Epidemic Microclusters of Blood-Culture Proven Sepsis in Very-Low-Birth Weight Infants: Experience of the German Neonatal Network

INTRODUCTION: We evaluated blood culture-proven sepsis episodes occurring in microclusters in very-low-birth-weight infants born in the German Neonatal Network (GNN) during 2009-2010. METHODS: Thirty-seven centers participated in GNN; 23 centers enrolled ≥50 VLBW infants in the study period. Data quality was approved by on-site monitoring. Microclusters of sepsis were defined as occurrence of at least two blood-culture proven sepsis events in different patients of one center within 3 months with the same bacterial species. For microcluster analysis, we selected sepsis episodes with typically cross-transmitted bacteria of high clinical significance including gram-negative rods and Enterococcus spp. RESULTS: In our cohort, 12/2110 (0.6%) infants were documented with an early-onset sepsis and 235 late-onset sepsis episodes (≥72 h of age) occurred in 203/2110 (9.6%) VLBW infants. In 182/235 (77.4%) late-onset sepsis episodes gram-positive bacteria were documented, while coagulase negative staphylococci were found to be the most predominant pathogens (48.5%, 95%CI: 42.01-55.01). Candida spp. and gram-negative bacilli caused 10/235 (4.3%, 95%CI: 1.68% -6.83%) and 43/235 (18.5%) late-onset sepsis episodes, respectively. Eleven microclusters of blood-culture proven sepsis were detected in 7 hospitals involving a total 26 infants. 16/26 cluster patients suffered from Klebsiella spp. sepsis. The median time interval between the first patient's Klebsiella spp. sepsis and cluster cases was 14.1 days (interquartile range: 1-27 days). First patients in the cluster, their linked cases and sporadic sepsis events did not show significant differences in short term outcome parameters. DISCUSSION: Microclusters of infection are an important phenomenon for late-onset sepsis. Most gram-negative cluster infections occur within 30 days after the first patient was diagnosed and Klebsiella spp. play a major role. It is essential to monitor epidemic microclusters of sepsis in surveillance networks to adapt clinical practice, inform policy and further improve quality of care

Less invasive surfactant administration and complications of preterm birth

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

Polymorphisms in FTO and MAF Genes and Birth Weight, BMI, Ponderal Index, Weight Gain in a Large Cohort of Infants with a Birth Weight below 1500 Grams.

<label>BACKGROUND</label>The FTO gene, located on chromosome 16q12.2, and the MAF gene, located on chromosome 16q22-23, were identified as genes harboring common variants with an impact on obesity predisposition. We studied the association of common variants with birth weight, gain of body weight, body mass index (BMI), Ponderal index and relevant neonatal outcomes in a large German cohort of infants with a birth weight below 1500 grams.<label>METHODS</label>The single nucleotide polymorphisms rs9939609 (FTO gene) and rs1424233 (MAF gene) were genotyped using allelic discrimination assays in a prospective multicenter cohort study conducted in 15 neonatal intensive care units in Germany from September 2003 until January 2008. DNA samples were extracted from buccal swabs according to standard protocols.<label>RESULTS</label>1946 infants were successfully genotyped at FTO and 2149 infants at MAF. Allele frequencies were not significantly different from other European cohorts. The polymorphisms were in Hardy-Weinberg equilibrium. The polymorphisms did not show associations with birth weight, BMI and Ponderal Index at discharge, and weight gain, neither testing for a dominant, additive nor for a recessive model.<label>DISCUSSION</label>Since an association of the polymorphisms with weight gain has been demonstrated in multiple populations, the lack of association in a population of preterm infants with regular tube feeding after birth and highly controlled feeding volumes provides evidence for the hypothesis that these polymorphisms affect food intake behavior and hunger rather than metabolism and energy consumption

Two-year outcome data suggest that less invasive surfactant administration (LISA) is safe. Results from the follow-up of the randomized controlled AMV (avoid mechanical ventilation) study

