Single-Cell RNA Sequencing Reveals Repair Features of Human Umbilical Cord Mesenchymal Stromal Cells.

RATIONALE: The chronic lung disease bronchopulmonary dysplasia (BPD) is the most severe complication of extreme prematurity. BPD results in impaired lung alveolar and vascular development and long-term respiratory morbidity, for which only supportive therapies exist. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) improve lung structure and function in experimental BPD. Results of clinical trials with MSCs for many disorders do not yet match the promising preclinical studies. A lack of specific criteria to define functionally distinct MSCs persists. OBJECTIVES: To determine and correlate single-cell UC-MSC transcriptomic profile with therapeutic potential. METHODS: UC-MSCs from five term donors and human neonatal dermal fibroblasts (HNDFs, control cells of mesenchymal origin) transcriptomes were investigated by single-cell RNA sequencing analysis (scRNA-seq). The lung-protective effect of UC-MSCs with a distinct transcriptome and control HNDFs was tested in vivo in hyperoxia-induced neonatal lung injury in rats. MEASUREMENTS AND MAIN RESULTS: UC-MSCs showed limited transcriptomic heterogeneity, but were different from HNDFs. Gene ontology enrichment analysis revealed distinct - progenitor-like and fibroblast-like - UC-MSC subpopulations. Only the treatment with progenitor-like UC-MSCs improved lung function and structure and attenuated pulmonary hypertension in hyperoxia-exposed rat pups. Moreover, scRNA-seq identified major histocompatibility complex class I as a molecular marker of non-therapeutic cells and associated with decreased lung retention. CONCLUSIONS: UC-MSCs with a progenitor-like transcriptome, but not with a fibroblast-like transcriptome, provide lung protection in experimental BPD. High expression of major histocompatibility complex class I is associated with reduced therapeutic benefit. scRNA-seq may be useful to identify subsets of MSCs with superior repair capacity for clinical application.

Evaluation of the telemedical health care network "SAFE BIRTH" for pregnant women at risk, premature and sick newborns and their families: study protocol of a cluster-randomized controlled stepped-wedge trial.

BACKGROUND: The Perinatal Center of the University Hospital Carl Gustav Carus Dresden has initiated the telemedical healthcare network "SAFE BIRTH" to coordinate and improve specialized care in non-metropolitan regions for pregnant women and newborns. The network incorporates five intervention bundles (IB): (1) Multi-professional, inter-disciplinary prenatal care plan; (2) Neonatal resuscitation; (3) Neonatal antibiotic stewardship; (4) Inter-facility transfer of premature and sick newborns; (5) Psycho-social support for parents. We evaluate if the network improves care close to home for pregnant women, premature and sick newborns. METHODS: To evaluate the complex healthcare intervention "SAFE BIRTH" we will conduct a cluster-randomized controlled stepped-wedge trial in five prenatal medical outpatient offices and eight non-metropolitan hospitals in Saxony, Germany. The offices and hospitals will be randomly allocated to five respectively eight sequential steps over a 30-month period to implement the telemedical IB. We define one specific primary process outcome for each IB (for instance IB#1: "Proportion of patients with inclusion criterion IB#1 who have a prenatal care plan and psychosocial counseling within one week"). We estimated a separate multilevel logistic regression model for each primary process outcome using the intervention status as a regressor (control or intervention group). Across all IB, a total of 1,541 and 1,417 pregnant women or newborns need to be included in the intervention and control group, respectively, for a power above 80% for small to medium intervention effects for all five hypothesis tests. Additionally, we will assess job satisfaction and sense of safety of health professionals caring for newborns (questionnaire survey) and we will assess families' satisfaction, resilience, quality of life and depressive, anxiety and stress symptoms (questionnaire surveys). We will also evaluate the cost-effectiveness of "SAFE BIRTH" (statutory health insurance routine data, process data) and barriers to its implementation (semi-structured interviews). We use multilevel regression models adjusting for relevant confounders (e.g. socioeconomic status, age, place of residence), as well as descriptive analyses and qualitative content analyses. DISCUSSION: If the telemedical healthcare network "SAFE BIRTH" proves to be effective and cost-efficient, strategies for its translation into routine care should be developed. TRIAL REGISTRATION: German clinical trials register. DRKS-ID: DRKS00031482.

