aimed to assess variations in the absolute counts of various leukocyte subsets in the peripheral blood of women with pregnancies affected by preterm prelabour rupture of membranes (PPROM), in relation to the presence of intra-amniotic inflammation (IAI). METHODS: The study included fifty-two women with singleton pregnancies experiencing PPROM. Absolute counts of different leukocyte subpopulations, such as granulocytes, monocytes, lymphocytes, T cells and their subsets, B cells and their subsets, and NK cells and their subsets, were measured in maternal peripheral blood samples using multicolour flow cytometry. IAI was identified by elevated concentrations of interleukin 6 (IL-6) in the amniotic fluid, which was collected through transabdominal amniocentesis. RESULTS: Women with IAI exhibited higher absolute counts of leukocytes (p = 0.003), granulocytes (p = 0.008), and monocytes (p = 0.009). However, the presence of IAI did not significantly affect the absolute counts of lymphocytes or their subpopulations. CONCLUSIONS: The study found that IAI is associated with changes in the absolute counts of leukocytes from the innate immunity compartment in the peripheral blood of women with pregnancies complicated by PPROM. Conversely, it does not significantly alter the counts of cells from the adaptive immune system. The changes observed may reflect the natural, temporal, and localised characteristics of IAI.

Preterm birth is the most serious complication in contemporary perinatal medicine. Preterm birth, which is defined as a labour before the completion of 37 weeks of pregnancy, is often accompanied by premature rupture of the amniotic membranes and drainage of amniotic fluid. Such a situation is often complicated by inflammation, which adversely affects the health of the foetus. A number of procedures and markers have been developed for the diagnosis of inflammation, but they are determined from hard-to-reach amniotic fluid. It is therefore appropriate to try to find reliable markers of inflammation in the much more accessible maternal peripheral blood. Such a marker can be increased numbers of leukocytes, which have been repeatedly investigated in this context. However, little attention is directed to other leukocyte populations and especially to various lymphocyte subpopulations. This study aimed to test changes in absolute counts of different types of leukocytes and lymphocyte subpopulations in women with premature rupture of membranes with respect to ongoing inflammation. The results of the study showed that inflammation is accompanied by increased numbers of leukocytes, granulocytes and monocytes, however, the results did not show significant changes in the number of lymphocytes and their subpopulations.

Characterization of Inflammation/Immune-, Acute Phase-, Extracellular Matrix-, Adhesion-, and Serine Protease-Related Proteins in the Amniotic Fluid of Women With Early Preterm Prelabor Rupture of Membranes.

PROBLEM: To determine whether altered concentrations of various inflammation/immune-, acute phase-, extracellular matrix-, adhesion-, and serine protease-related proteins in the amniotic fluid (AF) are independently associated with microbial invasion of the amniotic cavity and/or intra-amniotic inflammation (MIAC/IAI), imminent spontaneous preterm delivery (SPTD; ≤7 days), and major neonatal morbidity/mortality (NMM) in women with early preterm prelabor rupture of membranes (PPROM). METHOD OF STUDY: This was a retrospective cohort study involving 111 singleton pregnant women with PPROM (24-31 weeks) undergoing amniocentesis to diagnose MIAC/IAI. The following proteins were measured in stored AF samples by enzyme-linked immunosorbent assay (ELISA): APRIL, DKK-3, Gal-3BP, IGFBP-2, IL-8, VDBP, lumican, MMP-2, MMP-8, SPARC, TGFBI, TGF-ß1, E-selectin, ICAM-5, P-selectin, haptoglobin, hepcidin, SAA1, kallistatin, and uPA. RESULTS: Multivariate logistic regression analyses revealed that (i) elevated APRIL, IL-8, MMP-8, and TGFBI levels in the AF, reduced lumican and SPARC levels in the AF, and high percentages of samples above the lower limit of quantification for AF TGF-ß1 and uPA were significantly associated with MIAC/IAI; (ii) elevated AF levels of IL-8 and MMP-8 were significantly associated with SPTD within 7 days; and (iii) elevated AF IL-6 levels were significantly associated with increased risk for major NMM, when adjusted for baseline covariates. CONCLUSION: ECM (lumican, SPRAC, TGFBI, and TGF-ß1)- and serine protease (uPA)-associated proteins in the AF are involved in the regulation of the host response to infection/inflammation in the amniotic cavity, whereas AF inflammation (IL-8, MMP-8, and IL-6)-associated mediators are implicated in the development of preterm parturition and major NMM in early PPROM.

Placental chronic inflammatory histopathology and fetal growth in a cohort with universal placental examination.

INTRODUCTION: Chronic placental inflammation is a routinely diagnosed group of placental lesions that reflect immunologic dysfunction of the mother, fetus, or both. METHODS: Complete placental pathology examinations were performed for all term births at New York Presbyterian- Brooklyn Methodist Hospital from January 2010-August 2016. Diagnoses were blinded except to gestational age. CPI lesions were marked as chronic choriodeciduitis, decidual plasma cells, chronic inflammation of basal plate with anchoring villitis, and chronic villitis. RESULTS: In this cohort of term pregnancies, 257 (11.6 %) males and 218 (9.8 %) females had ≥1 CPI lesions. Chronic villitis was the most common (319 or 14 %), with chronic choriodeciduitis, decidual plasma cells, and chronic inflammation of basal plate with anchoring villitis in 94 (4 %), 69 (3 %) and 170 (8 %), respectively. In males, chronic villitis was associated with lower gestational adjusted birthweight and had no association with placental weight. In females, chronic villitis was associated with lower gestational adjusted birthweight, but the effect became nonsignificant after adjustment for placental weight. DISCUSSION: In summary, CPI lesions' incidence and association with birth weight vary by sex. Chronic villitis is associated with lower birthweight in females; this effect is completely mediated by placental weight. Chronic villitis showed a weak direct association of chronic villitis in males, but no association with lower placental weight in males. We suggest that differences between our results and previous publications reflect effects of sampling bias.