Reliability of IL-6 Alone and in Combination for Diagnosis of Late Onset Sepsis: A Systematic Review.

Diagnosis of neonatal sepsis is difficult due to nonspecific signs and symptoms. Interleukin-6 (IL-6) is a promising marker for neonatal sepsis. We aimed to test the accuracy of IL-6 in neonates after 72 h of life in case of late onset sepsis (LOS). We searched for studies regarding IL-6 accuracy for the diagnosis of LOS between 1990 and 2020 using the PubMed database. Following study selection, the reported IL-6 sensitivities and specificities ranged between 68% and 100% and 28% and 100%, with median values of 85.7% and 82% and pooled values of 88% and 78% (respectively) in the 15 studies including 1306 infants. Subgroup analysis revealed a better sensitivity (87% vs. 82%), but not specificity (both 86%), in preterm infants compared to term infants or mixed populations. Early sample collection revealed the highest sensitivity (84%), but had the lowest specificity (86%). To assess quality, we used a STARD checklist adapted for septic neonates and the QUADAS criteria. Limitations of this review include the heterogeneous group of studies on the one side and the small number of studies on the other side that analyzed different combinations of biomarkers. We concluded that IL-6 demonstrated good performance especially in the preterm infant population and the best results were achieved by measurements at the time of LOS suspicion.

Respiratory Syncytial Virus and Influenza During the COVID-19 Pandemic: A Two-center Experience.

BACKGROUND: The aim of the study was to determine the burden of respiratory syncytial virus (RSV) and influenza disease during the COVID-19 pandemic at 2 Austrian urban pediatric centers between October 1, 2019 and April 30, 2022. METHODS: We performed a retrospective observational 2-center study on RSV- and influenza virus-associated hospitalizations in infants and children up to 18 years at the University Hospital of Graz and the Clinic Donaustadt of Vienna from October 1, 2019 to April 30, 2022. Hospitalization had to be associated with the infectious disease, proven by polymerase chain reaction, including presence of respiratory symptoms. Demographic data including underlying diseases and treatment strategies were compared between centers and diseases, respectively. RESULTS: There were 826 cases in Graz and 379 in Vienna with significant more RSV cases in Graz and more influenza cases in Vienna (RSV: 76% vs. 59%, influenza: 24% vs. 41%; both P < 0.001). One death occurred in Graz due to RSV and another due to influenza in Vienna. Seasonality only slightly differed between centers and severity of diseases was not aggravated when measured by pediatric intensive care unit admission rates, need for supplemental oxygen and respiratory support between first and last seasons. Treatment regimen differed regarding higher use of antibiotics and rates of intravenous fluids in Vienna compared to higher rates of bronchodilators, corticosteroids and nose drops in Graz. CONCLUSIONS: We observed higher numbers of hospitalizations due to both viruses after the lockdown but not increased severity of the diseases; and mortality remained extremely low. Preventive measures should be implemented with high priority especially focused on infants with underlying diseases.

Diagnosis of Neonatal Sepsis: The Role of Inflammatory Markers.

This is a narrative review on the role of biomarkers in the diagnosis of neonatal sepsis. We describe the difficulties to obtain standardized definitions in neonatal sepsis and discuss the limitations of published evidence of cut-off values and their sensitivities and specificities. Maternal risk factors influence the results of inflammatory markers as do gestational age, the time of sampling, the use of either cord blood or neonatal peripheral blood, and some non-infectious causes. Current evidence suggests that the use of promising diagnostic markers such as CD11b, CD64, IL-6, IL-8, PCT, and CRP, either alone or in combination, might enable clinicians discontinuing antibiotics confidently within 24-48 h. However, none of the current diagnostic markers is sensitive and specific enough to support the decision of withholding antibiotic treatment without considering clinical findings. It therefore seems to be justified that antibiotics are often initiated in ill term and especially preterm infants. Early markers like IL-6 and later markers like CRP are helpful in the diagnosis of neonatal sepsis considering the clinical aspect of the neonate, the gestational age, maternal risk factors and the time (age of the neonate regarding early-onset sepsis) of blood sampling.

Long-term Follow-up of Preterm Infants Having Been Colonized With Extended Spectrum Beta-lactamase-producing Enterobacterales Over the First 6 Years of Life.

We performed a retrospective case-control cohort study following 146 preterm infants (≤32 weeks of gestation) who had been colonized with extended spectrum beta-lactamase producing Enterobacterales and compared them with 1:1 matched controls regarding rates of hospitalizations and outpatient visits because of infectious and gastrointestinal diseases and developmental impairment up to school age. Preterm infants with extended spectrum beta-lactamase producing Enterobacterales colonization did have neither higher rates of gastrointestinal or infectious diseases nor higher rates of developmental impairments up to the age of 6 years.

