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Background and objectiveNeonatal outcome research and clinical follow-up principally focus on neurodevelopmental impairment (NDI) after extremely preterm birth, as defined by the scientific community, without parental input. This survey aimed to investigate parental perspectives about the health and development of their preterm children.MethodsParents of children aged 18 months to 7 years born Results248 parents of 213 children (mean gestational age 26.6±1.6 weeks, 20% with severe NDI) were recruited. Parents evaluated their children’s health at a median of 9/10. Parental priorities for health improvements were (1) development, mainly behaviour, emotional health and language/communication (55%); (2) respiratory heath and overall medical fragility (25%); and (3) feeding/growth issues (14%). Nineteen per cent explicitly mentioned ‘no improvements’. Parents were more likely to state ‘no improvements’ if child had no versus severe NDI OR 4.33 (95% CI 1.47 to 12.75)) or if parents had no versus at least a high school diploma (OR 4.01 (95% 1.99 to 8.10)).ConclusionsParents evaluate the health of their preterm children as being very good, with positive perspectives. Parental concerns outside the developmental sphere should also be addressed both in clinical follow-up and research.

Rationale: Bronchopulmonary dysplasia increases the risk of disability in extremely preterm infants. Although the pathophysiology remains uncertain, prior exposure to intermittent hypoxemia may pla...

ObjectivesHealth status (HS)/ health-related quality of life measures, completed by self or proxy, are important outcome indicators. Most HS literature on children born preterm includes adolescents and adults with limited data at preschool age. This study aimed to describe parent-reported HS in a large national cohort of extreme preterm children at preschool age and to identify clinical and sociodemographic variables associated with HS.MethodsInfants born before 29 weeks’ gestation between 2009 and 2011 were enrolled in a prospective longitudinal national cohort study through the Canadian Neonatal Network (CNN) and the Canadian Neonatal Follow-Up Network (CNFUN). HS, at 36 months’ corrected age (CA), was measured with the Health Status Classification System for Pre-School Children tool completed by parents. Information about HS predictors was extracted from the CNN and CNFUN databases.ResultsOf 811 children included, there were 79, 309 and 423 participants in 23–24, 25–26 and 27–28 weeks’ gestational age groups, respectively. At 36 months’ CA, 78% had a parent-reported health concern, mild in >50% and severe in 7%. Most affected HS attributes were speech (52.1%) and self-care (41.4%). Independent predictors of HS included substance use during pregnancy, infant male sex, Score for Neonatal Acute Physiology-II, bronchopulmonary dysplasia, severe retinopathy of prematurity, caregiver employment and single caregiver.ConclusionMost parents expressed no or mild health concerns for their children at 36 months’ CA. Factors associated with health concerns included initial severity of illness, complications of prematurity and social factors.

To evaluate neurodevelopment and growth in extremely preterm infants with or without necrotizing enterocolitis or spontaneous intestinal perforation.We conducted a retrospective cohort study of infants admitted to Canadian neonatal intensive care units in 2010 to 2011. We assessed outcomes at 18 to 24 months' corrected ages for preterm infants29 weeks of gestational age at birth with spontaneous intestinal perforation or non-perforated or perforated necrotizing enterocolitis, and for preterm infants with none of these gastrointestinal complications. The primary outcome was a composite of death or significant neurodevelopmental impairment at 18 to 24 months' corrected age. We used multivariable logistic regression models to adjust for gestational age, small for gestational age, prenatal steroids, cesarean section, multiple gestations, and SNAP-II score.Of 2,019 infants total, 39 (1.9%) had spontaneous intestinal perforation, 61 (3%) had perforated necrotizing enterocolitis, and 115 (5.7%) had non-perforated necrotizing enterocolitis. Infants with spontaneous intestinal perforation (aOR 2.11; 95% CI 1.01-4.42), necrotizing enterocolitis (aOR 2.58; 95% CI 1.81-3.68), or any bowel perforation (aOR 3.97; CI 2.43-6.48) had higher odds of death or significant neurodevelopmental impairment compared to infants with none of these bowel diseases.Spontaneous intestinal perforation, necrotizing enterocolitis, or any bowel perforation are risk factors for death or significant neurodevelopmental impairment in extremely preterm infants.Study type: prognosis study (cohort study: retrospective) LEVEL OF EVIDENCE RATING: II.

Primary Subject area Neonatal-Perinatal Medicine Background Late-onset sepsis (LOS) is associated with adverse neonatal outcome. There is limited data on the long-term neurodevelopmental (ND) outcomes of infants based on type of bacteria causing LOS. We hypothesize that the type of bacterial pathogen causing late-onset sepsis influences the developmental outcome in extremely preterm infants. Objectives To compare the neurodevelopmental (ND) outcomes at 18-24 months corrected age (CA) of infants born < 29 weeks who had late-onset sepsis (LOS) caused by: (1) gram-positive bacteria; (2) gram-negative bacteria; (3) mixed (both gram-positive and gram-negative bacteria); and (4) those with no sepsis (that is, no sepsis or culture-negative sepsis). Design/Methods In this retrospective multicentre cohort study, we studied infants born at Results Of the 3640 infants included, 823 (22.6%) had late-onset sepsis (LOS). Of the 823 infants with LOS, 569 (69.1%) infants had gram-positive sepsis, 172 (20.9%) had gram-negative sepsis, and 82 (10%) had mixed sepsis. Maternal and neonatal characteristics and outcome are reported in Table 1. Outcome data after adjustment for gestational age (GA), sex, antenatal steroids, SNAP-II score, small for gestational age (SGA), maternal age, and caesarian delivery are presented in Table 2. Conclusion Late-onset bacterial sepsis, especially gram-negative sepsis and mixed infections, were associated with increased risk of composite outcome of death or neurodevelopmental impairment (NDI), or NDI alone, at 18-24 months corrected age (CA) in infants

OBJECTIVE The purpose of this study was to determine how preterm white matter injury (WMI) and long-term thalamic growth interact to predict 8-year neurodevelopmental outcomes. METHODS A prospective cohort of 114 children born at 24 to 32 weeks' gestational age (GA) underwent structural and diffusion tensor magnetic resonance imaging early in life (median 32 weeks), at term-equivalent age and at 8 years. Manual segmentation of neonatal WMI was performed on T1-weighted images and thalamic volumes were obtained using the MAGeT brain segmentation pipeline. Cognitive, motor, and visual-motor outcomes were evaluated at 8 years of age. Multivariable regression was used to examine the relationship among neonatal WMI volume, school-age thalamic volume, and neurodevelopmental outcomes. RESULTS School-age thalamic volumes were predicted by neonatal thalamic growth rate, GA, sex, and neonatal WMI volume (p

Smartphone-based approaches for Human Activity Recognition have become prevalent in recent years. Despite the amount of research undertaken in the field, issues such as cross-subject variability are still posing an obstacle to the deployment of solutions in large scale, free-living settings. Personalized methods ( i.e. aiming to adapt a generic classifier to a specific target user) attempt to solve this problem. The lack of labeled data for training purposes, however, represents a major barrier. This is especially the case when taking into consideration that personalization generally requires labeled data to be user-specific. This paper presents a novel personalization method combining a semi-population based approach with user adaptation. Personalization is achieved through the following. Firstly, the proposed method identifies a subset of users from the available population as best candidates for initializing the classifier to the target user. Subsequently, a semi-population Neural Network classifier is trained using data from this subset of users. The classifier’s network weights are then updated using a small amount of labeled data from the target user subsequently implementing personalization. This approach was validated on a large publicly available dataset collected in a free-living scenario. The personalized approach using the proposed method has shown to improve the overall F-score to 74.4% compared to 70.9% when using a generic non-personalized approach. Results obtained, with statistical significance being confirmed on a set of 57 users, indicate that model initialization using the semi-population approach can reduce the amount of labeled data required for personalization. As such, the proposed method for model initialization could facilitate the real-world deployment of systems implementing personalization by reducing the amount of data needed for personalization.

Background A 2006 Canadian survey showed a large variability in neonatal follow-up practices. In 2010, all 26 tertiary level Neonatal Follow-Up clinics joined the Canadian Neonatal Follow-Up Network (CNFUN) and agreed to implement a standardized assessment (including the Bayley Scales of Infant and Toddler Development-III (Bayley-III) at 18 months corrected age for children born < 29 weeks’ gestation. It is unknown whether the variability in follow-up practices lessened as a result. Objectives To describe the current status of neonatal follow-up services in Canada and changes over time. Methods A comprehensive online survey was sent to all tertiary level CNFUN Follow-up programs. Questions were based on previous survey results, current literature, and investigator expertise and consensus. Results Respondents included 23 of 26 (88%) CNFUN programs. All sites provide neurodevelopmental screening and referrals in a multidisciplinary setting with variations in staffing. CNFUN programs vary with most offering five to seven visits. Since 2006, assessments at 18 months CA increased from 84% to 91% of sites, Bayley-III use increased from 21% to 74% (P=0.001) and eligibility for follow-up was expanded for children with stroke, congenital diaphragmatic hernia and select anomalies detected in utero. Audit data is collected by > 80% of tertiary programs. Conclusion Care became more consistent after CNFUN; 18-month assessments and Bayley-III use increased significantly. However, marked variability in follow-up practices persists.

The ability to definitively diagnose cerebral palsy (CP) at 18-24 months is unknown.To describe very preterm children who, at 19 months, have suspected CP defined as neither having a definitive diagnosis of CP nor no CP and compare them with children with and without CP.Longitudinal national cohort study of births29 weeks' gestation with linked Canadian Neonatal Network and Canadian Neonatal Follow-up Network data with 19 month assessments and 3-year questionnaires (Ages and Stages-3 and Health Status Classification System-Preschool). CP, no CP and suspected CP groups, classified at 19 months, were compared using chi square and ANOVA.Of 3086 survivors, 2280 had complete 19-month corrected age (CA) and 1261 had 3-year CA data. Suspected CP (3.6%), CP (6.4%) and no CP (90%) groups differed (p 0.05) in birth weight, gestational age, complications of prematurity and NICU length of stay. Children with suspected CP had Bayley-III motor, cognitive and language composite scores at 18 months midway between CP and no CP, had the lowest sensory impairment rates and highest hospital readmission rates. At 3 years, gross motor, fine motor, problem-solving, communication and social skill abilities differed: abnormal outcomes were intermediate for children with suspected CP (p 0.01).CP incidence varied from 6.4% to 10% with exclusion or inclusion of children with suspected CP. Children with suspected CP have characteristics mostly midway between those with and without CP and developmental concerns persist to 3 years and require surveillance beyond 19 months.

Genetic disorders are one of the leading causes of infant mortality and are frequent in neonatal intensive care units (NICUs). Rapid genome-wide sequencing (GWS; whole genome or exome sequencing (ES)), due to its diagnostic capabilities and immediate impacts on medical management, is becoming an appealing testing option in the NICU setting. RAPIDOMICS was a trio-based rapid ES pilot study of 25 babies with suspected genetic disorders in the BC Women's Hospital NICU. ES and bioinformatic analysis were performed after careful patient ascertainment. Trio analysis was performed using an in-house pipeline reporting variants in known disease-causing genes. Variants interpreted by the research team as definitely or possibly causal of the infant's phenotype were Sanger validated in a clinical laboratory. The average time to preliminary diagnosis was 7.2 days. Sanger validation was pursued in 15 patients for 13 autosomal dominant and 2 autosomal recessive disorders, with an overall diagnostic rate (partial or complete) of 60%.Conclusion: In total, 72% of patients enrolled had a genomic diagnosis achieved through ES, multi-gene panel testing or chromosomal microarray analysis. Among these, there was an 83% rate of significant and immediate impact on medical decision-making directly related to new knowledge of the diagnosis. Health service implementation challenges and successes are discussed. What is Known: • Rapid genome-wide sequencing in the neonatal intensive care setting has a greater diagnostic hit rate and impact on medical management than conventional genetic testing. However, the impact of consultation with genetics and patient ascertainment requires further investigation. What is New: • This study demonstrates the importance of genetic consultation and careful patient selection prior to pursuing exome sequencing (ES). • In total, 15/25 (60%) patients achieved a diagnosis through ES and 18/25 (72%) through ES, multi-gene panel testing or chromosomal microarray analysis with 83% of those having immediate effects on medical management.

OBJECTIVES Neurodevelopmental disability is the most common complication among congenital heart surgery survivors. The Bayley scales are standardized instruments to assess neurodevelopment. The most recent edition (Bayley Scales of Infant and Toddler Development 3rd Edition, Bayley-III) yields better-than-expected scores in typically developing and high-risk infants than the second edition (Bayley Scales of Infant Development 2nd Edition, BSID-II). We compared BSID-II and Bayley-III scores in infants undergoing cardiac surgery. METHODS We evaluated 2198 infants who underwent operations with cardiopulmonary bypass between 1996 and 2009 at 26 institutions. We used propensity score matching to limit confounding by indication in a subset of patients (n = 705). RESULTS Overall, unadjusted Bayley-III motor scores were higher than BSID-II Psychomotor Development Index scores (90.7 ± 17.2 vs 77.6 ± 18.8, P CONCLUSIONS The Bayley-III yielded higher scores than the BSID-II and classified fewer children as severely impaired. The systematic bias towards higher scores with the Bayley-III precludes valid comparisons between early and contemporary cardiac surgery cohorts.

To compare neurodevelopmental outcomes of preterm infants at 18–21 months corrected age (CA) whose mothers smoked during pregnancy to those whose mothers did not smoke. Preterm infants born at

Quality improvement initiatives in neonatology have yielded positive results; however, few programs have demonstrated sustainability. We evaluated an ongoing, national quality improvement initiative (Evidence-based Practice for Improving Quality Phase 3 (EPIQ-3)) on outcomes of preterm neonates with a gestational age (GA) of 220–286weeks (i.e., from 22 weeks and 0 days of gestation to 28 weeks and 6 days of gestation). Data from 7459 neonates admitted to 25 Canadian centers between 2013 and 2017 were studied. Trends in mortality and major morbidities were evaluated. The number of neonates with a GA of 220–236weeks increased from 90 in 2013 to 139 in 2017 without a significant change in any other GA categories. In the entire cohort, the odds of composite outcome of mortality or any major morbidity (adjusted odds ratio (AOR) 0.72, 95% confidence interval (CI) 0.61–0.84) and of necrotizing enterocolitis (AOR 0.66, 95% CI 0.49–0.89) were lower in 2017 than in 2013. When calculated per year, the odds of composite outcome (AOR 0.93, 95% CI 0.89–0.97) and odds of necrotizing enterocolitis (AOR 0.89, 95% CI 0.82–0.96) decreased significantly. Among the subgroup of neonates with a GA of 260–286weeks, the odds of composite outcome (AOR 0.63, 95% CI 0.51–0.79), necrotizing enterocolitis (AOR 0.44, 95% CI 0.26–0.73), and nosocomial infection (AOR 0.64, 95% CI 0.49–0.84) were reduced. The collaborative, multidisciplinary, nationwide EPIQ-3 program improved outcomes of preterm neonates, and the improvement was sustainable over 5 years.

IntroductionHaving an infant admitted to the neonatal intensive care unit (NICU) is associated with increased parental stress, anxiety and depression. Enhanced support for parents may decrease parental stress and improve subsequent parent and child outcomes. The Coached, Coordinated, Enhanced Neonatal Transition (CCENT) programme is a novel bundled intervention of psychosocial support delivered by a nurse navigator that includes Acceptance and Commitment Therapy-based coaching, care coordination and anticipatory education for parents of high-risk infants in the NICU through the first year at home. The primary objective is to evaluate the impact of the intervention on parent stress at 12 months.Methods and analysisThis is a multicentre pragmatic randomised controlled superiority trial with 1:1 allocation to the CCENT model versus control (standard neonatal follow-up). Parents of high-risk infants (n=236) will be recruited from seven NICUs across three Canadian provinces. Intervention participants are assigned a nurse navigator who will provide the intervention for 12 months. Outcomes are measured at baseline, 6 weeks, 4, 12 and 18 months. The primary outcome measure is the total score of the Parenting Stress Index Fourth Edition Short Form at 12 months. Secondary outcomes include parental mental health, empowerment and health-related quality of life for calculation of quality-adjusted life years (QALYs). A cost-effectiveness analysis will examine the incremental cost of CCENT versus usual care per QALY gained. Qualitative interviews will explore parent and healthcare provider experiences with the intervention.Ethics and disseminationResearch ethics approval was obtained from Clinical Trials Ontario, Children’s Hospital of Eastern Ontario Research Ethics Board (REB), The Hospital for Sick Children REB, UBC Children’s and Women’s REB and McGill University Health Centre REB. Results will be shared with Canadian level III NICUs, neonatal follow-up programmes and academic forums.Trial registration numberClinicalTrials.gov Registry (NCT03350243).

ObjectiveTo compare mortality and rates of significant neurosensory impairment (sNSI) at 18–36 months’ corrected age in infants born extremely preterm across three international cohorts.DesignRetrospective analysis of prospectively collected neonatal and follow-up data.SettingThree population-based observational cohort studies: the Australian and New Zealand Neonatal Network (ANZNN), the Canadian Neonatal and Follow-up Networks (CNN/CNFUN) and the French cohort Etude (Epidémiologique sur les Petits Ages Gestationnels: EPIPAGE-2).PatientsExtremely preterm neonates of Main outcome measuresPrimary outcome was composite of mortality or sNSI defined by cerebral palsy with no independent walking, disabling hearing loss and bilateral blindness.ResultsOverall, 3055 infants (ANZNN n=960, CNN/CNFUN n=1019, EPIPAGE-2 n=1076) were included in the study. Primary composite outcome rates were 21.3%, 20.6% and 28.4%; mortality rates were 18.7%, 17.4% and 26.3%; and rates of sNSI among survivors were 4.3%, 5.3% and 3.3% for ANZNN, CNN/CNFUN and EPIPAGE-2, respectively. Adjusted for gestational age and multiple births, EPIPAGE-2 had higher odds of composite outcome compared with ANZNN (OR 1.71, 95% CI 1.38 to 2.13) and CNN/CNFUN (OR 1.72, 95% CI 1.39 to 2.12). EPIPAGE-2 did have a trend of lower odds of sNDI but far short of compensating for the significant increase in mortality odds. These differences may be related to variations in perinatal approach and practices (and not to differences in infants’ baseline characteristics).ConclusionsComposite outcome of mortality or sNSI for extremely preterm infants differed across high-income countries with similar baseline characteristics and access to healthcare.

Primary Subject area Neonatal-Perinatal Medicine Background Quality improvement programs across Canadian Neonatal Network (CNN) sites have led to increased neonatal survival without major neonatal morbidity among infants born extremely preterm. The next step is to determine if such activities impact longer-term survival and neurodevelopmental outcomes. Objectives This cohort study aimed to compare death or significant neurodevelopmental impairment (sNDI) (Bayley-III scores < 70, severe cerebral palsy, blind, or hearing aided) at 18-24 months corrected age among infants born < 29 weeks’ gestation admitted to CNN sites, between 2 Epochs: 1 (2009-2012) and 2 (2013-2016). Secondary objectives included death or neurodevelopmental impairment (NDI) (Bayley-III < 85, any cerebral palsy, visual or hearing impairment), death, sNDI, NDI, and components of neurodevelopmental impairment. Design/Methods Only sites with ≥ 70% follow-up rates were included. Differences in maternal-infant characteristics and neonatal morbidities were assessed by Pearson Chi-square and Student t-test testing. Adjusted odds ratios with 95% CIs were calculated for outcome change between the 2 Epochs, accounting for patient characteristic differences in the model. Results Study population included 4426 children; Epoch 1: 1895 (43%) and Epoch 2: 2531 (57%). In Epoch 2, more mothers received MgSO4 (56.3% vs. 28.4%; p20 (30.7% vs. 35.2%; p Conclusion Significant reductions in rate of death or sNDI, and in visual and hearing impairment, were identified between Epoch 2 to Epoch 1. An increase in poor cognitive outcome rates requires further study.

Synthetic aperture sonar (SAS) bathymetric mapping provides centimeter-scale horizontal resolution of the seafloor. Typically, SAS data has been visualized as 2D images or gridded 2.5D surfaces, but it can also be plotted as 3D point clouds. Even if the imaging system is not fully volumetric, the imaging geometry leaves the possibility of having data points that reside in the same lateral positions in a ground coordinate system. Visualizing these without geometric distortion or loss of data is challenging. In this paper we investigate the use of full-fledged 3D rendering with artificial lighting and shading techniques in order to convey more of the available information. We aim to produce better 3D visualization of shipwrecks. We provide an overview of which data products are available from state-of-the-art SAS processing, and explore existing visualization methods. We discuss the use of surfaces and point clouds for 3D rendering, and various shading and rendering techniques. Our goal is to display SAS bathymetry in a way that is both intuitive and can convey more supplemental information to the observer. Finally, we show image and video examples of rendering large shipwreck scenes using data collected by a HISAS1032 SAS carried by a HUGIN autonomous underwater vehicle.

Background: Children born very preterm (

ObjectivesTo assess the association of head circumference (HC) DesignIn a prospective cohort, semiautomatically segmented TCV and manually segmented white matter injury (WMI) volumes were obtained. Multivariable regressions were used to study the association of HC and TCV with neurodevelopmental outcomes, accounting for birth gestational age, WMI and postnatal illness.SettingParticipants born in 2006–2013 at British Columbia Women’s Hospital were recruited.Patients168 neonates had HC measurements at birth and discharge and MRI at term-equivalent age (TEA). 143 children were assessed at 4.5 years.Main outcome measuresMotor, cognitive and language outcomes at 4.5 years were assessed using the Movement Assessment Battery for Children Second Edition (M-ABC) and Wechsler Preschool and Primary Scale of Intelligence Third Edition Full Scale IQ (FSIQ) and Verbal IQ (VIQ).ResultsSmall birth HC was associated with lower M-ABC and FSIQ scores. In children with small birth HC, small discharge HC was associated with lower M-ABC, FSIQ and VIQ scores, while normal HC at discharge was no longer associated with adverse outcomes. HC strongly correlated with TCV at TEA. TCV did not correlate with outcomes.ConclusionsSmall birth HC is associated with poorer neurodevelopment, independent of postnatal illness and WMI. Normalisation of HC during NICU care appears to moderate this risk.

There have been concerns about the development of children conceived through assisted reproductive technology. Despite multiple studies investigating the outcomes of assisted conception, data focusing specifically on the neurodevelopmental outcomes of infants conceived through assisted reproductive technology and born preterm are limited.This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally.This retrospective cohort study included inborn, nonanomalous infants, born at29 weeks' gestation between January 1, 2010, and December 31, 2016, who had a neurodevelopmental assessment at 18 to 24 months' corrected age at any of the 10 Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment at 18 to 24 months, defined as the presence of any of the following: cerebral palsy; Bayley-III cognitive, motor, or language composite score of85; sensorineural or mixed hearing loss; and unilateral or bilateral visual impairment. Secondary outcomes included mortality, composite of mortality or neurodevelopmental impairment, significant neurodevelopmental impairment, and each component of the primary outcome. We compared outcomes between infants conceived through assisted reproductive technology and those conceived naturally, using bivariate and multivariable analyses after adjustment.Of the 4863 eligible neonates, 651 (13.4%) were conceived using assisted reproductive technology. Maternal age; education level; and rates of diabetes mellitus, receipt of antenatal corticosteroids, and cesarean delivery were higher in the assisted reproduction group than the natural conception group. Neonatal morbidity and death rates were similar except for intraventricular hemorrhage, which was lower in the assisted reproduction group (33% [181 of 546] vs 39% [1284 of 3318]; P=.01). Of the 4176 surviving infants, 3386 (81%) had a follow-up outcome at 18 to 24 months' corrected age. Multivariable logistic regression adjusting for gestational age, antenatal steroids, sex, small for gestational age, multiple gestations, mode of delivery, maternal age, maternal education, pregnancy-induced hypertension, maternal diabetes mellitus, and smoking showed that infants conceived through assisted reproduction was associated with lower odds of neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.52-0.86) and the composite of death or neurodevelopmental impairment (adjusted odds ratio, 0.67; 95% confidence interval, 0.54-0.84). Conception through assisted reproductive technology was associated with decreased odds of a Bayley-III composite cognitive score of85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88).Compared with natural conception, assisted conception was associated with lower odds of adverse neurodevelopmental outcomes, especially cognitive and language outcomes, at 18 to 24 months' corrected age among preterm infants born at29 weeks' gestation. Long-term follow-up studies are required to assess the risks of learning disabilities and development of complex visual-spatial and processing skills in these children as they reach school age.

ObjectiveTo examine whether the family integrated care (FICare) programme, a multifaceted approach which enables parents to be engaged as primary caregivers in the neonatal intensive care unit, impacts infant neurodevelopment and growth at 18 months’ corrected age.Design/MethodsProspective cohort study of infants born ResultsOf 756 infants ConclusionsVery preterm infants exposed to FICare had no significant difference in incidence of cognitive or language delay but had better motor development.Trial registration numberParticipants in this cohort study were previously enrolled in a registered trial: NCT01852695

OBJECTIVE To compare neurodevelopmental outcomes of large and appropriate for gestational age (LGA, AGA) infants

Importance Maternal docosahexaenoic acid (DHA) supplementation may prevent bronchopulmonary dysplasia, but evidence remains inconclusive. Objective To determine whether maternal DHA supplementation during the neonatal period improves bronchopulmonary dysplasia–free survival in breastfed infants born before 29 weeks of gestation. Design, Setting, and Participants Superiority, placebo-controlled randomized clinical trial at 16 Canadian neonatal intensive care units (June 2015-April 2018 with last infant follow-up in July 2018). Lactating women who delivered before 29 weeks of gestation were enrolled within 72 hours of delivery. The trial intended to enroll 800 mothers, but was stopped earlier. Interventions There were 232 mothers (273 infants) assigned to oral capsules providing 1.2 g/d of DHA from randomization to 36 weeks’ postmenstrual age and 229 mothers (255 infants) assigned to placebo capsules. Main Outcomes and Measures The primary outcome was bronchopulmonary dysplasia–free survival in infants at 36 weeks’ postmenstrual age. There were 22 secondary outcomes, including mortality and bronchopulmonary dysplasia. Results Enrollment was stopped early due to concern for harm based on interim data from this trial and from another trial that was published during the course of this study. Among 461 mothers and their 528 infants (mean gestational age, 26.6 weeks [SD, 1.6 weeks]; 253 [47.9%] females), 375 mothers (81.3%) and 523 infants (99.1%) completed the trial. Overall, 147 of 268 infants (54.9%) in the DHA group vs 157 of 255 infants (61.6%) in the placebo group survived without bronchopulmonary dysplasia (absolute difference, –5.0% [95% CI, –11.6% to 2.6%]; relative risk, 0.91 [95% CI, 0.80 to 1.04],P = .18). Mortality occurred in 6.0% of infants in the DHA group vs 10.2% of infants in the placebo group (absolute difference, –3.9% [95% CI, –6.8% to 1.4%]; relative risk, 0.61 [95% CI, 0.33 to 1.13],P = .12). Bronchopulmonary dysplasia occurred in 41.7% of surviving infants in the DHA group vs 31.4% in the placebo group (absolute difference, 11.5% [95% CI, 2.3% to 23.2%]; relative risk, 1.36 [95% CI, 1.07 to 1.73],P = .01). Of 22 prespecified secondary outcomes, 19 were not significantly different. Conclusions and Relevance Among breastfed preterm infants born before 29 weeks of gestation, maternal docosahexaenoic acid supplementation during the neonatal period did not significantly improve bronchopulmonary dysplasia–free survival at 36 weeks’ postmenstrual age compared with placebo. Study interpretation is limited by early trial termination. Trial Registration ClinicalTrials.gov Identifier:NCT02371460

We present a new method to identify anatomical subnetworks of the human connectome that are optimally predictive of targeted clinical variables, developmental outcomes or disease states. Given a training set of structural or functional brain networks, derived from diffusion MRI (dMRI) or functional MRI (fMRI) scans respectively, our sparse linear regression model extracts a weighted subnetwork. By enforcing novel backbone network and connectivity based priors along with a non-negativity constraint, the discovered subnetworks are simultaneously anatomically plausible, well connected, positively weighted and reasonably sparse. We apply our method to (1) predicting the cognitive and neuromotor developmental outcomes of a dataset of 168 structural connectomes of preterm neonates, and (2) predicting the autism spectrum category of a dataset of 1013 resting-state functional connectomes from the Autism Brain Imaging Data Exchange (ABIDE) database. We find that the addition of each of our novel priors improves prediction accuracy and together outperform other state-of-the-art prediction techniques. We then examine the structure of the learned subnetworks in terms of topological features and with respect to established function and physiology of different regions of the brain.

Background Behaviour problems are prevalent among children born very preterm (≤ 32 weeks gestation), and have been associated with morphine exposure. Morphine accumulation in the brain is determined by genetic variations related to morphine biotransformation. The objective of the study was to investigate whether morphine-biotransformation genotypes contribute to individual differences in long-term effects of morphine on behaviour at 18 months corrected age (CA). Methods 198 children born very preterm (24–32 weeks gestation) were followed from birth and seen at 18 months CA. Relationships between child behavior (Internalizing, Externalizing on the Child Behavior Checklist), morphine exposure, neonatal clinical variables, and morphine biotransformation gene variants in ABCB1, UGT1A9, UGT 2B7*2, ABCC2, ABCC3, SLCO1B1, CYP3A4, COMT were examined. Findings Neonatal clinical predictors and genotypes accounted for 39% of the overall variance in behaviour. In children with the minor allele of UGT1A9 rs17863783 (marker of UGT1A6*4, UDP-glucuronosyltransferase), greater morphine exposure (p = ·0011) was associated with more Internalizing behaviour. More Externalizing behaviour was predicted by greater morphine exposure in children with the COMT rs4680 Met/Met genotype (p = ·0006). Interpretation Genetic variations that affect relative accumulation of morphine in the brain, together with neonatal clinical factors, are differentially related to anxiety and depressive symptoms (internalizing) and to acting out (externalizing) behaviours at 18 months CA in children born very preterm. Fund NIH/NICHD HD039783 (REG); CIHR MOP86489 (REG), MOP68898 (SPM), MOP79262 (SPM, REG).

Children born preterm display altered sensory processing, which may manifest as hyper- and/or hypo-sensitivity to sensory information. In this vulnerable population, exposure to neonatal pain-related stress is associated with altered stress regulation, as indexed by alterations in cortisol levels. It is unknown whether sensory processing behaviors are also affected by early life adversity, and whether dysregulated cortisol is related to sensory processing problems in preterm children. We examined relationships between neonatal pain-related stress, sensory processing profiles and cortisol levels at age 4 years, and whether pathways were sex-specific. In a longitudinal prospective cohort study, N = 146 infants born 24-32 weeks gestational age were recruited from BC Women's Hospital, Vancouver, BC, Canada; neonatal factors were collected from daily chart review. At age 4 years, saliva to assay cortisol was collected three times across cognitive assessment (pre-test, during, end) and parents completed the Short Sensory Profile questionnaire. Using generalized linear modeling, independent of other neonatal factors, higher number of invasive procedures (pain/stress) was associated with more sensory processing problems (total, hypo- and hyper-sensitivity) for girls only. After accounting for neonatal factors, greater cortisol output across the assessment was associated with more total sensory processing problems in girls only, and hypersensitivity to sensory input in both boys and girls. Findings suggest that in children born very preterm, how a child responds to sensory input and cortisol reactivity to stress are related but may have different precursors. Girls may be somewhat more susceptible to neonatal pain-related stress exposure in relation to sensory processing at preschool age.

Objective To examine the association between cerebellar hemorrhage (CBH) size and location and preschool-age neurodevelopment in very preterm neonates. Methods Preterm magnetic resonance images of 221 very preterm neonates (median gestational age = 27.9 weeks) were manually segmented for CBH quantification and location. Neurodevelopmental assessments at chronological age 4.5 years included motor (Movement Assessment Battery for Children, 2nd Edition [MABC-2]), visuomotor integration (Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition), cognitive (Wechsler Primary and Preschool Scale of Intelligence, 3rd Edition), and behavioral (Child Behavior Checklist) outcomes. Multivariable linear regression models examined the association between CBH size and 4.5-year outcomes accounting for sex, gestational age, and supratentorial injury. Probabilistic maps assessed CBH location and likelihood of a lesion to predict adverse outcome. Results Thirty-six neonates had CBH: 14 (6%) with only punctate CBH and 22 (10%) with ≥1 larger CBH. CBH occurred mostly in the inferior aspect of the posterior lobes. CBH total volume was independently associated with MABC-2 motor scores at 4.5 years (β = -0.095, 95% confidence interval = -0.184 to -0.005), with a standardized β coefficient (-0.16) that was similar to that of white matter injury volume (standardized β = -0.22). CBH size was similarly associated with visuomotor integration and externalizing behavior but not cognition. Voxelwise odds ratio and lesion-symptom maps demonstrated that CBH extending more deeply into the cerebellum predicted adverse motor, visuomotor, and behavioral outcomes. Interpretation CBH size and location on preterm magnetic resonance imaging were associated with reduced preschool motor and visuomotor function and more externalizing behavior independent of supratentorial brain injury in a dose-dependent fashion. The volumetric quantification and localization of CBH, even when punctate, may allow opportunity to improve motor and behavioral outcomes by providing targeted intervention. ANN NEUROL 2020;88:1095-1108.

Background Very preterm infants are at high risk of death or severe morbidity. The objective was to determine the significance of severe congenital heart defects ( CHDs ) for these risks. Methods and Results This cohort study included infants from 10 countries born from 2007–2015 at 24 to 31 weeks’ gestation with birth weights CHDs were defined by International Classification of Diseases, Ninth Revision ( ICD‐9 ) and Tenth ( ICD‐10 ) codes and categorized as those compromising systemic output, causing sustained cyanosis, or resulting in congestive heart failure. The primary outcome was in‐hospital mortality. Secondary outcomes were neonatal brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity. Adjusted and propensity score–matched odds ratios ( ORs ) were calculated. Analyses were stratified by type of CHD , gestational age, and network. A total of 609 (0.77%) infants had severe CHD and 76 371 without any malformation served as controls. The mean gestational age and birth weight were 27.8 weeks and 1018 g, respectively. The mortality rate was 18.6% in infants with CHD and 8.9% in controls (propensity score–matched OR , 2.30; 95% CI , 1.61–3.27). Severe CHD was not associated with neonatal brain injury, necrotizing enterocolitis, or retinopathy of prematurity, whereas the OR for bronchopulmonary dysplasia increased. Mortality was higher in all types, with the highest propensity score–matched OR (4.96; 95% CI, 2.11–11.7) for CHD causing congestive heart failure. While mortality did not differ between groups at OR for mortality in infants with CHD increased to 10.9 (95% CI, 5.76–20.70) at 31 weeks’ gestational age. Rates of CHD and mortality differed significantly between networks. Conclusions Severe CHD is associated with significantly increased mortality in very preterm infants.

ObjectiveTo test the hypothesis that a strategy of prolonged arterial line (AL) and central venous line (CVL) use is associated with reduced neonatal invasive procedures and improved growth of the thalamus in extremely preterm neonates (MethodsTwo international cohorts of very preterm neonates (n = 143) with prolonged (≥14 days) or restricted (ResultsProlonged AL/CVL use in neonates (n = 86) was associated with fewer skin breaks (median 34) during the hospital stay compared to restricted AL/CVL use (n = 57, median 91, 95% confidence interval [CI] 60.35–84.89). Neonates with prolonged AL/CVL use with fewer skin breaks had significantly larger thalamic volumes early in life compared to neonates with restricted line use (B = 121.8, p = 0.001, 95% CI 48.48–195.11). Neonatal thalamic growth predicted preschool-age cognitive (B = 0.001, 95% CI 0.0003–0.001, p = 0.002) and motor scores (B = 0.01, 95% CI 0.001–0.10, p = 0.02). Prolonged AL/CVL use was not associated with greater incidence of sepsis or multiple infections.ConclusionsProlonged AL/CVL use in preterm neonates may provide an unprecedented opportunity to reduce invasive procedures in preterm neonates. Pain reduction in very preterm neonates is associated with optimal thalamic growth and neurodevelopment.

Neonatal fungemia is associated with adverse neonatal outcomes and higher overall healthcare expenditure. Our objective is to review the epidemiology of invasive fungal infections (IFIs) in neonates in Canada.A retrospective cohort study using data collected by the Canadian Neonatal Network (CNN) was conducted. Using a nested matched cohort study design, risk factors and outcomes of neonates born33 weeks gestation (n = 39,305) during 2003-2013 were compared between neonates diagnosed with an IFI during their stay to infection-free controls.Overall incidence of IFI among all admitted neonates was 0.22% (n = 286), while the incidence of IFI in the group of neonates born33 weeks gestation was 0.64%. Of the isolates, 170 (59%) had Candida albicans and 59 (21%) had Candida parapsilosis. Risk factors for IFI were lower gestation, male sex, Apgar score7 at 5 minutes, higher severity of illness score, maternal diabetes and vaginal birth. Neonates with IFI had higher odds of mortality [adjusted odds ratio (aOR): 1.60; 95% confidence interval (CI): 1.06-2.43], necrotizing enterocolitis (aOR: 2.97; 95% CI: 1.76-5.01) and severe retinopathy of prematurity (aOR: 2.15; 95% CI: 1.26-3.67).The overall incidence of IFI in neonates was low in Canada in comparison to other large population cohort studies; however, the mortality and morbidity remained high.

Despite improved survival of preterm infants, there has not been an equivalent improvement in long-term neurodevelopmental outcomes. Adverse neurodevelopmental outcome rates and severity are inversely related to the degree of prematurity, but only 1.6% are born very preterm and the motor, cognitive, behavioral, and psychiatric disabilities in the large moderate and late preterm population have a greater impact. The disability-free preterm adult has a lower educational achievement and income but similar health-related quality of life to term controls. Reducing the long-term neurodevelopmental impact of prematurity is the next frontier of neonatal care.

Objective The aim of this study was to evaluate the association between neonatal seizure and neurodevelopmental impairment (NDI) at 18 to 24 months in extremely preterm neonates. The association between anticonvulsants use and NDI was also assessed. Study Design In this retrospective cohort study of infants born at Results Of the 2,762 eligible neonates, 133 (4.8%) had seizures. Infants who had seizures were of lower gestation (25.2 vs. 26.2 weeks) and birth weight (819 vs. 920 g) and had higher rates of adverse outcomes. Neonatal seizure was associated with higher odds of composite outcome of death or significant NDI (74 vs. 27%; adjusted odds ratio [OR]: 3.4; 95% confidence interval [CI]: 2.2–5.4). Death or significant NDI was higher in infants with seizures treated with anticonvulsants than those without treatment (89 vs. 70%); however, when adjusted for confounders, it was not significantly different (adjusted OR: 3.5; 95% CI: 0.83–14.6). Conclusion Neonatal seizures were independently associated with higher odds of death or significant NDI at 18 to 24 months of age. Relationship of anticonvulsant and neurodevelopmental outcomes needs further studies.

Objectives Preeclampsia is characterized by maternal systemic inflammation and coagulation activation, akin to the sepsis syndrome. Recombinant human activated protein C (rhAPC; drotrecogin alfa [activated]) may modify disease progression to safely prolong pregnancies and improve perinatal outcomes. Both maternal and perinatal risks are highest remote from term. Study design Open-label, single arm safety and efficacy trial of rhAPC in consenting pregnant women with severe early-onset preeclampsia. Disease severity-matched rhAPC-naive controls were identified from an existing database. An additional six women were recruited as biomarker controls. Main outcome measures Primary safety outcome: incidence of peripartum bleeding; primary efficacy outcome: duration of pregnancy after enrolment. Results Twelve (31.6%) of 38 eligible women consented; 3 did not receive the infusion due to staffing. Therefore, 9 women received rhAPC (24 μg/kg/hr for ≤96 h antenatally). No safety issues were identified. There was a marginal prolongation in eligibility-to-delivery intervals for women receiving rhAPC (Mantel-Cox p = 0.052; Gehan-Breslow-Wilcoxon p = 0.049). Compared with both the pre-infusion phase in the rhAPC-treated women themselves and with fullPIERS rhAPC-naive women, rhAPC was associated with increased urine output during the infusion (6/9 vs 1/9 had urine output >100 mL/h during the infusion, Fisher’s exact p = 0.003). Conclusions These data support further investigation of APC in women with severe early-onset preeclampsia; recombinant and purified human APC is available. In addition, these data will inform the design and implementation of randomized controlled trials aiming to modify and/or moderate the proinflammatory and proacoagulant state of preeclampsia.

Preterm infants are at higher risk of developing hypothermia and complications from cold stress, resulting in high mortality and short-term morbidity. Our objective is to evaluate the association between admission temperatures of extremely low-gestational age neonates (ELGAN) (

BACKGROUND:Brain injury (BI) is reported in 60% of newborns with critical congenital heart disease as white matter injury (WMI) or stroke. Neurodevelopmental (ND) impairments are reported in these patients. The relationship between neonatal BI and ND outcome has not been established. OBJECTIVES:This study sought to determine the association between peri-operative BI and ND outcomes in infants with single ventricle physiology (SVP) and d-transposition of the great arteries (d-TGA). METHODS:Term newborns with d-TGA and SVP had pre-operative and post-operative brain magnetic resonance imaging and ND outcomes assessed at 12 and 30months with the Bayley Scales of Infant Development-II. BI was categorized by the brain injury severity score and WMI was quantified by volumetric analysis. RESULTS:A total of 104 infants had follow-up at 12months and 70 had follow-up at 30months. At 12months, only clinical variables were associated with ND outcome. At 30months, subjects with moderate-to-severe WMI had significantly lower Psychomotor Development Index (PDI) scores (13 points lower) as compared with those with none or minimal WMI for d-TGA and SVP (p=0.03 and p=0.05, respectively) after adjusting for various factors. Quantitative WMI volume was likewise associated. Stroke was not associated with outcome. The Bland-Altman limits of agreement for PDI scores at 12 and 30months were wide (-40.3 to 31.2) across the range of mean PDI values. CONCLUSIONS:Increasing burden of WMI is associated with worse motor outcomes at 30months for infants with criticalcongenital heart disease, whereas no adverse association was seen between small strokes and outcome. Theseresults support the utility of neonatal brain magnetic resonance imaging in this population to aid in predictinglateroutcomes and the importance of ND follow-up beyond 1 year of age.

Objective The objective is to evaluate the association between antibiotic utilization and neurodevelopmental outcomes at 18 to 21 months' corrected age among extremely low gestational age neonates without culture-proven sepsis or necrotizing enterocolitis (NEC). Study Design We conducted a retrospective cohort study of infants born between April 2009 and September 2011 at Result There were 1,373 infants who fulfilled our inclusion criteria. Compared with infants in the lowest AUR quartile (Q1), those in the highest quartile (Q4) had higher odds of death or sNDI (adjusted odds ratio [AOR] = 7.44; 95% confidence interval [CI]: 4.55, 12.2) and death (AOR = 39.3; 95% CI: 16.1, 95.9). Conclusion Our results indicate an association between high AUR and a composite outcome of death or adverse neurodevelopmental outcomes at 18 to 21 months' corrected age.

KEY POINTS Congenital diaphragmatic hernia (CDH), which occurs in about 1 in 3300 live births, is a congenital defect in the diaphragm that allows herniation of abdominal viscera into the thorax.[1][1] The resulting abnormal lung development leads to pulmonary hypoplasia and pulmonary hypertension

Background Preterm birth (birth before 37 wk of gestation) occurs in about 8% of pregnancies in Canada and is associated with high mortality and morbidity rates that substantially affect infants, their families and the health care system. Our overall goal is to create a transdisciplinary platform, the Canadian Preterm Birth Network (CPTBN), where investigators, stakeholders and families will work together to improve childhood outcomes of preterm neonates. Methods Our national cohort will include 24 maternal-fetal/obstetrical units, 31 neonatal intensive care units and 26 neonatal follow-up programs across Canada with planned linkages to provincial health information systems. Three broad clusters of projects will be undertaken. Cluster 1 will focus on quality-improvement efforts that use the Evidence-based Practice for Improving Quality method to evaluate information from the CPTBN database and review the current literature, then identify potentially better health care practices and implement identified strategies. Cluster 2 will assess the impact of current practices and practice changes in maternal, perinatal and neonatal care on maternal, neonatal and neurodevelopmental outcomes. Cluster 3 will evaluate the effect of preterm birth on babies, their families and the health care system by integrating CPTBN data, parent feedback, and national and provincial database information in order to identify areas where more parental support is needed, and also generate robust estimates of resource use, cost and cost-effectiveness around preterm neonatal care. Interpretation These collaborative efforts will create a flexible, transdisciplinary, evaluable and informative research and quality-improvement platform that supports programs, projects and partnerships focused on improving outcomes of preterm neonates.

