Respiratory outcomes and survival after unplanned extubation in the NICU: a prospective cohort study from the SEPREVEN trial.

OBJECTIVE: To compare reintubation rates after planned extubation and unplanned extubation (UE) in patients in neonatal intensive care units (NICUs), to analyse risk factors for reintubation after UE and to compare outcomes in patients with and without UE. DESIGN: Prospective, observational study nested in a randomised controlled trial (SEPREVEN/Study on Epidemiology and PRevention of adverse EVEnts in Neonates). Outcomes were expected to be independent of the intervention tested. SETTING: 12 NICUs in France with a 20-month follow-up, starting November 2015. PATIENTS: n=2280 patients with a NICU stay >2 days, postmenstrual age ≤42 weeks on admission. INTERVENTIONS/EXPOSURE: Characteristics of UE (context, timing, sedative administration in the preceding 6 hours, weaning from ventilation at time of UE) and patients. MAIN OUTCOME MEASURES: Healthcare professional-reported UE rates, reintubation/timing after extubation, duration of mechanical ventilation, mortality and bronchopulmonary dysplasia (BPD). RESULTS: There were 162 episodes of UE (139 patients, median gestational age (IQR) 27.3 (25.6-31.7) weeks). Cumulative reintubation rates within 24 hours and 7 days of UE were, respectively, 50.0% and 57.5%, compared with 5.5% and 12.3% after a planned extubation. Independent risk factors for reintubation within 7 days included absence of weaning at the time of UE (HR, 95% CI) and sedatives in the preceding 6 hours (HR 1.93, 95% CI 1.04 to 3.60). Mortality at discharge did not differ between patients with planned extubation or UE. UE was associated with a higher risk of BPD. CONCLUSION: In the SEPREVEN trial, reintubation followed UE in 58% of the cases, compared with 12% after planned extubation. TRIAL REGISTRATION NUMBER: NCT02598609.

Use of neonatal lung ultrasound in European neonatal units: a survey by the European Society of Paediatric Research.

OBJECTIVE: Regarding the use of lung ultrasound (LU) in neonatal intensive care units (NICUs) across Europe, to assess how widely it is used, for what indications and how its implementation might be improved. DESIGN AND INTERVENTION: International online survey. RESULTS: Replies were received from 560 NICUs in 24 countries between January and May 2023. LU uptake varied considerably (20%-98% of NICUs) between countries. In 428 units (76%), LU was used for clinical indications, while 34 units (6%) only used it for research purposes. One-third of units had <2 years of experience, and only 71 units (13%) had >5 years of experience. LU was mainly performed by neonatologists. LU was most frequently used to diagnose respiratory diseases (68%), to evaluate an infant experiencing acute clinical deterioration (53%) and to guide surfactant treatment (39%). The main pathologies diagnosed by LU were pleural effusion, pneumothorax, transient tachypnoea of the newborn and respiratory distress syndrome. The main barriers for implementation were lack of experience with technical aspects and/or image interpretation. Most units indicated that specific courses and an international guideline on neonatal LU could promote uptake of this technique. CONCLUSIONS: Although LU has been adopted in neonatal care in most European countries, the uptake is highly variable. The main indications are diagnosis of lung disease, evaluation of acute clinical deterioration and guidance of surfactant. Implementation may be improved by developing courses and publishing an international guideline.

Gastrointestinal effects of caffeine in preterm infants: a systematic review and Bayesian meta-analysis.

OBJECTIVE: Caffeine is widely used in preterm infants to prevent or treat apnoea of prematurity. Adverse gastrointestinal effects of caffeine have not been thoroughly researched in preterm infants. With this systematic review and meta-analysis, we aim to summarise the results of trials on the gastrointestinal effects of caffeine in preterm infants. DESIGN: We searched MEDLINE, Web of Science, Scopus and ClinicalTrials.gov up to 21 April 2023. We included randomised controlled trials assessing caffeine versus placebo in preterm neonates and reporting gastrointestinal side effects. Risk of bias was assessed using the Cochrane Risk of Bias tool. A Bayesian meta-analysis was performed to estimate the pooled OR of gastrointestinal side effects. RESULTS: Nine trials involving 2746 preterm infants were analysed. Seven trials assessing necrotising enterocolitis and four trials assessing feeding intolerance in our meta-analysis found no differences between caffeine and placebo (OR=1.007 (95% credible interval 0.021, 5.462), I2=97.4%, and OR=1.266 (95% credible interval 0.064, 28.326), I2=84.8%, respectively). Four trials assessed the outcomes spontaneous intestinal perforation, constipation, gastrointestinal disorder (composite outcome: gastro-oesophageal regurgitation or dilated bowel loops), age at oral feeding and cholestasis syndrome and found no differences between groups. One trial assessed the outcomes gastro-oesophageal symptoms and duration of tube feeding and found that caffeine was associated with a reduced burden of gastro-oesophageal reflux symptoms at 2 weeks (p<0.05), but not at term. CONCLUSIONS: According to this systematic review and meta-analysis, the use of caffeine at usual doses in preterm infants does not seem to be associated with significant gastrointestinal adverse effects.