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.

[Perinatal Networks: Ensuring Regional Care of Pregnant Woman and Newborns]. / Perinatologische Kompetenznetzwerke: Die Versorgung von Schwangeren und Neugeborenen in einer Region.

Health care of pregnant women and their newborns is facing major challenges due to the decline in birth rate and shortage of specialists. In the current discussion about future concepts, the centralization associated with minimum quantities and the necessary safeguarding of care in the area are often construed as conflicting goals. Instead, concepts are needed to guarantee that pregnant women and their children will continue to receive care close to home. The example of the saxony center for feto/neonatal health is used to show how partners in a region can jointly ensure care during pregnancy, birth and the neonatal period on a supra-local and cross-hospital basis. The close cooperation of maximum care providers with regional partners enables comprehensive health care. At the same time, this cooperation enables hospitals to remain attractive employers in structurally weak regions and to provide comprehensive care for young families in need of medical services related to pregnancy and birth through good family and social integration close to home and work. The overriding goals of the saxony center for feto/neonatal health are optimal, guideline-based, interdisciplinary and intersectoral care of pregnant women and premature or sick newborns in the region.

COVID-19, Pregnancy, and Diabetes Mellitus.

During the severe acute respiratory distress virus coronavirus type 2 (SARS-CoV-2) pandemic, many women were infected during their pregnancies. The SARS-CoV-2-induced coronavirus disease 19 (COVID-19) has an impact on maternal health and pregnancy outcomes; peripartum and perinatal morbidity and mortality are increased. Pregnancy is considered a risk factor for severe COVID-19 course. Additional risk factors during pregnancy are diabetes mellitus, gestational diabetes mellitus (GDM), and obesity. Systemic inflammation can lead to severe metabolic dysregulation with ketoacidosis. The endocrine pancreas is a target organ for SARS-CoV-2 and the fetal risk depends on inflammation of the placenta. Up to now there is no evidence that SARS-CoV-2 infection during pregnancy leads to permanent diabetes in mothers or their offspring via triggering autoimmunity or beta cell destruction. The frequently observed increased prevalence of GDM compared to the years before the pandemic is most likely due to changed lifestyle during lockdown. Furthermore, severe COVID-19 may be associated with the development of GDM due to worsening of glucose tolerance. Vaccination with a mRNA vaccine is safe and highly effective to prevent infection and to reduce hospitalization. Registries support offering evidence-based recommendations on vaccination for pregnant women. Even with the current omicron virus variant, there are increased risks for symptomatic and unvaccinated pregnant women.

Post-COVID in women after SARS-CoV-2 infection during pregnancy - a pilot study with follow-up data from the COVID-19-related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Pregnant women are at an increased risk of severe COVID-19 and adverse pregnancy outcomes; data on maternal long-term outcome is scarce. We analyzed long-term follow-ups on women who experienced a SARS-CoV-2 infection during pregnancy to evaluate post-COVID symptoms, particularly fatigue, and their association with quality of life (QoL). METHODS: 773 women who enrolled in the CRONOS registry between April 2020 and August 2021 were contacted for follow-up from December 2022 to April 2023. Data was gathered through a web-based questionnaire. Subsequently, study coordinators matched the follow-up data with the existing CRONOS data. RESULTS: 110/773 (14%) women provided data. 20.9% experienced only acute symptoms during their SARS-CoV-2 infection in pregnancy, while 2.7% women experienced symptoms lasting longer than 4 weeks (long COVID). Symptoms lasting longer than 12 weeks (post-COVID) were reported by 63.6% women and occurred more often after severe COVID-19. Fatigue was the most frequently reported symptom (88%), with 55% of women still experiencing it more than one year after initial infection. 76% of women rated their QoL as "good" or "very good". Women experiencing post-COVID reported a significantly lower QoL. CONCLUSION: This is the first German long-term data on women after SARS-CoV-2 infection during pregnancy, showing a high rate of post-COVID, a persistence of fatigue, and the impact on QoL. Continuous monitoring of pregnant women with COVID-19 is needed to develop comprehensive management strategies.

