Vertical transmission of SARS-CoV-2 - data from the German COVID-19 related obstetric and neonatal outcome study (CRONOS).

OBJECTIVES: We aimed to determine the frequency of SARS-CoV-2 positivity in newborns born to mothers with peripartum SARS-CoV-2 infection in a German cohort, to identify potential risk factors associated with neonatal SARS-CoV-2 infection, and to present short-term outcomes of newborns with vertical transmission of SARS-CoV-2. METHODS: Data on women with SARS-CoV-2 infection occurring anytime during their pregnancy was gathered prospectively within the CRONOS registry. From April 2020 to February 2023 a total of 8,540 women had been registered. The timing and the probability of mother-to-child transmission in neonates born to women with perinatal SARS-CoV-2 infection were classified using the WHO classification system. The severity of maternal infection, maternal vaccination status, type of dominant virus, and perinatal outcome parameters were analyzed as potential risk factors for neonatal SARS-CoV-2 infection. RESULTS: 6.3 % resp. 42.9 % of tested newborns and stillbirths were SARS-CoV-2 positive. 2.1 % of newborns with confirmed and possible SARS-CoV-2 infection were identified. Severe maternal COVID-19 (odds ratio 4.4, 95 % confidence interval 1.8-11.1) and maternal infection with the Delta virus (OR 3.2, 1.4-7.7) were associated with neonatal SARS-CoV-2 infection. Newborns with a confirmed or possible infection were significantly more often admitted to the NICU (65.2 % neonatal infection vs. 27.5 % non, p<0.001). CONCLUSIONS: The rate of neonatal SARS-CoV-2 positivity was higher in our cohort than previously reported, neonatal SARS-CoV-2 infections were rare. Our data emphasizes confirmative testing should be performed in newborns of SARS-CoV-2 infected mothers to identify neonatal SARS-CoV-2 infection as an underlying pathology leading to NICU admission.

Surfactant administration during endotracheal CPAP: Feasibility, risk factors for failure and short-term outcomes of DD-SURF.

AIM: Whereas there is agreement that surfactant should be administered without mechanical ventilation, there is still a debate concerning the optimal method. DD-SURF combines the benefits of INSURE and less invasive surfactant administration (LISA). The efficacy of this approach has not been evaluated yet. METHODS: Retrospective cohort study of all preterm newborns below 300/7 weeks gestational age admitted to the neonatal intensive care unit. Data on surfactant therapy, respiratory support during the first 96 h of life and neonatal morbidities until hospital discharge were collected from the electronic patient charts to evaluate the efficacy and safety of our approach. RESULTS: In total, 222 newborns met the inclusion criteria; 174 (78%) received surfactant in the delivery room by the DD-SURF procedure and 21 infants (10%) were not extubated after surfactant administration (Surf-and-vent group). After DD-SURF, 75% of patients did not require reintubation. Intraventricular haemorrhage and bronchopulmonary dysplasia occured more often in infants after DD-SURF failure than after successful DD-SURF. CONCLUSION: DD-SURF potentially combines the benefits of INSURE and LISA and represents a useful alternative of surfactant delivery with comparable success rates to thin-catheter surfactant administration.

[Telemedical support of feto-neonatal care in one region - Part II: Structural requirements and areas of application in neonatology]. / Telemedizinische Unterstützung der feto-neonatalen Versorgung in einer Region ­ Teil II: Strukturelle Voraussetzungen und Anwendungsbereiche in der Neonatologie.

Telemedical infrastructure for patient assessment, care and follow-up as well as interdisciplinary exchange can contribute to ensuring patient care that is close to home and meets the highest quality standards, even outside specialised centres. In neonatology, synchronous audio-visual communication across institutions has been used for many years, especially in the Anglo-American countries. Areas of application include extended neonatal primary care and resuscitation, specific diagnostic applications, e.g. ROP screening and echocardiography, as well as parental care, regular telemedical ward rounds and further training of medical staff, especially using simulation training. For the implementation of such telemedical infrastructures, certain organisational, medical-legal and technical requirements for hardware, software and structural and process organisation must be met. The concrete realisation of a telemedical infrastructure currently being implemented for the region of Eastern Saxony is demonstrated here using the example of the Saxony Center for feto/neonatal Health (SCFNH). Within the framework of feto-neonatal competence networks such as the SCFNH, the quality of medical care, patient safety and satisfaction in a region can be increased by means of a comprehensive, well-structured and established telemedical infrastructure.

