Neonatal Exhaled Breath Sampling for Infrared Spectroscopy: Biomarker Analysis.

Monitoring health conditions in neonates for early therapeutic intervention in case deviations from physiological conditions is crucial for their long-term development. Due to their immaturity preterm born neonates are dependent on particularly careful physical and neurological diagnostic methods. Ideally, these should be noninvasive, noncontact, and radiation free. Infrared spectroscopy was used to analyze exhaled breath from 71 neonates with a special emphasis on preterm infants, as a noninvasive, noncontact, and radiation-free diagnostic tool. Passive sample collection was performed by skilled clinicians. Depending on the mode of respiratory support of infants, four different sampling procedures were adapted to collect exhaled breath. With the aid of appropriate reference samples, infrared spectroscopy has successfully demonstrated its effectiveness in the analysis of breath samples of neonates. The discernible increase in concentrations of carbon dioxide, carbon monoxide, and methane in collected samples compared to reference samples served as compelling evidence of the presence of exhaled breath. With regard to technical hurdles and sample analysis, samples collected from neonates without respiratory support proved to be more advantageous compared to those obtained from intubated infants and those with CPAP (continuous positive airway pressure). The main obstacle lies in the significant dilution of exhaled breath in the case of neonates receiving respiratory support. Metabolic analysis of breath samples holds promise for the development of noninvasive biomarker-based diagnostics for both preterm and sick neonates provided an adequate amount of breath is collected.

Short-term outcomes of asphyxiated neonates depending on requirement for transfer in the first 24 h of life.

IMPORTANCE: In neonates with birth asphyxia (BA) and hypoxic-ischemic encephalopathy, therapeutic hypothermia (TH), initiated within six hours, is the only safe and established neuroprotective measure to prevent secondary brain injury. Infants born outside of TH centers have delayed access to cooling. OBJECTIVE: To compare in-hospital mortality, occurrence of seizures, and functional status at discharge in newborns with BA depending on postnatal transfer for treatment to another hospital within 24 h of admission (transferred (TN) versus non-transferred neonates (NTN)). DESIGN: Nationwide retrospective cohort study from a comprehensive hospital dataset using codes of the International Classification of Diseases, 10th modification (ICD-10). Clinical and outcome information was retrieved from diagnostic and procedural codes. Hierarchical multilevel logistic regression modeling was performed to quantify the effect of being postnatally transferred on target outcomes. SETTING: All discharges from German hospitals from 2016 to 2021. PARTICIPANTS: Full term neonates with birth asphyxia (ICD-10 code: P21) admitted to a pediatric department on their first day of life. EXPOSURES: Postnatal transfer to a pediatric department within 24 h of admission to an external hospital. MAIN OUTCOMES: In-hospital death; secondary outcomes: seizures and pediatric complex chronic conditions category (PCCC) ≥ 2. RESULTS: Of 11,703,800 pediatric cases, 25,914 fulfilled the inclusion criteria. TNs had higher proportions of organ dysfunction, TH, organ replacement therapies, and neurological sequelae in spite of slightly lower proportions of maternal risk factors. In TNs, the adjusted odds ratios (OR) for death, seizures, and PCCC ≥ 2 were 4.08 ((95% confidence interval 3.41-4.89), 2.99 (2.65-3.38), and 1.76 (1.52-2.05), respectively. A subgroup analysis among infants receiving TH (n = 3,283) found less pronounced adjusted ORs for death (1.67 (1.29-2.17)) and seizures (1.26 (1.07-1.48)) and inverse effects for PCCC ≥ 2 (0.81 (0.64-1.02)) in TNs. CONCLUSION AND RELEVANCE: This comprehensive nationwide study found increased odds for adverse outcomes in neonates with BA who were transferred to another facility within 24 h of hospital admission. Closely linking obstetrical units to a pediatric department and balancing geographical coverage of different levels of care facilities might help to minimize risks for postnatal emergency transfer and optimize perinatal care.

The effect of live music therapy on white matter microstructure in very preterm infants - A randomized controlled trial.

