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Background: The rate of caesarean sections increased in the last decades to about 30% of births in western populations. Many caesarean sections are electively planned without an urgent medical reason for mother or child. Especially in women with a foregoing caesarean section, the procedure is planned early. An early caesarean section though may harm the newborn. Our aim is to evaluate the gestational time point after the 37th gestational week (after prematurity = term) of performing an elective caesarean section with the lowest morbidity for mother and child.
Methods: This is an update of a systematic review previously carried out on behalf of the German Federal Ministry of Health. We will perform a systematic literature search in MEDLINE, EMBASE, CENTRAL and CINAHL. Our primary outcome is the rate of admissions to the neonatal intensive care unit in early versus late term neonates. We will include (quasi) randomized controlled trials and cohort studies. The studies should include pregnant women who have an elective caesarean section at term. We will screen titles and abstracts and the identified full texts of studies for eligibility. Risk of bias will be assessed with the Cochrane Risk of Bias Tool for Randomized Trials or with the Risk of Bias Tool for Non-Randomized Studies of Interventions (ROBINS-I). These tasks will be performed independently by two reviewers. Data will be extracted in beforehand piloted extraction tables. A dose-response meta-analysis will be performed.
Discussion: Our aim is to reach a higher validity in the assessment of the time point of elective caesarean sections by performing a meta-analysis to support recommendations for clinical practice. We assume to identify less randomized controlled trials but a large number of cohort studies analyzing the given question. We will discuss similarities and differences in included studies as well as methodological strengths and weaknesses.
Systematic review registration: PROSPERO CRD42017078231
Tumor progression and pregnancy share many common features, such as immune tolerance and invasion. The invasion of trophoblasts in the placenta into the uterine wall is essential for fetal development, and is thus precisely regulated. Its deregulation has been implicated in preeclampsia, a leading cause for maternal and perinatal mortality and morbidity. Pathogenesis of preeclampsia remains to be defined. Microarray-based gene profiling has been widely used for identifying genes responsible for preeclampsia. In this review, we have summarized the recent data from the microarray studies with preeclamptic placentas. Despite the complex of gene signatures, suggestive of the heterogeneity of preeclampsia, these studies identified a number of differentially expressed genes associated with preeclampsia. Interestingly, most of them have been reported to be tightly involved in tumor progression. We have discussed these interesting genes and analyzed their potential molecular functions in preeclampsia, compared with their roles in malignancy development. Further investigations are warranted to explore the involvement in molecular network of each identified gene, which may provide not only novel strategies for prevention and therapy for preeclampsia but also a better understanding of cancer cells. The trophoblastic cells, with their capacity for proliferation and differentiation, apoptosis and survival, migration, angiogenesis and immune modulation by exploiting similar molecular pathways, make them a compelling model for cancer research.
A message from the human placenta: structural and immunomodulatory defense against SARS-CoV-2
(2020)
The outbreak of the coronavirus disease 2019 (COVID-19) pandemic has caused a global public health crisis. Viral infections may predispose pregnant women to a higher rate of pregnancy complications, including preterm births, miscarriage and stillbirth. Despite reports of neonatal COVID-19, definitive proof of vertical transmission is still lacking. In this review, we summarize studies regarding the potential evidence for transplacental transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), characterize the expression of its receptors and proteases, describe the placental pathology and analyze virus-host interactions at the maternal-fetal interface. We focus on the syncytium, the barrier between mother and fetus, and describe in detail its physical andstructuraldefenseagainstviralinfections. Wefurtherdiscussthepotentialmolecularmechanisms, whereby the placenta serves as a defense front against pathogens by regulating the interferon type III signaling, microRNA-triggered autophagy and the nuclear factor-κB pathway. Based on these data, we conclude that vertical transmission may occur but rare, ascribed to the potent physical barrier, the fine-regulatedplacentalimmunedefenseandmodulationstrategies. Particularly,immunomodulatory mechanismsemployedbytheplacentamaymitigateviolentimmuneresponse,maybesoftencytokine storm tightly associated with severely ill COVID-19 patients, possibly minimizing cell and tissue damages, and potentially reducing SARS-CoV-2 transmission.
Background: Health care accessibility is known to differ geographically. With this study we focused on analysing accessibility of general and specialized obstetric units in England and Germany with regard to urbanity, area deprivation and neonatal outcome using routine data.
Methods: We used a floating catchment area method to measure obstetric care accessibility, the degree of urbanization (DEGURBA) to measure urbanity and the index of multiple deprivation to measure area deprivation.