Less invasive surfactant administration (LISA) is a method to deliver surfactant to spontaneously breathing premature infants via a thin catheter. Here we report the two-year outcome from the AMV (avoid mechanical ventilation) study, the first randomized controlled trial on this mode of surfactant delivery. No statistically significant differences in weight, length or neurodevelopmental outcome (Bayley II scores) were found between the LISA intervention group (n = 95) and the control group (n = 84) that received standard treatment. Conclusion: No differences in outcome were observed at 2 years. LISA seems safe in that aspect.What is Known:center dot LISA is a method that is in increasing use for surfactant delivery to spontaneously breathing infants. LISA reduces the need for mechanical ventilation.What is New:center dot Outcome data at 2 years from the first randomized study with LISA raise no safety concerns in comparison to a group of infants that received standard treatment

Avoidance of mechanical ventilation by surfactant treatment of spontaneously breathing preterm infants (AMV): an open-label, randomised, controlled trial

Background Surfactant is usually given to mechanically ventilated preterm infants via an endotracheal tube to treat respiratory distress syndrome. We tested a new method of surfactant application to spontaneously breathing preterm infants to avoid mechanical ventilation. Method In a parallel-group, randomised controlled trial, 220 preterm infants with a gestational age between 26 and 28 weeks and a birthweight less than 1.5 kg were enrolled in 12 German neonatal intensive care units. Infants were independently randomised in a 1:1 ratio with variable block sizes, to standard treatment or intervention, and randomisation was stratified according to centre and multiple birth status. Masking was not possible. Infants were stabilised with continuous positive airway pressure and received rescue intubation if necessary. In the intervention group, infants received surfactant treatment during spontaneous breathing via a thin catheter inserted into the trachea by laryngoscopy if they needed a fraction of inspired oxygen more than 0.30. The primary endpoint was need for any mechanical ventilation, or being not ventilated but having a partial pressure of carbon dioxide more than 65 mm Hg (8.6 kPa) or a fraction of inspired oxygen more than 0.60, or both, for more than 2 h between 25 h and 72 h of age. Analysis was by intention to treat. This study is registered, number ISRCTN05025922. Findings 108 infants were assigned to the intervention group and 112 infants to the standard treatment group. All infants were analysed. On day 2 or 3 after birth, 30 (28%) infants in the intervention group were mechanically ventilated versus 51 (46%) in the standard treatment group (number needed to treat 6, 95% CI 3-20, absolute risk reduction 0.18, 95% CI 0.30-0.05, p=0.008). 36 (33%) infants in the intervention group were mechanically ventilated during their stay in the hospital compared with 82 (73%) in the standard treatment group (number needed to treat: 3, 95% CI 2-4, p<0.0001). The intervention group had significantly fewer median days on mechanical ventilation, (0 days. IQR 0-3 vs 2 days, 0-5) and a lower need for oxygen therapy at 28 days (30 infants [30%] vs 49 infants [45%], p=0.032) compared with the standard treatment group. We recorded no differences between groups for mortality (seven deaths in the intervention group vs five in the standard treatment group) and serious adverse events (21 vs 28). Interpretation The application of surfactant via a thin catheter to spontaneously breathing preterm infants receiving continuous positive airway pressure reduces the need for mechanical ventilation

Nonintubated Surfactant Application vs Conventional Therapy in Extremely Preterm Infants A Randomized Clinical Trial

