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 ß-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 ß-lactams remained unchanged (P = 0.308). There were large variations in consumption of vancomycin, broad-spectrum ß-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 ß-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.

Biochemical profiles and organ dysfunction in neonates with hypoxic-ischemic encephalopathy post-hoc analysis of the THIN trial.

BACKGROUND: Therapeutic hypothermia for infants with moderate to severe hypoxic-ischemic encephalopathy is well established as standard of care in high-income countries. Trials from low- and middle-income countries have shown contradictory results, and variations in the level of intensive care provided may partly explain these differences. We wished to evaluate biochemical profiles and clinical markers of organ dysfunction in cooled and non-cooled infants with moderate/severe hypoxic-ischemic encephalopathy. METHODS: This secondary analysis of the THIN (Therapeutic Hypothermia in India) study, a single center randomized controlled trial, included 50 infants with moderate to severe hypoxic-ischemic encephalopathy randomized to therapeutic hypothermia (n = 25) or standard care with normothermia (n = 25) between September 2013 and October 2015. Data were collected prospectively and compared by randomization groups. Main outcomes were metabolic acidosis, coagulopathies, renal function, and supportive treatments during the intervention. RESULTS: Cooled infants had lower pH than non-cooled infants at 6-12 h (median (IQR) 7.28 (7.20-7.32) vs 7.36 (7.31-7.40), respectively, p = 0.003) and 12-24 h (median (IQR) 7.30 (7.24-7.35) vs 7.41 (7.37-7.43), respectively, p < 0.001). Thrombocytopenia (< 100 000) was, though not statistically significant, twice as common in cooled compared to non-cooled infants (4/25 (16%) and 2/25 (8%), respectively, p = 0.67). No significant difference was found in the use of vasopressors (14/25 (56%) and 17/25 (68%), p = 0.38), intravenous bicarbonate (5/25 (20%) and 3/25 (12%), p = 0.70) or treatment with fresh frozen plasma (10/25 (40%) and 8/25 (32%), p = 0.56)) in cooled and non-cooled infants, respectively. Urine output < 1 ml/kg/h was less common in cooled infants compared to non-cooled infants at 0-24 h (7/25 (28%) vs. 16/23 (70%) respectively, p = 0.004). CONCLUSIONS: This post hoc analysis of the THIN study support that cooling of infants with hypoxic-ischemic encephalopathy in a level III neonatal intensive care unit in India was safe. Cooled infants had slightly lower pH, but better renal function during the first day compared to non-cooled infants. More research is needed to identify the necessary level of intensive care during cooling to guide further implementation of this neuroprotective treatment in low-resource settings. TRIAL REGISTRATION: Data from this article was collected during the THIN-study (Therapeutic Hypothermia in India; ref. CTRI/2013/05/003693 Clinical Trials Registry - India).

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 ≥ 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.

Curriculum and assessment tool for less invasive surfactant administration: an international Delphi consensus study.

BACKGROUND: Training and assessment of operator competence for the less invasive surfactant administration (LISA) procedure vary. This study aimed to obtain international expert consensus on LISA training (LISA curriculum (LISA-CUR)) and assessment (LISA assessment tool (LISA-AT)). METHODS: From February to July 2022, an international three-round Delphi process gathered opinions from LISA experts (researchers, curriculum developers, and clinical educators) on a list of items to be included in a LISA-CUR and LISA-AT (Round 1). The experts rated the importance of each item (Round 2). Items supported by more than 80% consensus were included. All experts were asked to approve or reject the final LISA-CUR and LISA-AT (Round 3). RESULTS: A total of 153 experts from 14 countries participated in Round 1, and the response rate for Rounds 2 and 3 was >80%. Round 1 identified 44 items for LISA-CUR and 22 for LISA-AT. Round 2 excluded 15 items for the LISA-CUR and 7 items for the LISA-AT. Round 3 resulted in a strong consensus (99-100%) for the final 29 items for the LISA-CUR and 15 items for the LISA-AT. CONCLUSIONS: This Delphi process established an international consensus on a training curriculum and content evidence for the assessment of LISA competence. IMPACT: This international consensus-based expert statement provides content on a curriculum for the less invasive surfactant administration procedure (LISA-CUR) that may be partnered with existing evidence-based strategies to optimize and standardize LISA training in the future. This international consensus-based expert statement also provides content on an assessment tool for the LISA procedure (LISA-AT) that can help to evaluate competence in LISA operators. The proposed LISA-AT enables standardized, continuous feedback and assessment until achieving proficiency.