[Telemedical Support of Feto-Neonatal Care in One Region - Part I: Demand Analysis Using the Example of East Saxony]. / Telemedizinische Unterstützung der feto-neonatalen Versorgung in einer Region ­ Teil I: Bedarfsanalyse am Beispiel Ost-Sachsen.

Excellence in feto-neonatal care forms the basis for health in adulthood and requires a collaboration of stakeholders in the health care system. As in other regions, demographic changes such as rural depopulation pose a risk to feto-neonatal care in Eastern Saxony. Areas in need of regional, perinatal collaboration have been identified: (I) multi-professional counselling of families with a suspected fetal disease, (II) immediately available expertise of a neonatologist during neonatal resuscitation, (III) evidence-based neonatal antibiotic therapy, (IV) backtransfer of extremely preterm infants or sick neonates, and (V) adequate psychosocial support of families with extremely preterm infants or sick neonates. Telemedicine enables regional partners to communicate efficiently and gives an audiovisual impression of the patient. The Saxony Center for feto/neonatal Health (SCFNH) collaborates with regional partners to establish a feto-neonatal telemedicine network "Sichere Geburt". The network will be scientifically evaluated and might be of help as a model for other regions with structural challenges.

Tactile stimulation in very preterm infants and their needs of non-invasive respiratory support.

Aim: Despite the lack of evidence, current resuscitation guidelines recommend tactile stimulation in apneic infants within the first minutes of life. The aim was to investigate whether timing, duration or intensity of tactile stimulation influences the extent of non-invasive respiratory support in extremely preterm infants during neonatal resuscitation. Methods: In an observational study, we analyzed 47 video recordings and physiological parameters during postnatal transition in preterm infants below 320/7 weeks of gestational age. Infants were divided into three groups according to the intensity of respiratory support. Results: All infants were stimulated at least once during neonatal resuscitation regardless of their respiratory support. Only 51% got stimulated within the first minute. Rubbing the feet was the preferred stimulation method and was followed by rubbing or touching the chest. Almost all very preterm infants were exposed to stimulation and manipulation most of the time within their first 15 min of life. Tactile stimulation lasted significantly longer but stimulation at multiple body areas started later in infants receiving prolonged non-invasive respiratory support. Conclusion: This observational study demonstrated that stimulation of very preterm infants is a commonly used and easy applicable method to stimulate spontaneous breathing during neonatal resuscitation. The concomitant physical stimulation of different body parts and therefore larger surface areas might be beneficial.

Restrictive prescription of antibiotics in preterm infants with premature rupture of membranes.

BACKGROUND: In preterm infants with premature rupture of membranes, antibiotic treatment is frequently started but rates of early onset sepsis are lower. In line with national guidelines, a stratified approach in the decision to start antibiotic treatment using maternal history, clinical impression and biomarkers has been implemented in our level III neonatal center and its results are evaluated. METHODS: Retrospective cohort study of all preterm newborns with rupture of membranes at least 1 h prior to delivery admitted to our tertiary neonatal intensive care unit. Data on antibiotic exposure, mortality and major neonatal complications were extracted from the electronic patient charts to evaluate the effects and safety of our stratified approach. RESULTS: Four hundred fifty-six infants met the inclusion criteria. 120 (26%) received primary antibiotics whereas 336 (74%) did not. Of those receiving primary antibiotics, 13 (11%) had a blood culture positive sepsis, 46 (38%) met the criteria of clinical sepsis and in 61 (51%) sepsis was ruled out and antibiotics were stopped after 48-96 h. All infants with blood culture positive sepsis were identified and treated within the first 24 h of life using this approach. None of the 336 infants who were not started on antibiotics primarily needed antibiotic therapy within the first 5 days of life. There were no deaths or major neonatal complications in the group that did not receive empiric antibiotics. CONCLUSIONS: Our stratified approach for preterm infants with premature rupture of membranes allows a safe reduction of antibiotic exposure even in this high risk population. As a result, only 25% of high risk preterm newborns are treated with antibiotics of which more than half receive less than 5 days of treatment. To treat one infant with blood culture positive sepsis, only 9 infants receive empiric antibiotics.

Survey on currently applied interventions in neonatal resuscitation (SCIN): A study protocol.