OBJECTIVE: Music therapy (MT) is proposed to enrich the acoustic environment of very preterm infants (VPT) on the neonatal intensive care unit during a vulnerable period of brain development. The objective of this study was to investigate the effect of MT on the white matter (WM) microstructure. It is hypothesized that MT affects WM integrity in VPT. METHODS: Randomized controlled trial enrolling infants born <32 weeks' gestation. Infants were randomized to MT or standard care. Live MT was provided twice weekly from the second postnatal week onwards by a trained music therapist. At term equivalent age, participants underwent a cranial magnetic resonance imaging scan including sequences for diffusion tensor imaging analysis. Differences in WM microstructure were assessed using tract based spatial statistics with fractional anisotropy. RESULTS: Of 80 infants enrolled, 42 were eligible for diffusion tensor imaging analysis (MT: n = 22, standard care: n = 20). While primary tract based spatial statistics analysis revealed no significant differences between groups, post hoc analysis with uncorrected p-values and a significance threshold of p < 0.01 revealed significant fractional anisotropy differences in several WM tracts including the bilateral superior longitudinal fasciculus, the left forceps minor and left fasciculus uncinatus, the corpus callosum, the left external capsule, and the right corticospinal tract. CONCLUSION: Post hoc analysis results suggest an effect of MT on WM integrity in VPT. Larger studies including long-term outcome are necessary to confirm these effects of MT on WM microstructure and to assess its impact on clinical neurodevelopment. CLINICAL TRIAL REGISTRATION: Clinical trial number DRKS00025753.

Perinatal Outcomes of Immigrant Mothers and Their Infants Born Very Preterm across Germany.

BACKGROUND: In Germany, more than 40% of infants are born to immigrant parents. Increased survival rates of very preterm (below 32 weeks gestation at birth; VP) infants have not resulted in equally improved life chances and quality of life. More information on perinatal variations in outcomes according to social inequalities, migration background, and language barriers is needed. We tested whether mothers' immigrant status and language barriers are associated with perinatal health and short-term neonatal outcomes. METHODS: The data are from the national multi-centre German Neonatal Network (GNN) cohort, including VP births from 2009 onwards. In total, 3606 (n = 1738 female) children were assessed, and 919 (n = 449 female) of these children had immigrant backgrounds. Immigrant status was operationalised as a binary variable based on the children's mothers' countries of birth (born in Germany vs. foreign-born). Self-reported home language (L1) was used to calculate the average linguistic distance to German as one continuous variable. RESULTS: Mixed-effects models showed that two out of fourteen effects of interest survived the adjustment for known confounders and accounting for the nestedness of data within birth hospitals. Linguistic distance from mothers' L1s to German was independently associated with diagnoses of preeclampsia (OR = 1.01, 95% CI = [1.00, 1.01]). Infants of foreign-born mothers had higher odds for amniotic infection syndrome (AIS; OR = 1.45 [1.13, 1.86]) than infants of German mothers. CONCLUSIONS: Our findings from this large multi-centre longitudinal cohort of VP-born children indicate that maternal immigrant status and language barriers have limited impact on perinatal health and severe neonatal outcomes. This suggests that, regardless of background or language skills, there may be few inequalities in the perinatal health of pregnant women and their newborn preterm infants.

Reproducibility of Air Displacement Plethysmography in Term and Preterm Infants-A Study to Enhance Body Composition Analysis in Clinical Routine.

The quality-initiative analysis of weekly duplicate PEAPOD® body composition measurements was conducted from clinical practice (January to September 2021) on preterm and term infants without respiratory support. Statistical analysis, including regression analysis, Bland-Altman plots and cv-root-mean-square tests, was performed. A total of 188 duplicate (376 individual) measurements were collected from 119 infants (88 preterm, 31 term). The median absolute difference between duplicates was 31.5 g for fat-free mass (FFM). Linear correlation analysis showed R2 = 0.97 for FFM. The absolute differences in FFM and fat mass did not significantly correlate with increasing age. The %FFM differed (p = 0.02) across body weight groups of 1 kg < BW ≤ 2 kg (1.8%; IQR: 0.8, 3.6) and BW > 3 kg (0.9%; IQR: 0.3, 2.1). The median absolute differences were 1 g (IQR: 0.4, 3.1) for body weight and 5.6 mL (IQR: 2.1, 11.8) for body volume. Body volume estimation is charged with a constant absolute error, which is the main factor for differences between repeated body composition assessments. This error becomes more prominent in infants with lower body weights. Nevertheless, reproducibility of weekly PEAPOD testing is sufficient to monitor body compartment changes, offering a foundation for nutritional decisions in both preterm and term infants.

