Evolution of Fetal Growth in Symptomatic Sars-Cov-2 Pregnancies.

INTRODUCTION: SARS-CoV-2 is a viral disease with potentially devastating effects. Observational studies of pregnant women infected with SARS-CoV-2 report an increased risk for FGR. This study utilizes data from a prospective SARS-CoV-2 registry in pregnancy, investigating the progression of fetuses to fetal growth restriction (FGR) at birth following maternal SARS-CoV-2 and evaluating the hypothesis of whether the percentage of SGA at birth is increased after maternal SARS-CoV-2 taking into account the time interval between infection and birth. MATERIALS & METHODS: CRONOS is a prospective German registry enrolling pregnant women with confirmed SARS-CoV-2 infection during their pregnancy. SARS-CoV-2 symptoms, pregnancy- and delivery-specific information were recorded. The data evaluated in this study range from March 2020 until August 2021. Women with SARS-CoV-2 were divided into three groups according to the time of infection/symptoms to delivery: Group I<2 weeks, Group II 2-4 weeks, and Group III>4 weeks. FGR was defined as estimated and/or birth weight<10% ile, appropriate for gestational age (AGA) was within 10 and 90%ile, and large for gestational age (LGA) was defined as fetal or neonatal weight>90%ile. RESULTS: Data for a total of 2,650 SARS-CoV-2-positive pregnant women were available. The analysis was restricted to symptomatic cases that delivered after 24+0 weeks of gestation. Excluding those cases with missing values for estimated fetal weight at time of infection and/or birth weight centile, 900 datasets remained for analyses. Group I consisted of 551 women, Group II of 112 women, and Group III of 237 women. The percentage of changes from AGA to FGR did not differ between groups. However, there was a significantly higher rate of large for gestational age (LGA) newborns at the time of birth compared to the time of SARS-CoV-2 infection in Group III (p=0.0024), respectively. CONCLUSION: FGR rates did not differ between symptomatic COVID infections occurring within 2 weeks and>4 weeks before birth. On the contrary, it presented a significant increase in LGA pregnancies in Group III. However, in this study population, an increase in the percentage of LGA may be attributed to pandemic measures and a reduction in daily activity.

Statement of the Obstetrics and Prenatal Medicine Working Group (AGG - Preterm Birth Section) on "Outpatient Management for Pregnant Women with Preterm Premature Rupture of Membranes (PPROM)".

Preterm premature rupture of membranes (PPROM) is one of the leading causes of perinatal morbidity and mortality. After a PPROM, more than 50% of pregnant women are delivered within 7 days. Fetal and maternal risks are primarily due to infection and inflammation, placental abruption, umbilical cord complications and preterm birth. Standard care usually consists of an expectant approach. Management includes the administration of antenatal steroids and antibiotic therapy. Patients with PPROM require close monitoring. The management of pregnant women with PPROM (inpatient vs. outpatient) is still the subject of controversial debate. The international guidelines also do not offer a clear stance. The statement presented here discusses the current state of knowledge.

Does structured obstetric management play a role in the delivery mode and neonatal outcome of twin pregnancies?

PURPOSE: While the optimal delivery method of twin pregnancies is debated, the rate of cesarean deliveries is increasing. This retrospective study evaluates delivery methods and neonatal outcome of twin pregnancies during two time periods and aims to identify predictive factors for the delivery outcome. METHODS: 553 twin pregnancies were identified in the institutional database of the University Women's Hospital Freiburg, Germany. 230 and 323 deliveries occurred in period I (2009-2014) and period II (2015-2021), respectively. Cesarean births due to non-vertex position of the first fetus were excluded. In period II, the management of twin pregnancies was reviewed; adjusted and systematic training with standardized procedures was implemented. RESULTS: Period II showed significantly lower rates of planned cesarean deliveries (44.0% vs. 63.5%, p < 0.0001) and higher rates of vaginal deliveries (68% vs. 52.4%, p = 0.02). Independent risk factors for primary cesarean delivery were period I, maternal age > 40 years, nulliparity, a history with a previous cesarean, gestational age < 37 completed weeks, monochorionicity and increasing birth weight difference (per 100 g or > 20%). Predictive factors for successful vaginal delivery were previous vaginal delivery gestational age between 34 and 36 weeks and vertex/vertex presentation of the fetuses. The neonatal outcomes of period I and II were not significantly different, but planned cesareans in general were associated with increased admission rates to the neonatal intensive care units. Inter-twin interval had no significant impact on neonatal outcome. CONCLUSION: Structured regular training of obstetrical procedures may significantly reduce high cesarean rates and increase the benefit-risk ratio of vaginal deliveries.

