Effect of chorioamnionitis on postnatal growth in very preterm infants: a population-based study in Japan.

PURPOSE: There is growing evidence that preterm infants born to mothers with chorioamnionitis (CAM) have increased risk of various neonatal morbidities and long-term neurological disorders; however, the effect of CAM on postnatal growth remains insufficiently investigated. This study evaluated the effect of histological CAM on postnatal growth trajectories in very preterm infants using a nationwide neonatal database in Japan. METHOD: A multicenter retrospective study was conducted using clinical data of 4220 preterm neonates who weighed ≤ 1500 g and were born at < 32 weeks of gestation between 2003-2017 (CAM group: n = 2110; non-CAM group: n = 2110). Z-scores for height and weight were evaluated at birth and 3 years of age. Univariable and multivariable analyses were conducted to evaluate the effect of histological CAM on ΔZ-scores of height and weight during the first three years with a stratification by infant sex and the stage of histological CAM. RESULTS: Multivariable analyses showed that histological CAM was associated with accelerated postnatal increase (ΔZ-score) in weight (ß coefficient [95% confidence interval]; 0.10 [0.00 to 0.20]), but not in height among females (0.06 [- 0.04 to 0.15]) and not in height and weight among males (0.04 [- 0.04 to 0.12] and 0.02 [- 0.07 to 0.11], respectively). An interaction analysis demonstrated no significant difference in the effect of histological CAM on the ΔZ-scores of height and weight during the first three years between male and female infants (height, p = 0.81; weight p = 0.25). CONCLUSIONS: Intrauterine exposure to maternal CAM contributes to accelerated postnatal weight gain in female preterm infants during the first three years.

Comparison of the Fetomaternal Outcome in Women With Preterm Premature Rupture of Membranes on Expectant Management Versus Delivery at 34 Weeks.

CONTEXT: This study aimed to study feto-maternal outcomes in women with preterm prelabor rupture of membranes (PTPROM) on expectant management versus delivery at 34 weeks of gestation and correlate the period of latency and inflammatory markers with delivery outcomes. We have chosen this research topic as there is a paucity of specific guidelines regarding the optimal period of gestation for delivering women with PTPROM. AIM: The study correlated the feto-maternal outcomes in women with PTPROM on expectant management till 37 weeks versus delivery at 34 weeks with a period of latency and maternal inflammatory markers. METHODS AND MATERIALS: This was a prospective observational study conducted on 262 women with PTPROM from 28-33+6 weeks of gestation. Women were monitored till 37 weeks with biweekly total leukocyte count and weekly C-reactive protein, urine routine microscopy, urine culture, high vaginal culture sensitivity, and ultrasound. Women were monitored expectantly till 37 weeks. However, intervention was done at any time during the feto-maternal compromise. There were 52 women who delivered <34 weeks and 210 women who delivered ≥34 weeks. Feto-maternal outcomes were documented. Group A was assigned to women who delivered before 34 weeks and Group B was assigned to women who delivered after 34 weeks. Statistical analysis was done using SPSS software. A p-value <0.05 was considered significant. RESULTS: Among the study group, 238 (90.8%) women were managed expectantly while 24(9.1%) required intervention. A latency of 3-4 weeks was observed in 131(50%) women. Chorioamnionitis developed in 7 women (4.4%) in group A and 13 women (4.9%) in group B. Neonates developed sepsis in 5.7% in group A and 5.8 % in group B and were comparable in both the groups (p=1.000). Early neonatal death (END) occurred in 10 (3.8%) among which seven died because of low birth weight (LBW), two due to sepsis, and one due to respiratory distress. LBW was significantly associated with END (p<0.001) Conclusion: Expectant management beyond 34 weeks with close monitoring can improve neonatal outcomes without increasing maternal morbidity in women with PTPROM.

International expert consensus statement on physiological interpretation of cardiotocograph (CTG): First revision (2024).