Introduction: Around 140 million children are born every year and post-natal transition is uncomplicated in the vast majority. However, around 5%-15% of neonates receive supportive interventions during transition. Recent data on the interventions used is scarce. More data on the frequencies with which these interventions are used is needed to evaluate neonatal resuscitation, guide recommendations and to generate hypotheses for further research. The following protocol describes an international, multicentre survey on the interventions currently applied during neonatal resuscitation. Objectives: To determine the frequencies at which different supportive interventions recommended by European Resuscitation Council (ERC) guidelines for neonatal resuscitation are used. To compare the frequencies between hospitals and patient groups and to investigate possible factors influencing any differences found. Methods: Participating hospitals will collect data on all interventions performed during neonatal resuscitation over a period of 6 months. All hospitals providing perinatal care are eligible regardless of size and designated level of neonatal care. Every neonate requiring more interventions than basic drying and tactile stimulation during the first 30 min of life will be included. The targeted sample size is at least 4,000 neonates who receive interventions. After anonymization, the data is pooled in a common database and descriptive and statistical analysis is performed globally and in subgroups. Possible correlations will be investigated with phi coefficient and chi square testing. Ethics and dissemination: Consent of the institutional review board of the Technical University Dresden was obtained for the local data collection under the number BO-EK-198042022. Additionally, approval of local ethical or institutional review boards will be obtained by the participating hospitals if required. Results will be published in peer-reviewed journals and presented at suitable scientific conferences.

Peripheral Arterial Lines in Extremely Preterm Neonates: A Potential Alternative to Umbilical Arterial Catheters.

BACKGROUND: Arterial catheterization is a routine procedure in extremely preterm neonates. Umbilical arterial catheters (UACs) are typically used for this purpose, but life-threatening complications have been described. Peripheral arterial lines (PALs) might offer a valuable alternative, but their feasibility in extremely preterm newborns is unclear. PURPOSE: To investigate efficacy and complications of PALs in extremely preterm neonates. METHODS: Retrospective analysis of patients born below 26 weeks of gestation in 2011-2014 (cohort 1, UAC as primary arterial access) and 2015-2019 (cohort 2, PAL as primary arterial access). Arterial line placement during their first 14 days of life, duration of arterial access, reasons for discontinuation, and long-term complications were recorded from health records. RESULTS: In total, 161 of 202 newborns had an arterial line during their first 14 days of life. In cohort 2, the life span of a PAL was significantly longer than that in cohort 1. Signs of dysfunction were the primary reason to discontinue a PAL. Signs of peripheral ischemia were present in 36 of 105 cases (34%) when the PAL was removed but persisted in only 2 patients. UAC-associated persistent ischemic damage occurred in 2 of 97 patients. IMPLICATIONS FOR PRACTICE AND RESEARCH: PALs are a valuable alternative to UACs even in preterm newborns below 26 weeks of gestational age. A special focus on ischemic complications is warranted. Prospective, multicenter studies to verify safety and efficacy of arterial line management and complications in extremely preterm infants are warranted.

Reference Charts for Neonatal Cranial Volume Based on 3D Laser Scanning to Monitor Head Growth.

Background: Postnatal brain growth is an important predictor of neurodevelopmental outcome in preterm infants. A new reliable proxy for brain volume is cranial volume, which can be measured routinely by 3-D laser scanning. The aim of this study was to develop reference charts for normal cranial volume in newborn infants at different gestational ages starting from late preterm for both sexes. Methods: Cross-sectional cohort study in a German university hospital, including singleton, clinically stable, neonates born after 34 weeks of gestation. Cranial volume was measured in the first week of life by a validated 3-D laser scanner. Cranial volume data was modeled to calculate percentile values by gestational age and birth weight and to develop cranial volume reference charts for girls and boys separately. Results: Of the 1,703 included infants, 846 (50%) were female. Birth weights ranged from 1,370 to 4,830 grams (median 3,370). Median cranial volume ranged from 320 [interquartile range (IQR) 294-347] ml at 34 weeks to 469 [IQR 442-496] ml at 42 weeks and was higher in boys than in girls. Conclusions: This study presents the first reference charts of cranial volume which can be used in clinical practice to monitor brain growth between 34 and 42 weeks gestation in infants.

Mother's Own Milk Feeding in Preterm Newborns Admitted to the Neonatal Intensive Care Unit or Special-Care Nursery: Obstacles, Interventions, Risk Calculation.

Early nutrition of newborns significantly influences their long-term health. Mother's own milk (MOM) feeding lowers the incidence of complications in preterm infants and improves long-term health. Unfortunately, prematurity raises barriers for the initiation of MOM feeding and its continuation. Mother and child are separated in most institutions, sucking and swallowing is immature, and respiratory support hinders breastfeeding. As part of a quality-improvement project, we review the published evidence on risk factors of sustained MOM feeding in preterm neonates. Modifiable factors such as timing of skin-to-skin contact, strategies of milk expression, and infant feeding or mode of delivery have been described. Other factors such as gestational age or neonatal complications are unmodifiable, but their recognition allows targeted interventions to improve MOM feeding. All preterm newborns below 34 weeks gestational age discharged over a two-year period from our large German level III neonatal center were reviewed to compare institutional data with the published evidence regarding MOM feeding at discharge from hospital. Based on local data, a risk score for non-MOM feeding can be calculated that helps to identify mother-baby dyads at risk of non-MOM feeding.

