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.

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.

Clinical NEC prevention practices drive different microbiome profiles and functional responses in the preterm intestine.

Preterm infants with very low birthweight are at serious risk for necrotizing enterocolitis. To functionally analyse the principles of three successful preventive NEC regimens, we characterize fecal samples of 55 infants (<1500 g, n = 383, female = 22) longitudinally (two weeks) with respect to gut microbiome profiles (bacteria, archaea, fungi, viruses; targeted 16S rRNA gene sequencing and shotgun metagenomics), microbial function, virulence factors, antibiotic resistances and metabolic profiles, including human milk oligosaccharides (HMOs) and short-chain fatty acids (German Registry of Clinical Trials, No.: DRKS00009290). Regimens including probiotic Bifidobacterium longum subsp. infantis NCDO 2203 supplementation affect microbiome development globally, pointing toward the genomic potential to convert HMOs. Engraftment of NCDO 2203 is associated with a substantial reduction of microbiome-associated antibiotic resistance as compared to regimens using probiotic Lactobacillus rhamnosus LCR 35 or no supplementation. Crucially, the beneficial effects of Bifidobacterium longum subsp. infantis NCDO 2203 supplementation depends on simultaneous feeding with HMOs. We demonstrate that preventive regimens have the highest impact on development and maturation of the gastrointestinal microbiome, enabling the establishment of a resilient microbial ecosystem that reduces pathogenic threats in at-risk preterm infants.

Morbidities and rehospitalizations during the first year of life in moderate and late preterm infants: more similarities than differences?

BACKGROUND: The aim was to compare neonatal morbidities in moderate and late preterm infants and to analyze rates and causes for rehospitalizations during the first year of life. METHODS: Prospective follow-up of a group of moderate and late preterm infants at a tertiary care hospital. RESULTS: The study population comprised 215 infants (58% males; 60% singletons; 99 moderate and 116 late preterm infants) with a median gestational age of 34 weeks and birth weight of 2100 grams; 20% of them were small for gestational age. Moderate preterm infants more often had a diagnosis of mild respiratory distress syndrome (26% vs. 13%, P<0.01) and feeding problems with longer need for nasogastric tube feeding (median 9.5 vs. 4.2 days, P<0.01) and parenteral nutrition (3.5 vs. 2.7 days, P<0.01), and longer duration of stay at either NICU (10.6 vs. 3.7 days; P<0.01) or hospital (13 vs. 11 days; P<0.01). Fifty-two infants (24.3%) were hospitalized at 67 occasions without differences regarding readmission rates and causes between groups. Median age at readmission was 3 months, median stay 4 days. The most common diagnosis was respiratory illness (43.3%). CONCLUSIONS: Moderate preterm infants had more neonatal morbidities diagnosed, but the same rehospitalization rates than late preterm infants.

Reliability of Interleukin-6 Alone and in Combination for Diagnosis of Early Onset Neonatal Sepsis: Systematic Review.

Neonatal sepsis is a major cause of morbidity and mortality in both preterm and term infants. Early-onset neonatal sepsis (EONS) presents within the first 72 h of life. Diagnosis is difficult as signs and symptoms are non-specific, and inflammatory markers are widely used to confirm or rule out neonatal sepsis. Interleukin-6 (IL-6) is part of the fetal inflammatory response syndrome (FIRS) and therefore an interesting early marker for neonatal sepsis. The main objective for this review was to assess the diagnostic potential of IL-6, alone and in combination, for diagnosis of early neonatal sepsis (EONS) in term and preterm infants, in cord and peripheral blood, and in dependence of timing of sample collection. IL-6 diagnostic accuracy studies for diagnosing EONS published between 1990 and 2020 were retrieved using the PubMed database. We included 31 out of 204 articles evaluating the potential of IL-6 for the diagnosis of EONS in a study population of newborns with culture-proven and/or clinically suspected sepsis. We excluded articles dealing with neonatal bacterial infections other than sepsis and biomarkers other than inflammatory markers, those written in languages other than English or German, studies that did not distinguish between EONS and late-onset sepsis, and animal and in vitro studies. Full-text articles were checked for other relevant studies according to the PRISMA criteria. We identified 31 studies on IL-6 diagnostic accuracy for EONS diagnosis between 1990 and 2020 including a total of 3,276 infants. Sensitivity and specificity were reported, and subgroup analysis was performed. A STARD checklist adapted for neonates with neonatal sepsis was used for quality assessment. The range of IL-6 sensitivity and specificity in neonatal samples was 42.1-100% and 43-100%; the median values were 83 and 83.3%, respectively. IL-6 accuracy was better in preterm infants than in mixed-study populations. Early sample collection at the time of sepsis suspicion had the highest sensitivity when compared to other time points. Cord blood IL-6 had higher diagnostic value compared to peripheral blood. The biomarker combination of IL-6 and CRP was found to be highly sensitive, but poorly specific. Limitations of this review include use of only one database and inclusion of a heterogeneous group of studies and a small number of studies looking at biomarker combinations; a strength of this review is its focus on early-onset sepsis, since type of sepsis was identified as a significant source of heterogeneity in IL-6 diagnostic accuracy studies. We concluded that IL-6 has a good performance as an early diagnostic marker of EONS within a study population of preterm infants, with best results for cord blood IL-6 using cutoff values above 30 pg/ml.

