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

The association between infant salivary cortisol and parental presence in the neonatal intensive care unit during and after COVID-19 visitation restrictions: A cross-sectional study

Objectives: Parent-infant interaction in the neonatal intensive care unit (NICU) promotes health and reduces infant stress. During the COVID-19 pandemic, however, NICUs restricted parent-infant interaction to reduce viral transmission. This study examined the potential relationship between pandemic visitation restrictions, parental presence and infant stress as measured by salivary cortisol. Methods: A two-NICU cross-sectional study of infants with gestational age (GA) 23–41 weeks, both during (n = 34) and after (n = 38) visitation restrictions. We analysed parental presence with and without visitation restrictions. The relationship between infant salivary cortisol and self-reported parental NICU presence in hours per day was analysed using Pearson's r. A linear regression analysis included potential confounders, including GA and proxies for infant morbidity. The unstandardised B coefficient described the expected change in logtransformed salivary cortisol per unit change in each predictor variable. Results: Included infants had a mean (standard deviation) GA of 31(5) weeks. Both maternal and paternal NICU presence was lower with versus without visitation restrictions (both p ≤0.05). Log-transformed infant salivary cortisol correlated negatively with hours of parental presence (r = − 0.40, p = .01). In the linear regression, GA (B = -0.03, p = .02) and central venous lines (B = 0.23, p = .04) contributed to the variance in salivary cortisol in addition to parental presence (B = -0.04 p = .04). Conclusion: COVID-19–related visitation restrictions reduced NICU parent-infant interaction and may have increased infant stress. Low GA and central venous lines were associated with higher salivary cortisol. The interaction between immaturity, morbidity and parental presence was not within the scope of this study and merits further investigation

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

Advanced Clinical Neonatal Nursing Students’ Transfer of Performance: From Skills Training With Real-Time Feedback on Ventilation to a Simulated Neonatal Resuscitation Scenario

Background: Advanced clinical neonatal nurses are expected to have technical skills including bag-mask ventilation. Previous studies on neonatal bag-mask ventilation skills training focus largely on medical students and/or physicians. The aim of this study was to investigate whether advanced clinical neonatal nursing students’ bag-mask ventilation training with real-time feedback resulted in transfer of bag-mask ventilation performance to a simulated setting without feedback on ventilation. Materials and Methods: Students in advanced clinical neonatal nursing practiced bagmask ventilation on a premature manikin (Premature Anne, Laerdal Medical, Stavanger, Norway) during skills training. A flow sensor (Neo Training, Monivent AB, Gothenburg, Sweden) was placed between the facemask and the self-inflating bag (Laerdal Medical), and visual feedback on mask leak (%), expiratory tidal volume (VTe in ml/kg), ventilation rate and inflation pressure was provided. Two months later, the students participated in a simulated neonatal resuscitation scenario. The same variables were recorded, but not fed back to the students. We compared ventilation data from skills- and simulation training. A structured questionnaire was used to investigate the students’ self-perceived neonatal ventilation competence before and after the skills- and simulation training. Results: Mask leakage and ventilation rate was higher, and VTe lower and highly variable in the simulated scenario compared with skills training (all p < 0.001). There was no statistically significant difference in inflation pressure (p = 0.92). The fraction of ventilations with VTe within the target range was lower during simulation (21%) compared to skills training (30%) (p < 0.001). There was no difference in the students’ self-perceived competence in bag-mask ventilation before vs. after skills- and simulation training. Conclusion: Skills training with real-time feedback on mask leak, ventilation rate, tidal volume, and inflation pressure did not result in objective or subjective improvements in bag-mask ventilation in a simulated neonatal resuscitation situation. Incorrect VTe delivery was common even when feedback was provided. It would be of interest to study whether more frequent training, and training both with and without feedback, could improve transfer of performance to a simulated resuscitation setting.publishedVersio

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

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

Retrospectively Assessed Muscle Tone and Skin Colour following Airway Suctioning in Video-Recorded Infants Receiving Delivery Room Positive Pressure Ventilation