Association of bilaterally suppressed EEG amplitudes and outcomes in critically ill children.

Background and objectives: Amplitude-integrated EEG (aEEG) is used to assess electrocortical activity in pediatric intensive care if (continuous) full channel EEG is unavailable but evidence regarding the meaning of suppressed aEEG amplitudes in children remains limited. This retrospective cohort study investigated the association of suppressed aEEG amplitudes in critically ill children with death or decline of neurological functioning at hospital discharge. Methods: Two hundred and thirty-five EEGs derived from individual patients <18 years in the pediatric intensive care unit at the University Hospital Essen (Germany) between 04/2014 and 07/2021, were converted into aEEGs and amplitudes analyzed with respect to age-specific percentiles. Crude and adjusted odds ratios (OR) for death, and functional decline at hospital discharge in patients with bilateral suppression of the upper or lower amplitude below the 10th percentile were calculated. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) were assessed. Results: The median time from neurological insult to EEG recording was 2 days. PICU admission occurred due to neurological reasons in 43% and patients had high overall disease severity. Thirty-three (14%) patients died and 68 (29%) had a functional decline. Amplitude suppression was observed in 48% (upper amplitude) and 57% (lower amplitude), with unilateral suppression less frequent than bilateral suppression. Multivariable regression analyses yielded crude ORs between 4.61 and 14.29 and adjusted ORs between 2.55 and 8.87 for death and functional decline if upper or lower amplitudes were bilaterally suppressed. NPVs for bilaterally non-suppressed amplitudes were above 95% for death and above 83% for pediatric cerebral performance category Scale (PCPC) decline, whereas PPVs ranged between 22 and 32% for death and 49-52% for PCPC decline. Discussion: This study found a high prevalence of suppressed aEEG amplitudes in critically ill children. Bilaterally normal amplitudes predicted good outcomes, whereas bilateral suppression was associated with increased odds for death and functional decline. aEEG assessment may serve as an element for risk stratification of PICU patients if conventional EEG is unavailable with excellent negative predictive abilities but requires additional information to identify patients at risk for poor outcomes.

Correlation of Comfort Score and Narcotrend Index during Procedural Sedation with Midazolam and Propofol in Children.

Background/Objectives: Precise assessment of hypnotic depth in children during procedural sedation with preserved spontaneous breathing is challenging. The Narcotrendindex (NI) offers uninterrupted information by continuous electrocortical monitoring without the need to apply a stimulus with the risk of assessment-induced arousal. This study aimed to explore the correlation between NI and the Comfort Scale (CS) during procedural sedation with midazolam and propofol and to identify an NI target range for deep sedation. Methods: A prospective observational study was conducted on 176 children (6 months to 17.9 years) undergoing procedural sedation with midazolam premedication and continuous propofol infusion. Statistical analyses included Pearson correlation of NI and CS values, logistic regression, and receiver operating curves. Results: Median NI values varied with CS and age. The correlation coefficient between CS and NI was 0.50 and slightly higher in procedure-specific subgroup analyses. The optimal NI cut-off for deep sedation was between 50 and 60 depending on the analyzed subgroup and displayed high positive predictive values for sufficient sedation throughout. Conclusion: Our study found a moderate correlation between NI and CS, demonstrating reliable identification of adequately sedated patients.

Pediatric Community-Acquired Brain Abscesses: A Single-center Retrospective Study.

The European Society for Clinical Microbiology and Infectious Diseases recommends 3rd generation cephalosporins and metronidazole for empirical treatment of community-acquired brain abscesses. In 53 retrospectively analyzed pediatric patients with community-acquired brain abscesses at a German University Hospital Staphylococcus aureus was identified as a relevant pathogen (21%). Therefore, it may be reasonable to cover S. aureus when selecting empirical therapy.

Gestational Age-Related Urinary Peptidome Changes in Preterm and Term Born Infants.