IMPORTANCE Treatment of respiratory distress syndrome in premature infants with continuous positive airway pressure (CPAP) preserves surfactant and keeps the lung open but is insufficient in severe surfactant deficiency. Traditional surfactant administration is related to short periods of positive pressure ventilation and implies the risk of lung injury. CPAP with surfactant but without any positive pressure ventilation may work synergistically. This randomized trial investigated a less invasive surfactant application protocol (LISA). OBJECTIVE To test the hypothesis that LISA increases survival without bronchopulmonary dysplasia (BPD) at 36 weeks' gestational age in extremely preterm infants. DESIGN, SETTING, AND PARTICIPANTS The Nonintubated Surfactant Application trial was a multicenter, randomized, clinical, parallel-group study conducted between April 15, 2009, and March 25, 2012, in 13 level III neonatal intensive care units in Germany. The final follow-up date was June 21, 2012. Participants included 211 of 558 eligible (37.8%) spontaneously breathing preterm infants born between 23.0 and 26.8 weeks' gestational age with signs of respiratory distress syndrome. In an intention-to-treat design, infants were randomly assigned to receive surfactant either via a thin endotracheal catheter during CPAP-assisted spontaneous breathing (intervention group) or after conventional endotracheal intubation during mechanical ventilation (control group). Analysis was conducted from September 6, 2012, to June 20, 2013. INTERVENTION LISA via a thin catheter. MAIN OUTCOMES AND MEASURES Survival without BPD at 36 weeks' gestational age. RESULTS Of 211 infants who were randomized, 104 were randomized to the control group and 107 to the LISA group. Of the infants who received LISA, 72 (67.3%) survived without BPD compared with 61 (58.7%) of those in the control group. The reduction in absolute risk was 8.6%(95% CI, -5.0% to 21.9%; P = .20). Intervention group infants were less frequently intubated (80 infants [74.8%] vs 103 [99.0%]; P < .001) and required fewer days of mechanical ventilation. Significant reductions were seen in pneumothorax (5 of 105 intervention group infants [4.8%] vs 13 of 103 12.6%]; P = .04) and severe intraventricular hemorrhage (11 infants [10.3%] vs 23 [22.1%]; P = .02), and the combined survival without severe adverse events was increased in the intervention group (54 infants [50.5%] vs 37 [35.6%]; P = .02; absolute risk reduction, 14.9; 95% CI, 1.4 to 28.2). CONCLUSIONS AND RELEVANCE LISA did not increase survival without BPD but was associated with increased survival without major complications. Because major complications are related to lifelong disabilities, LISA may be a promising therapy for extremely preterm infants

Less invasive surfactant administration is associated with improved pulmonary outcomes in spontaneously breathing preterm infants

AimProviding less invasive surfactant administration (LISA) to spontaneously breathing preterm infants has been reported to reduce mechanical ventilation and bronchopulmonary dysplasia (BPD) in randomised controlled trials. This large cohort study compared these outcome measures between LISA-treated infants and controls. MethodsInfants receiving LISA, who were born before 32 gestational weeks and enrolled in the German Neonatal Network, were matched to control infants by gestational age, umbilical cord pH, Apgar-score at 5min, small for gestational age status, antenatal treatment with steroids, gender and highest supplemental oxygen during the first 12h of life. Outcome data were compared with chi-square and Mann-Whitney U-tests and adjusted for multiple comparisons. ResultsBetween 2009 and 2012, 1103 infants were treated with LISA at 37 centres. LISA infants had lower rates of mechanical ventilation (41% versus 62%, p<0.001), postnatal dexamethasone treatment (2.5% versus 7%, p<0.001), BPD (12% versus 18%, p=0.001) and BPD or death (14% versus 21%, p<0.001) than the controls. ConclusionSurfactant treatment of spontaneously breathing infants was associated with lower rates of mechanical ventilation and BPD. Additional large-scale randomised controlled trials are needed to assess the possible long-term benefits of LISA

Developmental outcome of extremely preterm infants is improved after less invasive surfactant application: Developmental outcome after LISA

Aim The aim of this study was to evaluate neurocognitive outcome at 24 months of corrected age after less invasive surfactant application (LISA) in preterm infants born at 23-26 weeks of gestational age. Methods Surviving participants of a LISA trial conducted in 13 German level III neonatal intensive care units were reviewed for assessment of developmental outcome, hearing and vision problems, growth and rehospitalisation days. Maternal depression, breastfeeding rates and socio-economic factors were evaluated as potentially confounding factors. Results In total, 156/182 infants took part in the study, 78 had received surfactant via LISA and 78 via endotracheal intubation. 22% of LISA infants compared to 42% of intubated infants had a psychomotor development index (PDI) <70 (0.012). A significant difference in mental development index (MDI) was observed in the stratum of more mature infants (25 and 26 weeks of GA). For this group, MDI < 70 was observed in 4% of LISA infants vs 21% of intubated infants (P = 0.008). Conclusion At 24 months of age, the LISA-treated infants scored less often PDI < 70 and had similar results in MDI. Infants born at 25 and 26 weeks treated with LISA had lower rates of severe disability. LISA is safe and may be superior

Hypertrophy and hypotrophy and clinical data in German vlbw infant population.

<p>Hypertrophy and hypotrophy and clinical data in German vlbw infant population.</p