Results: Accessibility of general obstetric units was significantly higher in Germany compared to England (accessibility index of 16.2 vs. 11.6; p < 0.001), whereas accessibility of specialized obstetric units was higher in England (accessibility index for highest level of care of 0.235 vs. 0.002; p < 0.001). We further demonstrated higher obstetric accessibility for people living in less deprived areas in Germany (r = − 0.31; p < 0.001) whereas no correlation was present in England. There were also urban–rural disparities present, with higher accessibility in urban areas in both countries (r = 0.37–0.39; p < 0.001). The analysis did not show that accessibility affected neonatal outcomes. Finally, our computer generated model for obstetric care provider demand in terms of birth counts showed a very strong correlation with actual birth counts at obstetric units (r = 0.91–0.95; p < 0.001).
Conclusion: In Germany the focus of obstetric care seemed to be put on general obstetric units leading to higher accessibility compared to England. Regarding specialized obstetric care the focus in Germany was put on high level units whereas in England obstetric care seems to be more balanced between the different levels of care with larger units on average leading to higher accessibility.
Purpose: We aim to describe the sonographic uterine anatomy after a cesarean section (CS), test the reproducibility of predefined measurements from the BSUM study, and report the distribution of these measurements. Methods: This is a descriptive observational study where 200 women with a history of only one CS were recruited 12–24 months postoperatively. A 5–13 MHz micro-convex transvaginal transducer was used for the acquisition of volumetric datasets for evaluating the CS scars. We defined 15 distinct measurements including the residual myometrial thickness (RMT). RMT ratio was calculated as a percentage of RMT to the assumed pre-cesarean anterior uterine wall thickness. A P value below 0.05 is utilized for significant statistical analysis. Results: Patients were included on average 18.5 months post-cesarean. The uterus was anteflexed in 82.5% and retroflexed in 17.5%. Myometrial defects at the site of CS manifest in two forms, either as a niche or as fibrosis. Patients are classified into four groups: those with isolated niches (45%), combined niches and fibrosis (38.5%), isolated fibrosis (11%), and lacking both (5%). The median RMT ratio for these groups was 63.09, 40.93, 59.84, and 100% with a standard deviation of 16.73, 12.95, 16.59, and 0, respectively. The interclass correlation coefficient (ICC) remained above 0.9 for all distinct measurements among these groups except for those of RMT, where ICC varied between 0.47 and 0.96. The RMT ratio shows a constant ICC at 0.94 regardless of the group. Conclusion: The post-cesarean uterus is often anteflexed, and a myometrial loss of about 50% is normally expected. The pattern of this loss is in the form of a predominantly sharp-edged and echogenic niche, fibrosis, or a combination of both. The proposed RMT ratio takes these changes into consideration and results in a reproducible quantification. We hypothesize that different adverse outcomes could be attributed to the different scar patterns.
Polo-like kinase 1, a pivotal regulator of mitosis and cytokinesis, is highly expressed in a broad spectrum of tumors and its expression correlates often with poor prognosis, suggesting its potential as a therapeutic target. p53, the guardian of the genome, is the most important tumor suppressor. In this review, we address the intertwined relationship of these two key molecules by fighting each other as eternal rivals in many signaling pathways. p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. Plk1 inhibitors target all rapidly dividing cells irrespective of tumor cells or non-transformed normal but proliferating cells. Upon treatment with Plk1 inhibitors, p53 in tumor cells is activated and induces strong apoptosis, whereas tumor cells with inactive p53 arrest in mitosis with DNA damage. Thus, inactive p53 is not associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and could rather foster the induction of polyploidy/aneuploidy in surviving cells. In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer.
Doppler examination of the umbilical artery and the fetal middle cerebral artery is evaluated predominantly in pregnancies with fetuses in cephalic presentation and never has been elucidated in breech presentation. Evidence on the accuracy of fetal weight estimation in dependence of the fetal presentation is controversial. Nevertheless, clinical decisions including recommendations for a cesarean section or labor induction based on these examinations are applied to pregnancies with fetuses in breech presentation. The objective of this study was to investigate the influence of the fetal presentation on fetal weight estimation accuracy, umbilical artery and middle cerebral artery resistance indices (RI) in a prospective case control study. Ultrasound examinations in 305 uncomplicated term pregnancies (153 vertex presentations, 152 breech) were investigated. Non-parametric variables were compared using Pearson’s chi2 test and Wilcoxon chi2 test, depending on variable scaling. Fetal weight estimation accuracy was not significantly different between vertex presentation group (VP) (6.97%) and breech presentation group (BP) (7.96%, p = 0.099). Fetal head circumference measurements were significantly larger in BP (350 mm vs. 341 mm in VB, p > 0.0001) while abdominal circumferences were significantly smaller (VP: 338 mm, BP: 331 mm, p = 0.0039) and weight estimation was not significantly different. Umbilical artery RIs were not significantly different between VP (54.5) and BP (55.3, p = 0.354). Fetal middle cerebral artery RIs also showed no significant differences (VP: 71.2, BP: 70.7, p = 0.335). Our study shows that fetal Doppler (RI) and weight estimation ultrasound originally calibrated in cephalic pregnancies are applicable to pregnancies with fetuses in breech presentation.
