Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.

Congenital Chylothorax of the Newborn: A Systematic Analysis of Published Cases between 1990 and 2018.

BACKGROUND: Congenital chylothorax (CCT) of the newborn is a rare entity but the most common cause of pleural effusion in this age-group. We aimed to find the optimal treatment strategy. MATERIAL AND METHODS: A PubMed search was performed according to the PRISMA criteria. All cases were analyzed according to prenatal, perinatal, and postnatal treatment modalities and follow-ups. RESULTS: We identified 753 cases from 157 studies published between 1990 and 2018. The all-cause mortality rate was 28%. Prematurity was present in 71%, male gender dominated 57%, mean gestational age was 34 weeks, and birth weight was 2,654 g. Seventy-nine percent of newborns had bilateral CCT, the most common associated congenital anomalies with CCT were pulmonary lymphangiectasia and pulmonary hypoplasia, and the most common chromosomal aberrations were Down, Noonan, and Turner syndromes, respectively. Mechanical ventilation was reported in 381 cases for mean 17 (range 1-120) days; pleural punctuations and drainages were performed in 32% and 64%, respectively. Forty-four percent received total parenteral nutrition (TPN) for mean 21 days, 46% medium-chain triglyceride (MCT) diet for mean 37 days, 20% octreotide, and 3% somatostatin; chemical pleurodesis was performed in 116 cases, and surgery was reported in 48 cases with a success rate of 69%. In 462 cases (68%), complete restitution was reported; in 34 of 44 cases (77%), intrauterine intervention was carried out. CONCLUSION: Respiratory support, pleural drainages, TPN, and MCT diet as octreotide remain to be the cornerstones of CCT management. Pleurodesis with OK-432 done prenatally and povidone-iodine postnatally might be discussed for use in life-threatening CCT.

Ethical Issues and Management of Fetal Hemolytic Anemia Caused by Anti-Rh17 in a Multipara with Rare -D- Phenotype.

BACKGROUND: The development of allo-anti-Rh17 (anti-Hr0) in a -D- phenotype whose red blood cells (RBCs) lack CcEe antigens is most likely triggered by transfusion, transplantation, or pregnancy. Gene conversion is the predominating factor in generating RHD-CE-D and RHCE-D-CE hybrids like -D-. METHODS: We report here immunohematological and obstetrical data from 2 of the 5 pregnancies of a 24-year-old woman presenting with the -D- phenotype with anti-Rh17. Blood group typing, antibody screening, antibody differentiation, direct antiglobulin test (DAT), and antibody titers were performed by routine gel technology and tube testing. Additionally, molecular genetic analysis was performed. Fetal surveillance was done by sonographic evaluation of the fetal middle cerebral artery peak systolic velocity (MCA-PSV). RESULTS: Blood group typing showed O, C-c-D+E-e- and the DAT was negative. DNA sequencing revealed homozygosity for an RHCE-D(3-9)-CE null allele. Anti-Rh17 titers in the fourth pregnancy remained between 1:8 and 1:128, and no signs for a fetal anemia were observed. However, in the fifth pregnancy, the antibody titers increased up to 1:4,096. Signs of moderate fetal anemia were detected and cesarean section was performed at 34 + 6 weeks of gestation. The newborn presented with hemolytic anemia (cord blood hemoglobin [Hb] = 8.5 mg/dL). She received 2 compatible (small) packed RBC concentrates, phototherapy, and intravenous immunoglobulins. CONCLUSION: Our case shows that the risk for hemolytic complications increases with the number of pregnancies of sensitized women. Only people who also lack CcEe antigens are compatible as donors. The role of such rare donors as lifesavers, their freedom, and voluntariness conflict with the urgent need for compatible blood.

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.

Expert consensus on palivizumab use for respiratory syncytial virus in developed countries.

