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ObjectiveTo assess the rate, location, risk factors, management, and outcomes of neonatal thrombosis (NT).DesignA retrospective study investigating infants admitted to NICUs in Canadian Neonatal Network between January 2014 and December 2016 and diagnosed with NT. Each infant with NT was matched with an infant without NT.ResultsOf 39,971 infants, 587 (1.5%) were diagnosed with NT: 440 (75%) venous, 112 (19%) arterial, 29 (5%) both. NT rate was 1.4% in full-term and 1.7% in preterm infants. Venous thrombi occurred most commonly in the portal vein and arterial thrombi in the cerebral artery. Conservative management and low molecular weight heparin were the most common treatment modalities. Hospital stay was longer (p < 0.001) in the NT patients, but mortality was similar.ConclusionsNT was diagnosed in ~15/1000 NICU admissions and most commonly in the portal vein and cerebral arteries. Management varied based on the type and location of thrombi. Large multicenter trials are needed to address the best management strategies.

ObjectiveTo evaluate the effect of prophylactic probiotic (PP) administration on rates of necrotizing enterocolitis (NEC), late-onset sepsis (LOS), and mortality in preterm infants.Study designWe conducted a retrospective cohort study of infants < 29 weeks’ gestation, admitted to neonatal intensive care units participating in the Canadian Neonatal Network between 1 January 2014 and 31 December 2015. Infants in the exposure group received PP. A multiple logistic regression model with generalized estimation equation was used.ResultsA total of 3093 infants were included, 652 infants (21%) received PP. The adjusted odds ratios (aOR) of NEC (aOR 0.64, 95% confidence interval [CI] 0.410, 0.996), mortality (aOR 0.41, 95% CI 0.26, 0.63), and a composite of NEC or mortality were significantly lower in the PP group. There was no significant difference in the aOR of LOS.ConclusionProphylactic probiotic administration is associated with a reduction in NEC and mortality in preterm infants.

Purpose: Is machine learning (ML) superior to the traditionally used logistic regression (LR) in prediction of neurodevelopmental outcomes in preterm infants? Objectives: To develop and internally validate a ML model to predict neurodevelopmental impairment (NDI) in very preterm infants (<31 weeks) at 36 months corrected age, using clinical predictors. Methods: A retrospective cohort of very preterm infants (230–306 weeks) born between January 2004 and December 2016 in Nova Scotia, Canada. Survivors with neurodevelopmental assessment at 36 months corrected age were included. The study sample was randomly split (80:20) into a development and testing datasets. We compared four methods: LR, elastic net (EN), random forest ensemble (RF) and gradient boosting (XGB), in relation to discrimination (AUC), calibration, and diagnostic properties. Results: Of 811 eligible infants, 663 were included (mean gestational age 28 weeks, mean birth weight 1137 g and 52% male). Of those, 195 (29%) developed NDI and 468 (71%) did not. On internal validation using the testing dataset, all four models provided good discrimination of NDI with comparable AUC. RF was superior to the other three methods with a higher AUC (0.79 vs. 0.74, 0.74, and 0.73 for XGB, EN and LR, respectively), but all models have overlapped CIs. Conclusions: In this population-based cohort of very preterm infants, RF was superior to conventional LR in prediction of NDI at 3 years corrected age. Accurate prediction of preterm infants at risk of NDI enables early referrals for intervention programs and resources allocation toward those who are most likely to benefit.

Objective: The aim of this study was to evaluate the neurodevelopmental outcome at 18–24 months in surviving preterm infants with grades I–IV intraventricular hemorrhages (IVHs) compared to those with no IVH. Study Design: We included preterm survivors <29 weeks’ GA admitted to the Canadian Neonatal Network’s NICUs from April 2009 to September 2011 with follow-up data at 18–24 months in a retrospective cohort study. The neonates were grouped based on the severity of the IVH detected on a cranial ultrasound scan and recorded in the database: no IVH; subependymal hemorrhage or IVH without ventricular dilation (grades I–II); IVH with ventricular dilation (grade III); and persistent parenchymal echogenicity/lucency (grade IV). The primary outcomes of neurodevelopmental impairment (NDI), significant neurodevelopmental impairment (sNDI), and the effect modification by other short-term neonatal morbidities were assessed. Using multivariable regression analysis, the adjusted ORs (AOR) and 95% of the CIs were calculated. Results: 2327 infants were included. The odds of NDI were higher in infants with grades III and IV IVHs (AOR 2.58, 95% CI 1.56, 4.28 and AOR 2.61, 95% CI 1.80, 3.80, respectively) compared to those without IVH. Infants with an IVH grade ≤II had similar outcomes for NDI (AOR 1.08, 95% CI 0.86, 1.35) compared to those without an IVH, but the odds of sNDI were higher (AOR 1.58, 95% CI 1.16, 2.17). Conclusions: There were increased odds of sNDI in infants with grades I–II IVHs, and an increased risk of adverse NDI in infants with grades ≥III IVHs is corroborated with the current literature.