Postponed Withholding: Balanced Decision-Making at the Margins of Viability.

Advances in neonatology have led to improved survival for periviable infants. Immaturity still carries a high risk of short- and long-term harms, and uncertainty turns provision of life support into an ethical dilemma. Shared decision-making with parents has gained ground. However, the need to start immediate life support and the ensuing difficulty of withdrawing treatment stands in tension with the possibility of a fair decision-making process. Both the parental "instinct of saving" and "withdrawal resistance" involved can preclude shared decision-making. To help health care personnel and empower parents, we propose a novel approach labeled "postponed withholding." In the absence of a prenatal advance directive, life support is started at birth, followed by planned redirection to palliative care after one week, unless parents, after a thorough counseling process, actively ask for continued life support. Despite the emotional challenges, this approach can facilitate ethically balanced decision-making processes in the gray zone.

Learning Curve for Arthroscopic Shoulder Latarjet Procedure Shows Shorter Operating Time and Fewer Complications with Experience.

PURPOSE: To evaluate the learning curve of the arthroscopic Latarjet procedure in a consecutive series of 103 shoulders in 102 patients by comparing the early clinical and radiologic outcomes and complications of the first 25 patients with the latter 25 patients. Our hypothesis was that the studied parameters would be enhanced over time. METHODS: A consecutive cohort of 103 shoulders in 102 patients treated with arthroscopic Latarjet procedure was prospectively registered from December 2014 until November 2019. Patients in this cohort represent the first cases of arthroscopic Latarjet for the 2 shoulder surgeons. All patients had a double screw fixation technique. The Western Ontario Shoulder Instability Index (WOSI) score preoperatively and at 1-year follow-up and 3-dimensional computed tomography scans preoperatively, postoperatively, and at 1-year follow-up were prospectively registered. Patient demographics, intraoperative data, complications, and reoperations were all recorded. In total, 85 of 103 shoulders (83%) had complete data sets. Patient demographics, WOSI scores, operating time, complications, satisfaction rate, and radiology scores in the first and last 25 patients were compared to evaluate learning curve. RESULTS: There was longer operating time in the early group compared with the latter (130 vs 105 minutes, P = .001) and number of complications was reduced with experience (16 vs 4, P = .0005). Serious complications requiring a reoperation were 4 (16%) in the early group compared to 1 (4%) in the latter group (P = .157). Clinical results were good with major improvement in WOSI scores and 84 % satisfaction rates in both groups. CONCLUSIONS: Arthroscopic Latarjet was associated with a learning curve where the early group had longer operating time and greater rates of complications. This is a procedure with few serious complications, acceptable surgery time and learning curve. LEVEL OF EVIDENCE: Level III, retrospective comparative observation trial.

NeoDoppler: New ultrasound technology for continous cerebral circulation monitoring in neonates.

BACKGROUND: There is a strong need for continuous cerebral circulation monitoring in neonatal care, since suboptimal cerebral blood flow may lead to brain injuries in preterm infants and other critically ill neonates. NeoDoppler is a novel ultrasound system, which can be gently fixed to the anterior fontanel and measure cerebral blood flow velocity continuously in different depths of the brain simultaneously. We aimed to study the feasibility, accuracy, and potential clinical applications of NeoDoppler in preterm infants and sick neonates. METHOD: Twenty-five infants born at different gestational ages with a variety of diagnoses on admission were included. The probe was placed over the anterior fontanel, and blood flow velocity data were continuously recorded. To validate NeoDoppler, we compared the measurements with conventional ultrasound; agreement was assessed using Bland-Altman plots. RESULTS: NeoDoppler can provide accurate and continuous data on cerebral blood flow velocity in several depths simultaneously. Limits of agreement between the measurements obtained with the two methods were acceptable. CONCLUSION: By monitoring the cerebral circulation continuously, increased knowledge of cerebral hemodynamics in preterm infants and sick neonates may be acquired. Improved monitoring of these vulnerable brains during a very sensitive period of brain development may contribute toward preventing brain injuries.