How to Provide Breast Milk for the Preterm Infant and Avoid Symptomatic Cytomegalovirus Infection with Possible Long-Term Sequelae.

Cytomegalovirus (CMV) is able to replicate in the breast milk of lactating mothers and thus the offspring might be affected by mild to severe symptoms of postnatal CMV disease in case of prematurity; not in term infants. Sepsis-like syndrome affects only very low birth infants; and few cases have been reported. The neurodevelopmental long-term outcome of those preterm infants revealed possible subtle deficiencies, but no major neurodevelopmental impairment. Neurodevelopmental sequelae are still in discussion and seem somewhat overestimated after careful evaluation of the published evidence. The main focus of postnatal CMV disease lies upon the extremely low birth weight of infants. Elimination of CMV is provided by short-term heating methods like the most widely used Holder pasteurization. Freezing and thawing methods leave a risk for CMV acquisition. The benefits of untreated breast milk have to be considered to outweigh the possible sequelae of postnatal CMV infection in the most vulnerable preterm infants.

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.

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.

Prospective Randomized Observational Pilot Trial Evaluating the Effect of Information of Early Childhood Intervention on Stress Levels of Parents of Extremely Low Gestational Age Infants at the NICU.

It is not known to what extent early information on early childhood intervention (ECI) by ECI professionals reduces or increases stress levels of parents having an extremely preterm infant at the neonatal intensive care unit (NICU). Using an observational pilot study, we gave information on ECI in a randomized matter to parents of an extremely low gestational age newborn (ELGAN) at the chronological age of 3-4 weeks (cases) or not (controls). After informed consent, parents judged the infants at the age of 5-7 weeks with the Parental Stressor Scales: Neonatal Intensive Care Unit [PSS: NICU test has three subscales = "Sights and Sounds" (five items), "Parental Role Alteration" (14 items), and "Look and Behave" (seven items)]. Total scales score and subscales scores were comparable between 13 cases and 13 controls over a study period of 1.5 years. Total scores were 9.32 ± 0.72 in the cases compared to 10.02 ± 0.76 in the controls, (95% CI -6.93 to 4.93). Overall, the cases scored lower in most of the items. Early information on ECI at the NICU was provided to parents with an ELGAN did not result in higher stress levels measured with the PSS: NICU. Whether early information on ECI is a strategy, which might be able to reduce parental stress levels, has to be proven in larger studies.

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.

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.

Neurodevelopmental outcome of very preterm infants with gastrointestinal tract perforations does not differ compared to controls.

