Early empirical antibiotics and adverse clinical outcomes in infants born very preterm: A population-based cohort

Objective The objective of this study was to evaluate the association between empirical antibiotic therapy in the first postnatal week in uninfected infants born very preterm and the risk of adverse outcomes until discharge. Study design Population-based, nationwide registry study in Norway including all live-born infants with a gestational age <32 weeks surviving first postnatal week without sepsis, intestinal perforation, or necrotizing enterocolitis (NEC) between 2009 and 2018. Primary outcomes were severe NEC, death after the first postnatal week, and/or a composite outcome of severe morbidity (severe NEC, severe bronchopulmonary dysplasia [BPD], severe retinopathy of prematurity, late-onset sepsis, or cystic periventricular leukomalacia). The association between empirical antibiotics and adverse outcomes was assessed using multivariable logistic regression models, adjusting for known confounders. Results Of 5296 live-born infants born very preterm, 4932 (93%) were included. Antibiotics were started in first postnatal week in 3790 of 4932 (77%) infants and were associated with higher aOR of death (aOR 9.33; 95% CI: 1.10-79.5, P = .041), severe morbidity (aOR 1.88; 95% CI: 1.16-3.05, P = .01), and severe BPD (aOR 2.17; 95% CI: 1.18-3.98; P = .012), compared with those not exposed. Antibiotics ³ 5 days were associated with higher odds of severe NEC (aOR 2.27; 95% CI: 1.02-5.06; P = .045). Each additional day of antibiotics was associated with 14% higher aOR of death or severe morbidity and severe BPD. Conclusions Early and prolonged antibiotic exposure within the first postnatal week was associated with severe NEC, severe BPD, and death after the first postnatal week

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 ( 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

Associations between unit workloads and outcomes of first extubation attempts in extremely premature infants below a gestational age of 26 weeks

Objective: The objective was to explore whether high workloads in neonatal intensive care units were associated with short-term respiratory outcomes of extremely premature (EP) infants born <26 weeks of gestational age. Methods: This was a population-based study using data from the Norwegian Neonatal Network supplemented by data extracted from the medical records of EP infants <26 weeks GA born from 2013 to 2018. To describe the unit workloads, measurements of daily patient volume and unit acuity at each NICU were used. The effect of weekend and summer holiday was also explored. Results: We analyzed 316 first planned extubation attempts. There were no associations between unit workloads and the duration of mechanical ventilation until each infant’s first extubation or the outcomes of these attempts. Additionally, there were no weekend or summer holiday effects on the outcomes explored. Workloads did not affect the causes of reintubation for infants who failed their first extubation attempt. Conclusion: Our finding that there was no association between the organizational factors explored and short-term respiratory outcomes can be interpreted as indicating resilience in Norwegian neonatal intensive care units.publishedVersio

Sepsis treatment options identified by 10-year study of microbial isolates and antibiotic susceptibility in a level-four neonatal intensive care unit

Aim: This observational study investigated the microbiology of blood culture-positive sepsis episodes and susceptibility to empiric antibiotics in early-onset sepsis (EOS) and late-onset sepsis (LOS) in a level-four neonatal intensive care unit (NICU) from 2010 to 2019. Methods: It was based on patient records and data that Oslo University Hospital, Norway, routinely submitted to the Norwegian Neonatal Network database. Clinical data were merged with blood culture results, including antibiotic susceptibility. Results: We studied 5249 infants admitted to the NICU 6321 times and identified 324 positive blood cultures from 287 infants, with 30 EOS and 305 LOS episodes. Frequent causative agents for EOS were group B streptococci (33.3%), Escherichia coli (20.0%) and Staphylococcus aureus (16.7%). All were susceptible to empiric ampicillin and gentamicin. LOS was most frequently caused by coagulase-negative staphylococci (CONS) (73.8%), Staphylococcus aureus (15.7%) and Enterococci (6.9%). CONS, Staphylococcus aureus, Enterococci, Escherichia coli, Klebsiella and Enterobacter represented 91.9% of LOS episodes and were susceptible to vancomycin and cefotaxime (96.1%), vancomycin and gentamicin (97.0%) and cloxacillin and gentamicin (38.1%). Conclusion: Empiric treatment with ampicillin and gentamicin was adequate for EOS. Combining vancomycin and gentamicin may be a safer alternative to cefotaxime for LOS, as this reduces exposure to broad-spectrum antibiotics