Investigation of an outbreak caused by antibiotic-susceptible Klebsiella oxytoca in a neonatal intensive care unit in Norway.

AIM: Klebsiella spp. have been stated to be the most frequent cause of neonatal intensive care unit (NICU) outbreaks. We report an outbreak of Klebsiella oxytoca in a NICU at a tertiary care hospital in Norway between April 2016 and April 2017. This study describes the outbreak, infection control measures undertaken and the molecular methods developed. METHODS: The outbreak prompted detailed epidemiological and microbial investigations, where whole-genome sequencing (WGS) was particularly useful for both genotyping and development of two new K. oxytoca-specific real-time PCR assays. Routine screening of patients, as well as sampling from numerous environmental sites, was performed during the outbreak. A bundle of infection control measures was instigated to control the outbreak, among them strict cohort isolation. RESULTS: Five neonates had symptomatic infection, and 17 were found to be asymptomatically colonised. Infections varied in severity from conjunctivitis to a fatal case of pneumonia. A source of the outbreak could not be determined. CONCLUSION: This report describes K. oxytoca as a significant pathogen in a NICU outbreak setting and highlights the importance of developing appropriate microbiological screening methods and implementing strict infection control measures to control the outbreak in a setting where the source could not be identified.

Skin-to-skin contact during eye examination did not reduce pain compared to standard care with parental support in preterm infants.

AIM: We compared the pain relieving effect of skin-to-skin contact versus standard care in the incubator during screening for retinopathy of prematurity. METHODS: This randomised crossover study included 35 preterm infants of less than 32 weeks of gestational age admitted to St Olavs University Hospital, Trondheim, Norway, between January 2014 and June 2016. Randomisation was for skin-to-skin with one of the parents or standard care with supportive positioning by parents for the first of two consecutive eye examinations. The pain score was measured twice using the Premature Infant Pain Profile (PIPP) during and after the eye examination. The infants' movement activity was video recorded after the examination. RESULTS: There was no difference in mean pain scores with skin-to-skin contact versus standard care during (10.2 vs. 10.3, p = 0.91) or after (7.0 vs. 6.8, p = 0.76) the procedure. Independent of the randomisation group, PIPP scores were lower than previous comparable studies have found. Bouts of movement activity were also the same whether the examination was conducted in skin-to-skin position or in the incubator (p = 0.91). CONCLUSION: Skin-to-skin contact during the eye examination did not provide additional pain relief compared to standard care where the parents were already a part of the multidimensional approach.

Randomised controlled trial showed that neonates received better pain relief from a higher dose of sucrose during venepuncture.

AIM: We compared the effect of two different doses of sucrose on neonatal pain scores during venepuncture. METHODS: This randomised crossover study focused on neonates born weighing more than 1000 g from December 2014 to June 2016, who received neonatal intensive care at two hospitals: one in Empangeni, South Africa, and one in Trondheim, Norway. During two consecutive venepuncture procedures, 27 neonates from South Africa and 26 neonates from Norway were randomised to receive 0.2 mL or 0.5 mL sucrose. Half was administered two minutes before venepuncture and the rest immediately before the procedure. South Africa used 25% sucrose and Norway 24%. Pain scores were measured twice using the Premature Infant Pain Profile-Revised: during skin puncture and after the needle was removed. RESULTS: The mean pain scores during skin puncture were significantly lower with 0.5 mL sucrose than with 0.2 mL (5.3 versus 6.8, p=0.008), but the mean pain scores after the needle was removed were similar with both doses (4.7 versus 5.4, p=0.29). We found no significant association between weight and pain scores. CONCLUSION: We showed that neonates received better pain relief from 0.5 mL than 0.2 mL sucrose during venepuncture but not after the needle was removed.

Computer-based video analysis identifies infants with absence of fidgety movements.