Neonatal and young infant sepsis by Group B Streptococci and Escherichia coli: a single-center retrospective analysis in Germany-GBS screening implementation gaps and reduction in antibiotic resistance.

The last nationwide surveillance study on neonatal and young infant sepsis due to Group B Streptococci (GBS) and Escherichia coli in Germany was conducted between 2009 and 2010. The aim of this study is to provide longitudinal epidemiological data on neonatal and young infant sepsis caused by GBS and E. coli to reevaluate existing data and to inform clinical decision-making. Every positive blood culture for GBS and E. coli within the first 90 days of life that occurred at our center from 2008 until 2018 was identified. The epidemiological, clinical, laboratory, and microbiological data of all affected patients were analyzed through retrospective chart review, along with the pathogen's antimicrobial susceptibility results. In total, 106 episodes of neonatal sepsis were described; 31% (n = 33) being caused by GBS and 69% (n = 73) by E. coli; 87% of GBS early-onset disease (EOD) cases did not receive intrapartum antibiotic prophylaxis (IAP). Contrary to general trends, the proportion of resistant E. coli isolates decreased for all tested antibiotics over time. Coincidentally, antenatal antibiotic use beyond IAP during that period decreased significantly in our center.Conclusions: (1) Data at our center suggests at least a regional implementation gap in GBS screening and IAP. (2) The decline in the resistance rate of E. coli for all antimicrobial substances might indicate that the reduction of prenatal antibiotics use is beneficial and that neonatal antibiotic stewardship programs should include pregnant women as well. What is Known: • GBS screening and intrapartum antibiotic prophylaxis led to a 32%-reduction in GBS disease in Germany with a 0.75 (92:122) ratio of early-onset disease to late-onset disease in 2009-2010. • Prenatal antibiotic use might increase the risk of E. coli early-onset disease and antibiotic resistances. What is New: • The GBS early-onset disease rates were twice as high as those of late-onset disease, the ratio was 1.75 (21:12) in 2008-2018 at our institution. This suggests that there are at least regional implementation gaps in the antenatal GBS screening in Germany. • We found a decline in E. coli resistance rates over time for all antimicrobial substances. Reduction in use of prenatal antibiotics might be an explanation.

[Intrauterine Growth Restriction: Transsectoral, Interdisciplinary and Multiprofessional Care for Pregnant Women and Newborns in a Feto-neonatal Pathway: A Project of the Innovationsfonds]. / Intrauterine Wachstumsrestriktion: Transsektorale, interdisziplinäre und multiprofessionelle Betreuung von Schwangeren und Neugeborenen im Feto-Neonat-Pfad: Ein Projekt des Innovationsfonds.

Intrauterine growth restriction (IUGR) is present in fetuses that do not achieve their full in-utero growth potential. IUGR needs to be discriminated from small for gestational age (SGA) because IUGR newborns in particular experience long-term side effects from their small growth. IUGR fetuses have a significantly increased risk of prematurity and a distinct risk profile compared to adequate-for-gestational-age preterm newborns. Complications of prematurity are more frequent, including bronchopulmonary dysplasia, intraventricular hemorrhage, and meconium ileus. IUGR newborns are at risk of long-term health issues like cerebral palsy, impaired lung function, and delayed speech development. Interdisciplinary and interprofessional care of IUGR pregnancies in the context of a standardized health care research project is feasible: Pregnant women at risk are identified, early therapy with acetylsalicylic acid is started as indicated, risk-adapted care at level III centers is organized including psychosocial interventions and neonatal consultations. Postnatally, integrated neonatal care focusing on parent-child interaction and optimized nutrition is a hallmark. Afterwards, in-depth pediatric follow-up visits with local pediatricians help to identify growth and neurodevelopment problems early. The effects, acceptance. and cost efficiency of this approach are evaluated prospectively as part of an Innovationsfonds project.

Repin1 deficiency in liver tissue alleviates NAFLD progression in mice.