Functional morphometry: non-invasive estimation of the alveolar surface area in extremely preterm infants.

BACKGROUND: The main pathophysiologic characteristic of chronic respiratory disease following extremely premature birth is arrested alveolar growth, which translates to a smaller alveolar surface area (SA). We aimed to use non-invasive measurements to estimate the SA in extremely preterm infants. METHODS: Paired measurements of the fraction of inspired oxygen and transcutaneous oxygen saturation were used to calculate the ventilation/perfusion ratio, which was translated to SA using Fick's law of diffusion. The SA was then adjusted using volumetric capnography. RESULTS: Thirty infants with a median (range) gestational age of 26.3 (22.9-27.9) weeks were studied. The median (range) adjusted SA was 647.9 (316.4-902.7) cm2. The adjusted SA was lower in the infants who required home oxygen [637.7 (323.5-837.5) cm2] compared to those who did not [799.1 (444.2-902.7) cm2, p = 0.016]. In predicting the need for supplemental home oxygen, the adjusted SA had an area under the receiver operator characteristic curve of 0.815 (p = 0.017). An adjusted SA ≥688.6 cm2 had 86% sensitivity and 77% specificity in predicting the need for supplemental home oxygen. CONCLUSIONS: The alveolar surface area can be estimated non-invasively in extremely preterm infants. The adjusted alveolar surface area has the potential to predict the subsequent need for discharge home on supplemental oxygen. IMPACT: We describe a novel biomarker of respiratory disease following extremely preterm birth. The adjusted alveolar surface area index was derived by non-invasive measurements of the ventilation/perfusion ratio and adjusted by concurrent measurements of volumetric capnography. The adjusted alveolar surface area was markedly reduced in extremely preterm infants studied at 7 days of life and could predict the need for discharge home on supplemental oxygen. This method could be used at the bedside to estimate the alveolar surface area and provide an index of the severity of lung disease, and assist in monitoring, clinical management and prognosis.

Predicting adverse outcomes in pregnant patients positive for SARS-CoV-2: a machine learning approach- a retrospective cohort study.

BACKGROUND: Pregnant people are particularly vulnerable to SARS-CoV-2 infection and to ensuing severe illness. Predicting adverse maternal and perinatal outcomes could aid clinicians in deciding on hospital admission and early initiation of treatment in affected individuals, streamlining the triaging processes. METHODS: An international repository of 1501 SARS-CoV-2-positive cases in pregnancy was created, consisting of demographic variables, patient comorbidities, laboratory markers, respiratory parameters, and COVID-19-related symptoms. Data were filtered, preprocessed, and feature selection methods were used to obtain the optimal feature subset for training a variety of machine learning models to predict maternal or fetal/neonatal death or critical illness. RESULTS: The Random Forest model demonstrated the best performance among the trained models, correctly identifying 83.3% of the high-risk patients and 92.5% of the low-risk patients, with an overall accuracy of 89.0%, an AUC of 0.90 (95% Confidence Interval 0.83 to 0.95), and a recall, precision, and F1 score of 0.85, 0.94, and 0.89, respectively. This was achieved using a feature subset of 25 features containing patient characteristics, symptoms, clinical signs, and laboratory markers. These included maternal BMI, gravidity, parity, existence of pre-existing conditions, nicotine exposure, anti-hypertensive medication administration, fetal malformations, antenatal corticosteroid administration, presence of dyspnea, sore throat, fever, fatigue, duration of symptom phase, existence of COVID-19-related pneumonia, need for maternal oxygen administration, disease-related inpatient treatment, and lab markers including sFLT-1/PlGF ratio, platelet count, and LDH. CONCLUSIONS: We present the first COVID-19 prognostication pipeline specifically for pregnant patients while utilizing a large SARS-CoV-2 in pregnancy data repository. Our model accurately identifies those at risk of severe illness or clinical deterioration, presenting a promising tool for advancing personalized medicine in pregnant patients with COVID-19.

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.

Gestational diabetes mellitus and COVID-19: results from the COVID-19-Related Obstetric and Neonatal Outcome Study (CRONOS).