BackgroundAbsence of fidgety movements (FMs) at 3 months' corrected age is a strong predictor of cerebral palsy (CP) in high-risk infants. This study evaluates the association between computer-based video analysis and the temporal organization of FMs assessed with the General Movement Assessment (GMA).MethodsInfants were eligible for this prospective cohort study if referred to a high-risk follow-up program in a participating hospital. Video recordings taken at 10-15 weeks post term age were used for GMA and computer-based analysis. The variation of the spatial center of motion, derived from differences between subsequent video frames, was used for quantitative analysis.ResultsOf 241 recordings from 150 infants, 48 (24.1%) were classified with absence of FMs or sporadic FMs using the GMA. The variation of the spatial center of motion (CSD) during a recording was significantly lower in infants with normal (0.320; 95% confidence interval (CI) 0.309, 0.330) vs. absence of or sporadic (0.380; 95% CI 0.361, 0.398) FMs (P<0.001). A triage model with CSD thresholds chosen for sensitivity of 90% and specificity of 80% gave a 40% referral rate for GMA.ConclusionQuantitative video analysis during the FMs' period can be used to triage infants at high risk of CP to early intervention or observational GMA.

Case-control study demonstrates that surfactant without intubation delayed mechanical ventilation in preterm infants.

AIM: This Norwegian study explored whether administering surfactant without intubation (SWI) delayed the need for early mechanical ventilation and reduced respiratory and nonrespiratory complications in infants born before 32 weeks of gestational age. METHODS: We compared 262 infants admitted to a level-three neonatal intensive care unit: 134 born before the introduction of SWI on 1 December 2011 were in the control group and 128 infants born after this date were in the study group. RESULTS: The proportion of infants treated with surfactant did not differ between the groups, but mechanical ventilation before 72 hours of life was lower in the study group than the control group, with an odds ratio (OR) of 0.58 and a 95% confidence interval (CI) of 0.35-0.96. Fewer study group infants needed supplemental oxygen at 28 days of life. One study infant and nine control infants had intraventricular haemorrhage grades 3-4 and, or, cystic periventricular leukomalacia (OR 0.10, 95% CI 0.01-0.83). These results were strengthened in analyses restricted to surfactant-treated infants and the proportion needing supplemental oxygen at 36 weeks was reduced. CONCLUSION: Surfactant without intubation reduced the need for early mechanical ventilation and major brain injuries in infants born at <32 weeks of gestation.

Randomized trial of hemiarthroplasty versus internal fixation for femoral neck fractures: no differences at 6 years.

BACKGROUND: Hemiarthroplasty has been shown superior to internal fixation for displaced femoral neck fractures (FNF) in the first 2 years. However, there are unanswered questions about the performance of hemiarthroplasty over the longer term compared with internal fixation. QUESTIONS/PURPOSES: We sought to compare hemiarthroplasty with internal fixation in terms of (1) outcomes scores for pain, hip function, and quality of life at a minimum of 5 years after surgery in a randomized trial. A secondary purpose was to compare (2) patient survival and (3) frequency of reoperation in the two groups. METHODS: A total of 222 consecutive patients older than 60 years, including those cognitively impaired, with FNF were randomized to either internal fixation with two parallel screws or bipolar hemiarthroplasty. At a minimum followup of 4.9 years (mean, 5.9 years; range, 4.9-7.2 years), 68 of the 70 surviving patients were examined by a study nurse and study physiotherapist blinded to initial treatment. Questionnaires on hip function (Harris hip score), quality of life (Eq5D), and activity of daily living function (Barthel ADL) were administered. The Barthel ADL index score was split into good function (score 95 or 100) and reduced function (score below 95). RESULTS: The mean survival of the groups was similar with 66.4% (73 of 110) of the patients undergoing hemiarthroplasty and 70.5% (79 of 112) of the patients undergoing internal fixation having died since surgery (p = 0.51). Only 12 of 31 living patients in the internal fixation group had retained their native hips at a mean of 6 years. Between 2 and 6 years, there were two new major reoperations (both in the internal fixation group, for avascular necrosis and deep wound infection). The mean Harris hip score was 66 (SD 19) and 67 (SD 20) in the internal fixation and hemiarthroplasty groups, respectively (p = 0.96). The mean Eq5D index was 0.50 (SD 0.40) in the internal fixation group and 0.34 (SD 0.36) in the hemiarthroplasty group (p = 0.10). Function in terms of ADLs was comparable between the groups; of the patients in the internal fixation group, 42% reported good function on the Barthel ADL index, and the corresponding number in the hemiarthroplasty group was 51% (p = 0.44). CONCLUSIONS: Hemiarthroplasty has predictable and good long-term results after FNF and is the treatment of choice compared with internal fixation. Further studies will evaluate if total hip arthroplasty has advantages over hemiarthroplasty in patients with fracture with long life expectancy.