ObjectiveTo evaluate outcomes of preterm infants <26 weeks gestational age (GA) following postdelivery extensive cardiopulmonary resuscitation (ECPR) compared with airway and breathing support (ABS).Study designRetrospective review of Canadian Neonatal Network data during January 2010 to December 2016. The primary outcome was death or severe morbidity (intraventricular hemorrhage ≥grade 3 or periventricular leucomalacia, retinopathy of prematurity ≥stage 3, bronchopulmonary dysplasia, or necrotizing enterocolitis).ResultAmong 3633 infants analyzed, 433 (11.9%) received ECPR. In multivariable analysis, death or severe morbidity was higher in the ECPR versus ABS group [adjusted odds ratio 2.26 (95% confidence interval 1.49, 3.43)]. The majority of the difference was due to increased mortality, which occurred mostly during the first week of life.ConclusionThese data from a recent cohort of infants near the limits of viability may be useful for prognostication for health care providers and counseling of parents.

Neurodevelopmental challenges in children born very preterm are common and not improving. This study tested the feasibility of using Evidence-based Practice to Improve Quality (EPIQ), a proven quality improvement technique that incorporates scientific evidence to target improving language abilities in very preterm populations in 10 Canadian neonatal follow-up programs. Feasibility was defined as at least 70% of sites completing four intervention cycles and 75% of cycles meeting targeted aims. Systematic reviews were reviewed and performed, an online quality improvement educational tool was developed, multidisciplinary teams that included parents were created and trained, and sites provided virtual support to implement and audit locally at least four intervention cycles of approximately 6 months in duration. Eight of ten sites implemented at least four intervention cycles. Of the 48 cycles completed, audits showed 41 (85%) met their aim. Though COVID-19 was a barrier, parent involvement, champions, and institutional support facilitated success. EPIQ is a feasible quality improvement methodology to implement family-integrated evidence-informed interventions to support language interventions in neonatal follow-up programs. Further studies are required to identify potential benefits of service outcomes, patients, and families and to evaluate sustainability.

IntroductionVentilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality among neonates requiring life-saving mechanical ventilation in neonatal intensive care units (NICUs), particularly those who are born prematurely and/or with very-low-birth-weight (VLBW), or critically ill. Despite its clinical significance, neonatal VAP lacks standardised diagnostic criteria, resulting in variability in incidence reporting, over or under diagnosis and inappropriate antimicrobial use which further exacerbates the emergence of antibiotic-resistant organisms. Current diagnostic criteria and prevention strategies, often adapted from paediatric populations and adults, fail to address the unique anatomical and clinical characteristics of neonates. Building on a pilot investigation across Canadian NICUs, the goal of this study is to establish standardised, neonatal-specific VAP diagnostic criteria and prevention strategies to improve diagnostic accuracy, promote antimicrobial stewardship and enhance clinical outcomes.Methods and analysisBeginning in 2025, a 4-year, multicentre, prospectively-designed retrospective cohort study will be conducted across tertiary NICUs in Canada. All VLBW (birth weight <1500 g) neonates admitted to participating NICUs will be included. Our first aim is to use the Canadian Neonatal Network (CNN) platform, integrated with advanced data screening tools, to collect standardised demographic, clinical, ventilatory and microbiological data to assess VAP incidence and outcomes based on existing definitions. Next, we will develop a neonatal-specific VAP diagnostic criteria, by combining statistical analyses, including univariate analysis, multivariable logistic regression and receiver operating characteristic analyses, with expert consensus building through the Delphi method. Concurrently, we will focus on implementing evidence-based VAP prevention strategies and evaluate outcome measures, such as VAP incidence, adherence to prevention bundles and antimicrobial stewardship practices.Ethics and disseminationThis study has received ethics approval from the University of Alberta Health Research Ethics Board-Health Panel (Pro00149177). Findings will be disseminated through open-access publications, conference presentations and online platforms to promote widespread adoption.Trial registration numberNCT07109791.