Duration of Mechanical Ventilation and Extubation Success among Extremely Premature Infants

Objective: The objective of this study was to examine the duration of mechanical ventilation (MV) in days until the first successful extubation and the cumulative duration of MV until discharge of infants with gestational age (GA) <26 weeks. We also aimed to explore associations between early clinical variables and the cumulative duration of MV. Design and Setting: This population-based study analysed data reported to the Norwegian Neonatal Network on extremely premature infants admitted between January 1, 2013, and December 31, 2018. Results: A total of 406 infants were included, of which 293 (72%) survived to discharge. The proportion successfully extubated on their first attempt was 34% of the infants born at GA 22–23 weeks, 50% at GA 24 weeks, and 70% at GA 25 weeks. Median postmenstrual age (PMA) at the first successful extubation was 27 weeks. The median duration of MV was 35, 24, and 12 days for infants born at GA 22–23, 24, and 25 weeks, respectively. Male sex and low 5-min Apgar score were independent early predictors for prolonged MV duration adjusted for GA in regression analyses. Conclusions: Most of the infants born at GA 25 weeks were successfully extubated on the first attempt. However, half of the infants born <26 weeks experienced unsuccessful extubations, indicating a lack of useful clinical predictors of successful extubation. The median duration of MV in survivors was 4 weeks longer for infants at GA 22–23 weeks than for infants born at GA 25 weeks, while the difference in median PMA at the first successful extubation was 2 weeks

Duration of Mechanical Ventilation and Extubation Success among Extremely Premature Infants

Objective: The objective of this study was to examine the duration of mechanical ventilation (MV) in days until the first successful extubation and the cumulative duration of MV until discharge of infants with gestational age (GA) &lt;26 weeks. We also aimed to explore associations between early clinical variables and the cumulative duration of MV. Design and Setting: This population-based study analysed data reported to the Norwegian Neonatal Network on extremely premature infants admitted between January 1, 2013, and December 31, 2018. Results: A total of 406 infants were included, of which 293 (72%) survived to discharge. The proportion successfully extubated on their first attempt was 34% of the infants born at GA 22–23 weeks, 50% at GA 24 weeks, and 70% at GA 25 weeks. Median postmenstrual age (PMA) at the first successful extubation was 27 weeks. The median duration of MV was 35, 24, and 12 days for infants born at GA 22–23, 24, and 25 weeks, respectively. Male sex and low 5-min Apgar score were independent early predictors for prolonged MV duration adjusted for GA in regression analyses. Conclusions: Most of the infants born at GA 25 weeks were successfully extubated on the first attempt. However, half of the infants born &lt;26 weeks experienced unsuccessful extubations, indicating a lack of useful clinical predictors of successful extubation. The median duration of MV in survivors was 4 weeks longer for infants at GA 22–23 weeks than for infants born at GA 25 weeks, while the difference in median PMA at the first successful extubation was 2 weeks

Phototherapy is commonly used for neonatal jaundice but greater control is needed to avoid toxicity in the most vulnerable infants.

AIM: Limited information is available about how guidelines on phototherapy for neonatal jaundice are applied in practice and toxicity is a concern. We studied the use of phototherapy in relation to birthweight and gestational age (GA) in Norwegian neonatal intensive care units (NICUs). METHODS: The study population was all 5382 infants admitted to the 21 NICUs in Norway between September 1, 2013 and August 31, 2014. Data were recorded daily in the Norwegian Neonatal Network database and anonymised data on patient characteristics, diagnoses, duration, the ages at the start and discontinuation of phototherapy were analysed. RESULTS: More than a quarter (26.6%) of all infants admitted to Norwegian NICUs during the study period received phototherapy. The use of phototherapy was inversely related to GA and birthweight. More than 80% of the preterm infants under 28 weeks of GA received phototherapy. The duration was significantly longer in the lowest birthweight and GA groups and decreased with increasing birthweight and GA. CONCLUSION: Phototherapy is proved to be a strong candidate for the most common therapeutic modality in NICU infants. However, in the light of reported toxicity in the smallest, most vulnerable infants, we recommend increased emphasis on quality control. The final version of this research has been published in Acta Paediatrica. © 2017 Wile

