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In a large cohort study of the German Neonatal Network (GNN) we aimed to evaluate whether less invasive surfactant administration (LISA) strategy is associated with complications of preterm birth. Within the observational period n = 7533 very-low-birth-weight infants (VLBWI) with gestational age 22 0/7 to 28 6/7 weeks were enrolled in GNN; n = 1214 VLBWI never received surfactant, n = 2624 VLBWI were treated according to LISA procedure, n = 3695 VLBWI had surfactant via endotracheal tube (ETT). LISA was associated with a reduced risk for adverse outcome measures including mortality [odds ratio (OR) 0.66 (95% CI: 0.51–0.84), p < 0.001] bronchopulmonary dysplasia [BPD; OR 0.55 (95% CI: 0.49–0.62), p < 0.001], intracerebral hemorrhage (ICH) grade II-IV [OR 0.55 (95% CI: 0.48–0.64), p < 0.001] and retinopathy of prematurity [ROP; OR 0.62 (95% CI: 0.45–0.85), p < 0.001]. Notably, LISA was associated with an increased risk for focal intestinal perforation [FIP; OR 1.49 (95% CI: 1.14–1.95), p = 0.002]. The differences in FIP rates were primarily observed in VLBWI born <26 weeks (LISA: 10.0 vs. ETT: 7.4%, p = 0.029). Our observational data confirm that LISA is associated with improved outcome. In infants <26 weeks we noted an increased risk for FIP. Future randomized controlled trials including LISA need to integrate safety analyses for this particular subgroup.

We report 3 cases of probable invasive pulmonary disease caused by Bjerkandera spp. fungi in immunocompromised patients in Germany. Accurate identification required internal transcribed spacer sequencing. Response to antifungal treatment varied. Our report underlines the pathogenic potential of Bjerkandera spp. and the importance of molecular diagnostics in rare fungal infections.

IntroductionPreterm infants, particularly those born before 29 weeks of gestation, are at increased risk of developing bronchopulmonary dysplasia (BPD) and other complications of prematurity. Substantial evidence suggests that respiratory tract colonisation with Ureaplasma species significantly contributes to pulmonary inflammation, impaired lung function and subsequent lung disease especially in very immature infants. Moreover, Ureaplasma exposure has been implicated in the pathogenesis of other inflammation-related sequelae of prematurity. Although representing a potentially actionable risk factor for adverse short-term and long-term neonatal outcome, controversies on Ureaplasma-associated morbidity remain and recommendations for screening practices in preterm infants are missing. The NEO-CONSCIOUS (Neonatal Colonisation and Infection with Ureaplasma in very immature preterm infants born <29 weeks of gestation) study aims to assess the incidence of Ureaplasma colonisation and infection in very preterm infants at high risk of adverse outcome, the extent of potentially accompanying inflammation and the impact on short-term and long-term morbidity.Methods and analysisThis is a prospective observational multicentre study being conducted in level III neonatal intensive care units in Germany and Austria. In total, 400 infants born before 29 weeks of gestation are screened for Ureaplasma colonisation immediately after birth. In addition, biomarkers of systemic inflammation are determined on day 1 and day 28. The study infants are followed up until discharge and at 2 years corrected age. The primary outcome BPD and/or death is assessed at 36 weeks postmenstrual age. Secondary outcomes include systemic inflammation, secondary infections, intraventricular haemorrhage, periventricular leukomalacia, necrotising enterocolitis, retinopathy of prematurity and neurodevelopmental outcome at 24 months corrected age.Ethics and disseminationThe study has been approved by the ethics committees in Würzburg and Leipzig and the local ethics committees of all participating centres. Results will be disseminated through peer-reviewed international publications and conferences. The study is registered with the German Clinical Trials Register, ID DRKS00033001.Trial registration numberGerman Clinical Trials Register (DRKS00033001).

Background: Very immature preterm infants are at risk of developing symptomatic or severe infection if cytomegalovirus is transmitted via breast milk. It is still a matter of debate whether human cytomegalovirus (HCMV) infection may lead to long-term sequelae. Objectives: We hypothesized that symptomatic and severe HCMV infection transmitted via breast milk affects extremely immature infants at a very high rate. Methods: In 2012, untreated breast milk was fed to extremely low birth weight infants after parental informed consent was obtained. We retrospectively analyzed data on HCMV infection of infants born in 2012 between 22 and 24 weeks of gestation. Results: 17 infants were born to HCMV IgG-seropositive mothers. 11 (65%) of these were diagnosed with symptomatic infection. In all cases, thrombocytopenia was the reason to analyze the infant's urine. HCMV infection was diagnosed at a median time of 12 weeks after birth. In 5 (45%) infants, thrombocytopenia was the only symptom and resolved without antiviral therapy or platelet transfusion. 6 (55%) infants developed sepsis-like disease with mildly elevated CRP values and showed signs of respiratory failure. 3 (27%) were able to be stabilized on CPAP, 3 (27%) had to be intubated and mechanically ventilated. 4 children were treated with ganciclovir and/or valganciclovir. 55% failed otoacoustic emissions and/or automated auditory brainstem response testing at discharge. Conclusions: In very immature infants born at the border of viability and suffering from multiple preexisting problems, HCMV infection may trigger a severe deterioration of the clinical course.