Respiratory syncytial virus (RSV) infection is a leading cause of hospitalisation in early childhood and palivizumab is the only licensed intervention for prevention. Palivizumab guidelines should reflect the latest evidence, in addition to cost-effectiveness and healthcare budgetary considerations. RSV experts from Europe, Canada and Israel undertook a systematic review of the evidence over the last 5 years and developed recommendations regarding prophylaxis in industrialised countries. Almost 400 publications were reviewed. This group recommended palivizumab for: preterm infants (<29 and ≤31 weeks gestational age [wGA] and ≤9 and ≤6 months of age, respectively; high-risk 32-35wGA), former preterm children ≤24 months with chronic lung disease/bronchopulmonary dysplasia, children ≤24 months with significant congenital heart disease; and other high-risk populations, such as children ≤24 months with Down syndrome, pulmonary/neuromuscular disorders, immunocompromised, and cystic fibrosis. Up to 5 monthly doses should be administered over the RSV season. It is our impression that the adoption of these guidelines would help reduce the burden of RSV.

Histological demonstration of BSEP/ABCB11 inhibition in transient neonatal cholestasis: a case report.

BACKGROUND: Idiopathic or transient neonatal cholestasis (TNC) represents a group of cholestatic disorders with unidentified origin and remains a diagnosis of exclusion. Dysfunction of hepatobiliary transporters mediating excretion of biliary constituents from hepatocytes may play a central role in the pathogenesis of cholestasis. Despite variants of bile salt (BS) export pump (BSEP/ABCB11) have already been described in TNC, the pathogenic role of BSEP dysfunction in TNC remained so far elusive. CASE PRESENTATION: We report on a newly-identified heterozygous ABCB11 missense variant (c.1345G > A, p.Glu449Lys) which was associated with prolonged cholestasis in a term infant after a complicated neonatal period. Moreover, we show for the first time almost completely abolished BSEP expression on the hepatocellular membrane in TNC. CONCLUSION: This report demonstrates for the first time a close association between the prolonged cholestasis in infancy and impaired BSEP expression on the hepatocyte canalicular membrane in a heterozygous carrier of newly-identified ABCB11 variant.

Respiratory Syncytial Virus Associated Hospitalizations in Infants of 33 to 42 Weeks' Gestation: Does Gestational Age Matter?

BACKGROUND: To evaluate rates and characteristics of respiratory syncytial virus hospitalizations (RSV-H) in infants of 33 to 42 weeks of gestational age (GA). PATIENTS: All infants with a history of neonatal hospitalization and a GA of 33 to 42 weeks born between 2005 and 2015 and follow-up at least over one RSV season (first year of life). Infants with congenital heart disease and other congenital anomalies were excluded. METHODS: Retrospective single-center cohort STROBE compliant study. Data were collected regarding demographic data and re-hospitalization characteristics due to respiratory illness and due to RSV infection; and data were compared between moderate-late preterm, near term, term, and post term infants, respectively. RESULTS: A total of 81.656 live born infants were registered in our catchment area with gestational age from 33 to 42 weeks during the study period; and 2188 of 2356 preterm infants and 1004 of 1168 term infants with history of neonatal hospitalization were included for analysis. Rehospitalizations due to respiratory illness occurred in 301 preterm (13.8%) and 136 term (13.5%) infants for 381 and 183 times, respectively. In total 84 of 3192 infants (2.6%) were tested RSV positive, 61 of 2188 preterm (2.8%) and 23 of 1004 term (2.3%). Preterm infants without history of neonatal hospitalization had a RSV hospitalization (RSV-H) rate of 1.7% (61/3488) and term infants of 1.3% (967/74.644) that were significantly lower compared to study infants (p=0.004 and 0.002, respectively). Moderate and late preterm (2.8%), near term (3.1%) and post term (3.5%) infants had significantly higher RSV-H rates compared to term infants (1.2%). Risk factors for RSV-H in preterm infants included discharge during RSV season (4.2 vs. 2.0%, p=0.017) and presence of older siblings (4.2 vs. 2.1%, p=0.023), in term infants presence of older siblings (p=0.019). The course of RSV disease did not differ between groups. DISCUSSION: Interestingly, we did not observe decreasing RSV-H rates with increasing GA. Term infants represented the group with lowest RSV-H rates. Neonatal hospitalization was a risk factor for RSV-H for both preterm and term infants. Near term infants do more resemble the late preterm than term infants regarding RSV-H rates. CONCLUSION: We found comparable higher RSV-H rates in all groups compared to term infants without differences in the course of disease and identified neonatal hospitalization as an independent risk factor.