The first international consensus guideline on physiological interpretation of cardiotocograph (CTG) produced by 44 CTG experts from 14 countries was published in 2018. This guideline ensured a paradigm shift from classifying CTG by arbitrarily grouping certain features of the fetal heart rate into different "categories", and then, randomly combining them to arrive at an overall classification of CTG traces into "Normal, Suspicious and Pathological" (or Category I, II and III) to a classification which is based on the understanding of fetal pathophysiology. The guideline recommended the recognition of different types of fetal hypoxia, and the determination of features of fetal compensatory responses as well as decompensation to ongoing hypoxic stress on the CTG trace. Since its first publication in 2018, there have been several scientific publications relating physiological interpretation of CTG, especially relating to features indicative of autonomic instability due to hypoxic stress (i.e., the ZigZag pattern), and of fetal inflammation. Moreover, emerging evidence has suggested improvement in maternal and perinatal outcomes in maternity units which had implemented physiological interpretation of CTG. Therefore, the guideline on Physiological Interpretation of CTG has been revised to incorporate new scientific evidence, and the interpretation table has been expanded to include features of chorioamnionitis and relative utero-placental insufficiency of labour (RUPI-L).

Escherichia coli induced matrix metalloproteinase-9 activity and type IV collagen degradation is regulated by progesterone in human maternal decidual.

BACKGROUND: Escherichia coli (E. coli) is one of the main bacteria associated with preterm premature rupture of membranes by increasing pro-matrix metalloproteinase 9 (proMMP-9) and degradation of type IV collagen in human feto-maternal interface (HFMi). proMMP-9 is regulated by progesterone (P4) but it is unclear whether P4 inhibits proMMP in human maternal decidual (MDec). This study aimed to determine a role of P4 on proMMP-2 and - 9 and type IV collagen induced by E. coli infection in MDec. METHODS: Nine HFMi were mounted in a Transwell system. MDec was stimulated with P4 or E. coli for 3-, 6-, or 24-hours. proMMP-2, -9 and type IV collagen were assessed. RESULTS: Gelatin zymography revealed an increase in proMMP-9 after 3, 6, and 24 h of stimulating MDec with E. coli. Using immunofluorescence, it was confirmed the increase in the HFMi tissue and a reduction on the amount of type IV collagen leading to the separation of fetal amniochorion and MDEc. The degradative activity of proMMP-9 was reduced by 20% by coincubation with P4. CONCLUSIONS: P4 modulates the activity of proMMP-9 induced by E. coli stimulation but it was unable to completely reverse the degradation of type IV collagen in human MDec tissue.

The dual role of glucocorticoid regeneration in inflammation at parturition.

Introduction: Fetal membrane inflammation is an integral event of parturition. However, excessive pro-inflammatory cytokines can impose threats to the fetus. Coincidentally, the fetal membranes express abundant 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1), which generates biologically active cortisol to promote labor through induction of prostaglandin synthesis. Given the well-recognized anti-inflammatory actions of glucocorticoids, we hypothesized that cortisol regenerated in the fetal membranes might be engaged in restraining fetus-hazardous pro-inflammatory cytokine production for the safety of the fetus, while reserving pro-labor effect on prostaglandin synthesis to ensure safe delivery of the fetus. Methods: The hypothesis was examined in human amnion tissue and cultured primary human amnion fibroblasts as well as a mouse model. Results: 11ß-HSD1 was significantly increased in the human amnion in infection-induced preterm birth. Studies in human amnion fibroblasts showed that lipopolysaccharide (LPS) induced 11ß-HSD1 expression synergistically with cortisol. Cortisol completely blocked NF-κB-mediated pro-inflammatory cytokine expression by LPS, but STAT3-mediated cyclooxygenase 2 expression, a crucial prostaglandin synthetic enzyme, remained. Further studies in pregnant mice showed that corticosterone did not delay LPS-induced preterm birth, but alleviated LPS-induced fetal organ damages, along with increased 11ß-HSD1, cyclooxygenase 2, and decreased pro-inflammatory cytokine in the fetal membranes. Discussion: There is a feed-forward cortisol regeneration in the fetal membranes in infection, and cortisol regenerated restrains pro-inflammatory cytokine expression, while reserves pro-labor effect on prostaglandin synthesis. This dual role of cortisol regeneration can prevent excessive pro-inflammatory cytokine production, while ensure in-time delivery for the safety of the fetus.

