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Frontiers in Immunology 2024Rupture of the gestational membranes often precedes major pregnancy complications, including preterm labor and preterm birth. One major cause of inflammation in the...
INTRODUCTION
Rupture of the gestational membranes often precedes major pregnancy complications, including preterm labor and preterm birth. One major cause of inflammation in the gestational membranes, chorioamnionitis (CAM) is often a result of bacterial infection. The commensal bacterium , or Group B (GBS) is a leading infectious cause of CAM. Obesity is on the rise worldwide and roughly 1 in 4 pregnancy complications is related to obesity, and individuals with obesity are also more likely to be colonized by GBS. The gestational membranes are comprised of several distinct cell layers which are, from outermost to innermost: maternally-derived decidual stromal cells (DSCs), fetal cytotrophoblasts (CTBs), fetal mesenchymal cells, and fetal amnion epithelial cells (AECs). In addition, the gestational membranes have several immune cell populations; macrophages are the most common phagocyte. Here we characterize the effects of palmitate, the most common long-chain saturated fatty acid, on the inflammatory response of each layer of the gestational membranes when infected with GBS, using human cell lines and primary human tissue.
RESULTS
Palmitate itself slightly but significantly augments GBS proliferation. Palmitate and GBS co-stimulation synergized to induce many inflammatory proteins and cytokines, particularly IL-1β and matrix metalloproteinase 9 from DSCs, CTBs, and macrophages, but not from AECs. Many of these findings are recapitulated when treating cells with palmitate and a TLR2 or TLR4 agonist, suggesting broad applicability of palmitate-pathogen synergy. Co-culture of macrophages with DSCs or CTBs, upon co-stimulation with GBS and palmitate, resulted in increased inflammatory responses, contrary to previous work in the absence of palmitate. In whole gestational membrane biopsies, the amnion layer appeared to dampen immune responses from the DSC and CTB layers (the choriodecidua) to GBS and palmitate co-stimulation. Addition of the monounsaturated fatty acid oleate, the most abundant monounsaturated fatty acid in circulation, dampened the proinflammatory effect of palmitate.
DISCUSSION
These studies reveal a complex interplay between the immunological response of the distinct layers of the gestational membrane to GBS infection and that such responses can be altered by exposure to long-chain saturated fatty acids. These data provide insight into how metabolic syndromes such as obesity might contribute to an increased risk for GBS disease during pregnancy.
Topics: Humans; Female; Streptococcus agalactiae; Pregnancy; Interleukin-1beta; Streptococcal Infections; Chorioamnionitis; Palmitates; Extraembryonic Membranes; Toll-Like Receptor 2
PubMed: 38855112
DOI: 10.3389/fimmu.2024.1409378 -
Alternative Therapies in Health and... Jun 2024To investigate the relationship between different delivery timing and the outcome of premature rupture of membranes (PROM) in primiparous women.
OBJECTIVE
To investigate the relationship between different delivery timing and the outcome of premature rupture of membranes (PROM) in primiparous women.
METHODS
Within the context of exploring optimal delivery strategies for managing PROM, we conducted a retrospective study at Shijiazhuang Fourth Hospital. From May 2019 to May 2022, a total of 400 single pregnant women with premature rupture of membranes (PROM) at different gestational weeks (28-36 weeks) were enrolled. This study aims to understand the impact of delivery timing on pregnancy outcomes more clearly. Pregnant women were divided into two distinct groups based on gestational weeks: Group A (28 to 33 weeks, n=192) and Group B (34 to 36 weeks, n=208). The clinical data of pregnant women were analyzed retrospectively, and the methods of delivery, maternal and infant pregnancy outcomes, and factors affecting delivery outcomes were compared in different groups.