BACKGROUND: Gestational diabetes mellitus is one of the most frequent pregnancy complications with a global prevalence of 13.4% in 2021. Pregnant women with COVID-19 and gestational diabetes mellitus are 3.3 times more likely to be admitted to an intensive care unit than women without gestational diabetes mellitus. Data on the association of gestational diabetes mellitus with maternal and neonatal pregnancy outcomes in pregnant women with SARS-CoV-2 infection are lacking. OBJECTIVE: This study aimed to investigate whether gestational diabetes mellitus is an independent risk factor for adverse maternal and fetal and neonatal outcomes in pregnant women with COVID-19. STUDY DESIGN: The COVID-19-Related Obstetric and Neonatal Outcome Study is a registry-based multicentric prospective observational study from Germany and Linz, Austria. Pregnant women with clinically confirmed COVID-19 were enrolled between April 3, 2020, and August 24, 2021, at any stage of pregnancy. Obstetricians and neonatologists of 115 hospitals actively provided data to the COVID-19-Related Obstetric and Neonatal Outcome Study. For collecting data, a cloud-based electronic data platform was developed. Women and neonates were observed until hospital discharge. Information on demographic characteristics, comorbidities, medical history, COVID-19-associated symptoms and treatments, pregnancy, and birth outcomes were entered by the local sites. Information on the periconceptional body mass index was collected. A primary combined maternal endpoint was defined as (1) admission to an intensive care unit (including maternal mortality), (2) viral pneumonia, and/or (3) oxygen supplementation. A primary combined fetal and neonatal endpoint was defined as (1) stillbirth at ≥24 0/7 weeks of gestation, (2) neonatal death ≤7 days after delivery, and/or (3) transfer to a neonatal intensive care unit. Multivariable logistic regression analysis was performed to evaluate the modulating effect of gestational diabetes mellitus on the defined endpoints. RESULTS: Of the 1490 women with COVID-19 (mean age, 31.0±5.2 years; 40.7% nulliparous), 140 (9.4%) were diagnosed with gestational diabetes mellitus; of these, 42.9% were treated with insulin. Overall, gestational diabetes mellitus was not associated with an adverse maternal outcome (odds ratio, 1.50; 95% confidence interval, 0.88-2.57). However, in women who were overweight or obese, gestational diabetes mellitus was independently associated with the primary maternal outcome (adjusted odds ratio, 2.69; 95% confidence interval, 1.43-5.07). Women who were overweight or obese with gestational diabetes mellitus requiring insulin treatment were found to have an increased risk of a severe course of COVID-19 (adjusted odds ratio, 3.05; 95% confidence interval, 1.38-6.73). Adverse maternal outcomes were more common when COVID-19 was diagnosed with or shortly after gestational diabetes mellitus diagnosis than COVID-19 diagnosis before gestational diabetes mellitus diagnosis (19.6% vs 5.6%; P<.05). Maternal gestational diabetes mellitus and maternal preconception body mass index of ≥25 kg/m2 increased the risk of adverse fetal and neonatal outcomes (adjusted odds ratio, 1.83; 95% confidence interval, 1.05-3.18). Furthermore, overweight and obesity (irrespective of gestational diabetes mellitus status) were influential factors for the maternal (adjusted odds ratio, 1.87; 95% confidence interval, 1.26-2.75) and neonatal (adjusted odds ratio, 1.81; 95% confidence interval, 1.32-2.48) primary endpoints compared with underweight or normal weight. CONCLUSION: Gestational diabetes mellitus, combined with periconceptional overweight or obesity, was independently associated with a severe maternal course of COVID-19, especially when the mother required insulin and COVID-19 was diagnosed with or after gestational diabetes mellitus diagnosis. These combined factors exhibited a moderate effect on neonatal outcomes. Women with gestational diabetes mellitus and a body mass index of ≥25 kg/m2 were a particularly vulnerable group in the case of COVID-19.

Realistic 3D infant head surfaces augmentation to improve AI-based diagnosis of cranial deformities.