Introduction/Background Peripherally inserted central catheters (PICC) are an essential and common procedure in neonatal intensive care units (NICUs). Peripheral nerve injuries secondary to PICC extravasation are a rare occurrence in neonates, who commonly recover with no sequalae. Rarely, extravasation results in compression and ischemia involving adjacent nerves, muscles or joints. Peripheral nerve injury may be induced by compression from tissue infiltration or irritation by the infiltrate. Timely diagnosis and treatment are essential to avoid complex or irreversible nerve damage, such as compartment syndrome, requiring extensive interventions. Isolated radial nerve injury in infants and neonates is limited to a few cases reported in the literature, which have been commonly related to in-utero compression or birth injury due to peripheral positioning. We report a late presentation of an isolated radial nerve injury secondary to PICC extravasation in a preterm infant, leading to neuropraxia and long-term impairment of hand function. Case Description An extreme preterm female infant (245/7 weeks’ gestation, 640 grams) was admitted to the NICU with a complex neonatal course. At 6 days after birth, a right antecubital PICC was inserted for vascular access and to provide parenteral nutrition. It was removed after 18 days following extravasation. Two months later, she developed a right wrist drop, flexed fingers, and edema of the right hand. Her right wrist flexion, elbow flexion, shoulder joint range of motion, and sensation remained intact. A Doppler study showed a small non-occlusive clot in the right brachial vein, attributed to the previous PICC. She was unable to voluntarily open her right hand or extend her metacarpophalangeal (MCP) or interphalangeal (IP) joints (see Figure A, below). Clinical diagnosis of radial nerve palsy was made, and she was referred to physiotherapy (PT) and occupational therapy (OT). Splinting, passive exercise and left-hand constraint resulted in some improvement of the right hand’s strength. At 12 months of age, she had left hand preference with limited active extension of right MCPs and IPs (Figure B). She received a Botox injection to the right-hand flexors to allow strengthening of the extensor muscles. Follow-up at 18 months showed full extension of the index and middle finger MCPs and IPs, but residual lag in ring and small finger IPs. Discussion To our knowledge, this is the first case report of isolated radial nerve injury in an infant following PICC extravasation and soft tissue infiltration. Interestingly, the clinical signs of radial nerve injury in this case presented almost two months after PICC extravasation. Additionally, the left-hand preference and limitation of the active extension of the fingers of the right hand remained at one year of corrected age. Given that this has exceeded the expected recovery time of radial nerve palsy, Botox injection was performed with good response and near age-appropriate development of fine motor skills at 18 months of corrected age. Paediatricians should be aware that the manifestation of potential nerve injury in neonates may have a delayed presentation. Neurology consultation to confirm the diagnosis and rule out other causes of muscle weakness, and referral to PT/OT, are crucial for managing infants and neonates with peripheral nerve injury because treatment is largely focused on splinting and passive motion exercise. Generally, radial nerve palsy carries a relatively good prognosis, with complete functional recovery within 1-6 months. The fact that this case developed long-term complications with impaired right-hand function, despite nerve recovery, raises concerns about the prognosis. Conclusion Peripherally inserted central venous catheters are an everyday procedure in the NICU. Radial nerve palsy secondary to venous catheter extravasation is rare in infants and neonates. Clinicians should be aware of the clinical signs of radial nerve palsy and initiate consultation and referral to physiotherapy and occupational therapy early. Families can be reassured of the good prognosis and functional recovery.

Objective Accurate and early prediction of neurodevelopmental impairment is a crucial endeavor in caring for very preterm infants (<31 weeks’ gestation). Sequential cranial ultrasound is the standard of care for the evaluation of preterm brain injury. However, there is no consensus on the timing and frequency of ultrasound screening. At Izaak Walton Killam (IWK) Health Centre, Halifax, Canada, four-time points for routine ultrasound of very preterm infants are performed at weeks 1, 2, 6, and term age. The hypothesis behind this work is that a three-time-point model will be appropriate for neurodevelopmental impairment prognostication. Materials and methods In this retrospective cohort, all very preterm infants (22 0 –30 6  weeks) born between January 2004 and December 2018 with a neurodevelopmental assessment at 36 months corrected age were included. Three prediction models of neurodevelopmental impairment were compared: A reference model including the gestational age, infant sex, and 2-week and 6-week ultrasound A model including the gestational age, infant sex, and 6-week ultrasound A model including the gestational age, infant sex, and 2-week ultrasound Results Of 786 eligible preterm infants born during the study period, 656/786 survivors were included in the analysis (mean gestational age 27 5  weeks, mean birth weight 1,133 g, and 55% male infants). At 36 months of corrected age, 30% developed neurodevelopmental impairment. All three models provided comparable discrimination areas under the curve (AUC) of neurodevelopmental impairment at 36 months of corrected age. Both the 6-week and the reference model had similar AUC of 0.68 (95% CI 0.63–0.72) and were not noticeably different from the 2-week model (AUC 0.66 (95% CI 0.61–0.70)). The 6-week model provided the best prediction with the lowest Akaike information criterion (AIC) of 766 for the 6-week-only model, AIC 769 for combined weeks 2 and 6 (reference model), and AIC 784 for the 2-week-only model. Conclusion In this cohort of very preterm infants, a model including 6-week ultrasound only was comparable to a reference model combining 2-week and 6-week ultrasound and showed nearly identical predictive performance of neurodevelopmental impairment at 36 months corrected age across a broad set of metrics; thus, it is redundant to do both the 2-week and 6-week ultrasound. Clinical relevance statement Late ultrasound at 6 weeks of age provided comparable diagnostic and prognostic information to a reference model combining 2-week and 6-week ultrasound and, if anything, was slightly superior to the 2-week ultrasound model, across a broad set of metrics. The 2-week ultrasound can be eliminated with no impact on the prediction of neurodevelopmental impairment at 36 months, promoting prudent resource allocation and stewardship in healthcare. Graphical Abstract