Background: Recently, the International Liaison Committee on Resuscitation published a systematic review that concluded that routine suctioning of clear amniotic fluid in the delivery room might be associated with lower oxygen saturation (SpO2) and 10 min Apgar score. The aim of this study was to examine the effect of delivery room airway suctioning on the clinical appearance, including muscle tone and skin colour, of video-recorded term and preterm infants born through mainly clear amniotic fluid. Methods: This was a single-centre observational study using transcribed video recordings of neonatal stabilizations. All infants who received delivery room positive pressure ventilation (PPV) from August 2014 to November 2016 were included. The primary outcome was the effect of airway suctioning on muscle tone and skin colour (rated 0–2 according to the Apgar score), while the secondary outcome was the fraction of infants for whom airway suction preceded the initiation of PPV as a surrogate for “routine” airway suctioning. Results: Airway suctioning was performed in 159 out of 302 video recordings and stimulated a vigorous cry in 47 (29.6%) infants, resulting in improvements in muscle tone (p = 0.09) and skin colour (p < 0.001). In 43 (27.0%) infants, airway suctioning preceded the initiation of PPV. Conclusions: In this single-centre observational study, airway suctioning stimulated a vigorous cry with resulting improvements in muscle tone and skin colour. Airway suctioning was often performed prior to the initiation of PPV, indicating a practice of routine suctioning and guideline non-compliance

Variation in antibiotic consumption in very preterm infants-a 10 year population-based study

Objectives: Wide variations in antibiotic use in very preterm infants have been reported across centres despite similar rates of infection. We describe 10 year trends in use of antibiotics and regional variations among very preterm infants in Norway. Patients and Methods: All live-born very preterm infants (<32 weeks gestation) admitted to any neonatal unit in Norway during 2009–18 were included. Main outcomes were antibiotic consumption expressed as days of antibiotic therapy (DOT) per 1000 patient days (PD), regional variations in use across four health regions, rates of sepsis and sepsis-attributable mortality and trends of antibiotic use during the study period. Results: We included 5296 infants: 3646 (69%) were born at 28–31 weeks and 1650 (31%) were born before 28 weeks gestation with similar background characteristics across the four health regions. Overall, 80% of the very preterm infants received antibiotic therapy. The most commonly prescribed antibiotics were the combination of narrow-spectrum β-lactams and aminoglycosides, but between 2009 and 2018 we observed a marked reduction in their use from 100 to 40 DOT per 1000 PD (P < 0.001). In contrast, consumption of broad-spectrum β-lactams remained unchanged (P = 0.308). There were large variations in consumption of vancomycin, broad-spectrum β-lactams and first-generation cephalosporins, but no differences in sepsis-attributable mortality across regions. Conclusions: The overall antibiotic consumption was reduced during the study period. Marked regional variations remained in consumption of broad-spectrum β-lactams and vancomycin, without association to sepsis-attributable mortality. Our results highlight the need for antibiotic stewardship strategies to reduce consumption of antibiotics that may enhance antibiotic resistance development

Estimated daily intake of phthalates, parabens, and bisphenol A in hospitalised very low birth weight infants

Very low birth weight infants (VLBW, birth weight (BW) 1 indicates that EDI exceeded TDI with increased risk of adverse health effects. EDI was higher in VLBW infants compared to term-born infants and older children. VLBW infants born at earlier gestational age (GA), or with lower BW, had higher EDI than infants born at later GA or with higher BW. First week median EDI for BPA was higher than TDI in 100% of infants, in 75% for di(2-ethylhexyl) phthalate (DEHP), 90% for the sum of butyl benzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), DEHP and di-iso-nonyl phthalate (DiNP) = ∑BBzP+DnBP+DEHP+DiNP, and in 50% of infants for propylparaben (PrPa), indicating increased risk of adverse effects. Fifth week EDI remained higher than TDI in all infants for BPA, in 75% for DEHP and ∑BBzP+DnBP+DEHP+DiNP, and 25% of infants for PrPa, indicating prolonged risk. Maximum EDI for di-iso-butyl phthalate was higher than TDI suggesting risk of adverse effects at maximum exposure. VLBW infants born earlier than 28 weeks GA had higher EDI, above TDI, for PrPa compared to infants born later than 28 weeks GA. Infants with late-onset septicaemia (LOS) had higher EDI for DEHP, ∑BBzP+DnBP+DEHP+DiNP and BPA, above TDI, compared to infants without LOS. More 75% of the infants' EDI for DEHP and ∑BBzP+DnBP+DEHP+DiNP, 25% for PrPa, and 100% of infants' EDI for BPA, were above TDI resulting in HQs 1, indicating increased risk of adverse health effects