Early postnatal immature-to-total neutrophil ratio in the histological chorioamnionitis among neonatal intensive care unit infants.

OBJECTIVE: Histological chorioamnionitis (hCAM) is a major risk factor for early-onset sepsis. Predictive methods for hCAM are needed in clinical practice during the early postnatal period. To examine the relationship between hCAM and perinatal variables including early postnatal immature-to-total neutrophil ratio (ITR). STUDY DESIGN: A single-center study was undertaken at Ohta Nishinouchi Hospital between April 1, 2016 and June 30, 2023. Blood samples and placenta collected from study candidate infants admitted to the neonatal intensive care unit were assessed by univariate analyses and multivariate logistic regression analysis. We also assessed the test performance of ITR and maternal white blood cell (WBC) counts by area under a receiver operating characteristic (ROC) curves. RESULTS: A total of 725 infants were analyzed (496 in the non-hCAM group and 229 in the hCAM group). Significant relationships were observed between hCAM and ITR (p < 0.001, odds ratio (OR), 1.067; 95% confidence interval (CI), 1.041 to 1.093). Per the ROC curves, an ITR (%) of 7.15 could predict hCAM at a sensitivity of 55.9% and specificity of 71.9% [area under the curve (AUC) = 0.691, p < 0.001, 95% CI, 0.649 to 0.733]. Further, maternal WBC counts of 9.85 ( × 109/L) predicted hCAM with 69.0% sensitivity and 67.3% specificity (AUC = 0.710, p < 0.001, 95%CI, 0.669 to 0.750). CONCLUSIONS: Early postnatal ITR was high in cases with greater leukocyte invasion into the placenta tissue, which may be a biomarker of the presence and/or severity of hCAM. Histological CAM should be considered when the early neonatal ITR (%) is 7.15 or higher.

Epidemiology and placental pathology of intrauterine fetal demise in a tertiary hospital in the Philippines.

Objectives: The Philippines has at least 25,000 stillbirth or intrauterine fetal demise (IUFD) cases every year. Despite its burden, there is scarce information on IUFD epidemiology in the Philippines. Hence, this study reported the epidemiology and placental pathology of IUFD in a tertiary hospital in the Philippines. Study design: This cross-sectional study analyzed second- and third-trimester IUFD cases at the Philippine General Hospital from 2012 to 2021. We reviewed maternal sociodemographic and clinical characteristics and evaluated placental pathology. All statistical tests were done with GraphPad Prism software version 8.0. Results: We recorded 947 (2.28 %) cases of IUFD out of 41,562 obstetric deliveries from 2012 to 2021. Out of 947 IUFD cases, 532 had placental pathology reports. Second-trimester IUFD cases showed higher rates of no antenatal care (42.86 %) compared to third-trimester cases (10.61 %). Hypertensive disorders were more common in third-trimester IUFD. Infarcts (23.34 %), calcifications (4.12 %), and hemorrhages/hematomas (3.00 %) were the most prevalent placental abnormalities. While these abnormalities were more common in third-trimester IUFD, placental and fetal membrane infections like chorioamnionitis were more frequent in second-trimester IUFD. Conclusion: The results highlighted the differences in maternal sociodemographic and clinical characteristics, and placental pathology between second- and third-trimester cases of IUFD. These observations revealed distinct pathological processes and potential etiologies contributing to IUFD in the Philippines.

Assessment of Blood Prostaglandin E2 Metabolite Levels among Infants Born Preterm with Patent Ductus Arteriosus: A Prospective Study.

