Morbidity of Respiratory Syncytial Virus (RSV) Infections: RSV Compared With Severe Acute Respiratory Syndrome Coronavirus 2 Infections in Children Aged 0-4 Years in Cologne, Germany.

The aim of this retrospective analysis was to provide information on how infections with respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in symptoms, clinical course, outcome, and utilization of hospital care. We investigated 748 polymerase chain reaction results from symptomatic children aged 0-4 years in Cologne, Germany. One hundred sixty-nine patients tested positive for RSV (22.6%) and 24 children for SARS-CoV-2 (3.2%). Symptomatic patients with RSV infection were hospitalized significantly longer. RSV-positive patients needed oxygen supplementation significantly more often as well as high-flow therapy. With regard to care efforts, RSV-infected patients put higher pressure on the hospital and utilized more hospital resources.

Outcome of extremely low gestational age newborns after introduction of a revised protocol to assist preterm infants in their transition to extrauterine life.

AIM: To evaluate the outcome of a cohort of extremely low gestational age newborn infants (ELGAN) below 26-week gestation who were treated following a revised, gentle delivery room protocol to assist them in the transition and adaptation to extrauterine life. METHODS: A cohort of infants with a gestational age (GA) below 26 weeks (study group; n = 164) was treated according to a revised delivery room protocol. The protocol included an optimized prenatal management, strict use of continuous positive airway pressure (CPAP), avoiding mechanical ventilation and early administration of surfactant without intubation. The parameters management of respiratory distress syndrome, survival, neonatal morbidity and neurodevelopmental outcome were compared with a historical control group (n = 44). RESULTS: Seventy-four per cent of the study group infants were initially treated with CPAP and surfactant administration without intubation. In comparison with the control group, significantly less children were intubated in the delivery room (24% vs. 41%) and needed mechanical ventilation (51% vs. 72%; both p < 0.05). Furthermore, compared with the historical control overall mortality (20% vs. 39%), rate of bronchopulmonary dysplasia (18% vs. 37%) and IVH > II° (10% vs. 33%) in survivors were significantly lower during the observational period (all p < 0.05). Neurodevelopmental outcome was normal in 70% of examined study group infants. CONCLUSIONS: A revised delivery room management protocol was applied safely to infants with a GA below 26 completed weeks with improved rates of survival and morbidity.

Clinical Aspects of the Subsequent SARS-CoV-2 Waves in Children from 2020 to 2022-Data from a Local Cohort in Cologne, Germany (n = 21,635).

Almost two and a half years after the appearance of the first cases of SARS-CoV-2 in December 2019, more than 500 million people have been infected with SARS-CoV-2 and over 6 million have died of it worldwide. In terms of the pediatric cohort, it already became evident at an early stage that the infection causes milder symptoms in children and rarely runs a fatal course. OBJECTIVE: This work presents data gathered over a period of over two years in patients between the age of 0 and 18 years. The aim is to provide information on the clinical aspects of the five different SARS-CoV-2 waves. METHODS: Between 13 March 2020 and 22 April 2022, all nucleic acid amplification tests (NAATs) of children who received a swab for SARS-CoV-2 at our clinic were included. Data were collected on standardized questionnaires. The analysis of the data was anonymized and retrospective. RESULTS: We investigated 21,635 NAATs, of which 1028 of the tests were positive (4.8%). The highest rate of positive results was observed in the fifth wave (541/2.292 NAATs (23.6%)). Most of the children who were hospitalized were hospitalized in wave three (22.9%). The availability of a vaccine was followed by a decrease in positive NAATs in the corresponding age group thereafter. CONCLUSIONS: These data underline the fact that children infected with SARS-CoV-2, regardless of which VOC, are often only mildly affected. Vaccinations seem to remain the key to avoid massive numbers of infected people and a potential collapse of the healthcare systems.

The Alpha Variant (B.1.1.7) of SARS-CoV-2 in Children: First Experience from 3544 Nucleic Acid Amplification Tests in a Cohort of Children in Germany.