PURPOSE: To evaluate gastrointestinal tract (GIT) perforations in very low birth weight infants and the effects on neurodevelopmental outcome. METHODS: Between 2000 and 2017 all cases with GIT perforation were analyzed regarding causes, associated morbidities and neurodevelopmental outcome and compared with matched (gestational age, birth weight, gender, year of birth) by 1:2 controls. RESULTS: The incidence of GIT perforation was 2.0% (n = 38/1878). Diagnoses associated with GIT were meconium obstruction of prematurity (MOP,n = 19/50%), spontaneous intestinal perforation (SIP, n = 7/18%), necrotizing enterocolitis (NEC, n = 6/16%), iatrogenic perforation (n = 3/8%), volvulus (n = 2/5%) and meconium ileus (n = 1/3%). The NEC-associated perforations occurred later compared to those associated with MOP and SIP (median 8 days and 6 days vs. 17 days, p = 0.001 and 0.023, respectively) and main localization was the terminal ileum (84%). Cases had higher rates of late onset sepsis (55% vs. 24%, p = 0.003), longer duration of mechanical ventilation (median 30 days vs 18 days, p = 0.013) and longer stays at the hospital (median 122 days vs 83 days, p < 0.001); mortality rates did not differ. The 2­year neurodevelopment follow-up revealed no differences between groups (normal development 49% vs. 40%). CONCLUSION: Despite increased morbidities preterm infants with GIT perforation did not have a higher mortality rate and groups did not differ regarding neurodevelopmental outcome at the corrected for prematurity age of 2 years.

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.

Prospective Randomized Observational Pilot Trial Evaluating the Effect of Different Durations of Interdisciplinary Early Intervention and Family Support in Parents of Very Low Birth Weight Infants (Early Bird Study).

Background: Early childhood intervention (ECI) is a holistic approach for infants with or at risk for psychomotor and/or cognitive and/or behavioral impairment. It aims to optimally support them and positively influence their neurodevelopmental outcome. The right dosage of intervention and when the intervention should start are still to be determined. Hypothesis: Parents are more satisfied when the duration of ECI is longer (120 min once a week) than the usual 90-min session. Methods: We developed a parental questionnaire (both mother and father) that evaluated the level of satisfaction of parents with the intervention. We compared 120 with 90 min of ECI per week during the school year 2017/18. Included were parents of very low birth weight infants (<1,500 g) following informed consent. ECI was initiated at the NICU at an infant age of ≥ 2 weeks. Parents were randomized (https://www.randomizer.at/) to a 120- or 90-min duration and had to answer the questionnaire to the approximate time-point of 1, 3, and 6 months. Answers were classified as strongly agree, agree, neither agree nor disagree, disagree, and strongly disagree except for the last question, which directly rated the ECI professional. Results: Eleven fathers (55%) and 19 mothers (95%) of the 10 parents of each group participated in the study. Demographic data did not differ between groups, and the median time-points of questionnaire answers were 77, 137, and 220 days, respectively. Overall, 120-min ECI sessions were not superior to 90-min sessions for both parents regarding parental satisfaction during the study time. We found no differences between fathers and mothers and minimal changes over time. All parents were satisfied with the ECI professionals, irrespective of ECI duration. Conclusion: An ECI duration of 120 min once per week was not superior to a 9- min duration regarding parental satisfaction with ECI professionals and their work.

Hospital Regimens Including Probiotics Guide the Individual Development of the Gut Microbiome of Very Low Birth Weight Infants in the First Two Weeks of Life.

BACKGROUND: It is unknown to what extent the microbiome of preterm infants is influenced by hospital regimens including the use of different probiotics when it comes to the prevention of necrotizing enterocolitis (NEC). METHODS: Prospective controlled multicenter cohort study including very low birth weight infants from three neonatal intensive care units (NICUs) between October 2015 and March 2017. During this time span, stool was sampled every other day during the first two weeks and samples were subjected to amplicon-based microbiome analyses. Out of these, seventeen negative controls were processed (German Registry of Clinical Trials (No.: DRKS00009290)). RESULTS: The groups (3 × 18 infants) showed no statistically significant difference regarding gestational age, birth weight, APGAR scores and oxygen demand. 2029 different taxa were detected, including Enterococcus and Staphylococcus, as well as the probiotic genera Lactobacillus and Bifidobacterium predominating. The bacterial load was found to increase earlier on when probiotics were used. Without probiotics administration, Lactobacillus and Bifidobacterium contributed only marginally to the fecal microbiome. Some infants did not respond to probiotic administration. The samples from all centers participating reached a very similar diversity after two weeks while the microbiome samples from all three centers clustered significantly yet varied from each other. CONCLUSION: Probiotics proved to be safe and initiated an earlier increase of bacterial load (with marked individual divergences), which might play a crucial role in the prevention of neonatal morbidities. Meconium was found not to be free of bacterial DNA, and oral antibiotics did not influence the fecal microbiome development negatively, and hospital regimes led to a center-specific, distinct cluster formation.

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.