Evaluation of the head shape of newborns is needed to detect cranial deformities, disturbances in head growth, and consequently, to predict short- and long-term neurodevelopment. Currently, there is a lack of automatic tools to provide a detailed evaluation of the head shape. Artificial intelligence (AI) methods, namely deep learning (DL), can be explored to develop fast and automatic approaches for shape evaluation. However, due to the clinical variability of patients' head anatomy, generalization of AI networks to the clinical needs is paramount and extremely challenging. In this work, a new framework is proposed to augment the 3D data used for training DL networks for shape evaluation. The proposed augmentation strategy deforms head surfaces towards different deformities. For that, a point-based 3D morphable model (p3DMM) is developed to generate a statistical model representative of head shapes of different cranial deformities. Afterward, a constrained transformation approach (3DHT) is applied to warp a head surface towards a target deformity by estimating a dense motion field from a sparse one resulted from the p3DMM. Qualitative evaluation showed that the proposed method generates realistic head shapes indistinguishable from the real ones. Moreover, quantitative experiments demonstrated that DL networks training with the proposed augmented surfaces improves their performance in terms of head shape analysis. Overall, the introduced augmentation allows to effectively transform a given head surface towards different deformity shapes, potentiating the development of DL approaches for head shape analysis.

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.

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.

A critical appraisal of tools for delivery room assessment of the newborn infant.

Assessment of an infant's condition in the delivery room represents a prerequisite to adequately initiate medical support. In her seminal paper, Virginia Apgar described five parameters to be used for such an assessment. However, since that time maternal and neonatal care has changed; interventions were improved and infants are even more premature. Nevertheless, the Apgar score is assigned to infants worldwide but there are concerns about low interobserver reliability, especially in preterm infants. Also, resuscitative interventions may preclude the interpretation of the score, which is of concern when used as an outcome parameter in delivery room intervention studies. Within the context of these changes, we performed a critical appraisal on how to assess postnatal condition of the newborn including the clinical parameters of the Apgar score, as well as selected additional parameters and a proposed new scoring system. The development of a new scoring system that guide clinicians in assessing infants and help to decide how to support postnatal adaptation is discussed. IMPACT: This critical paper discusses the reliability of the Apgar score, as well as additional parameters, in order to improve assessment of a newborn's postnatal condition. A revised neonatal scoring system should account for infant maturity and the interventions administered. Delivery room assessment should be directed toward determining how much medical support is needed and how the infant responds to these interventions.

Are birth outcomes in low risk birth cohorts related to hospital birth volumes? A systematic review.

BACKGROUND: There is convincing evidence that birth in hospitals with high birth volumes increases the chance of healthy survival in high-risk infants. However, it is unclear whether this is true also for low risk infants. The aim of this systematic review was to analyze effects of hospital's birth volume on mortality, mode of delivery, readmissions, complications and subsequent developmental delays in all births or predefined low risk birth cohorts. The search strategy included EMBASE and Medline supplemented by citing and cited literature of included studies and expert panel highlighting additional literature, published between January/2000 and February/2020. We included studies which were published in English or German language reporting effects of birth volumes on mortality in term or all births in countries with neonatal mortality < 5/1000. We undertook a double-independent title-abstract- and full-text screening and extraction of study characteristics, critical appraisal and outcomes in a qualitative evidence synthesis. RESULTS: 13 retrospective studies with mostly acceptable quality were included. Heterogeneous volume-thresholds, risk adjustments, outcomes and populations hindered a meta-analysis. Qualitatively, four of six studies reported significantly higher perinatal mortality in lower birth volume hospitals. Volume-outcome effects on neonatal mortality (n = 7), stillbirths (n = 3), maternal mortality (n = 1), caesarean sections (n = 2), maternal (n = 1) and neonatal complications (n = 1) were inconclusive. CONCLUSION: Analyzed studies indicate higher rates of perinatal mortality for low risk birth in hospitals with low birth volumes. Due to heterogeneity of studies, data synthesis was complicated and a meta-analysis was not possible. Therefore international core outcome sets should be defined and implemented in perinatal registries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42018095289.

[Association between Socioeconomic Status and Developmental Status: Data Linkage of Results of the Daycare and School Entry Health Examinations of a Saxon Birth Cohort Study]. / Zusammenhang zwischen sozioökonomischem Status und Entwicklungsstand ­ Datenlinkage von Ergebnissen der Kita- und Schulaufnahmeuntersuchung mit einer sächsischen Geburtskohortenstudie.