Data quality review of the Brazilian nosocomial infections surveillance system.

BACKGROUND: Surveillance of healthcare-associated infections (HAIs) is an essential component of hospital infection prevention and control systems. We aimed to assess the quality of the data compiled by the Brazilian HAI Surveillance System from pediatric (PICUs) and neonatal intensive care units (NICUs), between 2012 and 2021. METHODS: Data Quality Review, including adherence, completeness, internal consistency, consistency over time, and consistency of population trend, were computed at both national and state levels based on quality metrics from World Health Organization Toolkit. Incidence rates (or incidence density) of ventilator-associated pneumonia (VAP) and central line-associated bloodstream infection (CLABSI) were obtained from the Brazilian National Nosocomial Infections Surveillance (NNIS) system. Data on sepsis-related mortality, spanning the period from 2012 to 2021, were extracted from the Brazilian National Health Service database (DATASUS). Additionally, correlations between sepsis-related mortality and incidence rates of VAP or CLABSI were calculated. RESULTS: Throughout the majority of the study period, adherence to VAP reporting remained below 75%, exhibiting a positive trend post-2016. Widespread outliers, as well as inconsistencies over time and in population trends, were evident across all 27 states. Only four states maintained consistent adherence levels above 75% for more than 8 years regarding HAI incidence rates. Notably, CLABSI in NICUs boasted the highest reporting adherence among all HAIs, with 148 periods out of 270 (54.8%) exhibiting reporting adherence surpassing 75%. Three states achieved commendable metrics for CLABSI in PICUs, while five states demonstrated favorable results for CLABSI in NICUs. CONCLUSIONS: While adherence to HAI report is improving among Brazilian states, an important room for improvement in the Brazilian NNIS exists. Additional efforts should be made by the Brazilian government to improve the reliability of HAI data, which could serve as valuable guidance for hospital infection prevention and control policies.

Are multiple projections necessary when assessing umbilical venous catheter placement in neonates? A retrospective study.

INTRODUCTION: There is variability in clinical practice regarding the number of radiographic views required to accurately determine umbilical venous catheter (UVC) tip position. Some units prefer performing a single anteroposterior (AP) view and others do both AP and lateral views. The aim of this study was to compare the need for one versus two radiographical views to accurately determine UVC tip position. METHODS: Radiographs of 382 infants (all gestations) from two level six neonatal units were included in the study. Patients with congenital anomalies and those who had adjustment of UVC position between AP and lateral films being performed were excluded. Six clinicians reviewed anonymized AP only images and documented UVC tip position. Subsequently, they reviewed both AP and lateral views and again documented the UVC tip position. Results were compared to the expert consensus which was taken from the consensus of two paediatric radiologists. RESULTS: The study population had a mean gestational age of 32.8 weeks and birth weight of 2190 g, with 58% males. The UVC tip positions were accurately determined 76% times by the AP view alone and 82% times by using both the AP and lateral views (P < 0.001). The low placed UVC tip position which is the most inappropriate for use was more accurately determined by two images (78% times) rather than single image (70% times) (P < 0.001). CONCLUSIONS: Utilising both AP and lateral views was superior in accurately determining UVC tip position to AP view alone.

Does extremely early expression of colostrum after very preterm birth improve mother's own milk quantity? A cohort study.