OBJECTIVE: To assess the role of prostaglandin E2 by measuring blood prostaglandin E2 metabolite (PGEM) concentrations in preterm infants with patent ductus arteriosus (PDA). STUDY DESIGN: A prospective observational study of preterm infants born before 32 weeks of gestational age (GA) was performed in a single tertiary hospital in Japan. Blood samples were collected to measure serum concentrations of PGEM, ibuprofen (IBU), and cytokines. Multiple regression analyses assessed associations between blood PGEM levels and perinatal factors, development of hemodynamically significant PDA (hsPDA), and IBU treatment response of hsPDA. RESULTS: Seventy-nine infants (median GA 28 weeks) were enrolled in this study. Forty-seven received IBU for hsPDA treatment 1 d after birth in median. PDA closure occurred in 25 infants after a single IBU treatment. Serum PGEM concentrations were associated with histologic chorioamnionitis (P < .01), but not with GA, respiratory distress syndrome, or serum IL-6 concentrations. Serum PGEM concentrations decreased after initial IBU treatment; however, they were not associated with hsPDA development (P = .39). IBU concentrations correlated with IBU treatment response (aOR 1.29, P < .01). However, pre-IBU serum PGEM levels and PGEM reduction ratio did not (P = .13, .15, respectively). CONCLUSIONS: Serum PGEM concentrations in preterm infants were associated with maternal histologic chorioamnionitis, but not hsPDA development. IBU treatment response was associated with higher blood IBU concentrations, but not PGEM concentrations.

Enhancing the Diagnostic Accuracy of Placental Pathology by Using the Amsterdam Consensus Criteria.

Background and objective Standardizing placental pathology diagnoses is crucial for improving diagnostic accuracy and clinical communication. The Amsterdam Consensus Criteria were developed to address inconsistencies in diagnosing significant placental pathologies. This study aimed to assess the application and effectiveness of the Amsterdam Consensus Criteria in diagnosing placental pathologies, with a focus on improving the reliability and precision of placental pathology reports. Methods A retrospective review of 100 consecutively archived placental pathology samples was performed at a tertiary care hospital. These samples, gathered from January through December 2021, were reassessed according to the Amsterdam criteria. The revised diagnoses were then compared with the original descriptive diagnoses. Results Significant changes were noted in all principal diagnoses, including maternal vascular malperfusion (MVM), fetal vascular malperfusion (FVM), chronic villitis of unknown etiology (VUE), and acute chorioamnionitis (ACA). This evaluation led to a recategorization of several cases. Frequently, parenchymal infarcts were reported without adequate information to ascertain their association with MVM. Additionally, there was a noticeable lack of understanding of FVM and VUE among pathologists. ACA was the condition most consistently documented. However, detailed grading and staging were often not included. Conclusions Our findings emphasize the need to use standardized diagnostic criteria, such as the Amsterdam criteria, to enhance diagnostic accuracy and facilitate communication between pathologists and clinicians. This will ultimately lead to improved patient care outcomes. It also underlines the necessity of continuous education and calibration for pathologists to mitigate interobserver variability. There is a demand to modify these criteria to ensure universal applicability and relevance in various clinical settings.

Comparison of Histological Chorioamnionitis in Pre-Term Delivery with and without Pre-Term Rupture of Membrane.

