Therapeutic hypothermia for encephalopathic newborns with congenital heart defect: A cross-sectional survey on current practices and opinions in Germany

BACKGROUND Therapeutic hypothermia (TH) reduces neonatal mortality and long-term neurodevelopmental impairment in infants with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) caused by perinatal asphyxia. There is an increasing trend to apply TH in other indications and populations, such as infants with mild HIE or neonates with congenital heart defects (CHD), even though there is little evidence to support or refute this. OBJECTIVE The aim of this survey was to analyze practice variations with respect to TH use in neonates with CHD and to assess expert opinions on this topic across tertiary neonatal departments in Germany. METHODS/DESIGN A web-based survey was sent to all tertiary neonatal departments in Germany. The questionnaire contained 32 multiple-choice questions. The survey inquired current practices on TH in newborns with CHD and expert opinions on various clinical scenarios. MAIN RESULTS A total 80 (51.3%) neonatal departments partially completed the survey, and 69 (44.2%) respondents filled out the whole questionnaire. All 80 (100.0%) departments perform TH. TH is offered by 76 (95.0%) respondents to encephalopathic newborns with simple CHD. In infants with critical/complex CHD, TH is offered after perinatal asphyxial HIE and in newborns with encephalopathy after severe acidosis associated with cardiac complications by 25 (31.3%), or 17 (22.1%) respondents, respectively, whereas a clear majority of centers reject TH in these infants. Unclear effects of TH on any ongoing prostaglandin therapy (57.6 and 52.3%, respectively), an increased risk for adverse reactions during TH (51.6 and 52.3%, respectively) and lack of evidence (33.3 and 53.8%, respectively) are the most frequently cited reasons for not performing TH in these infants. The majority of experts from neonatal departments providing comprehensive care for neonates with severe CHD support the initiation of TH in encephalopathic neonates. DISCUSSION The considerable heterogeneity in the use of TH in neonates with CHD emphasizes the need for further research to optimize treatment strategies for these patients

Trends in Apgar scores and umbilical artery pH: a population-based cohort study on 10,696,831 live births in Germany, 2008-2022

Low Apgar scores and low umbilical arterial (UA) blood pH are considered indicators of adverse perinatal events. This study investigated trends of these perinatal health indicators in Germany. Perinatal data on 10,696,831 in-hospital live births from 2008 to 2022 were obtained from quality assurance institutes. Joinpoint regression analysis was used to quantify trends of low Apgar score and UA pH. Additional analyses stratified by mode of delivery were performed on term singletons with cephalic presentation. Robustness against unmeasured confounding was analyzed using the E-value sensitivity analysis. The overall rates of 5-min Apgar scores < 7 and UA pH < 7.10 in liveborn infants were 1.17% and 1.98%, respectively. For low Apgar scores, joinpoint analysis revealed an increase from 2008 to 2011 (annual percent change (APC) 5.19; 95% CI 3.66-9.00) followed by a slower increase from 2011 to 2019 (APC 2.56; 95% CI 2.00-3.03) and a stabilization from 2019 onwards (APC - 0.64; 95% CI - 3.60 to 0.62). The rate of UA blood pH < 7.10 increased significantly between 2011 and 2017 (APC 5.90; 95% CI 5.15-7.42). For term singletons in cephalic presentation, the risk amplification of low Apgar scores was highest after instrumental delivery (risk ratio 1.623, 95% CI 1.509-1.745), whereas those born spontaneous had the highest increase in pH < 7.10 (risk ratio 1.648, 95% CI 1.615-1.682). CONCLUSION: Rates of low 5-min Apgar scores and UA pH in liveborn infants increased from 2008 to 2022 in Germany. What is Known: • Low Apgar scores at 5 min after birth and umbilical arterial blood pH are associated with adverse perinatal outcomes. • Prospective collection of Apgar scores and arterial blood pH data allows for nationwide quality assurance. What is New: • The rates of liveborn infants with 5-min Apgar scores < 7 rose from 0.97 to 1.30% and that of umbilical arterial blood pH < 7.10 from 1.55 to 2.30% between 2008-2010 and 2020-2022. • In spontaneously born term singletons in cephalic presentation, the rate of metabolic acidosis with pH < 7.10 and BE < -5 mmol/L in umbilical arterial blood roughly doubled between the periods 2008-2010 and 2020-2022