In May 2021, the Alpha variant (B.1.1.7) of SARS-CoV-2 was found in 91% of the SARS-CoV-2 cases in Germany. Not much is known about the symptoms, courses of disease, and infectiousness in pediatric patients with the Alpha variant. OBJECTIVE: The aim of this retrospective analysis was to gain information on the infection with the Alpha variant in children and adolescents. METHODS: Between 12 January 2021 and 3 June 2021, all nucleic acid amplification tests (NAATs) of children who received a swab for SARS-CoV-2 were included. Data were collected on standardized questionnaires. The analysis of data was anonymized and retrospective. RESULTS: We investigated 3544 NAATs; 95 children were tested positive (2.7%) for SARS-CoV-2. For the sub-analysis, 65 children were analyzed. In 59 children, the Alpha variant was found (90.8%), and 54.2% (n = 32/59) were symptomatic. The most common symptoms were fever, cough, and rhinitis. The median Ct value was 24.0 (min 17.0; max 32.7). CONCLUSIONS: We can underline early findings that children are still less effected by SARS-CoV-2 infection with the spread of the Alpha variant. We found no evidence that children infected with the Alpha variant showed more severe symptoms or suffered from a more severe clinical course than those infected with the wild type.

PNPT1 mutations may cause Aicardi-Goutières-Syndrome.

BACKGROUND: Aicardi-Goutières syndrome (AGS) is a clinically and genetically heterogenous autoinflammatory disorder caused by constitutive activation of the type I interferon axis. It has been associated with the genes TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR1, IFIH1. The clinical diagnosis of AGS is usually made in the context of early-onset encephalopathy in combination with basal ganglia calcification or white matter abnormalities on cranial MRI and laboratory prove of interferon I activation. CASE PRESENTATION: We report a patient with early-onset encephalopathy, severe neurodevelopmental regression, progressive secondary microcephaly, epilepsy, movement disorder, and white matter hyperintensities on T2 weighted MRI images. Via whole-exome sequencing, we identified a novel homozygous missense variant (c.1399C > T, p.Pro467Ser) in PNPT1 (NM_033109). Longitudinal assessment of the interferon signature showed a massively elevated interferon score and chronic type I interferon-mediated autoinflammation. CONCLUSION: Bi-allelic mutations in PNPT1 have been reported in early-onset encephalopathy. Insufficient nuclear RNA import into mitochondria with consecutive disruption of the respiratory chain was proposed as the main underlying pathomechanism. Recent studies have shown that PNPT1 deficiency causes an accumulation of double-stranded mtRNAs in the cytoplasm, leading to aberrant type I interferon activation, however, longitudinal assessment has been lacking. Here, we present a case of AGS with continuously elevated type I interferon signature with a novel likely-pathogenic homozygous PNTP1 variant. We highlight the clinical value of assessing the interferon signature in children with encephalopathy of unknown origin and suggest all patients presenting with a phenotype of AGS should be screened for mutations in PNPT1.

Propofol as an induction agent for endotracheal intubation can cause significant arterial hypotension in preterm neonates.

BACKGROUND: Propofol is gaining increasing popularity as induction agent for pediatric endotracheal intubation. Recently, propofol has been described for the first time as induction agent for endotracheal intubation in preterm neonates. Propofol seemed to be efficient, safe and ideally suited for the INSURE (Intubation SURfactant Extubation) procedure in preterm neonates. The purpose of this study was to document intubating conditions, vital signs, extubation times and outcome in preterm neonates receiving propofol as induction agent for the INSURE procedure. PATIENTS AND METHODS: Preterm neonates with a gestational age of 29-32 weeks and respiratory distress were eligible for INSURE with propofol if their postnatal age was <8 h. Exclusion criteria were any kind of disease not allowing early extubation. RESULTS: There were 13 inborn neonates enrolled for INSURE, mean gestational age was 30 weeks + 3 days, and mean birth weight was 1428 g (range 1170-1780 g). We stopped our observational study ahead of time as a result of significant cardiovascular side effects. Propofol generally offered good intubating conditions, but we encountered severe problems with arterial hypotension. A low propofol bolus of 1 mg kg(-1) caused a distinctive decline in mean arterial blood pressure from 38 mmHg (range 29-42 mmHg) prior premedication to 24 mmHg (22-40 mmHg) 10 min after propofol application. CONCLUSIONS: Our experience with propofol as induction agent for endotracheal intubation in preterm neonates reveals distinctive cardiovascular effects, which represent an important risk factor for serious complications of prematurity like intraventricular hemorrhage or periventricular leucomalacia. Propofol should be used with caution in very preterm neonates with respiratory distress during the first hours of life.