RESULTS
Compared with the delivery methods of the two groups, the proportion of vaginal delivery in group A (69.27%) was significantly higher than that in group B (49.04%). The proportion of assisted vaginal delivery and cesarean section (13.54% and 17.19%) was significantly lower than that in group B (18.75% and 32.21%) (P < .001). There was no difference in neonatal death outcomes between the two groups (P > .297). The incidence of chorioamnionitis, postpartum hemorrhage, and puerperal infection in group A (25.00%), (19.27%) and (11.46%) was significantly higher than that in group B (6.25%), (5.29%) and (2.40%), respectively. The incidence rates of neonatal asphyxia, neonatal respiratory distress syndrome (NRDS), and hypoxic-ischemic encephalopathy (HIE) in group A were 9.38%, 7.29%, and 6.77%, which were significantly higher than those in group B (1.92%, 0.48% and 0.48%) (P = .001). There was no difference in neonatal death outcomes at different delivery times (P = .259). The incidence rates of amniotic infection, postpartum hemorrhage, and puerperal infection were (3.98%), (7.39%) and (3.41%), which were significantly lower than those of pregnant women from PROM to delivery time ≥48 h (24.11%), (15.63%) and (9.38%). The incidence rates of neonatal asphyxia, NRDS, and HIE were (1.14%), (1.14%) and (2.27%) in neonates from PROM to delivery time < 48 h, significantly lower than those in neonates from PROM to delivery time ≥48 h (8.93%), (5.80%), and (4.46%) (P < .001). Logistic regression analysis showed that the older the gestational week was the protective factor for amniotic space infection, postpartum hemorrhage, puerperal infection, neonatal asphyxia, NRDS, and HIE. Late delivery time was an independent risk factor for amniotic cavity infection(P < .001), postpartum hemorrhage(P = .014), puerperal infection(P = .023), neonatal asphyxia(P = .004), and NRDS (P = .028).
CONCLUSION
In pregnant women with PROM who are not at full term, a greater gestational week is associated with a lower rate of adverse delivery outcomes. In contrast, a longer time interval between membrane rupture and delivery is associated with a higher rate of adverse delivery outcomes.
PubMed: 38836724
DOI: No ID Found -
Frontiers in Pediatrics 2024Cryopyrin-associated periodic syndrome (CAPS) is a genetic disorder and autoinflammatory disease characterized by chronic inflammation throughout the body. The most...
Cryopyrin-associated periodic syndrome (CAPS) is a genetic disorder and autoinflammatory disease characterized by chronic inflammation throughout the body. The most severe form of CAPS, Chronic Infantile Neurologic Cutaneous, and Articular (CINCA) syndrome, also known as Neonatal Onset Multisystem Inflammatory Disease (NOMID), has three main features: skin rash, CNS involvement, and joint symptoms. Although these symptoms are typically reported shortly after birth, there have been a few reports of prenatal inflammation. Here, we report our experience managing a case of a CAPS infant born in severe neonatal asphyxia due to a ruptured cord associated with severe funisitis. The baby was born at 38 weeks and 6 days of gestation, weighing 2,898 g, through an ultra-emergency Caesarian section prompted by variable deceleration. The Apgar score was 1 point at 1 min and 4 points at 5 min, necessitating intensive care due to hypoxic-ischemic encephalopathy. Upon delivery, it was observed that the umbilical cord had partially ruptured at the site of attachment to the baby, accompanied by arterial hemorrhage. Umbilical cord rupture was considered to be the cause of the sudden decrease in fetal heart rate. Pathological examination also showed that the inflammation of the cord was more severe on the side attached to the fetus and on the arterial side, suggesting that the inflammation had extended from the fetus. The father carried a genetic mutation associated with CINCA syndrome/NOMID ( c.2068G>A p.Glu690Lys Hetero), which was also found in the child. Histopathologic examination of the placenta and umbilical cord can provide crucial insights into the intrauterine onset of inflammation, which is the first manifestation of CINCA syndrome/NOMID in newborns. It should be noted that births with a genetic predisposition to CAPS may have complications related to the placenta and umbilical cord.
PubMed: 38808101
DOI: 10.3389/fped.2024.1397412 -
Journal of Neuroinflammation May 2024Intrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to...
BACKGROUND
Intrauterine inflammation is considered a major cause of brain injury in preterm infants, leading to long-term neurodevelopmental deficits. A potential contributor to this brain injury is dysregulation of neurovascular coupling. We have shown that intrauterine inflammation induced by intra-amniotic lipopolysaccharide (LPS) in preterm lambs, and postnatal dopamine administration, disrupts neurovascular coupling and the functional cerebral haemodynamic responses, potentially leading to impaired brain development. In this study, we aimed to characterise the structural changes of the neurovascular unit following intrauterine LPS exposure and postnatal dopamine administration in the brain of preterm lambs using cellular and molecular analyses.