INTRODUCTION: Preterm infants are at risk for a variety of somatic and neurological disorders. In recent years, biofluid proteomics has emerged as a potential diagnostic tool for biomarker analysis. The aim of this study was to determine gestational age (GA)-related patterns of the urinary peptidome in preterm infants for researching potential novel prognostic biomarkers. METHODS: We performed urinary peptidomics in longitudinal samples of 24 preterm (mean GA weeks 28 + 1 [24+1-31 + 6]) and 27 term born controls (mean GA weeks 39 + 2 [37+0-41 + 1]) using capillary electrophoresis combined with mass spectrometry (CE-MS). Peptides were sequenced using CE-MS/MS or LC-MS/MS analysis and were deposited, matched, and annotated in a Microsoft SQL database for statistical analysis. We compared their abundance in urine of preterm and term born infants and performed a validation analysis as well as correlations to GA and clinical risk scores. RESULTS: Our results confirmed significant differences in the abundance of peptides and the hypothesis of age-dependent urinary peptidome changes in preterm and term infants. In preterm infants, SLC38A10 (solute carrier family 38 member 10) is one of the most abundant peptides. Combined urinary peptides correlated with clinical risk scores (p < 0.05). CONCLUSION: This is the first study reporting GA-related urinary peptidome changes of preterm infants detected by CE-MS and a modulation of the peptidome with GA. Further research is required to locate peptidome clusters correlated with specific clinical complications and long-term outcome. This may identify preterm infants at higher risk for adverse outcome who would benefit from early intervention.

Current practice of intracranial pressure monitoring in children with severe traumatic brain injury-a nationwide prospective surveillance study in Germany.

Background: For management of severe traumatic brain injuries (sTBI) in children, the overall level of evidence to guide diagnostic and therapeutic procedures is low. Since 2016, international guidelines have subsequently suggested invasive intracranial pressure (ICP) monitoring in patients with initial Glasgow Coma Scale (GCS) ≤8. In Germany, ICP monitoring was an individual case decision from 2011 until the 2022 update of the German pediatric TBI guideline. The aim of this study was to evaluate current clinical practice of invasive ICP monitoring in Germany in children <10 years with respect to guideline recommendations. Methods: Anonymized clinical data on sTBI cases <10 years of age were collected in a nationwide prospective surveillance study via the German Pediatric Surveillance Unit ESPED from July 2019 until June 2022. Inclusion criteria for the surveillance study were sTBI (initial GCS ≤8) or neurosurgery following TBI. For this analysis, only cases with GCS ≤8 were subject to the present analysis. Descriptive analyses were performed to assess the proportion of ICP monitored patients and describe the cohort. Results: Out of 217 reported cases, 102 cases met the inclusion criteria and thus qualified for ICP monitoring. Of these, 37 (36%) received ICP monitoring. Monitored patients were older, had lower median GCS values at presentation (4 vs. 5), higher mortality (32% vs. 22%), and were more frequently diagnosed with cerebral edema (68% vs. 37%). Conclusion: In children <10 years with sTBI, the present clinical management regarding ICP monitoring deviates from the current German national and international guidelines. The reasons remain unclear, with the low level of evidence in the field of ICP monitoring and the recency of changes in guideline recommendations as potential contributors. Prospective interventional studies should elucidate the benefit of ICP monitoring and ICP directed therapies to provide evidence-based recommendations on ICP monitoring.

Incidence of brain injuries in a large cohort of very preterm and extremely preterm infants at term-equivalent age: results of a single tertiary neonatal care center over 10 years.

OBJECTIVES: Cerebral magnetic resonance imaging (cMRI) at term-equivalent age (TEA) can detect brain injury (BI) associated with adverse neurological outcomes in preterm infants. This study aimed to assess BI incidences in a large, consecutive cohort of preterm infants born < 32 weeks of gestation, the comparison between very (VPT, ≥ 28 + 0 to < 32 + 0 weeks of gestation) and extremely preterm infants (EPT, < 28 + 0 weeks of gestation) and across weeks of gestation. METHODS: We retrospectively analyzed cMRIs at TEA of VPT and EPT infants born at a large tertiary center (2009-2018). We recorded and compared the incidences of BI, severe BI, intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhage (CBH), cystic periventricular leukomalacia (cPVL), and punctate white matter lesions (PWML) between VPTs, EPTs, and across weeks of gestation. RESULTS: We included 507 preterm infants (VPT, 335/507 (66.1%); EPT, 172/507 (33.9%); mean gestational age (GA), 28 + 2 weeks (SD 2 + 2 weeks); male, 52.1%). BIs were found in 48.3% of the preterm infants (severe BI, 12.0%) and increased with decreasing GA. IVH, PVHI, CBH, cPVL, and PWML were seen in 16.8%, 0.8%, 10.5%, 3.4%, and 18.1%, respectively. EPT vs. VPT infants suffered more frequently from BI (59.3% vs. 42.7%, p < 0.001), severe BI (18.6% vs. 8.7%, p = 0.001), IVH (31.9% vs. 9.0%, p < 0.001), and CBH (18.0% vs. 6.6%, p < 0.001). CONCLUSION: Brain injuries are common cMRI findings among preterm infants with a higher incidence of EPT compared to VPT infants. These results may serve as reference values for clinical management and research. CLINICAL RELEVANCE STATEMENT: Our results with regard to gestational age might provide valuable clinical insights, serving as a key reference for parental advice, structured follow-up planning, and enhancing research and management within the Neonatal Intensive Care Unit. KEY POINTS: • Brain injury is a common cMRI finding in preterm infants seen in 48.3% individuals. • Extremely preterm compared to very preterm infants have higher brain injury incidences driven by brain injuries such as intraventricular and cerebellar hemorrhage. • Reference incidence values are crucial for parental advice and structured follow-up planning.