Background: Monochorionic (MC) twins are at risk for severe twin-to-twin transfusion syndrome (TTTS) or twin anemia-polycythemia sequence (TAPS). In the case of preterm delivery, cesarean section (CS) with immediate umbilical cord clamping (ICC) of both twins is usually performed. While the recipient is at risk for polycythemia and may benefit from ICC, this procedure may result in aggravation of anemia with increased morbidity in the anemic donor. The purpose of this study was to demonstrate that the novel approach of selective extrauterine placental perfusion (EPP) with delayed umbilical cord clamping (DCC) in the donor infant is feasible in neonatal resuscitation of MC twins and may prevent severe anemia in donor and polycythemia in the recipient. Methods: Preterm MC twins with antenatal suspected severe anemia of the donor as measured by Doppler ultrasound, born with birthweights < 1500 g by CS, were transferred to the neonatal resuscitation unit with placenta and intact umbilical cords. In the donor, the umbilical cord was left intact to provide DCC with parallel respiratory support (EPP approach), while the cord of the recipient was clamped immediately after identification. Results: Selective EPP was performed in three cases of MC twins with TAPS and acute peripartum TTTS. All donor twins had initial hemoglobin levels ≥ 13.0 g/dL, and none of them required red blood cell transfusion on the first day after birth. Conclusions: Selective EPP may be a feasible strategy for neonatal resuscitation of MC preterm twins with high stage TAPS and TTTS to prevent anemia-related morbidities and may improve infant outcome.

Background Differential diagnosis of prenatally detected hyperechogenic and enlarged kidneys can be challenging as there is a broad phenotypic overlap between several rare genetic and non-genetic disorders. Metabolic diseases are among the rarest underlying disorders, but they demand particular attention as their prognosis and postnatal management differ from those of other diseases. Methods We report two cases of cystic, hyperechogenic and enlarged kidneys detected on prenatal ultrasound images, resulting in the suspected diagnosis of autosomal recessive polycystic kidney disease (ARPKD). Postnatal clinical course and work-up, however, revealed early, neonatal forms of disorders of fatty acid oxidation (DFAO) in both cases, namely, glutaric acidemia type II, based on identification of the novel, homozygous splice-site mutation c.1117-2A > G in the ETFDH gene, in one case and carnitine palmitoyltransferase II deficiency in the other case. Results Review of pre- and postnatal sonographic findings resulted in the identification of some important differences that might help to differentiate DFAO from ARPKD. In DFAO, kidneys are enlarged to a milder degree than in ARPKD, and the cysts are located ubiquitously, including also in the cortex and the subcapsular area. Interestingly, recent studies have pointed to a switch in metabolic homeostasis, referred to as the Warburg effect (aerobic glycolysis), as one of the underlying mechanisms of cell proliferation and cyst formation in cystic kidney disease. DFAO are characterized by the inhibition of oxidative phosphorylation, resulting in aerobic glycolysis, and thus they do resemble the Warburg effect. We therefore speculate that this inhibition might be one of the pathomechanisms of renal hyperproliferation and cyst formation in DFAO analogous to the reported findings in ARPKD. Conclusions Neonatal forms of DFAO can be differentially diagnosed in neonates with cystic or hyperechogenic kidneys and necessitate immediate biochemical work-up to provide early metabolic management.

Pediatric spondylodiscitis (PSD) is a rare disease with a major impact on mobility and functional status. Data concerning demographic and microbiological characteristics, clinical course, treatment, and outcome are scarce. Therefore, the aim of this study was to present clinical experiences of a third-level hospital (2009–2019) in PSD and compare these with adult spondylodiscitis (ASD). Of a total of 10 PSD patients, most of the infants presented with unspecific pain such as hip pain or a limping, misleading an adequate diagnosis of spine origin. Eight patients could be treated conservatively whereas surgery was performed in two cases with one case of tuberculous PSD (tPSD). The causative agent was detected in three of the patients. The diagnosis of PSD is often difficult since clinical symptoms are unspecific and causative pathogens often remain undetected. Nevertheless, empirical anti-infective therapy also seems to be effective. Based on recent studies, clinicians should be encouraged to keep the duration of anti-infective therapy in children short. Since comorbidities are not presented in PSD it is unclear which children suffer from PSD; thus, studies are necessary to identify predisposing factors for PSD. In our study, PSD differs from ASD in diagnostic and especially in therapeutic aspects. Therefore, specific guidelines for PSD would be desirable.