METHODS
At 119-120 days of gestation (term = 147 days), LPS was administered into the amniotic sac in pregnant ewes. At 126-7 days of gestation, the LPS-exposed lambs were delivered, ventilated and given either a continuous intravenous infusion of dopamine at 10 µg/kg/min or isovolumetric vehicle solution for 90 min (LPS, n = 6; LPS, n = 6). Control preterm lambs not exposed to LPS were also administered vehicle or dopamine (CTL, n = 9; CTL, n = 7). Post-mortem brain tissue was collected 3-4 h after birth for immunohistochemistry and RT-qPCR analysis of components of the neurovascular unit.
RESULTS
LPS exposure increased vascular leakage in the presence of increased vascular density and remodelling with increased astrocyte "end feet" vessel coverage, together with downregulated mRNA levels of the tight junction proteins Claudin-1 and Occludin. Dopamine administration decreased vessel density and size, decreased endothelial glucose transporter, reduced neuronal dendritic coverage, increased cell proliferation within vessel walls, and increased pericyte vascular coverage particularly within the cortical and deep grey matter. Dopamine also downregulated VEGFA and Occludin tight junction mRNA, and upregulated dopamine receptor DRD1 and oxidative protein (NOX1, SOD3) mRNA levels. Dopamine administration following LPS exposure did not exacerbate any effects induced by LPS.
CONCLUSION
LPS exposure and dopamine administration independently alters the neurovascular unit in the preterm brain. Alterations to the neurovascular unit may predispose the developing brain to further injury.
Topics: Animals; Dopamine; Sheep; Female; Animals, Newborn; Lipopolysaccharides; Pregnancy; Brain; Inflammation; Blood-Brain Barrier; Premature Birth
PubMed: 38807204
DOI: 10.1186/s12974-024-03137-0 -
F&S Science May 2024The aim of this study is to investigate potential differences in pregnancy, delivery, and neonatal outcomes between two hyperandrogenic conditions in reproductive-aged...
OBJECTIVE
The aim of this study is to investigate potential differences in pregnancy, delivery, and neonatal outcomes between two hyperandrogenic conditions in reproductive-aged women; polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (CAH).
DESIGN
Retrospective population-based study with data from the Health Care Cost and Utilization Project-Nationwide Inpatient Sample database (HCUP-NIS) from 2004 to 2014.
SUBJECTS
14,881 women with polycystic ovary syndrome (PCOS) and 298 women with congenital adrenal hyperplasia (CAH).
MAIN OUTCOME MEASURES
Gestational diabetes mellitus, placenta previa, pregnancy-induced hypertension, gestational hypertension, preeclampsia, eclampsia, preeclampsia and eclampsia superimposed on hypertension, preterm birth, preterm premature rupture of membrane, abruptio placenta, chorioamnionitis, mode of delivery, maternal infection, hysterectomy, blood transfusion, venous thromboembolism (deep vein thrombosis and pulmonary embolism during pregnancy, intrapartum, or postpartum), maternal death, chorioamnionitis, septicemia during labor, postpartum endometritis, septic pelvic, peritonitis, small for gestational age, congenital anomalies, intrauterine fetal demise.
RESULTS
After adjusting for potential confounders we found that women with PCOS were at increased risk of developing pregnancy-induced hypertension (adjusted OR=1.76; 95% CI: 1.12-2.77; p=0.015) and gestational diabetes (adjusted OR=1.68; 95% CI: 1.12-2.52; p=0.012) when compared to women with CAH. Contrary women with CAH were at increased risk for delivery via cesarean section (adjusted OR 0.59; 95% CI: 0.44-0.80; p<0.001) and small for gestational age neonates (adjusted OR 0.32; 95% CI: 0.20-0.52; p<0.001).
CONCLUSION
This study is the first to directly compare obstetrical and neonatal outcomes between patients with PCOS and CAH. Despite the similar phenotypes and some common hormonal and biochemical profiles such as insulin resistance, hyperinsulinemia, and hyperandrogenism, our results suggest the existence of additional metabolic pathways implicated in the pathogenesis of pregnancy complications.
PubMed: 38795844
DOI: 10.1016/j.xfss.2024.05.001 -
International Journal of Molecular... May 2024Danger-associated molecular patterns (DAMPs) are elevated within the amniotic cavity, and their increases correlate with advancing gestational age, chorioamnionitis, and...