Use and Impact of Pessary, Cerclage, and Progesterone for the Secondary Prevention of Preterm Birth: Data from the German Neonatal Network.

BACKGROUND: To evaluate the use and effect of cervical stitch cerclage, pessary, and progesterone on pregnancy outcome in mothers of very low birth weight infants (VLBWI) born<32 weeks of gestation in the German Neonatal Network (GNN). METHODS: The GNN is a population-based cohort study enrolling VLBWI since 2009. We included 575 neonates from 424 mothers into our analysis, who were born between 2015 and 2019, after prenatal intervention with cerclage, pessary, progesterone or a combination between 20/0 to 25/0 weeks of gestation to prevent preterm birth. Median intervention-to-birth interval was the primary endpoint. RESULTS: 231 of 424 pregnant women had a cerclage only (54.5%), 76 women a pessary only (17.9%), and 27 were prescribed progesterone only (15.3%). The most common combination treatment (>1 intervention group) was cerclage plus progesterone (n=27), followed by cerclage plus pessary (n=13). The median intervention-to-birth interval for the whole cohort was 24 days (IQR 19.0 days). The earlier the intervention was started, the longer the intervention-to-birth interval lasted: When started at 20 weeks, the interval was 34 days in contrast to 11.5 days, when started at 25 weeks. The >1 group was born at a significantly higher median GA with 27.0 weeks (IQR 2.9 weeks) and a higher median birth weight of 980 g (IQR 394 g) accordingly. CONCLUSION: We propose that the earliest possible start of intervention leads to the most efficient pregnancy prolongation.

Aortic Steal Correlates with Acute Organ Dysfunction and Short-Term Outcomes in Neonates with Vein of Galen Malformation.

INTRODUCTION: Vein of Galen aneurysmal malformation (VGAM) is a rare, congenital cerebrovascular malformation with high morbidity and mortality. Parameters to foresee clinical progression and allow individualized parent counseling are lacking. The aim of this study was to evaluate aortic steal measured by Doppler ultrasound as a prognostic parameter in these neonates. METHODS: A retrospective monocentric analysis of cardiac ultrasound exams before embolization in neonates with VGAM was conducted. Percentage of aortic steal measured by time-averaged maximum velocity above and below the zero flow baseline by pulsed Doppler ultrasound at the preductal aortic isthmus was calculated. Association of aortic steal with parameters of acute organ dysfunction (Bicêtre neonatal evaluation score [BNES], neonatal multiple organ dysfunction score [NeoMODS]) and mortality and determination of correlation between aortic steal and cerebral damage on initial and follow-up cerebral magnetic resonance imaging (cMRI) were evaluated. RESULTS: Twelve neonates were included, of which 3 died. Per 10 percentage point increase of aortic steal, BNES decreased by 1.64 (95% confidence interval [CI]: 1.28-2.0) points and the maximum observed NeoMODS increased by 1.25 (CI: 0.94-1.57) points. The odds for mortality increased by 2.3 (CI: 1.14-13.67) per 10 percentage point increase of aortic steal. There was a correlation between aortic steal and cerebral damage at baseline (white matter ρ [rho] = 0.34, gray matter ρ = 0.81) and follow-up (white matter ρ = 0.80, gray matter ρ = 0.72). CONCLUSION: The degree of aortic steal in neonates with VGAM was highly associated with the severity of organ dysfunction, disease progression on cMRI, and mortality.