For nasal application of neurotrophins and mesenchymal stem cells, successful delivery to the brain and therapeutic effects are known from experimental data in animals. Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx. This is a first exploration on additional nasal breast milk and neuromorphological outcome after severe neonatal brain injury. We present a retrospective summary of 31 very low birth weight preterm infants with intraventricular hemorrhage °3/4 from one third-level neonatal center. All were breast milk fed. Sixteen infants additionally received nasal drops of fresh breast milk daily with informed parental consent for at least 28 days. Cerebral ultrasound courses were reviewed by a pediatric radiologist blinded to the intervention. The main outcome measure was severity of porencephalic defects before discharge. Clinical covariates were comparable in both groups. With nasal breast milk, a trend to a lower incidence for severe porencephalic defects (21% vs. 58%) was detected. Incidences were lower for progressive ventricular dilatation (71% vs. 91%) and surgery for posthemorrhagic hydrocephalus (50% vs. 67%).Conclusion: The hypothesis is generated that early intranasal application of breast milk could have a beneficial effect on neurodevelopment in preterm infants. Controlled investigation is needed.What is Known:• Successful delivery to the brain and therapeutic effects are known for nasal application of neurotrophins and mesenchymal stem cells from experimental data in animal studies.• Human breast milk contains neurotrophins and stem cells, but gavage tube feeding in preterm infants bypasses the naso-oropharynx.What is New:• This is the first report on additional nasal breast milk application in very low birth weight preterm infants with severe brain injury observing a trend for less severe porencephalic defects.• The hypothesis is generated that nasal breast milk might exert neuroprotective effects in preterm infants.

Purpose In recent years an earlier step down to oral antibiotic therapy has been advocated for numerous infections. Trained infectious disease specialists regularly consulting their colleagues may speed up the implementation of such recommendations into clinical practice and thus may improve treatment. Methods We retrospectively analyzed bone and joint infections in children admitted to the University Hospital of Cologne between 2010 and 2021. We assessed clinical, imaging, and microbiological findings and treatment modalities. Additionally, we assessed both the impact of a newly implemented pediatric infectious diseases consultation service and publications on revised treatment recommendations by comparing antibiotic therapy in two periods (2010–2016 versus 2017 to 2021). Results In total, 29 children presented with osteomyelitis, 16 with bacterial arthritis and 7 with discitis. In period 2 (2017–2021) we observed shorter duration of intravenous treatment ( p  = 0.009) and a higher percentage of oral antibiotic treatment in relation to the total duration of antibiotics (25% versus 59%, p  = 0.007) compared to period 1 (2010–2016). Yet, no differences were identified for the total length of antibiotic treatment. Additionally, biopsies or synovial fluid samples were retrieved and cultured in more children in period 2 ( p  = 0.077). The main pathogen identified in osteomyelitis and bacterial arthritis was Staphylococcus aureus (MSSA), diagnosis was confirmed predominantly with MRI. Conclusion Recent guidelines addressing the safety of an earlier step-down (to oral) antibiotic therapy have influenced clinical practice in the treatment of bone and joint infections in our hospital. A newly implemented pediatric infectious diseases consultation service might have accelerated this progress resulting in a faster step down to oral treatment.

Purpose Very low birth weight (VLBW) infants are at a risk of spontaneous focal intestinal perforation (FIP). Treatment includes supportive care, antibiotics, and drainage with/without surgery. Broad-spectrum antibiotic agents like carbapenems are applied frequently, although their use is not well-supported by the limited evidence of causal pathogens. We hypothesize that the use of carbapenems may not be necessary in VLBW infants with FIP. Our primary objective was to evaluate the antimicrobial use in VLBW infants with FIP in a cohort of the German Neonatal Network (GNN). The secondary objective was to characterize a subset in detail as a benchmark for future targets of stewardship. Methods Data on VLBW infants with FIP was collected prospectively within the GNN, a collaboration of 68 neonatal intensive care units (NICU). With regards to the primary objective, patient characteristics and antimicrobial treatment were extracted from the predefined GNN database. To address our secondary objective, an additional on-site assessment of laboratory and microbiological culture results were performed. Results In the GNN cohort, 613/21,646 enrolled infants (2.8%) developed FIP requiring surgery. They were frequently treated with carbapenems (500/613 (81.6%)) and vancomycin (497/613 (81.1%)). In a subset of 124 VLBW infants, 77 (72.6%) had proof of gram-positive bacteria in the abdominal cavity, coagulase-negative staphylococci (CoNS) predominantly. Despite the low prevalence of gram-negative bacteria ( n  = 6 (4.8%)), the combination of meropenem and vancomycin was prescribed most frequently ( n  = 96 (78.0%)). Conclusion The use of carbapenems as broad-spectrum antimicrobials agents might not be justified in most VLBW infants with FIP. Knowledge on the development of the neonatal gut microbiota, local resistance patterns and individual microbiological findings should be taken into consideration when implementing antimicrobial stewardship programs (ASPs).