Development of Movement and Postural Patterns in Full-Term Infants Who Are at Low Risk in Belgium, India, Norway, and the United States.

OBJECTIVE: The objective of this study was to investigate the influences on motor development in infants who are at low risk from Belgium, India, Norway, and the United States (US) using the General Movement Assessment (GMA) at 10-16 weeks post-term age. METHODS: This was a cross-sectional study of prospectively enrolled full-term infants at low risk (n = 186). Certified GMA observers rated the fidgety movements, quality of the movement patterns, age-adequacy of the movement repertoire, postural patterns, movement character, and overall Motor Optimality Score - Revised (MOS-R). Scores were evaluated for associations with sex, birth weight category, gestational age, post-term age at video, and country. RESULTS: The majority of infants had normal fidgety movements (179/186, 96.2%). This did not vary by sex, birth weight, gestational age, post-term age at video, or country. All infants showed normal>atypical movement patterns. Variability was seen for age adequacy (optimal: 137/183, 74.9%), postural patterns (normal>atypical: 164/183, 89.6%), and smooth/ fluent movement character (138/183, 75.4%). Gestational age and post-term age at video were associated with atypical postural patterns but in multivariable regression, only younger post-term age retained significance (OR 2.94, 95% CI: 1.05-8.24). Lack of age adequacy was associated with post-term age (OR 13.15, 95% CI: 4.36-39.72), and country (compared with Norway; Belgium OR 3.38 95% CI:12.4-9.22; India OR 3.16, 95% CI:1.01-9.87: US not significant). Infants from India also showed lower rates of an optimal MOS-R (25-28) than infants from Norway. CONCLUSIONS: The normality and temporal organization of fidgety movements did not differ by sex, birth weight, post-term age, or country, suggesting that the fidgety movements are free of cultural and environmental influences. The majority of full-term infants who were healthy in this cohort showed normal scores for all aspects of motor development tested using the MOS-R. Differences in age adequacy and MOS-R by country warrant investigation with larger cohorts and longitudinal follow up. IMPACT STATEMENT: Understanding variations in typical motor development is essential to interpreting patterns of movement and posture in infants at risk for atypical development. Using the framework of Prechtl's General Movements Assessment, this study showed that the development of movement and posture in healthy infants were affected by age and country of birth, but the development of the fidgety movements appeared to be free of these influences. Local norms may be needed to interpret the Motor Optimality Score-Revised in all populations but further research on this topic is needed.

Technical Skills Curriculum in Neonatology: A Modified European Delphi Study.

INTRODUCTION: Simulation-based training (SBT) aids healthcare providers in acquiring the technical skills necessary to improve patient outcomes and safety. However, since SBT may require significant resources, training all skills to a comparable extent is impractical. Hence, a strategic prioritization of technical skills is necessary. While the European Training Requirements in Neonatology provide guidance on necessary skills, they lack prioritization. We aimed to identify and prioritize technical skills for a SBT curriculum in neonatology. METHODS: A three-round modified Delphi process of expert neonatologists and neonatal trainees was performed. In round one, the participants listed all the technical skills newly trained neonatologists should master. The content analysis excluded duplicates and non-technical skills. In round two, the Copenhagen Academy for Medical Education and Simulation Needs Assessment Formula (CAMES-NAF) was used to preliminarily prioritize the technical skills according to frequency, importance of competency, SBT impact on patient safety, and feasibility for SBT. In round three, the participants further refined and reprioritized the technical skills. Items achieving consensus (agreement of ≥75%) were included. RESULTS: We included 168 participants from 10 European countries. The response rates in rounds two and three were 80% (135/168) and 87% (117/135), respectively. In round one, the participants suggested 1964 different items. Content analysis revealed 81 unique technical skills prioritized in round two. In round three, 39 technical skills achieved consensus and were included. CONCLUSION: We reached a European consensus on a prioritized list of 39 technical skills to be included in a SBT curriculum in neonatology.