Bronchopulmonary dysplasia in very preterm infants: Outcome up to preschool age, in a single center of Austria.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is the most frequent chronic lung disease in infancy and is associated with neonatal comorbidity and impairment in pulmonary and neurodevelopmental (ND) long-term outcome. METHODS: This was a retrospective, single-center, cohort study to compare a cohort of very preterm infants (gestational age [GA], 24+0 -28+6 weeks) with BPD (n = 44), with a cohort of GA-matched preterm infants without BPD (n = 44) with regard to neonatal morbidity, incidence of lower respiratory tract infection (LRTI), ND outcome and growth to 2 years' corrected age (CA) and preschool age. RESULTS: Bronchopulmonary dysplasia (incidence, 11.3%) was associated with a higher rate of neonatal pneumonia (26% vs 7%, P = 0.001), longer total duration of mechanical ventilation (mean days, 21 vs 13, P < 0.001), and a higher rate of pulmonary hypertension (20.5% vs 0%, P = 0.002) and of severe retinopathy of prematurity (13.6% vs 0%, P = 0.026). Incidence of LRTI was significantly higher in the BPD infants (50% vs 26%, P = 0.025). ND outcome did not differ between the two groups. Growth at neonatal intensive care unit discharge was similar. In the BPD cohort, rate of weight < 10th percentile was higher at 2 years' CA (52% vs 30%, P = 0.041) and rate of head circumference < 10th percentile was higher at preschool age (59% vs 27%, P = 0.028). CONCLUSION: Neonatal respiratory morbidity was significantly higher in the BPD cohort, but long-term ND outcome did not differ. Infants with BPD had poorer growth.

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.

Nosocomial Outbreak of Parechovirus 3 Infection among Newborns, Austria, 2014.

In 2014, sepsis-like illness affected 9 full-term newborns in 1 hospital in Austria. Although results of initial microbiological testing were negative, electron microscopy identified picornavirus. Archived serum samples and feces obtained after discharge were positive by PCR for human parechovirus 3. This infection should be included in differential diagnoses of sepsis-like illness in newborns.

Neonatal Ureaplasma urealyticum colonization increases pulmonary and cerebral morbidity despite treatment with macrolide antibiotics.

OBJECTIVE: To evaluate the influence of Ureaplasma urealyticum (UU) colonization on neonatal pulmonary and cerebral morbidity. METHODS: Single-center case-control study including all preterm infants with positive UU tracheal colonization between 1990 and 2012. Cases were matched with controls by birth year, gestational age, birth weight, and sex. All cases had received macrolide antibiotics for UU infection starting at the time of first positive culture results from tracheal aspirates. Main outcome parameters included presence and severity of hyaline membrane disease (IRDS), duration of ventilation, bronchopulmonary dysplasia at 36 postmenstrual age and neurological morbidities (seizures, intra-/periventricular hemorrhages-I/PVH, periventricular leukomalacia-PVL). RESULTS: Of 74 cases identified 8 died and 4 had to be excluded; thus, 62 preterm infants were compared to 62 matched controls. UU was significantly associated with IRDS (79 vs. 61 %, p = 0.015), BPD (24 vs. 6 %, p = 0.003), seizures (23 vs. 5 %, p = 0.002) and I/PVH (45 vs. 24 %, p = 0.028). Cases had longer duration of mechanical ventilation and total duration of invasive and non-invasive ventilation (median 11 vs. 6 days p = 0.006 and 25 vs. 16.5 days p = 0.019, respectively). CONCLUSION: UU was found to be significantly associated with pulmonary short- and long-term morbidity and mild cerebral impairment despite treatment with macrolide antibiotics.

Successful Unrelated Stem Cell Transplantation in an Infant With Congenital Acute Myelogenous Leukemia FAB M5 Showing Massive Cutaneous Infiltrations--A Challenging Multidisciplinary Approach.

The multidisciplinary management of a male neonate presenting with congenital acute myelogenous leukemia of monoblastic phenotype is reported using conventional chemotherapy, high dose conditioning, and matched unrelated donor stem cell transplantation. These therapies were combined to add a graft versus leukemia effect to the treatment. Although chimerism studies showed a decrease of donor white blood cells, T-cells remained stable of allogeneic origin. We hypothesize that a continuous graft versus leukemia effect results in minimal residual disease negativity for now more than 18 months since stem cell transplantation.

