Late-onset sepsis in very preterm infants in Norway in 2009-2018: a population-based study.

OBJECTIVE: To evaluate epidemiology and outcomes among very preterm infants (<32 weeks' gestation) with culture-positive and culture-negative late-onset sepsis (LOS). DESIGN: Cohort study using a nationwide, population-based registry. SETTING: 21 neonatal units in Norway. PARTICIPANTS: All very preterm infants born 1 January 2009-31 December 2018 and admitted to a neonatal unit. MAIN OUTCOME MEASURES: Incidences, pathogen distribution, LOS-attributable mortality and associated morbidity at discharge. RESULTS: Among 5296 very preterm infants, we identified 582 culture-positive LOS episodes in 493 infants (incidence 9.3%) and 282 culture-negative LOS episodes in 282 infants (incidence 5.3%). Extremely preterm infants (<28 weeks' gestation) had highest incidences of culture-positive (21.6%) and culture-negative (11.1%) LOS. The major causative pathogens were coagulase-negative staphylococci (49%), Staphylococcus aureus (15%), group B streptococci (10%) and Escherichia coli (8%). We observed increased odds of severe bronchopulmonary dysplasia (BPD) associated with both culture-positive (adjusted OR (aOR) 1.7; 95% CI 1.3 to 2.2) and culture-negative (aOR 1.6; 95% CI 1.3 to 2.6) LOS. Only culture-positive LOS was associated with increased odds of cystic periventricular leukomalacia (cPVL) (aOR 2.2; 95% CI 1.4 to 3.4) and severe retinopathy of prematurity (ROP) (aOR 1.8; 95% CI 1.2 to 2.8). Culture-positive LOS-attributable mortality was 6.3%, higher in Gram-negative (15.8%) compared with Gram-positive (4.1%) LOS, p=0.009. Among extremely preterm infants, survival rates increased from 75.2% in 2009-2013 to 81.0% in 2014-2018, p=0.005. In the same period culture-positive LOS rates increased from 17.1% to 25.6%, p<0.001. CONCLUSIONS: LOS contributes to a significant burden of disease in very preterm infants and is associated with increased odds of severe BPD, cPVL and severe ROP.

Effects of Natural versus Synthetic Surfactant with SP-B and SP-C Analogs in a Porcine Model of Meconium Aspiration Syndrome.

BACKGROUND: Meconium displaces surfactant from the alveolar surface and inhibits its function. The development of active synthetic surfactants is complicated, especially to synthesize the hydrophobic surfactant proteins SP-B and SP-C. A synthetic surfactant, CHF5633 containing SP-B and SP-C analogs, has been designed to act similarly to the natural surfactant poractant alfa. OBJECTIVE: To test the resistance to meconium inactivation of CHF5633 compared to poractant alfa. Secondary outcome measurements were respiratory and inflammatory parameters. METHODS: Twenty-six newborn pigs, bodyweight 1.4-2.0 kg were randomized to receive either poractant alfa or CHF5633. After anesthesia, surgery and final stabilization, meconium was instilled endotracheally followed by surfactant. Bronchial lavage fluid was obtained before intervention and every second hour. Respiratory parameters were registered and blood samples drawn before intervention and every hour. RESULTS: Surfactant was inactivated in both groups 6 h after meconium instillation, but CHF5633 was more resistant than poractant alfa in terms of lipid peroxidation. Respiratory parameters were similar in both groups. Inflammatory and hemostatic parameters differed between groups, suggesting that the surfactants may play different roles in the meconium-induced inflammatory process. Due to the differential effects and complex pattern observed, the data do not indicate that one of the surfactants was superior with respect to inflammatory and hemostatic responses. CONCLUSION: This study indicates that CHF5633 is as efficient as poractant alfa in experimental meconium aspiration syndrome.

Albumin lavage does not improve the outcome of meconium aspiration syndrome.

OBJECTIVE: Meconium aspiration syndrome is still a serious condition with high mortality and morbidity. No specific treatment is yet available, although surfactant is known to reduce the need for extracorporeal membrane oxygenation and surfactant lavage has shown promising results in animal studies. Our group has previously shown reduced oxygenation index in an experimental model of meconium aspiration syndrome in newborn pigs when mixing albumin with meconium before endotracheal instillation. Lung compliance increased when albumin was instilled after meconium as a rescue. The aim of this study was to combine the effect of albumin and lavage. METHODS: Sixteen newborn pigs (six in the meconium-albumin group, six in the meconium group, and four control animals) were anesthetized and tracheotomized. Meconium 4 mL/kg was instilled endotracheally. After five minutes, albumin 15 mL/kg was instilled in the meconium-albumin group followed by endotracheal suctioning. The observation time was six hours. Respiratory and hemodynamic parameters were measured. The terminal complement complex and proinflammatory cytokines were analyzed in plasma. RESULTS: Oxygenation index, ventilatory index, and the terminal complement complex (sC5b-9) increased significantly in both groups, but significantly more in the meconium-albumin group. Compliance decreased, but significantly more in the meconium-albumin group. The terminal sC5b-9 complex increased in both groups, but significantly more in the meconium-albumin group. Tumor necrosis factor-alpha, interleukin (IL)- 1beta, and IL-6 increased significantly in both groups. CONCLUSION: Albumin-lavage did not improve the outcome of experimental meconium aspiration syndrome.