The Subdiaphragmatic Angle Of The Gastric Tube In Neonates - A Potential Predictor For Perforations?

BACKGROUND: Traumatic subdiaphramatic perforation of esophagus or stomach in neonates represents a rare clinical complication following the insertion of a gastric tube and is associated with high morbidity and mortality. The aim of the present study was to evaluate whether the angle of the gastric tube depicted on a plain radiograph may serve as a diagnostic tool to predict subdiaphragmatic traumatic (or iatrogenic) perforation. PATIENTS AND METHODS: Thoraco-abdominal radiographs of 128 preterm and term neonates without perforation and 15 neonates with perforation of the esophagogastric junction or the stomach were retrospectively analysed. RESULTS: The angle of the gastric tube increases with postnatal age (p=0.0380). In the control group, the angle of the gastric tube varied between 13° and 48° (median: 31°), whereas the values ranged from -31° to 42° (median: 11°) in neonates with subdiaphragmatic perforation. Perforation should thus be suspected in cases with an angle of<20° (sensitivity: 93.3%; specificity: 91.4%). Moreover, an unusual localization of the tip beyond the gastric bubble is highly indicative of perforation. DISCUSSION: The present study emphasizes the importance of verifying the correct course of an inserted gastric tube. CONCLUSIONS: In daily clinical practice, an angle of<20° should be followed by thorough physical examination, abdominal ultrasound and if applicable contrast medium examinations to exclude perforation.

Current diagnosis and treatment practice for pulmonary hypertension in bronchopulmonary dysplasia-A survey study in Germany (PUsH BPD).

Pulmonary hypertension (PH) is the most severe complication in preterm infants with bronchopulmonary dysplasia (BPD) and associated with significant mortality. Diagnostic and treatment strategies, however, still lack standardization. By the use of a survey study (PH in BPD), we assessed clinical practice (diagnosis, treatment, follow-up) in preterm infants with early postnatal persistent pulmonary hypertension of the newborn (PPHN) as well as at risk for or with established BPD-associated PH between 06/2018 and 10/2020 in two-thirds of all German perinatal centers with >70 very low birthweight infants/year including their cardiology departments and outpatient units. Data were analyzed descriptively by measures of locations and distributional shares. In routine postnatal care, clinical presentation and echocardiography were reported as the main diagnostic modalities to screen for PPHN in preterm infants, whereas biomarkers brain natriuretic peptide/N-terminal pro b-type natriuretic peptide were infrequently used. For PPHN treatment, inhaled nitric oxide was used in varying frequency. The majority of participants agreed to prescribe diuretics and steroids (systemic/inhaled) for infants at risk for or with established BPD-associated PH and strongly agreed on recommending respiratory syncytial virus immunization and the use of home monitoring upon discharge. Reported oxygen saturation targets, however, varied in these patients in in- and outpatient care. The survey reveals shared practices in diagnostic and therapeutic strategies for preterms with PPHN and BPD-associated PH in Germany. Future studies are needed to agree on detailed echo parameters and biomarkers to diagnose and monitor disease next to a much-needed agreement on the use of pulmonary vasodilators, steroids, and diuretics as well as target oxygen saturation levels.

Diagnostic Accuracy of Multiplex Polymerase Chain Reaction in Early Onset Neonatal Sepsis.

Early onset neonatal sepsis is a significant contributor to neonatal morbidity and mortality. Although blood cultures remain the diagnostic gold standard, they detect pathogens in only a minority of suspected cases. This study compared the accuracy of blood cultures with a rapid multiplex PCR test. Newborns at risk of neonatal sepsis were prospectively screened as recommended per national guidelines. Evaluations included laboratory parameters (CrP, IL6, differential blood count), blood culture, and a molecular multiplex PCR test (ROCHE LightCycler SeptiFast®) identifying 20 common microbial agents. Blood samples were taken simultaneously from umbilical cord or venous sources on the first day of life. Of 229 infants included, 69% were born preterm. Blood culture and multiplex PCR sensitivity were 7.4% and 14.8%, respectively. Specificity, negative and positive predictive values between methods showed no significant variance, although multiplex PCR had more false positives due to contamination. The limited sensitivity of blood cultures for early onset neonatal sepsis is concerning. Despite quicker results, multiplex PCR does not enhance diagnostic accuracy or antibiotic therapy guidance, thus it cannot be recommended for this indication.