OBJECTIVE: Assess the relationship of time to first expression after very preterm birth and mothers' own milk quantity. DESIGN: A cohort study (nested within a randomised trial). SETTING: Four neonatal units in the UK. PATIENTS: 132 mothers of single or twin infants born at 23+0 to 31+6 weeks postmenstrual age. EXPOSURES: Time to the first attempt to express after birth. PRIMARY OUTCOMES: 24-hour mother's own milk yield on days 4, 14 and 21 after birth. RESULTS: Median time to first expression attempt was 6 hours. 51.7% expressed within 6 hours of birth (62/120) and 48.3% expressed more than 6 hours after birth (58/120). Expressing within 6 hours of birth was associated with higher milk yield on day 4 (88.3 g, 95% CI 7.1 to 169.4) and day 14 (155.7 g, 95% CI 12.2 to 299.3) but not on day 21 (73.6 g, 95% CI -91.4 to 238.7). There was an interaction between expressing frequency and time to first expression (p<0.005), with increased expressing frequency being associated with higher yield only in those who expressed within 6 hours. Expressing within 2 hours of birth was not associated with further milk yield increase. CONCLUSIONS: Mothers who expressed within 6 hours of birth had higher milk yield, and a greater yield per expressing session, in the first 3 weeks after birth. This information will be highly motivating for families and the clinicians supporting them. There was no evidence of further benefit of extremely early expression (first 2 hours after birth). TRIAL REGISTRATION NUMBER: ISRCTN 16356650.

Outcomes following the adoption of standard parenteral nutrition in preterm infants: a whole-population non-concurrent control study.

OBJECTIVE: To evaluate the impact of a quality improvement project of the adoption of standard parenteral nutrition (SPN) in preterm infants. DESIGN: Retrospective, multicentre, whole-population, non-concurrent control study using data from the UK National Neonatal Research Database between 1 January 2014 and 31 December 2020. SETTING: Neonatal units in London UK organised by geographical network. PATIENTS: Preterm infants <31 weeks' gestation. INTERVENTIONS: Introduction of two SPN formulations previously tested in randomised controlled trials (NEON and SCAMP). SCAMP delivers a higher target macronutrient intake. MAIN OUTCOME MEASURES: The primary outcome was survival to discharge from neonatal care without major morbidities. Secondary outcomes included the individual components of the primary outcome and a comparison of outcomes between the NEON and the SCAMP formulations. RESULTS: Of 6538 eligible infants, 4693 were admitted to neonatal care before and 1845 after the adoption of SPN. Morbidity-free survival decreased by an average of 8.6% (95% CI 5.8% to 11.4%, p<0.0001) following adoption. The effect varied by type of formulation; the cohort that adopted NEON showed no difference in morbidity-free survival, whereas the cohort that adopted SCAMP showed a statistically significant decrease in morbidity-free survival. Overall survival decreased by an average of 2.0% (95% CI 0.01% to 4.0%, p=0.048). CONCLUSIONS: Research is urgently needed to identify the optimal composition of parenteral nutrition for preterm babies. This study also adds to the growing body of evidence that suggests that early and high intakes of macronutrients in preterm babies may be harmful.

One-step vs. two-step gestational diabetes mellitus screening and pregnancy outcomes: an updated systematic review and meta-analysis.

OBJECTIVE: We performed a systematic review and meta-analysis comparing maternal and neonatal outcomes of patients screened with one-step or two-step screening methods for GDM. DATA SOURCES: Pubmed, Scopus, Cochrane, ClinicalTrials.gov, and LILACS were searched from inception up to September 2022. STUDY ELIGIBILITY CRITERIA: Only randomized controlled trials (RCTs) were included. Studies that had overlapping populations were excluded (PROSPERO CRD42022358903). STUDY APPRAISAL AND SYNTHESIS METHODS: Risk ratios (RR) were computed with 95% confidence intervals (CI) by two authors. Unpublished data were requested. Large for gestational age (LGA) was the primary outcome. RESULTS: The search yielded 394 citations. Seven RCTs met inclusion criteria. A total of 54,650 participants were screened for GDM by either the one-step method (N=27,163) or the two-step method (N=27,487). For LGA, there were no significant differences found between groups (RR 0.99; 95% CI 0.93-1.05; I2=0%). Newborns of patients in one-step testing had higher rates of neonatal hypoglycemia (RR 1.24; 95% CI 1.14-1.34; I2 =0%) and NICU admissions (RR 1.13; 95% CI 1.04-1.21; I2=0%). Patients in the one-step group were more likely to be diagnosed with GDM (RR 1.73; 95% CI 1.44-2.09; I2=80%). In addition, among trials that tested all patients prior to and excluded patients with pregestational diabetes, newborns were more likely to have macrosomia (RR 1.27; 95% CI 1.21- 1.34; I2=0%). Overall risk of bias assessment was of low concern. CONCLUSIONS: LGA did not differ between patients screened by one-step method and those by two-step method. However, patients randomized to one-step method had higher rates of neonatal hypoglycemia and NICU admission as well as maternal GDM diagnosis than the two-step method.