[Evaluation of Psychological Distress in Obstetric Patients during the Visit Ban in Hospitals in the SARS-CoV-2 Pandemic: A Prospective, Multicentre, Controlled Study]. / Evaluation der psychischen Belastung geburtshilflicher Patientinnen während des Besuchsverbots der Kliniken im Rahmen der SARS-CoV-2-Pandemie: Eine prospektive, multizentrische, kontrollierte Studie.

INTRODUCTION: Risk factors for postpartum depression include a lack of social support and perceived social isolation. We would like to determine whether the isolation of inpatients on the maternity wards during Covid-19 leads to increased psychological stress. METHODS: This is a multicentre, controlled study of obstetric patients who gave birth during an inpatient stay. Patients were included during the visitation ban (study group) and after the visitation ban (control group). Psychological stress was evaluated with the Edinburgh Postnatal Depression Scale (EPDS) during the inpatient stay and six to eight weeks postpartum. RESULTS: A total of 194 women were included, 107 in the study group and 87 in the control group. The overall result of the first EPDS shows a higher score in the study group compared to the control group (7.0 vs. 4.9 points). Primipara show a higher score in the first EPDS compared to multipara (7.28 vs. 4.82). Caesarean section, regardless of isolation, shows a higher score in the first EPDS than vaginal birth (8.42 vs. 5.11). Comparison of vaginal birth shows a higher score only in the study group (5.97 vs. 4.07). CONCLUSION: In the context of Covid-19, women giving birth and new mothers, especially primipara, are exposed to increased psychological stress in the clinics. Caesarean section leads to increased psychological stress.

Multiomic spatial landscape of innate immune cells at human central nervous system borders.

The innate immune compartment of the human central nervous system (CNS) is highly diverse and includes several immune-cell populations such as macrophages that are frequent in the brain parenchyma (microglia) and less numerous at the brain interfaces as CNS-associated macrophages (CAMs). Due to their scantiness and particular location, little is known about the presence of temporally and spatially restricted CAM subclasses during development, health and perturbation. Here we combined single-cell RNA sequencing, time-of-flight mass cytometry and single-cell spatial transcriptomics with fate mapping and advanced immunohistochemistry to comprehensively characterize the immune system at human CNS interfaces with over 356,000 analyzed transcriptomes from 102 individuals. We also provide a comprehensive analysis of resident and engrafted myeloid cells in the brains of 15 individuals with peripheral blood stem cell transplantation, revealing compartment-specific engraftment rates across different CNS interfaces. Integrated multiomic and high-resolution spatial transcriptome analysis of anatomically dissected glioblastoma samples shows regionally distinct myeloid cell-type distributions driven by hypoxia. Notably, the glioblastoma-associated hypoxia response was distinct from the physiological hypoxia response in fetal microglia and CAMs. Our results highlight myeloid diversity at the interfaces of the human CNS with the periphery and provide insights into the complexities of the human brain's immune system.

Sensitivity, specificity, and diagnostic accuracy of WHO 2013 criteria for diagnosis of gestational diabetes mellitus in low risk early pregnancies: international, prospective, multicentre cohort study.