Antibiotic Use in Term and Near-Term Newborns

OBJECTIVES - We aimed to study whether national and local antibiotic stewardship projects have reduced the antibiotic use in newborns and to monitor potential changes in adverse outcomes. METHODS - In a nationwide, population-based study from Norway, we included all hospital live births from 34 weeks' gestation (n = 282 046) during 2015 to 2019. The primary outcome was the proportion of newborns treated with antibiotics from 0 to 28 days after birth. The secondary outcomes were the overall duration of antibiotic treatment and by categories: culture-positive sepsis, clinical sepsis, and no sepsis. RESULTS - A total of 7365 (2.6%) newborns received intravenous antibiotics during the period, with a reduction from 3.1% in 2015 to 2.2% in 2019 (30% decrease; P 72 hours of life, and sepsis-attributable deaths remained at a low level. CONCLUSIONS - During the study period, a substantial decrease in the proportion of newborns treated with antibiotics was observed together with a decline in treatment duration for newborns without culture-positive sepsis

Uniform national guidelines do not prevent wide variations in the clinical application of phototherapy for neonatal jaundice.

AIM: This study compared the use of phototherapy for neonatal jaundice in all 21 Norwegian neonatal intensive care units (NICUs) from 2013-2014 to improve practice. METHODS: Information on all types of phototherapy devices was collected, and irradiance was measured from random units at 20 cm and 50 cm from the light source. We gathered information on local practice rules, including the use of single, double or triple phototherapy, how infants were positioned, the frequency of blood sampling, rules for using reflective surfaces and interrupting phototherapy. In every NICU, we asked one nurse with more than five years of experience and one with less than one year to set up phototherapy equipment, then measured the irradiance and distance. RESULTS: Photodiodes were the most common of the eight types of phototherapy devices used. Rules for the distance from the device to the infant varied from 10 to 40 cm and in practice they varied from 15 to 48 cm, with irradiance ranging from 11.1-56.1 W/m2 . There were significant variations between NICUs with regard to the overall treatment duration and duration in most birthweight categories. CONCLUSION: There were considerable variations in phototherapy practices among Norwegian NICUs. In particular, the significant variations in duration need to be addressed. The final version of this research has been published in Acta Paediatrica. © 2017 Wile

Early surfactant and non-invasive ventilation versus intubation and surfactant: a propensity score-matched national study

Objective To compare outcome after less invasive surfactant administration (LISA) and primary endotracheal intubation (non-LISA) in infants born before gestational age (GA) 28 weeks.Setting All neonatal intensive care units (NICUs) in Norway during 2012–2018.Methods Defined population-based data were prospectively entered into a national registry. We compared LISA infants with all non-LISA infants and with non-LISA infants who received surfactant following intubation. We used propensity score (PS) matching to identify non-LISA infants who were similar regarding potential confounders.Main outcome variables Rate and duration of mechanical ventilation (MV), survival, neurological and gastrointestinal morbidity, and need of supplemental oxygen or positive pressure respiratory support at postmenstrual age (PMA) 36 and 40 weeks.Results We restricted analyses to GA 25–27 weeks (n=843, 26% LISA) because LISA was rarely used at lower GAs. There was no significant association between NICUs regarding proportions treated with LISA and proportions receiving MV. In the PS-matched datasets, fewer LISA infants received MV (61% vs 78%, p&lt;0.001), and they had fewer days on MV (mean difference 4.1, 95% CI 0.0 to 8.2 days) and lower mortality at PMA 40 weeks (absolute difference 6%, p=0.06) compared with all the non-LISA infants, but only a lower rate of MV (64% vs 97%, p&lt;0.001) and fewer days on MV (mean difference 5.8, 95% CI 0.6 to 10.9 days) compared with non-LISA infants who received surfactant after intubation.Conclusion LISA reduced the rate and duration of MV but had no other clear benefits