There is an increasing prevalence of obesity and metabolic syndrome, which promote the development of non-alcoholic fatty liver disease (NAFLD), a disease that can evolve into cirrhosis and hepatocellular carcinoma. Repin1 loss was previously shown to have beneficial effects on lipid and glucose metabolism and obesity regulation. Herein, we characterized NAFLD in mice with hepatic deletion of Repin1 (LRep1-/-). For this purpose, liver disease was analysed in male LRep1-/- and wild-type mice treated with streptozotocin/high fat diet or a control diet over a period of 20 wks. Streptozotocin/high fat diet treated LRep1-/- mice showed a significant decrease in systemic and hepatic lipid accumulation, accompanied by diminished chronic inflammation and a subsequent reduction in liver injury. Remarkably, Repin1-deficient mice exhibited a lower tumour prevalence and tumour frequency, as well as a reduced liver weight/body weight index. A therapeutic approach using Repin1 siRNA in the early phase of NAFLD verified the observed beneficial effects of Repin1 deficiency. This study provides evidence that loss of Repin1 in the liver attenuates NAFLD progression, most likely by reducing fat accumulation and alleviating chronic tissue inflammation. Thus, modulating Repin1 expression may become a novel strategy and potential tool to inhibit NAFLD progression.

A Newborn with Simmering Bleeding after Circumcision.

We present a case of a healthy male neonate born at term, circumcised on Day 1 of life. Facing ongoing bleeding at the incision site, the baby was transferred to a level III neonatal intensive care unit for further investigation and management. His family history was unremarkable for bleeding disorders. On arrival, the baby was hemodynamically stable with abnormal coagulation values. Further investigations revealed a diagnosis compatible with severe hemophilia A. He deteriorated on Day 2, developing acute severe anemia which required two red blood cell transfusions. This rare but potentially fatal event reminds clinicians to remain extremely vigilant with minor surgical procedures such as circumcision even in the absence of family history.

Human Umbilical Cord Mesenchymal Stromal Cells Improve Survival and Bacterial Clearance in Neonatal Sepsis in Rats.

Sepsis is the main cause of morbidity and mortality in neonates. Mesenchymal stromal cells (MSCs) are potent immune-modulatory cells. Their effect in neonatal sepsis has never been explored. We hypothesized that human umbilical cord-derived MSCs (hUC-MSCs) improve survival in experimental neonatal sepsis. Sepsis was induced in 3-day-old rats by intravenous injection of Escherichia coli (5 × 105/rat). One hour after infection, rats were treated intravenously with normal saline, hUC-MSCs, or with interferon-γ preconditioned hUC-MSCs (107 cells/kg). Eighteen hours after infection, survival, bacterial counts, lung neutrophil and macrophage influx, phagocytosis and apoptosis of splenocytes plasma, and LL-37 concentration were evaluated. Animals were observed for survival for 72 h after E. coli injection. Treatment with either hUC-MSCs or preconditioned hUC-MSCs significantly increased survival (hUC-MSCs, 81%; preconditioned hUC-MSCs, 89%; saline, 51%; P < 0.05). Both hUC-MSCs and preconditioned hUC-MSCs enhanced bacterial clearance. Lung neutrophil influx was decreased with preconditioned hUC-MSCs. The number of activated macrophages (CD206+) in the spleen was increased with hUC-MSCs and preconditioned hUC-MSCs; preconditioned hUC-MSCs increased the phagocytic activity of CD206+ macrophages. hUC-MSCs and preconditioned hUC-MSCs decreased splenocyte apoptosis in E. coli infected rats. Finally, LL-37 plasma levels were elevated in neonatal rats treated with hUC-MSCs or preconditioned hUC-MSCs. hUC-MSCs enhance survival and bacterial clearance in experimental neonatal sepsis. hUC-MSCs may be an effective adjunct therapy to reduce neonatal sepsis-related morbidity and mortality.

Nasal Intermittent Positive Pressure Ventilation for Preterm Neonates: Synchronized or Not?

Although continuous positive airway pressure (CPAP) is an effective strategy to prevent invasive ventilation, failure rates are high and many babies require endotracheal intubation. Prolonged exposure to mechanical ventilation is linked with bronchopulmonary dysplasia and other morbidities. Different techniques of nasal intermittent positive pressure ventilation (NIPPV) have been proposed as an alternative to CPAP. Bilevel NIPPV and conventional mechanical ventilator-driven NIPPV are used in clinical practice. Both methods differ substantially in pressures and cycling times, potentially affecting their mechanism of action. This review focuses on noninvasive ventilation strategies, their physiologic effects, impact on clinical outcome parameters, and effects of synchronization.