Objective: To evaluate the predictability of gestational diabetes mellitus wth a 75 g oral glucose tolerance test (OGTT) in early pregnancy, based on the 2013 criteria of the World Health Organization, and to test newly proposed cut-off values. Design: International, prospective, multicentre cohort study. Setting: Six university or cantonal departments in Austria, Germany, and Switzerland, from 1 May 2016 to 31 January 2019. Participants: Low risk cohort of 829 participants aged 18-45 years with singleton pregnancies attending first trimester screening and consenting to have an early 75 g OGTT at 12-15 weeks of gestation. Participants and healthcare providers were blinded to the results. Main outcome measures: Fasting, one hour, and two hour plasma glucose concentrations after an early 75 g OGTT (12-15 weeks of gestation) and a late 75 g OGTT (24-28 weeks of gestation). Results: Of 636 participants, 74 (12%) developed gestational diabetes mellitus, according to World Health Organization 2013 criteria, at 24-28 weeks of gestation. Applying WHO 2013 criteria to the early OGTT with at least one abnormal value gave a low sensitivity of 0.35 (95% confidence interval 0.24 to 0.47), high specificity of 0.96 (0.95 to 0.98), positive predictive value of 0.57 (0.41 to 0.71), negative predictive value of 0.92 (0.89 to 0.94), positive likelihood ratio of 10.46 (6.21 to 17.63), negative likelihood ratio of 0.65 (0.55 to 0.78), and diagnostic odds ratio of 15.98 (8.38 to 30.47). Lowering the postload glucose values (75 g OGTT cut-off values of 5.1, 8.9, and 7.8 mmol/L) improved the detection rate (53%, 95% confidence interval 41% to 64%) and negative predictive value (0.94, 0.91 to 0.95), but decreased the specificity (0.91, 0.88 to 0.93) and positive predictive value (0.42, 0.32 to 0.53) at a false positive rate of 9% (positive likelihood ratio 5.59, 4.0 to 7.81; negative likelihood ratio 0.64, 0.52 to 0.77; and diagnostic odds ratio 10.07, 6.26 to 18.31). Conclusions: The results of this prospective low risk cohort study indicated that the 75 g OGTT as a screening tool in early pregnancy is not sensitive enough when applying WHO 2013 criteria. Postload glucose values were higher in early pregnancy complicated by diabetes in pregnancy. Lowering the postload cut-off values identified a high risk group for later development of gestational diabetes mellitus or those who might benefit from earlier treatment. Results from randomised controlled trials showing a beneficial effect of early intervention are unclear. Trial registration: ClinicalTrials.gov NCT02035059.

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

[This corrects the article DOI: 10.1055/a-2044-0203.].

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

[This corrects the article DOI: 10.1055/a-2044-0345.].

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

Aim The revision of this guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of the guideline is to improve the prediction, prevention and management of preterm birth based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 2 of this short version of the guideline presents statements and recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

Aim This revised guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). It aims to improve the prediction, prevention, and management of preterm birth, based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 1 of this short version of the guideline presents statements and recommendations on the epidemiology, etiology, prediction, and primary and secondary prevention of preterm birth.

Postnatal genetic umbilical cord analysis for earliest possible detection of inherited hearing impairment.

INTRODUCTION: The most common sensorineural disorder in humans is hearing impairment and approximately 60% of prelingual hearing disorders are genetic. Especially parents with a congenital deaf child want to know as early as possible whether their second born child has the same genetic defect or not. The aim of this study is to demonstrate that postnatal genetic umbilical cord analysis is both the earliest detection possibility and sufficient. METHODS: We included first born children with severe hearing impairment that underwent cochlear implantation. All included patients were analyzed genetically and exhibited mutations of either DFNB1 loci or SLC26A4 gene. Additionally, the umbilical cord of the sibling underwent genetic analysis to detect hereditary genetic mutations as early as possible. RESULTS: 49 newborn children out of 22 families were included in this study. Genetic analysis revealed clinical relevant mutations in all first born children and in four siblings via umbilical cord analysis. All patients who have been diagnosed with a relevant genetic mutation that caused severe hearing impairment underwent hearing rehabilitation via cochlear implant surgery. CONCLUSION: This study demonstrates the sufficient and early as possible detection of known genetically hearing disorders via umbilical cord analysis. In case of a known familial genetic hearing disorder, it is advisable to analyze newborn siblings for the corresponding genetic defect as soon as possible, to be able to plan and initiate clinical care for the patient as early as possible. It is also extremely important for the parents to obtain clear information about the auditory status of the newborn.