Analgosedation for less-invasive surfactant administration: Variations in practice

BACKGROUND Less-invasive surfactant administration (LISA) is widely used for surfactant delivery to spontaneously breathing preterm infants on nasal CPAP. However, the use of analgesia and/or sedation for the LISA procedure remains controversial. METHODS We conducted a cross-sectional survey of all tertiary neonatal intensive care units (NICUs) in Austria, Germany, and Switzerland to assess current practices of analgosedation for LISA in preterm infants. RESULTS Eighty-eight of 172 (51.2%) NICUs responded to the survey, of which 83 (94.3%) perform LISA. Analgosedation for LISA is used in 60 (72.3%) NICUs. Twenty-eight of those (46.7%) have unit protocols to guide analgosedation while 32 (53.3%) administer medication at the discretion of the attending physician. Ketamine (45.0% of NICUs), propofol (41.7%), fentanyl (21.7%), morphine (20.0%), and midazolam (20.0%) were most frequently used for analgosedation for LISA. Nine (10.7%) NICUs reported the use of pain or distress scores during LISA. CONCLUSION LISA is well established among tertiary NICUs in the German-speaking countries. However, there are considerable variations regarding the use of analgosedation. More evidence is required to guide clinicians seeking to safely and effectively deliver surfactant via a thin catheter to spontaneously breathing preterm infants

Effects of Poly(ADP-Ribose) Polymerase-1 Inhibition in a Neonatal Rodent Model of Hypoxic-Ischemic Injury

Background. Hypoxia ischemia (HI) to the developing brain occurs in 1–6 in 1000 live births. Large numbers of survivors have neurological long-term sequelae. However, mechanisms of recovery after HI are not understood and preventive measures or clinical treatments are not effective. Poly(ADP-ribose) polymerase-1 is overactivated in response to ischemia. In neonatal mice HI activates PARP-1 but its role in perinatal brain injury remains uncertain. Objective. Aim of this study was to explore the effect of TES448 (PARP-1-inhibitor) and hypothermia after an ischemic insult. Design and Methods. 10-day-old Wistar rats underwent HI. TES448 was given 10 min, 3 hrs, and 6 hrs after hypoxia. Hypothermia was started 30 min after HI and brains were dissected at P12. Western blotting and histological staining were used to evaluate for degree of injury. Results. Protein expression of PARP-1 levels was diminished after TES448 treatment. Cresyl violet and TUNEL staining revealed decreased injury in male rat pups following TES448 and combined treatment. Female rats showed increased numbers of TUNEL-positive cells after combined therapy. TES448 inhibited microglia activation after hypoxic-ischemic injury. A cellular response including NeuN, Olig2, and MBP was not affected by PARP-1-inhibition. Conclusions. Inhibition of PARP-1 and hypothermia lead to an alteration of injury but this effect is sexually dimorphic

Effects of repetitive exposure to pain and morphine treatment on the neonatal rat brain

Background: Untreated exposure to pain in preterm neonates might damage the vulnerable premature brain and alter development. Pain treatment is limited because analgesic agents may also have adverse neurodevelopmental consequences in newborns. Objective: To study the effects of neonatal pain and morphine treatment on the developing brain in a n

MUSiC : a model-unspecific search for new physics in proton-proton collisions at root s=13TeV

Results of the Model Unspecific Search in CMS (MUSiC), using proton-proton collision data recorded at the LHC at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 35.9 fb(-1), are presented. The MUSiC analysis searches for anomalies that could be signatures of physics beyond the standard model. The analysis is based on the comparison of observed data with the standard model prediction, as determined from simulation, in several hundred final states and multiple kinematic distributions. Events containing at least one electron or muon are classified based on their final state topology, and an automated search algorithm surveys the observed data for deviations from the prediction. The sensitivity of the search is validated using multiple methods. No significant deviations from the predictions have been observed. For a wide range of final state topologies, agreement is found between the data and the standard model simulation. This analysis complements dedicated search analyses by significantly expanding the range of final states covered using a model independent approach with the largest data set to date to probe phase space regions beyond the reach of previous general searches.Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV