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Abstract Background: Minimally invasive surfactant therapy (MIST) is a new strategy to avoid mechanical ventilation (MV) in respiratory distress syndrome. The primary aim of this study was to test MIST as a means of avoiding MV exposure and pneumothorax occurrence in moderate and late preterm infants (32 to 36 weeks’ gestational age). Methods: This was a randomized controlled trial including three Canadian centres. Patients were randomized to standard management or to the intervention if they required nasal continuous positive airway pressure of 6 cm H2O and 35% FiO2 in the first 24 hours of life. Patients from the intervention group received MIST immediately after inclusion. The primary outcome was either need for MV or development of a pneumothorax requiring a chest tube. To ensure that clinicians were not biased toward delaying intubation in the intervention group, clinical failure criteria were also used as a primary outcome. The primary outcome was analyzed using bivariate and multivariate logistic regressions. Results: Among 45 randomized patients, 24 were assigned to MIST and 21 to standard management. Eight infants (33%) from the intervention group met the primary outcome criteria versus 19 (90%) in the control group (absolute risk reduction 0.57, 95% confidence interval 0.54 to 0.60). One patient in each group reached the primary outcome because of pneumothorax occurrence. The other patients were exposed to MV. None of the patients reached the clinical failure criteria. Conclusion: MIST for respiratory distress syndrome management in moderate and late preterm infants was associated with a significant reduction of MV exposure and pneumothorax occurrence.

IntroductionDocosahexaenoic acid (DHA), an omega-3 fatty acid, is important for brain development with possible implications in neurodevelopmental outcomes. In the two-arm, randomised, double-blind, placebo-controlled Maternal Omega-3 Supplementation to Reduce Bronchopulmonary Dysplasia in Very Preterm Infants trial, very preterm infants (<29 weeks’ gestation) were supplemented in high doses of DHA or placebo until they reached 36 weeks’ postmenstrual age. We propose a long-term neurodevelopmental follow-up of these children. This protocol details the follow-up at 5 years of age, which aims to (1) confirm our long-term recruitment capacity and (2) determine the spectrum of neurodevelopmental outcomes at preschool age following neonatal DHA supplementation.Methods and analysisThis long-term follow-up involves children (n=194) born to mothers (n=170) randomised to DHA (n=85) or placebo (n=85) from the five sites in Quebec when they will be 5 years’ corrected age. The primary outcome measure is related to the long-term recruitment capacity, which we determined as successful if 75% (±10%, 95% CI) of the eligible children consent to the 5-year follow-up study. Interviews with mothers will be conducted to assess various aspects of neurodevelopment at preschool age (executive functions, behavioural problems, global development and health-related quality of life), evaluated with standardised neurodevelopmental questionnaires. In addition, a semistructured interview conducted in a subset of the mothers will be used to determine their acceptability and identify barriers and enablers to their eventual participation to the next phase of the trial. This follow-up study will require approximately 22 months to be completed.Ethics and disseminationThis study was approved by the CHU de Québec-Université Laval Research Ethics Board (MP-20-2022-5926). Mothers will provide informed consent before participating in this study. Findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration number NCT02371460.

ABSTRACT Objectives To determine the outcomes and resource usage of infants born at ≤ 25 weeks gestational age (GA). Methods Retrospective study of infants born between April 2009 and September 2011 at ≤ 25 weeks’ GA in all neonatal intensive care units in Canada with follow-up in the neonatal follow-up clinics. Short-term morbidities, neurodevelopmental impairment, significant neurodevelopmental impairment, and resource utilization of infants born at ≤ 24 weeks were compared with neonates born at 25 weeks. Results Of 803 neonates discharged alive, 636 (80.4%) infants born at ≤ 25 weeks’ GA were assessed at 18 to 24 months. Caesarean delivery, lower birth weight, and less antenatal steroid exposure were more common in infants born ≤ 24 weeks as compared with 25 weeks. They had significantly higher incidences of ductus arteriosus ligation, severe intracranial hemorrhage, retinopathy of prematurity as well as longer length of stay, central line days, days on respiratory support, days on total parenteral nutrition, days on antibiotics, and need for postnatal steroids. Neurodevelopmental impairment rates were 68.9, 64.5, and 55.6% (P=0.01) and significant neurodevelopmental impairment rates were 39.3, 29.6, and 20.9% (P<0.01) for infants ≤ 23, 24, and 25 weeks GA, respectively. Postdischarge service referrals were higher for those ≤ 23 weeks. Nonsurviving infants born at 25 weeks GA had higher resource utilization during admission than infants born less than 25 weeks. Conclusions Adverse outcomes and resource usage were significantly higher among infants born ≤ 24 weeks GA as compared with 25 weeks GA.

ObjectivesIdentify determinants of neurodevelopmental outcome in preterm children.MethodsProspective national cohort study of children born between 2009 and 2011 at <29 weeks gestational age, admitted to one of 28 Canadian neonatal intensive care units and assessed at a Canadian Neonatal Follow-up Network site at 21 months corrected age for cerebral palsy (CP), visual, hearing and developmental status using the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley-III). Stepwise regression analyses evaluated the effect of (1) prenatal and neonatal characteristics, (2) admission severity of illness, (3) major neonatal morbidities, (4) neonatal neuroimaging abnormalities, and (5) site on neurodevelopmental impairment (NDI) (Bayley-III score < 85, any CP, visual or hearing impairment), significant neurodevelopmental impairment (sNDI) (Bayley-III < 70, severe CP, blind or hearing aided and sNDI or death.ResultsOf the 3700 admissions without severe congenital anomalies, 84% survived to discharge and of the 2340 admissions, 46% (IQR site variation 38%–51%) had a NDI, 17% (11%–23%) had a sNDI, 6.4% (3.1%–8.6%) had CP, 2.6% (2.5%–13.3%) had hearing aids or cochlear implants and 1.6% (0%–3.1%) had a bilateral visual impairment. Bayley-III composite scores of <70 for cognitive, language and motor domains were 3.3%, 10.9% and 6.7%, respectively. Gestational age, sex, outborn, illness severity, bronchopulmonary dysplasia, necrotising enterocolitis, late-onset sepsis, retinopathy of prematurity, abnormal neuroimaging and site were significantly associated with NDI or sNDI. Site variation ORs for NDI, sNDI and sNDI/death ranged from 0.3–4.3, 0.04–3.5 and 0.12–1.96, respectively.ConclusionMost preterm survivors are free of sNDI. The risk factors, including site, associated with neurodevelopmental status suggest opportunities for improving outcomes.

ObjectiveTo examine the differences and trends of outcomes of preterm boys and girls born at <29 weeks’ gestation.DesignA retrospective cohort study.SettingData collected by the Canadian Neonatal Network.PatientsNeonates born at <29 weeks’ gestation between January 2007 and December 2016.Main outcome measuresWe examined rate differences in mortality, major morbidities (bronchopulmonary dysplasia, severe brain injury, retinopathy of prematurity, necrotising enterocolitis and late-onset sepsis) and care practices (antenatal steroids, magnesium sulfate, maternal antibiotics, ventilation and surfactant administration) between boys and girls and evaluated trends in these rate differences over the study period. Our primary outcome was a composite of mortality and any one of the five morbidities.ResultsOur study included 8219 boys and 6934 girls with median gestational age of 26 (IQR 25–28) weeks. The composite of death or major morbidity was more common in boys (adjusted risk ratio 1.07, 95% CI 1.05 to 1.10) and remained higher in boys over the study period. The gap between boys and girls for mortality, however, decreased over time: the slope for boys was −0.043 (95% CI −0.071 to −0.015) and for girls was −0.012 (95% CI −0.045 to 0.020) (p=0.04). All other morbidities remained higher in boys. Care practices changed at similar rates between the sexes.ConclusionThe difference between the mortality rates for boys and girls decreased over the study period but the difference between rates of the major morbidities was unchanged. More research is needed to understand biological differences and outcome disparities.

ObjectiveTo compare the characteristics and outcomes of neonates with mild hypoxic-ischemic encephalopathy (HIE) who received hypothermia versus standard care.Study designWe conducted a retrospective cohort study of neonates ≥35 weeks’ gestation and ≥1800 g admitted with a diagnosis of Sarnat stage 1 encephalopathy. We evaluated length of hospital stay, duration of ventilation, evidence of brain injury on MRI, and neonatal morbidities.ResultsOf 1089 eligible neonates, 393 (36%) received hypothermia and 595 (55%) had neuroimaging. The hypothermia group was more likely to be outborn, born via C-section, had lower Apgar scores, and required extensive resuscitation. They had longer durations of stay (9 vs. 6 days, P < 0.001), respiratory support (3 vs. 2 days, P < 0.001), but lower odds of brain injury on MRI (adjusted odds ratio 0.33, 95% CI: 0.22–0.52) compared with standard care group.ConclusionDespite prolongation of hospital stay, hypothermia may be potentially beneficial in neonates with mild HIE; however, selection bias cannot be ruled out.

