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Placental implantation over prior cesarean scar causes activation of fetal regulatory T cells.

ABSTRACT: INTRODUCTION:Maternal-fetal chimerism is miniscule, a testament to the integrity of the uteroplacental interface. The soundness of this border region is potentially altered through cesarean delivery of prior babies with uncertain consequences for the following pregnancies. METHODS:Using multicolor flow cytometry and quantitative PCR of non-inherited maternal antigens we performed a retrospective case control pilot study and formulated the null hypothesis that placental implantation over a prior uterine scar does not result in the presence of memory Treg (CD45RO+) in the fetus. We then performed a power calculation and performed a blinded, appropriately powered prospective case control study to test the null hypothesis. RESULTS:Fetuses born to mothers with prior uterine scar have a roughly five times higher maternal to fetal microchimerism when the placenta directly interacts with the uterine scar. Unlike exposure to antigens in adult life, in utero antigenic exposure induces tolerogenic (Treg) responses in fetuses and we here report the presence of fetal Treg with a memory phenotype (CD45RO+). However, we only find such CD45RO+ fetal Tregs when the placenta abuts the uterine scar (Risk Ratio?=?5 [p?

SUBMITTER: Nguyen TA

PROVIDER: S-EPMC5946153 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Placental implantation over prior cesarean scar causes activation of fetal regulatory T cells.

Nguyen Tina A TA Kahn Daniel A DA Loewendorf Andrea I AI

Immunity, inflammation and disease 20180212 2

<h4>Introduction</h4>Maternal-fetal chimerism is miniscule, a testament to the integrity of the uteroplacental interface. The soundness of this border region is potentially altered through cesarean delivery of prior babies with uncertain consequences for the following pregnancies.<h4>Methods</h4>Using multicolor flow cytometry and quantitative PCR of non-inherited maternal antigens we performed a retrospective case control pilot study and formulated the null hypothesis that placental implantatio ...[more]

PMID: 29430878

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Project description:ImportanceApproximately 60% of women develop a uterine niche after a cesarean delivery (CD). A niche is associated with various gynecological symptoms including abnormal uterine bleeding, pain, and infertility, but there is little consensus in the literature on the distinction between the sonographic finding of a niche and the constellation of associated symptoms.ObjectiveTo achieve consensus on defining the clinical condition that constitutes a symptomatic uterine niche and agree upon diagnostic criteria and uniform nomenclature for this condition.Design, setting, and participantsA consensus based modified electronic Delphi (eDelphi) study, with a predefined Rate of Agreement (RoA) of 70% or higher. Experts were selected according to their expertise with niche-related consultations, publications, and participation in expert groups and received online questionnaires between November 2021 and May 2022.Main outcomes and measuresDefinition, nomenclature, symptoms, conditions to exclude, and diagnostic criteria of an illness caused by a symptomatic uterine niche.ResultsIn total, 31 of the 60 invited experts (51.7%) participated, of whom the majority worked in university-affiliated hospitals (28 of 31 [90.3%]), specialized in benign gynecology (20 of 31 [64.5%]), and worked in Europe (24 of 31 [77.4%]). Three rounds were required to achieve consensus on all items. All participants underlined the relevance of a new term for a condition caused by a symptomatic niche and its differentiation from a sonographic finding only. Experts agreed to name this condition cesarean scar disorder, defined as a uterine niche in combination with at least 1 primary or 2 secondary symptoms (RoA, 77.8%). Defined primary symptoms were postmenstrual spotting, pain during uterine bleeding, technical issues with catheter insertion during embryo transfer, and secondary unexplained infertility combined with intrauterine fluid. Secondary symptoms were dyspareunia, abnormal vaginal discharge, chronic pelvic pain, avoiding sexual intercourse, odor associated with abnormal blood loss, secondary unexplained infertility, secondary infertility despite assisted reproductive technology, negative self-image, and discomfort during participation in leisure activities. Consensus was also achieved on certain criteria that should be met and conditions that should be excluded before making the diagnosis.Conclusions and relevanceIn this modified Delphi study, a panel of 31 international niche experts reached consensus for the constellation of symptoms secondary to a uterine niche and named it cesarean scar disorder.

Project description:BackgroundCesarean scar defect (CSD) is a potential complication following cesarean section (CS), which has significant clinical implications, and is usually clinically diagnosed by ultrasound. However, the optimal timing for ultrasound diagnosis of CSD after CS has not been well established. This study aimed to evaluate the appropriate time for the diagnosis of CSD after CS by ultrasonography.MethodsThe prospective study involved 120 women who delivered by elective CS with single birth and term birth from January 2021 to June 2022. Sample enrollment was consecutive in the study. Each woman underwent 3 ultrasound examinations for CSD diagnosis at 6 weeks, 6 months, and 12 months postpartum according to a modified Delphi method. The ultrasound indicators about the incision situation were recorded and statistically analyzed. Paired 4-fold table chi-square test was used to evaluate the consistency between the 3 diagnoses. The diagnostic sensitivity and specificity were calculated using a 4-cell table. According to whether the diagnosis was consistent to that at 6 or 12 months, the 120 cases at week 6 were separated into a consistent group and inconsistent group for statistical evaluation of the ultrasound indicators. Additionally, the menstrual duration of the included women was also recorded to analyze the correlation to ultrasound indicators of CSD at 6 months postpartum using the Person correlation coefficient.ResultsThe included 120 women were divided into normal (3-7 days, n=52) and prolonged menstrual period (>7 days, n=68) groups. The 2 groups had no statistical differences in age, body mass index (BMI), gestational week of delivery, assisted reproduction rates, or postpartum complications. Among the 120 women, 100, 66, and 61 women were diagnosed as CSD at 6 weeks, 6 months, and 12 months postpartum, respectively. The results indicated that the diagnostic results of 6 weeks were inconsistent with those of 6 or 12 months postpartum, but the last 2 diagnostic results were consistent. The diagnostic sensitivity of 6 months was 100% and the specificity was 91.53% [95% confidence interval (CI): 85.84-95.26%]. Further, significant differences were found in depth of the defect, and the thickness (T) and ratio of residual muscle between the inconsistent group and the consistent group at 6 weeks. The patients could be considered self-recovered from CSD at 6 months when the defect depth was equal to or less than 4.04±0.82 mm at 6 weeks after CS. Additionally, in the CSD group at 6 months, the length (r=0.828, P<0.001), depth (r=0.784, P<0.001), width (r=0.787, P<0.001) of the defect, the T (r=0.831, P<0.001) and ratio of residual muscle (r=0.821, P<0.001) were strongly correlated with menstrual duration.ConclusionsCSD evaluation at week 6 after CS may cause misdiagnosis or overdiagnosis. The diagnosis of CSD was suggested to be made following 6 months or longer postpartum.

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Placental implantation over prior cesarean scar causes activation of fetal regulatory T cells.

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Placental implantation over prior cesarean scar causes activation of fetal regulatory T cells.

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