Extended-spectrum beta-lactamase (ESBL) producing Enterobacterales in stool surveillance cultures of preterm infants are no risk factor for necrotizing enterocolitis: a retrospective case-control study over 12 years.

PURPOSE: Microbial dysbiosis has been found preceding necrotizing enterocolitis (NEC) in preterm infants; thus, we aimed to investigate whether there is evidence that neonates with extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) positive stool cultures are at higher risk for NEC at the NICU. METHODS: We included very preterm inborn infants of ≤ 32 weeks of gestational age being fecal carriers of ESBL-E and compared them with 1:1 matched (gestational age, birth weight, gender and year) controls tested negative for ESBL-E in the stool between 2005 and 2016. An association with NEC was defined as the first detection of ESBL-E before or at the time of definite diagnosis of NEC. RESULTS: During the study period, we diagnosed 217 infants with a total of 270 ESBL-E. We identified ten different species with ESBL-producing Klebsiella oxytoca being the most common one (46%) followed by Klebsiella pneumoniae (19%), and Citrobacter freundii (17%). Ten out of 217 infants had any kind of NEC in the case group compared to two of the controls (p < 0.01), but only four cases with predefined criteria were associated with NEC ≥ stage IIa (1.8 vs. 0.5%, p = 0.089, OR 4.1, CI95% 0.45-36.6). NEC mortality rate was 2/8 (25%). CONCLUSIONS: We observed a threefold increase of ESBL-E in stool surveillance cultures during study time and germs were dominated by ESBL-producing Klebsiella spp. There was no evidence that preterm infants colonized with ESBL-E in the stool were at higher risk for definite NEC.

Epidemiology of Respiratory Syncytial Virus-related Hospitalizations and the Influence of Viral Coinfections in Southern Austria in a 7-year Period.

OBJECTIVE: The aim of this study was to determine the respiratory syncytial virus (RSV) epidemiology and to analyze the influence of risk factors and coinfections over the last years. METHODS: Retrospectively all infants, children and adolescents hospitalized due to respiratory disease with positive RSV test [hospitalized for RSV infection (RSV-H)] between January 1, 2009, and December 31, 2015, at a tertiary care center in the southern part of Austria were included for analysis. Patients were all identified by a search via International Classification of Diseases and Related Health Problems, 10th Edition codes, and all medical data were collected from the local electronic databases called openMedocs. RSV tests had to prove true infection case definition. RESULTS: During a 7-year study period, 745 infants, children and adolescents exhibited RSV-H. Main diagnosis was bronchiolitis (70%). Nearly half of all cases (44%) were born during the first half of the RSV season (November-January), and seasonal peak of RSV-H was in January. Predominant underlying condition was history of prematurity in 15% followed by neurologic impairment (3.5%) and hemodynamically significant congenital heart disease (2.95%). Age ≤2 months and underlying conditions/morbidities were associated with more severe disease. The majority of cases (96%) had an age below 24 months, and 91% below 12 months. Viral coinfection (most common influenza virus, adenovirus and rhinovirus) was diagnosed in 37 cases (5%) resulting in a more severe course of disease. Main risk factors of coinfection were siblings and crowding. Mortality was 0.27% (2/745). Both children had coinfection with influenza A virus and were multihandicapped (15 and 20 years of age, respectively). CONCLUSIONS: Prematurity and underlying morbidities play a marked role in RSV-H. Viral coinfections aggravated disease with death in 2 multihandicapped adolescents.

Neonatal Extracorporeal Membrane Oxygenation Due to Respiratory Failure: A Single Center Experience Over 28 Years.

Background: ECMO therapy is worldwide declining in the neonatal population; hence, its therapeutic value is sometimes questioned. Objectives: To report our experience with neonatal ECMO due to respiratory failure over a 28 year time period. Methods: Retrospective single center observational study including all neonates admitted to ECMO due to respiratory failure between 1989 and 2016 at Graz, Austria. Data were collected regarding survival rate, duration of ECMO, complications, length of hospital stay, changes over time, and follow-up. Results: Sixty-seven neonates were admitted and 43 (64%) needed ECMO-median birth weight 3390 grams (range 1810-4150) and gestational age 39 weeks (32-43). Survival rate was 65% (28/43); with higher rates in meconium aspiration syndrome (MAS) 89% vs. congenital diaphragmatic hernia (CDH) 46% and septic shock 44% (p = 0.005 and p = 0.006, respectively). ECMO duration was median 5 days (1-30) and veno-arterial ECMO (52%) dominated. Need for ECMO therapy decreased over time (p < 0.001). Complications occurred in 31 (72%) neonates. Five neonates had cerebral hemorrhages (11.4%) and four had cerebral infarction (9.1%). Of 26 survivors 17 (65%) showed normal neurodevelopmental outcome at median follow-up of 73 months. Motor deficits were present in one case, cognitive deficits in 9 (35%). Median length of hospital stay was 78 days in those with deficits and 29 in those with normal neurodevelopmental outcome (p < 0.001). Conclusions: Survival rate did not change over the study time but indications for ECMO did. Cognitive impairment was the major long-term deficit following neonatal ECMO being associated with longer hospital stay.