Danger-associated molecular patterns (DAMPs) are elevated within the amniotic cavity, and their increases correlate with advancing gestational age, chorioamnionitis, and labor. Although the specific triggers for their release in utero remain unclear, it is thought that they may contribute to the initiation of parturition by influencing cellular stress mechanisms that make the fetal membranes (FMs) more susceptible to rupture. DAMPs induce inflammation in many different tissue types. Indeed, they precipitate the subsequent release of several proinflammatory cytokines that are known to be key for the weakening of FMs. Previously, we have shown that in vitro stretch of human amnion epithelial cells (hAECs) induces a cellular stress response that increases high-mobility group box-1 (HMGB1) secretion. We have also shown that cell-free fetal DNA (cffDNA) induces a cytokine response in FM explants that is fetal sex-specific. Therefore, the aim of this work was to further investigate the link between stretch and the DAMPs HMGB1 and cffDNA in the FM. These data show that stretch increases the level of cffDNA released from hAECs. It also confirms the importance of the sex of the fetus by demonstrating that female cffDNA induced more cellular stress than male fetuses. Our data treating hAECs and human amnion mesenchymal cells with HMGB1 show that it has a differential effect on the ability of the cells of the amnion to upregulate the proinflammatory cytokines and propagate a proinflammatory signal through the FM that may weaken it. Finally, our data show that sulforaphane (SFN), a potent activator of Nrf2, is able to mitigate the proinflammatory effects of stretch by decreasing the levels of HMGB1 release and ROS generation after stretch and modulating the increase of key cytokines after cell stress. HMGB1 and cffDNA are two of the few DAMPs that are known to induce cytokine release and matrix metalloproteinase (MMP) activation in the FMs; thus, these data support the general thesis that they can function as potential central players in the normal mechanisms of FM weakening during the normal distension of this tissue at the end of a normal pregnancy.
Topics: Humans; HMGB1 Protein; Female; Pregnancy; Inflammation; Extraembryonic Membranes; Cell-Free Nucleic Acids; Male; Amnion; Cytokines; Epithelial Cells; Cells, Cultured; Alarmins
PubMed: 38791199
DOI: 10.3390/ijms25105161 -
Pathogens (Basel, Switzerland) Apr 2024Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and... (Review)
Review
Female genital tract infections (FGTIs) include vaginal infections (e.g., bacterial vaginosis [BV]), endometritis, pelvic inflammatory disease [PID], and chorioamnionitis [amniotic fluid infection]. They commonly occur in women of reproductive age and are strongly associated with multiple adverse health outcomes including increased risk of HIV/sexually transmitted infection acquisition and transmission, infertility, and adverse birth outcomes such as preterm birth. These FGTIs are characterized by a disruption of the cervicovaginal microbiota which largely affects host immunity through the loss of protective, lactic acid-producing spp. and the overgrowth of facultative and strict anaerobic bacteria. species (spp.), anaerobic Gram-negative rods, are implicated in the pathogenesis of multiple bacterial FGTIs. Specifically, , , and have unique virulence factors in this setting, including resistance to antibiotics commonly used in treatment. Additionally, evidence suggests that the presence of spp. in untreated BV cases can lead to infections of the upper female genital tract by ascension into the uterus. This narrative review aims to explore the most common spp. in FGTIs, highlight their important role in the pathogenesis of FGTIs, and propose future research in this area.
PubMed: 38787215
DOI: 10.3390/pathogens13050364 -
Tropical Medicine and Infectious Disease May 2024Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives.... (Review)
Review
Vulvovaginal candidiasis (VVC) is a common condition that can lead to significant discomfort, affecting approximately 70-75% of women at least once in their lives. During pregnancy, the prevalence of VVC is estimated to be around 20%, peaking at about 30% in the third trimester, with a number of specific risk factors predisposing to yeast infection being identified and needing elucidation. This review aims to provide updated knowledge on candidiasis during pregnancy, addressing risk factors and maternal and neonatal outcomes, as well as discussing optimal therapeutic strategies to safeguard mothers and newborns. The bibliographic search involved two biomedical databases, PubMed and Embase, without imposing time limits. Among all spp., remains the most frequent causative species. The hyperestrogenic environment of the vaginal mucosa and reduced immune defenses, physiological effects of pregnancy, create conditions favorable for spp. vaginal colonization and hence VVC. Recent evidence shows an association between VVC and adverse obstetric outcomes, including premature membrane rupture (PROM), chorioamnionitis, preterm birth, and puerperal infections. Prompt and effective management of this condition is therefore crucial to prevent adverse obstetric outcomes, maternal-fetal transmission, and neonatal disease. Additional studies are required to confirm the benefits of systemic treatment for maternal candida infection or colonization in preventing premature birth or neonatal systemic candidiasis.