Prior vertical uterine incision: Effect on subsequent pregnancy characteristics and outcomes.

OBJECTIVE: To examine characteristics and outcomes of cesarean delivery (CD) in women with a history of vertical hysterotomy. METHOD: This is a comparative study that retrospectively queried the National Inpatient Sample from October 2016 to December 2018. Pregnancy characteristics and surgical outcomes of CD among 18 575 women with prior vertical uterine incision were compared to 1 072 949 women with prior low-transverse incision, assessed by multivariable generalized estimating equation model and propensity score weighting. RESULTS: In a multivariable analysis, women who had prior vertical uterine incision were more likely to have placenta percreta (odds ratio [OR] 3.41, 95% confidence interval [CI] 1.87-6.20), pre-labor uterine rupture (OR 2.70, 95% CI 1.52-4.80), in-labor uterine rupture (OR 2.33, 95% CI 1.55-3.51), and extreme preterm delivery <28 weeks (OR 17.8, 95% CI 15.2-20.7) in the current pregnancy, compared to those who had prior low-transverse uterine incision. In a weighted model, prior vertical hysterotomy was associated with increased surgical morbidity in current CD compared to prior low-transverse hysterotomy (10.6% vs. 4.8%, OR 2.02, 95% CI 1.81-2.26), including hemorrhage (OR 1.99, 95% CI 1.74-2.27) and hysterectomy (OR 3.67, 95% CI 2.97-4.53). CONCLUSION: Prior vertical uterine incision at CD was associated with increased risk of placenta percreta, uterine rupture, particularly before labor, and adverse outcomes in the subsequent pregnancy.

Emergency button cannula vs. umbilical catheter as neonatal emergency umbilical vein access - a randomized cross-over pilot study.

OBJECTIVES: Establishing immediate intravenous access to a newborn is challenging even for trained neonatologists in an emergency situation. Correct placement of umbilical catheter or an intraosseous needle needs consistent training. We evaluated the time required to correctly place an emergency umbilical button cannula (EUC) or an umbilical catheter (UC) using the standard intersection (S-EUC or S-UC, respectively) or lateral umbilical cord incision (L-EUC) by untrained medical personnel. METHODS: Single-center cross-over pilot-study using a model with fresh umbilical cords. Video-based teaching of medical students before probands performed all three techniques after assignment to one of three cycles with different sequence, using a single umbilical cord divided in three pieces for each proband. RESULTS: Mean time required to establish L-EUC was 89.3 s, for S-EUC 82.2 s and for S-UC 115.1 s. Both application routes using the EUC were significantly faster than the UC technique. There was no significant difference between both application routes using EUC (p=0.54). CONCLUSIONS: Using an umbilical cannula is faster than an umbilical catheter, using a lateral incision of the umbilical vein is an appropriate alternative.

Neonatal invasive disease caused by Streptococcus agalactiae in Europe: the DEVANI multi-center study.