Vibration-based mitigation of noxious-evoked responses to skin puncture in neonates and infants: a randomised controlled trial.

OBJECTIVE: To assess the effect of a non-noxious vibratory stimulus on noxious-evoked cortical responses to skin puncture and to determine whether the presence of certain behavioural components may be used to predict such cortical responses. DESIGN: Randomised controlled trial. SETTING: Level IV neonatal intensive care unit at a stand-alone children's hospital. PATIENTS: 134 hospitalised infants between 36 and 52 weeks' postmenstrual age and ordered to receive a clinically required laboratory draw. INTERVENTIONS: Infants randomised to receive the intervention, a vibratory stimulus at the site of skin puncture beginning 10 s prior to a heel stick, or the control, no vibration. MAIN OUTCOME MEASURES: Electroencephalography and video recording time-locked to the deployment of the lancet for the skin puncture. Noxious-evoked cortical responses were measured by the area under the curve in the somatosensory region contralateral to the skin puncture. Behavioural responses were coded through video analysis. RESULTS: Noxious-evoked cortical responses were significantly reduced in participants receiving the vibratory stimulus compared with the control (frontal, p<0.0001; central, p=0.0088; central-parietal, p=0.0111). There were no significant differences in behavioural responses between groups (all p>0.05). CONCLUSIONS: A non-noxious vibratory stimulus presented prior to and continuing simultaneously with skin puncture significantly mitigates nociception in hospitalised infants. The presence or absence of facial expression components is inadequate to reliably predict pain signalling in the brain. TRIAL REGISTRATION NUMBER: NCT04050384.

Birth weight and head circumference discordance and outcome in preterms: results from the EPIPAGE-2 cohort.

OBJECTIVE: To determine whether the relative measurement of birth weight (BW) and head circumference (HC) in preterm infants is associated with neurological outcomes. METHODS: The EPIPAGE-2 Study included 3473 infants born before 32 weeks' gestation, classified based on their Z-score of BW and HC on the Fenton curves as concordant (≤1 SD apart) or discordant (>1 SD difference). We defined four mutually exclusive categories: discordant smaller BW (sBW) with BW-1SD and concordant small measurement (CsM) with BW and HC concordant and both ≤-1SD. Neurological outcomes at 5.5 years were evaluated with standard tests. RESULTS: 2592 (74.8%) preterm neonates were categorised as CM, 258 (7.4%) CsM, 378 (10.9%) sHC and 239 (6.9%) sBW. Compared with the CM children, those born with CsM had significantly higher risks of cognitive deficiency (adjusted OR (aOR) 1.3, 95% CI (1.0 to 2.0)), developmental coordination disorders (aOR 2.6 (1.5 to 4.4)) and need for special school services (aOR 2.3 (1.5 to 3.7)). Those born with sBW had significantly lower risk of cognitive deficiency (aOR 0.6 (0.4 to 0.9)) and the sHC group significantly higher risk of developmental coordination disorders (aOR 1.8 (1.0 to 3.2)). CONCLUSIONS: The relative discordance of these preterm infants' BW and HC was associated with their neurological outcomes. It merits further exploration as an indirect indicator of development. TRIAL REGISTRATION NUMBER: NCT03078439.

Factors that impact second attempt success for neonatal intubation following first attempt failure: a report from the National Emergency Airway Registry for Neonates.

OBJECTIVE: To determine the factors associated with second attempt success and the risk of adverse events following a failed first attempt at neonatal tracheal intubation. DESIGN: Retrospective analysis of prospectively collected data on intubations performed in the neonatal intensive care unit (NICU) and delivery room from the National Emergency Airway Registry for Neonates (NEAR4NEOS). SETTING: Eighteen academic NICUs in NEAR4NEOS. PATIENTS: Neonates requiring two or more attempts at intubation between October 2014 and December 2021. MAIN OUTCOME MEASURES: The primary outcome was successful intubation on the second attempt, with severe tracheal intubation-associated events (TIAEs) or severe desaturation (≥20% decline in oxygen saturation) being secondary outcomes. Multivariate regression examined the associations between these outcomes and patient characteristics and changes in intubation practice. RESULTS: 5805 of 13 126 (44%) encounters required two or more intubation attempts, with 3156 (54%) successful on the second attempt. Second attempt success was more likely with changes in any of the following: intubator (OR 1.80, 95% CI 1.56 to 2.07), stylet use (OR 1.65, 95% CI 1.36 to 2.01) or endotracheal tube (ETT) size (OR 2.11, 95% CI 1.74 to 2.56). Changes in stylet use were associated with a reduced chance of severe desaturation (OR 0.74, 95% CI 0.61 to 0.90), but changes in intubator, laryngoscope type or ETT size were not; no changes in intubator or equipment were associated with severe TIAEs. CONCLUSIONS: Successful neonatal intubation on a second attempt was more likely with a change in intubator, stylet use or ETT size.