PubMed: 38787047
DOI: 10.3390/tropicalmed9050114 -
Revista Brasileira de Ginecologia E... 2024The aims of the study are to describe the association of coronavirus disease (COVID-19) with the abnormal histopathological findings in human placenta and to highlight...
OBJECTIVE
The aims of the study are to describe the association of coronavirus disease (COVID-19) with the abnormal histopathological findings in human placenta and to highlight the potential predictors of these histopathological findings.
METHODS
A retrospective cohort study, held in two obstetric units from January 2021- 2022, 34 patients who were confirmed cases of COVID- 19 were followed up till the time of delivery as their placenta were sent for histopathology. Patients diagnosed with other viral infections, chorioamnionitis, or were known case of as pre-term or term pre labour rupture of membrans (PROM) were excluded as well as pre exisiting diabetes mellitus or pre-eclampsia. Data analysis were performed using STATA software version 16.
RESULT
Specific histopatological findings (fetal vascular malperfusion, maternal vascular malperfusion, inflammatory pathology and thrombotic finding) were significantly high among 13 (38.2%) of the study group who got infected earlier in pregnancy (P<0.001). The period between the diagnosis of COVID-19 and the delivery significantly increases the odds of the presence of pathological findings by 2.75 times for each week the patients getting infected earlier.
CONCLUSION
Association of abnormal placental histopathological findings with COVID-19 infection in pregnancy and the potential predictor for the occurrence of placental findings is the longer duration between the diagnosis of the infection and the delivery.
Topics: Humans; Female; Pregnancy; Retrospective Studies; COVID-19; Placenta; Adult; Pregnancy Complications, Infectious; SARS-CoV-2; Placenta Diseases; Cohort Studies
PubMed: 38765541
DOI: 10.61622/rbgo/2024AO03 -
BMC Pregnancy and Childbirth May 2024Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal...
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal outcomes between women with an ADHD diagnosis and those without.
METHODS
A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) United States database. The study included all women who either delivered or experienced maternal death from 2004 to 2014. Perinatal outcomes were compared between women with an ICD-9 diagnosis of ADHD and those without.
RESULTS
Overall, 9,096,788 women met the inclusion criteria. Amongst them, 10,031 women had a diagnosis of ADHD. Women with ADHD, compared to those without, were more likely to be younger than 25 years of age; white; to smoke tobacco during pregnancy; to use illicit drugs; and to suffer from chronic hypertension, thyroid disorders, and obesity (p < 0.001 for all). Women in the ADHD group, compared to those without, had a higher rate of hypertensive disorders of pregnancy (HDP) (aOR 1.36, 95% CI 1.28-1.45, p < 0.001), cesarean delivery (aOR 1.19, 95% CI 1.13-1.25, p < 0.001), chorioamnionitis (aOR 1.34, 95% CI 1.17-1.52, p < 0.001), and maternal infection (aOR 1.33, 95% CI 1.19-1.5, p < 0.001). Regarding neonatal outcomes, patients with ADHD, compared to those without, had a higher rate of small-for-gestational-age neonate (SGA) (aOR 1.3, 95% CI 1.17-1.43, p < 0.001), and congenital anomalies (aOR 2.77, 95% CI 2.36-3.26, p < 0.001).
CONCLUSION
Women with a diagnosis of ADHD had a higher incidence of a myriad of maternal and neonatal complications, including cesarean delivery, HDP, and SGA neonates.
Topics: Humans; Female; Attention Deficit Disorder with Hyperactivity; Pregnancy; Adult; Retrospective Studies; Pregnancy Complications; Infant, Newborn; Pregnancy Outcome; United States; Databases, Factual; Young Adult; Cesarean Section; Delivery, Obstetric; Hypertension, Pregnancy-Induced
PubMed: 38750437
DOI: 10.1186/s12884-024-06561-5