PURPOSE: Group B streptococcus (GBS) remains a leading cause of invasive disease, mainly sepsis and meningitis, in infants < 3 months of age and of mortality among neonates. This study, a major component of the European DEVANI project (Design of a Vaccine Against Neonatal Infections) describes clinical and important microbiological characteristics of neonatal GBS diseases. It quantifies the rate of antenatal screening and intrapartum antibiotic prophylaxis among cases and identifies risk factors associated with an adverse outcome. METHODS: Clinical and microbiological data from 153 invasive neonatal cases (82 early-onset [EOD], 71 late-onset disease [LOD] cases) were collected in eight European countries from mid-2008 to end-2010. RESULTS: Respiratory distress was the most frequent clinical sign at onset of EOD, while meningitis is found in > 30% of LOD. The study revealed that 59% of mothers of EOD cases had not received antenatal screening, whilst GBS was detected in 48.5% of screened cases. Meningitis was associated with an adverse outcome in LOD cases, while prematurity and the presence of cardiocirculatory symptoms were associated with an adverse outcome in EOD cases. Capsular-polysaccharide type III was the most frequent in both EOD and LOD cases with regional differences in the clonal complex distribution. CONCLUSIONS: Standardizing recommendations related to neonatal GBS disease and increasing compliance might improve clinical care and the prevention of GBS EOD. But even full adherence to antenatal screening would miss a relevant number of EOD cases, thus, the most promising prophylactic approach against GBS EOD and LOD would be a vaccine for maternal immunization.

Association of Pregnancy Characteristics and Maternal Mortality With Amniotic Fluid Embolism.

Importance: Amniotic fluid embolism (AFE) is an uncommon pregnancy complication but is associated with high maternal mortality. Because of the rarity of AFE, associated risks factors and maternal outcomes have been relatively understudied. Objective: To examine the clinical, pregnancy, and delivery characteristics and the maternal outcomes related to AFE in a recent period in the US. Design, Setting, and Participants: This retrospective cohort study examined hospital deliveries from January 1, 2016, to December 31, 2019, from the Healthcare Cost and Utilization Project's National Inpatient Sample. Main Outcomes and Measures: The primary outcome was clinical, pregnancy, and delivery characteristics of AFE, assessed with a multivariable binary logistic regression model. The coprimary outcome was failure to rescue, defined as maternal mortality after AFE. Associations with other severe maternal morbidity indicators and failure to rescue per clinical and pregnancy characteristics were also assessed. Results: A total of 14 684 135 deliveries were examined, with AFE diagnosed in 880 women, corresponding to an incidence rate of 6.0 per 100 000 deliveries. The cohort-level median patient age was 29 years (IQR, 25-33 years). In a multivariable analysis, (1) patient factors of older age, Asian and Black race, Western US region, pregestational hypertension, asthma, illicit substance use, and grand multiparity; (2) pregnancy factors of placental accreta spectrum (PAS), placental abruption, uterine rupture, polyhydramnios, chorioamnionitis, preeclampsia, fetal growth restriction, and fetal demise; and (3) delivery factors of early gestational age, cervical ripening, cesarean delivery, operative delivery, and manual removal were associated with AFE. Among these characteristics, PAS had the largest association with AFE (adjusted odds ratio [aOR], 10.01; 95% CI, 7.03-14.24). When stratified by the PAS subtypes, more severe forms of PAS had a greater association with AFE (aOR for increta and percreta, 17.35; 95% CI, 10.21-28.48; and aOR for accreta, 7.62; 95% CI, 4.83-12.01). Patients who had AFE were more likely to have coagulopathy (aOR, 24.68; 95% CI, 19.38-31.44), cardiac arrest (aOR, 24.56; 95% CI, 17.84-33.81), and adult respiratory distress syndrome (aOR, 10.72; 95% CI, 8.09-14.20). The failure-to-rescue rate after AFE was 17.0% overall. However, the failure-to-rescue rate exceeded 30% when AFE co-occurred with other severe maternal morbidity indicators: 45.8% for AFE, cardiac arrest, and coagulopathy; 43.2% for AFE, shock, and cardiac rhythm conversion; and 38.6% for AFE, cardiac arrest, coagulopathy, and shock. The failure-to-rescue rate after AFE also exceeded 30% when AFE occurred in the setting of placental pathology: 42.9% for AFE and PAS and 31.3% for AFE and placental abruption. Conclusions and Relevance: This contemporaneous, national-level analysis validated previously known risk factors for AFE and confirmed the dismal outcomes of pregnancy complicated by AFE. The association between PAS and AFE, which was not previously reported, warrants further investigation.