Hypothermia combined with extracellular vesicles from clonally expanded immortalized mesenchymal stromal cells improves neurodevelopmental impairment in neonatal hypoxic-ischemic brain injury.

BACKGROUND: Neonatal encephalopathy following hypoxia-ischemia (HI) is a leading cause of childhood death and morbidity. Hypothermia (HT), the only available but obligatory therapy is limited due to a short therapeutic window and limited efficacy. An adjuvant therapy overcoming limitations of HT is still missing. Mesenchymal stromal cell (MSC)-derived extracellular vesicles (EVs) have shown promising therapeutic effects in various brain injury models. Challenges associated with MSCs' heterogeneity and senescence can be mitigated by the use of EVs from clonally expanded immortalized MSCs (ciMSCs). In the present study, we hypothesized that intranasal ciMSC-EV delivery overcomes limitations of HT. METHODS: Nine-day-old C57BL/6 mice were exposed to HI by occlusion of the right common carotid artery followed by 1 h hypoxia (10% oxygen). HT was initiated immediately after insult for 4 h. Control animals were kept at physiological body core temperatures. ciMSC-EVs or vehicle were administered intranasally 1, 3 and 5 days post HI/HT. Neuronal cell loss, inflammatory and regenerative responses were assessed via immunohistochemistry, western blot and real-time PCR 7 days after insult. Long-term neurodevelopmental outcome was evaluated by analyses of cognitive function, activity and anxiety-related behavior 5 weeks after HI/HT. RESULTS: In contrast to HT monotherapy, the additional intranasal therapy with ciMSC-EVs prevented HI-induced cognitive deficits, hyperactivity and alterations of anxiety-related behavior at adolescence. This was preceded by reduction of striatal neuronal loss, decreased endothelial, microglia and astrocyte activation; reduced expression of pro-inflammatory and increased expression of anti-inflammatory cytokines. Furthermore, the combination of HT with intranasal ciMSC-EV delivery promoted regenerative and neurodevelopmental processes, including endothelial proliferation, neurotrophic growth factor expression and oligodendrocyte maturation, which were not altered by HT monotherapy. CONCLUSION: Intranasal delivery of ciMSC-EVs represents a novel adjunct therapy, overcoming limitations of acute HT thereby offering new possibilities for improving long-term outcomes in neonates with HI-induced brain injury.

Abortion in the First Trimester. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015-094, December 2022) - Part 2 with Recommendations for Surgical Termination of Pregnancy and Follow-up Care After Termination of Pregnancy.

Purpose The aim was to develop evidence-based recommendations where possible. The guideline presents the medical principles and scientific evidence for indications, counselling of affected persons, performing terminations, the choice of method, and the care and monitoring of a terminated pregnancy up until week 12 + 0 of gestation p. c. Methods In accordance with the requirements for an S2k-guideline, the contents of the guideline were drafted following a systematic search of the literature by a representative interdisciplinary group of experts. Guideline authors held several formal meetings under the auspices of the German Society for Gynaecology and Obstetrics (DGGG) during which the contents of the guideline were finalised and agreed upon. Recommendations The guideline provides recommendations on the surgical termination of pregnancy and follow-up care after termination of pregnancy.

Abortion in the First Trimester. Guideline of the DGGG (S2k-Level, AWMF Registry No. 015-094, December 2022) - Part 1 with Recommendations on Care Structures, Information and Advice on Decision-Making, Measures Before Abortion and Medical Abortion.

Purpose The aim was to develop evidence-based recommendations where possible. The guideline presents the medical principles and scientific evidence for indications, the counselling of affected women, performing terminations, the choice of method, and the care and monitoring of a terminated pregnancy up until week 12 + 0 of gestation p. c. Methods In accordance with the requirements for S2k-guidelines, the contents of the guideline were drafted following a systematic search of the literature by a representative interdisciplinary group of experts. Guideline authors held several formal meetings under the auspices of the German Society for Gynaecology and Obstetrics (DGGG) during which the contents of the guideline were finalised and agreed upon. Recommendations A total of 61 recommendations are provided, covering care structures, provision of information and counselling to support decision-making, the measures to be taken before terminating the pregnancy, and medical termination of the pregnancy.