Pain response to vaccination in newborn infants of diabetic mothers.

BACKGROUND: Response to pain is altered in infants who were exposed to pain- and stressful events in the neonatal period. Infants of diabetic mothers receive several heel sticks after birth for measuring blood glucose and thus may show changes in their behavioral and physiologic response to pain. Moreover, maternal hyperglycemia may alter activity of the hypothalamic pituitary adrenal (HPA) axis reactivity. STUDY DESIGN: In total, 43 infants of diabetic mothers and 30 control infants were included into the study. Response to pain was assessed at 3 months of age following two intramuscular injections for vaccination. We assessed behavioral (Bernese pain scale), physiologic (heart rate) and hormonal (salivary cortisol) pain response to vaccination as well as spinal sensitization (flexion withdrawal reflex). RESULTS: Infants of diabetic mothers received a median number of 5 [4-19] painful events compared to 1 [1-3] in the control group. Heart rate reactivity differed significantly between groups. Infants of diabetic mothers had higher peaks (p = 0.002) and needed more time to recover to baseline (p < 0.001). Moreover, infants of diabetic mothers showed higher peak cortisol (p = 0.001) and a higher relative cortisol increase (p = 0.015). Flexor withdrawal reflex thresholds were significantly lower in infants of diabetic mothers (p = 0.003). CONCLUSION: The increase of physiologic and hormonal responses to pain in infants of diabetic mothers is probably caused by repeated painful events and an altered metabolic profile.

Prospective evaluation of the pharmacodynamics of piritramide in neonates and infants.

Piritramide is a synthetic opioid commonly used in Germany and Austria for the analgesia of pediatric patients. Little pharmacokinetic and pharmacodynamic data for the pediatric population is available. The aim of this investigation was to gain pharmacodynamic data on postsurgical analgesia and the side effects of piritramide. The study was approved by the Ethics Committee of the Medical Faculty. Data were collected in an open, prospective clinical trial. After obtaining the parents' informed written consent, patients received a bolus of piritramide 50 mug/kg for postsurgical analgesia or to prevent pain resulting from invasive procedures. Titration doses of 15 microg/kg were allowed. Vital signs and pain intensity were closely monitored. Data from 39 patients could be included in the analysis. Of the patients, 95% were in the immediate postsurgical course, 5% had piritramide for invasive procedures, and 46% of the patients were ventilated. The mean piritramide dosage was 64 +/- 24 microg/kg. Pharmacodynamic analysis showed adequate analgesia for at least 50% of the spontaneously breathing patients for 120 min after piritramide bolus. More than 50% of the ventilated patients showed inadequate analgesia at any point in time after piritramide bolus. Fifty-nine percent (59%) of the ventilated patients received additive analgesia versus 31% of spontaneously breathing patients. No relevant changes of vital signs could be observed. One patient received naloxone for apnea. We conclude that dosages of more than 50-70 microg/kg are needed for sufficient analgesia in ventilated postsurgical infants. In spontaneously breathing patients, 50-70 microg/kg provides a 120-min period of analgesia for more than 50% of patients. Cardiovascular stability of the patients was good and, with one exception, there was no respiratory depression.