Neonatal thrombocytopenia-causes and outcomes following platelet transfusions.

We evaluated the causes for neonatal thrombocytopenia (NT), the duration of NT, and the indications of platelet transfusions (PT) by means of a retrospective cohort study over a 23-year period. Neonates with NT were identified via ICD-10 code D69.6. Of 371 neonates (1.8/1000 live births) with NT, the majority (312; 84.1%) had early onset thrombocytopenia, and 282 (76%) were preterm born. The most frequent causes for NT were early and late onset sepsis and asphyxia. The mean duration of thrombocytopenia was 10.2 days and was negatively correlated (KK = - 0.35) with the number of PT. PT were given to 78 (21%) neonates, 38 (49%) of whom had very severe NT. The duration of NT was positively related to the severity of NT and the number of subsequent PT. A mortality rate of 10.8% was significantly associated with bleeding signs (p < 0.05) and correlated with increasing number of PT (p < 0.05) but not with the severity of NT (p = 0.4). In the case of relevant hemorrhage, PT did not influence the mortality rate (p = 0.09). All deaths followed neonatal sepsis. CONCLUSIONS: Prematurity and diagnoses including early and late onset sepsis and asphyxia were the most common causes of NT. Mortality was not associated with the severity of NT but increased with the number of PT. What is Known: • The causes for neonatal thrombocytopenia (NT) are well known. • The effects of platelet transfusions (PT) and its indications are still a matter of debate and recommendations differ widely. What is New: • The duration of NT is positively related to the severity of NT and the number of subsequent PT. • The mortality rate is not associated with the severity of NT but increases with increasing numbers of PT and in the case of relevant intraventricular hemorrhage (≥ grade II), PT does not influence the mortality rate.

Preeclampsia and Long-term Renal Function in Women Who Underwent Kidney Transplantation.

OBJECTIVE: Preeclampsia often complicates pregnancies after maternal kidney transplantation. We aimed to assess whether preeclampsia is associated with kidney function decline either during the pregnancy or in the long term. METHODS: We performed an international multicenter retrospective cohort study. Renal function at conception, pregnancy outcomes, and short- and long-term graft outcomes were collected for women who were pregnant after renal transplantation and had transplant and obstetric care at the participating centers. In women who had multiple pregnancies during the study period, only the last pregnancy was included. Univariate and multivariable analyses were performed. RESULTS: We retrieved pregnancy outcomes and long-term renal outcomes for 52 women. Chronic hypertension was present at baseline in 27%. Mean estimated glomerular filtration rate (GFR) at start of pregnancy was 52.4±17.5 mL/min/1.73 m. Mean estimated GFR at delivery was 47.6±21.6 mL/min/1.73 m, which was significantly lower than at conception (P=.03). Twenty women (38%) developed preeclampsia. In multivariable analysis, women who developed preeclampsia had a 10.7-mL/min/1.73 m higher drop in estimated GFR between conception and delivery than women who did not develop preeclampsia (P=.02). Long-term estimated GFR follow-up was obtained at a median of 5.8 years (range 1.3-27.5 years). Mean estimated GFR at last follow-up was 38±23 mL/kg/1.73 m. Seventeen women (33%) experienced graft loss over the follow-up period. Incidence of graft loss was similar in women with and without preeclampsia in their last pregnancy (30% and 34%, respectively; P=.99). In multivariable analysis, the decrease in estimated GFR between conception and last follow-up was similar in women who experienced preeclampsia during pregnancy and those who did not (difference -2.69 mL/min/1.73 m, P=.65). CONCLUSION: Preeclampsia commonly complicates pregnancies after renal transplantation but is not associated with long-term renal dysfunction or graft loss.

Quality of Life of Children with Cystic Periventricular Leukomalacia - A Prospective Analysis with the Child Health Questionnaire-Parent Form 50.