Can 3-dimensional cranial ultrasound be used to successfully reconstruct a 2-dimensional image without compromising on image quality in a neonatal population?

BACKGROUND: Cranial ultrasound is frequently performed in neonatal intensive care units and acquiring 2-dimensional (D) images requires significant training. Three-D ultrasound images can be acquired semi-automatically. OBJECTIVE: This proof-of-concept study aimed to demonstrate that 3-D study image quality compares well with 2-D. If this is successful, 3-D images could be acquired in remote areas and read remotely by experts. MATERIALS AND METHODS: This was a prospective study of 20 neonates, who underwent both routine 2-D and 3-D cranial ultrasounds. Images were reconstructed into standard views extracted from the 3-D volume and evaluated by three radiologists blinded to the acquisition method. The radiologists assessed for the presence of anatomical landmarks and overall image quality. RESULTS: More anatomical structures were identified in the 3-D studies (P<0.01). There was a trend that 3-D ultrasound demonstrated better image quality in the coronal plane, and 2-D in the sagittal plane, only reaching statistical significance for two coronal views and two sagittal views. CONCLUSION: Overall, this study has demonstrated that 3-D cranial ultrasound performs similarly to 2-D and could be implemented into neonatal practice.

Wales Infants' and childreN's Genome Service (WINGS): providing rapid genetic diagnoses for unwell children.

INTRODUCTION: This study reviews the first 3 years of delivery of the first National Health Service (NHS)-commissioned trio rapid whole genome sequencing (rWGS) service for acutely unwell infants and children in Wales. METHODS: Demographic and phenotypic data were prospectively collected as patients and their families were enrolled in the Wales Infants' and childreN's Genome Service (WINGS). These data were reviewed alongside trio rWGS results. RESULTS: From April 2020 to March 2023, 82 families underwent WINGS, with a diagnostic yield of 34.1%. The highest diagnostic yields were noted in skeletal dysplasias, neurological or metabolic phenotypes. Mean time to reporting was 9 days. CONCLUSION: This study demonstrates that trio rWGS is having a positive impact on the care of acutely unwell infants and children in an NHS setting. In particular, the study shows that rWGS can be applied in an NHS setting, achieving a diagnostic yield comparable with the previously published diagnostic yields achieved in research settings, while also helping to improve patient care and management.

Characteristics of children requiring admission to neonatal care and paediatric intensive care before the age of 2 years in England and Wales: a data linkage study.

OBJECTIVE: To quantify the characteristics of children admitted to neonatal units (NNUs) and paediatric intensive care units (PICUs) before the age of 2 years. DESIGN: A data linkage study of routinely collected data. SETTING: National Health Service NNUs and PICUs in England and Wales PATIENTS: Children born from 2013 to 2018. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Admission to PICU before the age of 2 years. RESULTS: A total of 384 747 babies were admitted to an NNU and 4.8% (n=18 343) were also admitted to PICU before the age of 2 years. Approximately half of all children admitted to PICU under the age of 2 years born in the same time window (n=18 343/37 549) had previously been cared for in an NNU.The main reasons for first admission to PICU were cardiac (n=7138) and respiratory conditions (n=5386). Cardiac admissions were primarily from children born at term (n=5146), while respiratory admissions were primarily from children born preterm (<37 weeks' gestational age, n=3550). A third of children admitted to PICU had more than one admission. CONCLUSIONS: Healthcare professionals caring for babies and children in NNU and PICU see some of the same children in the first 2 years of life. While some children are following established care pathways (eg, staged cardiac surgery), the small proportion of children needing NNU care subsequently requiring PICU care account for a large proportion of the total PICU population. These differences may affect perceptions of risk for this group of children between NNU and PICU teams.