ObjectiveTo assess the association of NICU occupancy with probability of discharge and length of stay (LOS) among infants born <33 weeks gestational age (GA).Study designRetrospective study of 3388 infants born 23–32 weeks GA, admitted to five Level 3/4 NICUs (2014-2018) and discharged alive. Standardized ratios of observed-to-expected number of discharges were calculated for each quintile of unit occupancy. Multivariable linear regression models were used to assess the association between occupancy and LOS.ResultsAt the lowest unit occupancy quintiles (Q1 and Q2), infants were 12% and 11% less likely to be discharged compared to the expected number. At the highest unit occupancy quintile (Q5), infants were 20% more likely to be discharged. Highest occupancy (Q5) was also associated with a 4.7-day (95% CI 1.7, 7.7) reduction in LOS compared Q1.ConclusionNICU occupancy was associated with likelihood of discharge and LOS among infants born <33 weeks GA.

ObjectiveIn a healthcare system with finite resources, hospital organisational factors may contribute to patient outcomes. We aimed to assess the association of nurse staffing and neonatal intensive care unit (NICU) occupancy with outcomes of preterm infants born <33 weeks’ gestation.DesignRetrospective cohort study.SettingFour level III NICUs.PatientsInfants born 23–32 weeks’ gestation 2015–2018.Main outcome measuresNursing provision ratios (nursing hours worked/recommended nursing hours based on patient acuity categories) and unit occupancy rates were averaged for the first shift, 24 hours and 7 days of admission of each infant. Primary outcome was mortality/morbidity (bronchopulmonary dysplasia, severe neurological injury, retinopathy of prematurity, necrotising enterocolitis and nosocomial infection). ORs for association of exposure with outcomes were estimated using generalised linear mixed models adjusted for confounders.ResultsAmong 1870 included infants, 823 (44%) had mortality/morbidity. Median nursing provision ratio was 1.03 (IQR 0.89–1.22) and median unit occupancy was 89% (IQR 82–94). In the first 24 hours of admission, higher nursing provision ratio was associated with lower odds of mortality/morbidity (OR 0.93, 95% CI 0.89 to 0.98), and higher unit occupancy was associated with higher odds of mortality/morbidity (OR 1.19, 95% CI 1.04 to 1.36). In causal mediation analysis, nursing provision ratios mediated 47% of the association between occupancy and outcomes.ConclusionsNICU occupancy is associated with mortality/morbidity among very preterm infants and may reflect lack of adequate resources in periods of high activity. Interventions aimed at reducing occupancy and maintaining adequate resources need to be considered as strategies to improve patient outcomes.

Abstract The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010–2017), we identified infants < 32-week gestational age with CPCDs, defined by “significant exposure” to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs (> 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6–7.5% and 0–100%, respectively) and late CPCDs (2.5–15% and 14–83%, respectively), all p < 0.01. Units’ late-CPCD incidence and mortality demonstrated an inverse relationship (slope =  −2.5, p < 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p < 0.01).Conclusions: Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work.What is Known:• Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide.• Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality.What is New:• This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state.• Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.

ObjectiveTo characterize variations in practices and outcomes for neonates with hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH) across Canadian tertiary Neonatal Intensive Care Units (NICUs).Study designRetrospective study of neonates admitted for HIE and treated with TH in 24 tertiary NICUs from the Canadian Neonatal Network, 2010–2020. The two primary outcomes of mortality before discharge and MRI-detected brain injury were compared across NICUs using adjusted standardized ratios (SR) with 95% CI.ResultsOf the 3261 neonates that received TH, 367 (11%) died and 1033 (37%) of the 2822 with MRI results had brain injury. Overall, rates varied significantly across NICUs for mortality (range 5–17%) and brain injury (range 28–51%). Significant variations in use of inotropes, inhaled nitric oxide, blood products, and feeding during TH were identified (p values < 0.01).ConclusionSignificant variations exist in practices and outcomes of HIE neonates treated with hypothermia across Canada.