Background: Histological chorioamnionitis (HCA) is a histologic response to intra-uterine inflammation that is usually confirmed by pathology examination after pre-term delivery and characterized by acute granulocyte infiltration into the fetal-maternal or fetal tissues. This study aimed to compare the HCA in pre-term delivery with and without pre-term rupture of membrane for assessment of its role on early neonatal outcomes and fetal heart rate patterns. Materials and Methods: This case-control study was conducted on placenta, chorionamnion, and cord of 100 cases with and without pre-term rupture of membrane between 28 0/7 and 36 6/7 weeks delivered between March 2018 and February 2021. The kind of delivery, gestational age, neonatal intensive care unit admission, a 5 min Apgar score <7, and fetal heart rate patterns in two groups with and without HCA were assessed. Results: The odds ratio (OR) for HCA was adjusted for fetal heart rate patterns, gestational age, and delivery mode (vaginal delivery or cesarean section). Vaginal delivery, gestational age, neonatal intensive care unit admission, and a 5 min Apgar score <7 were associated with HCA [OR: 2.4, 95% confidence interval (CI): 1.2-9.5, P < 0.05; OR: 0.8, 95% CI: 0.5-1.1, P < 0.05; OR: 1.1, 95% CI: 0.6-2.1, P < 0.05; and OR: 0.9, 95% CI: 0.7-1.3, P < 0.05), respectively. However, there were no specific fetal heart rate patterns associated with HCA. Conclusion: Placental histology examination in pre-term infants with low Apgar scores may be useful to investigate the association between neonatal complications in pre-term delivery and asymptomatic chorioamnionitis.

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.

Fetal origin of bronchopulmonary dysplasia: contribution of intrauterine inflammation.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in infants and the most frequent adverse outcome of premature birth, despite major efforts to minimize injury. It is thought to result from aberrant repair response triggered by either prenatal or recurrent postnatal injury to the lungs during development. Intrauterine inflammation is an important risk factor for prenatal lung injury, which is also increasingly linked to BPD. However, the specific mechanisms remain unclear. This review summarizes clinical and animal research linking intrauterine inflammation to BPD. We assess how intrauterine inflammation affects lung alveolarization and vascular development. In addition, we discuss prenatal therapeutic strategies targeting intrauterine inflammation to prevent or treat BPD.

A Review of the Literature: Amniotic Fluid "Sludge"-Clinical Significance and Perinatal Outcomes.

Introduction: This paper seeks to report and emphasize the most important aspects from the scientific literature about the diagnostic accuracy of the amniotic fluid "sludge" (AFS), its characterization, its treatment, and its association with premature birth. AFS is defined as a floating freely hyperechogenic material within the amniotic cavity in the proximity of the internal os. Materials and Methods: We conducted a search on Pubmed and Google Scholar for relevant articles on the subject of amniotic fluid "sludge" published until January 2024. Searches were focused on articles about diagnosis, treatment, maternal and neonatal outcomes, risk of preterm birth, and case reports. The full-text reading stage resulted in the inclusion of 51 studies. Results: AFS is independently associated with chorioamnionitis, preterm delivery, short cervix, increased risk of neonatal morbidity, and cervical insufficiency. This hyperechogenic free-floating material is linked with preterm birth before 32 weeks of gestation, especially when it is associated with short cervical length. Discussion: Present studies identify some controversial benefits of antibiotics in reducing the incidence of preterm birth in women with AFS. Nevertheless, in this review, we can conclude that the presence of AFS in pregnancy is a marker for the microbial invasion of the amniotic cavity, as it is associated with preterm birth. Further studies on a larger group of patients are necessary to clarify and exactly define the terms of managing these cases.

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.

Incorporating placental pathology into clinical care and research.

Despite recent standardization of placental evaluation and establishment of criteria for diagnosis of major patterns of placental injury, placental pathological examination remains undervalued and under-utilized. The placenta can harbor a significant amount of information relevant to both the pregnant person and offspring. Placental pathology can also provide a significant context for pathophysiological study of adverse pregnancy outcomes, helping to optimally subcategorize the 'great obstetric syndromes' of pre-eclampsia (PE), spontaneous preterm birth (sPTB), and fetal growth restriction (FGR), and to identify causes of stillbirth. We hereby propose that placental evaluation should be incorporated into routine delivery of obstetric and neonatal care, and further suggest that its integration into clinical, translational, and basic research could significantly advance our understanding of pregnancy complications and adverse neonatal outcomes.

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.

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.