[Individualized Somatic Classification of Newborns Using Birth Weight Percentiles Based On Maternal Body Height and Weight (Results of a Validation Study)]. / Individuelle somatische Klassifikation von Neugeborenen auf der Grundlage von Körperhöhe und Körpergewicht der Mutter (Ergebnisse einer Validierungsstudie).

INTRODUCTION: Birth weight is influenced by maternal anthropometry. The SGA-rate of newborns of short and light mothers (<158 cm,<53 kg) and the LGA-rate of tall and heavy mothers (>177 cm,>79 kg) are overestimated. The LGA-rate of newborns of shorter mothers and the SGA-rate of taller mothers are underestimated. Individualized birth weight percentiles (IBWP) based on 18 maternal groups (6 groups of height combined with 3 groups of weight), sex and weeks of gestation have been published. The aim of this study is to validate IBWP by evaluating SGA-, AGA-, and LGA-rates using perinatal data. METHODS: The validation study compares IBWP (1995 to 2000, n=2.2 million singletons) with percentile values from two German cohorts (i: 1995 to 2000; n=2.3 million and ii: 2007 to 2011, n=3.2 million singletons) using newborns from the Lower Saxony Perinatal Survey (n=0.56 million singleton newborns, 2001 to 2009). SGA-, AGA-, and LGA-rates were calculated using R statistical analysis. RESULTS: Common percentile charts based on the total population 1995-2000 and 2007-2011 yielded SGA-rates among shorter mothers of 21.1 to 21.6% and LGA-rates of 2.0 to 3.1%. In taller mothers, SGA-rates were 3.3 to 3.5% and LGA-rates were 26.6 to 27.1%. IBWP achieved SGA-rates of 9.0% and LGA-rates of 11.4 to 11.6% in shorter mothers and SGA- and LGA-rates of 10% in taller mothers. DISCUSSION: IBWP consider the maternal size for estimation of the fetal growth potential and achieve expected SGA- and LGA-rates of 10%. Consideration of individual growth potential avoids underestimation and overestimation of SGA- and LGA-rates. It aided analyses of birth weight with IBWP simplify the assessment of the nutritional status.

Exercise During Pregnancy.

BACKGROUND: Pregnancy is a good time to motivate women to implement health-promoting behaviors in their everyday lives. There is no official German-language guideline for the counseling of pregnant women by professionals involved in their care. The goal of this review is, therefore, to discuss the links between exercise and gestational diabetes mellitus (GDM), low birth weight, and prematurity. METHODS: This review is based on pertinent articles retrieved by a systematic search of PubMed and the Web of Science. The articles included in the evaluation were reports of randomized controlled trials (RCTs) and meta-analyses of RCTs of exercise interventions in pregnant women that were published from 1 January 2011 to 15 November 2021. RESULTS: A structured exercise program during pregnancy can lower the risk of gestational diabetes by as much as 49%. A 25% risk reduction for GDM was achieved with 140 minutes of exercise per week. The mean birth weight was not affected but the rate of excessively heavy newborns was lowered by 32-59% in the normal-weight subgroup. This effect was not seen in the overweight subgroup, possibly because of poorer compliance. Exercise did not elevate the risk of preterm delivery. CONCLUSION: Regular exercise during pregnancy lessens gestationally induced weight gain and lowers the risk of excessive weight gain, as well as the risk of GDM, without elevating the risk of preterm delivery.

Neonatal Platelets: Lower G12/13 Expression Contributes to Reduced Secretion of Dense Granules.