Skin-to-skin contact in the delivery room for very preterm infants: a randomised clinical trial.

OBJECTIVE: Evaluating safety, feasibility and effects on physiological parameters of skin-to-skin contact (SSC) from birth between mothers and very preterm infants in a high-income setting. DESIGN: Open-label randomised controlled trial. SETTING: Three Norwegian neonatal units. PATIENTS: Preterm infants at gestational age (GA) 280-316 weeks and birth weight >1000g delivered vaginally or by caesarean section (C-section). INTERVENTION: Two hours of early SSC between the mother and the infant compared to standard care (SC) where the infant is separated from the mother and transferred to the neonatal unit in an incubator. RESULTS: 108 infants (63% male, 57% C-section, mean (SD) GA 30.3 weeks (1.3) and birth weight 1437 g (260)) were included. Median (IQR) age at randomisation was 23 min (17-30). During the first 2 hours after randomisation, 4% (2 of 51) and 7% (4 of 57) were hypothermic (<36.0°C) in the SSC and SC group, respectively (p=0.68, OR 0.5, 95% CI 0.1 to 3.1). Significantly fewer infants in the SSC group had hyperthermia (>37.5°C) (26% (13 of 57) vs 47% (27 of 51), respectively, p=0.02, OR 0.4, 95% CI 0.2 to 0.9). No infant needed mechanical ventilation within the first 2 hours. Median (IQR) duration of SSC was 120 (80-120) min in the intervention group. There was no difference in heart rate, respiratory rate and oxygen saturation between groups during the first 24 hours. CONCLUSION: This study from a high-income setting confirmed that SSC from birth for very preterm infants was safe and feasible. Physiological parameters were not affected by the intervention. The long-term effects on neurodevelopment, maternal-infant bonding and maternal mental health will be collected. TRIAL REGISTRATION NUMBER: NCT02024854.

Continuous monitoring of cerebral blood flow during general anaesthesia in infants.

Background: General anaesthesia is associated with neurocognitive deficits in infants after noncardiac surgery. Disturbances in cerebral perfusion as a result of systemic hypotension and impaired autoregulation may be a potential cause. Our aim was to study cerebral blood flow (CBF) velocity continuously during general anaesthesia in infants undergoing noncardiac surgery and compare variations in CBF velocity with simultaneously measured near-infrared spectroscopy (NIRS), blood pressure, and heart rate. Methods: NeoDoppler, a recently developed ultrasound system, was used to monitor CBF velocity via the anterior fontanelle during induction and maintenance of general anaesthesia until the start of surgery, and during recovery. NIRS, blood pressure, and heart rate were monitored simultaneously and synchronised with the NeoDoppler measurements. Results: Thirty infants, with a median postmenstrual age at surgery of 37.6 weeks (range 28.6-60.0) were included. Compared with baseline, the trend curves showed a decrease in CBF velocity during induction and maintenance of anaesthesia and returned to baseline values during recovery. End-diastolic velocity decreased in all infants during anaesthesia, on average by 59%, whereas peak systolic- and time-averaged velocities decreased by 26% and 45%, respectively. In comparison, the reduction in mean arterial pressure was only 20%. NIRS values were high and remained stable. When adjusting for mean arterial pressure, the significant decrease in end-diastolic velocity persisted, whereas there was only a small reduction in peak systolic velocity. Conclusions: Continuous monitoring of CBF velocity using NeoDoppler during anaesthesia is feasible and may provide valuable information about cerebral perfusion contributing to a more targeted haemodynamic management in anaesthetised infants.

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.

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.