BACKGROUND: Child development is determined by both biological (e. g. gender, natal maturity) and psychosocial (e. g. socioeconomic status, daycare) factors. OBJECTIVES: To examine how familial socioeconomic status (SES) as well as biological and other psychosocial factors are associated with the state of development of 4- and 6-year-old children. METHODS: Data linkage of primary data from a birth cohort study and routine data from the Saxon public health departments on children born between 2007 and 2008, who underwent both daycare health examination and school entry health examination (N=615), was used to examine speech and motor skills, both fine and gross, for associations with psychosocial and biological factors. Potential associations were tested for significance and shown as odds ratios by using binary logistic regression. RESULTS: There were no noticeable problems in the development of the majority of Saxon children until school entry. Nevertheless, language seems to be a sensitive area of development, since 37% of the children showed problems at both time-points. Furthermore boys, preterm infants and children from a lower socio-economic class were more often affected by developmental delays, with preterm infants with low SES being at very high risk. Furthermore, the point of time of entering daycare seems to be of relevance for child development. CONCLUSIONS: The results are in line with national and international findings. An important new finding is the significantly increased likelihood of having developmental problems when biological and psychosocial risk factors coincide. However, longitudinal analyses are required to study developmental courses and to evaluate measures initiated to combat these issues.

[Newborn resuscitation and support of transition of infants at birth]. / Versorgung und Reanimation des Neugeborenen nach der Geburt: Leitlinien des European Resuscitation Council 2021.

The European Resuscitation Council has produced these newborn life support guidelines, which are based on the International Liaison Committee on Resuscitation (ILCOR) 2020 Consensus on Science and Treatment Recommendations (CoSTR) for Neonatal Life Support. The guidelines cover the management of the term and preterm infant. The topics covered include an algorithm to aid a logical approach to resuscitation of the newborn, factors before delivery, training and education, thermal control, management of the umbilical cord after birth, initial assessment and categorisation of the newborn infant, airway and breathing and circulation support, communication with parents, considerations when withholding and discontinuing support.

Delivery Room Management of Infants with Very Low Birth Weight in 3 European Countries-The Video Apgar Study.

OBJECTIVE: To assess delivery room management of infants born preterm at 4 Level III perinatal centers in 3 European countries. STUDY DESIGN: This was a prospective, multicenter observational study. Management at birth was video-recorded and evaluated (Interact version 9.6.1; Mangold-International, Arnstorf, Germany). Data were analyzed and compared within and between centers. RESULTS: The infants (n = 138) differed significantly with respect to the median (25%, 75%) birth weight (grams) (Center A: 1200 [700, 1550]; Center B: 990 [719, 1240]; Center C: 1174 [835, 1435]; Center D: 1323 [971, 1515] [B vs A, C, D: P < .05]), gestational week (Center A: 28.4 [26.3, 30.0]; Center B: 27.9 [26.7, 29.6]; Center C: 29.3 [26.4, 31.0]; Center D: 30.3 [28.0, 31.9]), Apgar scores, rates of cesarean delivery, and time spent in the delivery room. Management differed significantly for frequency and drying time, rates of electrocardiographic monitoring, suctioning or stimulation, and for fundamental interventions such as time for achieving a reliable peripheral oxygen saturation signal (seconds) (Center A: 97.6 ± 79.3; Center B: 65.1 ± 116.2; Center C: 97.1 ± 67.0; Center D: 114.4 ± 140.5; B vs A, C, D: P < .001) and time for intubation (seconds) (Center A: 48.7 ± 4.2; Center B: 49.0 ± 30.7; Center C: 69.1 ±37.9; Center D: 65.1 ± 23.8; B vs D, P < .025). Mean procedural times did not meet guideline recommendations. The sequence of interventions was similar at all centers. CONCLUSIONS: The Video Apgar Study showed great variability in and between 4 neonatal centers in Europe. The study also showed it is difficult to adhere to published guidelines for recommended times for important, basic measures such as peripheral oxygen saturation measurements and intubation.