Fetal and early neonatal interleukin-6 response.

In 1998, a systemic fetal cytokine response, defined as a plasma interleukin-6 (IL-6) value above 11 pg/mL, was reported to be a major independent risk factor for the subsequent development of neonatal morbid events even after adjustments for gestational age and other confounders. Since then, the body of literature investigating the use of blood concentrations of IL-6 as a hallmark of the fetal inflammatory response syndrome (FIRS), a diagnostic marker of early-onset neonatal sepsis (EONS) and a risk predictor of white matter injury (WMI), has grown rapidly. In this article, we critically review: IL-6 biological functions; current evidence on the association between IL-6, preterm birth, FIRS and EONS; IL-6 reference intervals and dynamics in the early neonatal period; IL-6 response during the immediate postnatal period and perinatal confounders; accuracy and completeness of IL-6 diagnostic studies for EONS (according to the Standards for Reporting of Diagnostic Accuracy statement); and recent breakthroughs in the association between fetal blood IL-6, EONS, and WMI.

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.

Severe primary pulmonary lymphangiectasis in a premature infant: management and follow up to early childhood.

Primary pulmonary lymphangiectasis (PPL) is a rare congenital developmental abnormality of the lung with a generally poor prognosis. Only a limited number of patients with neonatal-onset PPL have been reported to survive. We present the case of a male preterm infant (gestational age 34 weeks 6 days) with histologically confirmed PPL, complicated by hydrops fetalis, bilateral hydrothorax (treated in utero with pleuro-amniotic shunts), and immediate respiratory distress at birth. He survived after extensive neonatal intensive care therapy and was discharged home at the age of 7 months. At last follow up he was 3 years 7 months old, still requiring assisted ventilation via tracheostomy, having recurrent episodes of wheezing and had mild global developmental delay. This case demonstrates that survival beyond the neonatal period is possible even with severe PPL but long-term morbidity may be relevant, and multidisciplinary management and close follow up are essential.

Congenital pulmonary lymphangiectasis.

Congenital pulmonary lymphangiectasis (CPL) is a rare vascular malformation causing dilated lymph vessels and disturbed drainage of lymph fluid. Based on the pathogenesis and clinical phenotype it can be classified as primary or secondary CPL. Associated genetic syndromes with or without lymphedema, familial occurrence and gene mutations have been described. In utero, it may present as non-immune hydrops with pleural effusions. At birth neonates may have respiratory failure due to chylothorax and pulmonary hypoplasia, causing very high short term mortality rates. Other cases may become symptomatic any time later in childhood or even during adult life. CPL is usually diagnosed based on the combination of clinical signs, imaging and histological findings. Open-lung biopsy is considered the gold standard for the diagnosis of CPL. Treatment is primarily supportive featuring aggressive mechanical ventilation and the management of problems associated with congenital chylothorax including chest-drainage, medium-chain triglycerides (MCT) diet, and octreotide.

Cord blood procalcitonin and Interleukin-6 are highly sensitive and specific in the prediction of early-onset sepsis in preterm infants.

We studied the predictive value of cord blood procalcitonin (PCT) and interleukin-6 (IL-6) in the diagnosis of early-onset sepsis (EOS) in the preterm infant. Retrospectively, PCT and IL-6 were correlated with clinical and/or blood culture positive EOS and negative infectious status between February 2008 and March 2011. Receiver operating curves (ROC) were generated and the area under the curve (AUC) was calculated by use of Youden's Index to detect the best cut-off values for sensitivity and specificity. Thirty of 218 preterm infants (13.8%) were diagnosed as having EOS. The optimal cut-off value for PCT was 0.235 µg/L (sensitivity 78.6%, specificity 86.3%), and for IL-6 15.85 ng/L (sensitivity 73.7%, specificity 84.2%), the combination of PCT and IL-6 revealed sensitivity 77.1% and specificity 91.7%. The combined determination of PCT and IL-6 from cord blood was highly sensitive and specific in the prediction of EOS.

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.