Despite fully functional primary hemostasis, platelets of healthy neonates exhibit hypoaggregability and secretion defects, which may be adaptations to specific requirements in this developmental stage. The etiologies for reduced signal transduction vary with the type of agonist. The discovered peculiarities are lower receptor densities, reduced calcium mobilization, and functional impairments of G proteins. Reduced secretion of dense granules has been attributed to lower numbers of granules. Signaling studies with adult platelets have shown a regulating effect of the G12/13 signaling pathway on dense granule secretion via RhoA. We comparatively analyzed secretion profiles using flow cytometry and expression levels of Gq, Gi, and G12/13 using Western blot analysis in platelets from cord blood and adults. Furthermore, we evaluated Rho activation after in vitro platelet stimulation with thrombin using a pulldown assay. We observed a markedly reduced expression of the dense granule marker CD63 on neonatal platelets after thrombin stimulation. Gα12/13 expression was significantly decreased in neonatal platelets and correlated with lower Rho activation after thrombin stimulation. We conclude that lower expression of G12/13 in neonatal platelets results in attenuated activation of Rho and may contribute to reduced secretion of dense granules after exposure to thrombin.

[Updated recommendations on the treatment of infectious diseases in refugees in childhood and adolescence in Germany (situation as of 30 March 2022), registered as S1 guidelines (AWMF-Register Nr. 048-017)]. / Aktualisierte Empfehlungen zur infektiologischen Versorgung von Flüchtlingen im Kindes- und Jugendalter in Deutschland (Stand 30. März 2022), angemeldet als S1-Leitlinie (AWMF-Register Nr. 048-017): Stellungnahme der Deutschen Gesellschaft für Pädiatrische Infektiologie e. V. (DGPI), der Gesellschaft für Tropenpädiatrie und Internationale Kindergesundheit e. V. (GTP), des Berufsverbandes der Kinder- und Jugendärzte e. V. (BVKJ) und der Deutschen Gesellschaft für Kinder- und Jugendmedizin e. V. (DGKJ), unter Mitarbeit des Berufsverbands der Ärztinnen und Ärzte des Öffentlichen Gesundheitsdienstes e. V. (BVÖGD), der Deutschen Gesellschaft für Kinderchirurgie e. V. (DGKCH), der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe e. V. (DGGG), Deutsche Gesellschaft für Allgemeinmedizin und Familienmedizin (DEGAM), des Bündnis Kinder- und Jugendgesundheit e. V. (früher Deutsche Akademie für Kinder- und Jugendmedizin, DAKJ), der Deutschen Gesellschaft für Tropenmedizin, Reisemedizin und Globale Gesundheit e. V. (DTG), der Deutschen Gesellschaft für Globale und Tropenchirurgie e. V. (DTC) und der Pädiatrisch Infektiologischen Gruppe Schweiz (PIGS).

Background: Based on 190,000 applications for asylum, Germany remains a top destination for refugees and asylum seekers in Europe. The updated recommendations are considered evidence-based and targeted guidelines for the diagnosis and prevention of infectious diseases in underage refugees and asylum seekers. Objective: The objective of these recommendations is to guide medical staff in the care of minor refugees, in particular to:1. assure early recognition and completion of incomplete vaccination status,2. diagnose and treat common infectious diseases,3. recognize and treat imported infectious diseases that are considered uncommon to the German healthcare system. Material and methods: The recommendations have been formally written to be published as AWMF S1 guidelines.This includes a representative expert panel appointed by several professional societies, and formal adoption of the recommendations by the board of directors of all societies concerned. Results: Recommendations are given for the medical evaluation of minor refugees, including medical history and physical examination. A blood count as well as screening for tuberculosis and hepatitis B should be offered to all minor refugees. In addition, screening for other infectious diseases like hepatitis C, HIV or schistosomiasis should be considered depending on age and country of origin. Vaccinations are recommended based on both age and country of origin. Conclusion: As thousands of minor refugees continue to seek shelter in Germany every year, professional health care with adequate financial support needs to be established to ensure an appropriate medical treatment of this particularly vulnerable population.