OBJECTIVE: Cystic periventricular leukomalacia (PVL) is associated with moderate to severe physical and mental handicaps in preterm infants. We hypothesized whether or not those handicaps were associated with a poorer quality of life (QOL) of affected children and their families compared to matched controls. PATIENTS AND METHODS: All children with the diagnosis PVL collected from a local database of the Division of Neonatology of the Medical University of Graz, Austria, and born between 1997 and 2008 were included in the study group. Preterm infants matched for gestational age, birth weight, year of birth, and gender without PVL served as controls. Selected perinatal data and neurological outcome were documented. The interview of the parents was conducted using the Child Health Questionnaire-Parent Form 50 (CHQ-PF50), German version. The CHQ-PF50 consists of 50 items divided over 11 multi-item scales and 2 single-item questions. RESULTS: The CHQ-PF50 was answered by 21 parents of the study (26%) and 44 of the control (39%) group. Cases were diagnosed as having developmental delay, dystonia, strabismus, central visual impairment, seizures, and cerebral palsy (81 vs. 7%, p < 0.001) more common than controls. Analysis of the CHQ-PF 50 revealed significantly poorer results for cases regarding physical health (physical functioning: p < 0.001, physical social limitations: p < 0.001, and physical summary score: p < 0.001). Several psychosocial categories (behavior, mental health, and self-esteem) and the psychosocial summary score did not differ between groups. Only two categories (parental impact concerning time p = 0.004 and family activities: p = 0.026) revealed significantly poorer results in the cases as it was for the global category for health (p = 0.009). CONCLUSION: Children with PVL had an overall poorer QOL regarding physical aspects. However, PVL was not generally associated with a poorer QOL regarding psychosocial aspects.

The whole spectrum of cystic periventricular leukomalacia of the preterm infant: results from a large consecutive case series.

PURPOSE: The purpose of this study is to describe features of cystic periventricular leukomalacia (PVL) in a large consecutive cohort study including long-term neurodevelopmental follow-up. METHODS: We performed a retrospective single-centre cohort study including all preterm infants ≤35 weeks of gestational age with PVL diagnosed by ultrasound scans (US) from a tertiary care university hospital between 1988 and 2012. RESULTS: The majority of 160 consecutively diagnosed cases had a gestational age between 28 and 32 weeks (60.6%), and male sex was predominant (60.6%). The most common associated clinical findings included respiratory distress syndrome, preterm premature rupture of the membranes, and chorioamnionitis (57.5, 49.4, and 39.4%, respectively). Infants presented with apnoeas in 66.3 and neonatal seizures in 23.1%. Any kind of respiratory support was present in 75.0%. Associated low-grade intraventricular haemorrhage was evident in 33.1, high-grade haemorrhage in 9.4%. Cysts were located on both hemispheres in 75% and PVL grades 3 and 4 were predominant (75.6%). Neurodevelopmental follow-up of 146 cases at a median age of 72 months revealed normal development in 11.0, mental retardation in 50.0, and cerebral palsy in 83.6%. Visual impairment was diagnosed in 21.9% and hearing impairment in one case. A quarter of cases (27.4%) developed seizure disorders. Outcome data were significantly better in unilateral compared to bilateral PVL. CONCLUSIONS: Long-term neurodevelopmental outcome of bilateral PVL always was adverse and different from unilateral PVL. The latter might be negatively influenced by associated intra- and periventricular haemorrhages.

Should respiratory care in preterm infants include prophylaxis against respiratory syncytial virus infection? The case in favour.

Respiratory syncytial virus (RSV) is the most significant cause of acute respiratory tract infections (RTI) in infants and young children throughout the world. Preterm infants are at increased risk for severe RSV lower respiratory tract infection due to small lung volumes, a reduced lung surface area, small airways and an increased air space wall thickness. Additionally, the airways of preterm infants have been ventilated mechanically and suctioned and potentially damaged by many microtraumas with disruption of endothelial surfaces enabling pathogens to invade more easily. The immune system of preterm infants is immature resulting in low antibody titers (incomplete transplacental transfer of maternal antibodies) and a reduced cellular immunity with reduced viral clearance. Rehospitalization rates of preterm compared to term infants due to RSV infection are increased as are total morbidity and mortality associated with RSV disease. Palivizumab effectively reduces RSV related rehospitalisation in this high-risk population.

[Life threatening secondary bacterial infection of varicella skin lesions]. / Lebensbedrohliche bakterielle Infektionen ausgehend von Varizellen Hautläsionen.

As immunization coverage of varicella vaccination is low, the disease is still very frequent in Austria. Albeit the prognosis in general is good, the incidence of varicella-related hospitalization is about 6 per 100,000 in all children between 0-15 years of age, affecting mainly previously healthy children. Especially young children under the age of 5 are at risk with highest rates among children younger than one year. The most common complications are secondary bacterial infections, neurological and respiratory complications. Two cases of life threatening secondary bacterial infection are presented. One child suffered from a Toxic Shock Syndrome caused by group A streptococcus along with large necrotizing skin lesions. The second child nearly lost her left eye due to a deep orbital abscess. Both children survived without severe sequelae but had to undergo several procedures of plastic surgery. Implementation of the varicella vaccination program in the USA has shown a near elimination of deaths due to severe varicella complications. The initiation of the varicella vaccination program for children until the age of 2 in Austria should be considered to prevent complications and deaths caused by varicella.