Objective: To compare breech outcomes when mothers delivering vaginally are upright, on their back, or planning cesareans. Methods: A retrospective cohort study was undertaken of all women who presented for singleton breech delivery at a center in Frankfurt, Germany, between January 2004 and June 2011. Results: Of 750 women with term breech delivery, 315 (42.0%) planned and received a cesarean. Of 269 successful vaginal deliveries of neonates, 229 in the upright position were compared with 40 in the dorsal position. Upright deliveries were associated with significantly fewer delivery maneuvers (OR 0.45, 95% CI 0.31–0.68) and neonatal birth injuries (OR 0.08, 95% CI 0.01–0.58), second stages that were on average shorter (1 vs 1.75 hours), and nonsignificantly decreased serious perineal lacerations (OR 0.34, 95% CI 0.05–3.99). When upright position was used almost exclusively, the cesarean rate decreased. Serious fetal and neonatal morbidity potentially related to birth mode was low, and similar for upright vaginal deliveries compared with planned cesareans (OR 1.37, 95% CI 0.10–19.11). Three neonates died; all had lethal birth defects. Forceps were never required. Conclusion: Upright vaginal breech delivery was associated with reductions in duration of the second stage of labor, maneuvers required, maternal/neonatal injuries, and cesarean rate when compared with vaginal delivery in the dorsal position.
Purpose: The aim of this study is to utilize the Manchester scar scale (MSS) and ultrasound in investigating the association between uterine wall defects and cutaneous scar characteristics after cesarean section (CS).
Methods: This is a prospective cohort study. The degree of myometrial loss was quantified by calculating a residual myometrial thickness (RMT) ratio as a percentage of RMT to the pre-cesarean anterior uterine wall thickness. Cutaneous scar assessment was performed according to the MSS. Spearman’s correlation and the Kruskal–Wallis test with a cut-off value of p < 0.05 were used for statistical analysis.
Results: Two hundred forty seven women, of which 2.4% had an Asian, 3.6% an Afro-American, 82% a Caucasian and 12% a Mediterranean background, were recruited. The RMT ratio ranged between 11.9 and 100% with a median of 55.8% and an average of 56%. MSS scores ranged from 4 to 13 with a median of 5 and an average of 6. Spearman’s correlation between MSS and RMT ratio show a rho of − 0.01 with a p value of 0.8. The correlation between MSS and RMT ratio within the four ethnical groups showed a p value between 0.3 and 0.8 and a rho between 0.8 and − 0.8. The Kruskal–Wallis test showed an eta2 of 0.13 and a p value of 0.0002 for the effect of ethnicity on MSS and an eta2 of 0.009 and a p value of 0.68 for the effect of ethnicity on the RMT ratio.
Conclusion: CS laparotomy scars heal differently between ethnical groups, but generally with satisfying results. Ethnicity does not affect myometrial healing and scar appearance does not reflect myometrial healing after CS. Thus, separate uterine sonographic assessment is recommended.
Objective: About 2% of all pregnancies are complicated by the implantation of the zygote outside the uterine cavity and termed ectopic pregnancy. Whereas a multitude of guidelines exists and related research is constantly growing, no thorough assessment of the global research architecture has been performed yet. Hence, we aim to assess the associated scientific activities in relation to geographical and chronological developments, existing research networks and socioeconomic parameters.
Design: Retrospective, descriptive study.
Setting: On the basis of the NewQIS platform, scientometric methods were combined with novel visualising techniques such as density-equalising mapping to assess the scientific output on ectopic pregnancy. Using the Web of Science, we identified all related entries from 1900 to 2012.
Results: 8040 publications were analysed. The USA and the UK were dominating the field in regard to overall research activity (2612 and 723 publications), overall citation numbers and country-specific H-Indices (US: 80, UK: 42). Comparison to economic power of the most productive countries demonstrated that Israel invested more resources in ectopic pregnancy-related research than other nations (853.41 ectopic pregnancy-specific publications per 1000 billlion US$ gross domestic product (GDP)), followed by the UK (269.97). Relation to the GDP per capita index revealed 49.3 ectopic pregnancy-specific publications per US$1000 GDP per capita for the USA in contrast to 17.31 for the UK. Semiqualitative indices such as country-specific citation rates ranked Switzerland first (24.7 citations per ectopic pregnancy-specific publication), followed by the Scandinavian countries Finland and Sweden. Low-income countries did not exhibit significant research activities.
Conclusions: This is the first in-depth analysis of global ectopic pregnancy research since 1900. It offers unique insights into the global scientific landscape. Besides the USA and the UK, Scandinavian countries and Switzerland can also be regarded as leading nations with regard to their relative socioeconomic input.