To examine rates and determinants of mother's own milk (MOM) feeding at hospital discharge in a cohort of infants born very preterm within the Canadian Neonatal Network (CNN).This was a population-based cohort study of infants born at33 weeks of gestation and admitted to neonatal intensive care units (NICUs) participating in the CNN between January 1, 2015, and December 31, 2018. We examined the rates and determinants of MOM use at discharge home among the participating NICUs. We used multivariable logistic regression analysis to identify independent determinants of MOM feeding.Among the 6404 infants born very preterm and discharged home during the study period, 4457 (70%) received MOM or MOM supplemented with formula. Rates of MOM feeding at discharge varied from 49% to 87% across NICUs. Determinants associated with MOM feeding at discharge were gestational age 29-32 weeks compared with26 weeks (aOR 1.56, 95% CI 1.25-1.93), primipara mothers (aOR 2.12, 95% CI 1.86-2.42), maternal diabetes (aOR 0.79, 95% CI 0.66-0.93), and maternal smoking (aOR 0.27, 95% CI 0.19-0.38). Receipt of MOM by day 3 of age was the major predictor of breast milk feeding at discharge (aOR 3.61, 95% CI 3.17-4.12).Approximately two-thirds of infants born very preterm received MOM at hospital discharge, and rates varied across NICUs. Supporting mothers to provide breast milk in the first 3 days after birth may be associated with improved MOM feeding rates at discharge.

BackgroundHuman studies investigating the link between postnatal polyunsaturated fatty acids and preterm brain growth are limited, despite emerging evidence of potential effects on outcomes.MethodsSixty preterm neonates

To compare the neurodevelopmental outcomes at 18 to 21 months corrected age (CA) of infants born at29 weeks that received room air, an intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation.In this retrospective cohort study, we compared neonatal and neurodevelopmental outcomes at 18 to 21 months CA among inborn infants born before 29 weeks' gestation that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation.Of 1509 infants, 445 received room air, 483 received intermediate oxygen concentrations and 581 received 100% oxygen. Compared to infants that received room air, the primary outcome of death or neurodevelopmental impairment (NDI) was not different in intermediate oxygen (adjusted odds ratio (aOR) 1.01; 95% confidence interval (CI) 0.77, 1.34) or 100% oxygen (aOR 1.03; 95% CI 0.78, 1.35). Compared to room air, there was no difference in odds of death or severe NDI in intermediate oxygen (aOR 1.14; 95% CI 0.82, 1.58) or 100% oxygen group (aOR 1.22; 95% CI 0.90, 1.67). The odds of severe NDI among survivors were significantly higher in infants that received 100% oxygen as compared to room air (aOR 1.57, 95% CI 1.05, 2.35).We observed no significant difference in the primary composite outcomes of death or NDI and death or severe NDI at 18 to 21 months CA between infants that received room air, intermediate oxygen concentration or 100% oxygen at the initiation of resuscitation. However, use of 100% oxygen was associated with increased odds of severe NDI among survivors as compared to room air.

Background The efficacy of antenatal corticosteroid treatment for women with threatened preterm birth depends on timely administration within 7 days before delivery. We modelled the probability of delivery within 7 days of admission to hospital among women presenting with threatened preterm birth, using routinely collected clinical characteristics. Methods Data from the Canadian Perinatal Network (CPN) were used, 2005–11, including women admitted to hospital with preterm labour, preterm pre-labour rupture of membranes, short cervix without contractions, or dilated cervix or prolapsed membranes without contractions at preterm gestation. Women with fetal anomaly, intrauterine fetal demise, twin-to-twin transfusion syndrome, and quadruplets were excluded. Logistic regression was undertaken to create a predictive model that was assessed for its calibration capacity, stratification ability, and classification accuracy (ROC curve). Results We included 3012 women admitted at 24–28 weeks gestation, or readmitted at up to 34 weeks gestation, to 16 tertiary-care CPN hospitals. Of these, 1473 (48.9%) delivered within 7 days of admission. Significant predictors of early delivery included maternal age, parity, gestational age at admission, smoking, preterm labour, prolapsed membranes, preterm pre-labour rupture of membranes, and antepartum haemorrhage. The area under the ROC curve was 0.724 (95% CI 0.706–0.742). Conclusion We propose a useful tool to improve prediction of delivery within 7 days after admission among women with threatened preterm birth. This information is important for optimal corticosteroid treatment. Electronic supplementary material The online version of this article (doi:10.1186/s12884-017-1390-9) contains supplementary material, which is available to authorized users.

Objectives The objective of this study was to describe survival, short-term, and long-term morbidities of neonates with birth weight Study Design Retrospective cohort studies to calculate survival, short-term, and long-term morbidity rates of neonates born weighing Results Of 549 inborn neonates with birth weight Conclusion Only 4% of births

To compare neonatal outcomes of twins delivered33 weeks' gestation in tertiary centers in Canada according to the mode of birth and presentation.This retrospective cohort from the Canadian Neonatal Network database studied preterm twins born from 24 + 0 to 32 + 6 weeks' gestation between 2005 and 2012. Twins were grouped by the mode of birth: both vaginal, combined vaginal/cesarean section (CS), and both CS. Additionally, twins were grouped by the mode of presentation: both vertex, vertex/breech, breech/vertex, and both breech. The primary outcome was a composite of mortality or severe neonatal morbidity (severe neurological injury [intraventricular hemorrhage grade 3/4 or periventricular leukomalacia], bronchopulmonary dysplasia, retinopathy of prematurity, and necrotizing enterocolitis).Of the 6636 twins, 1934 (29%) were delivered vaginally, 418 (6%) by combined vaginal birth/CS, and 4284 (65%) were born by CS. The composite did not differ between the groups. However, severe neurological injury was decreased (adjusted odds ratio [AOR], 0.77; 95% confidence interval [CI], 0.61-0.98) and respiratory distress syndrome (AOR, 1.34; 95%CI, 1.15-1.56) was increased when both the twins were delivered by CS.Preterm twin infants born via CS experienced less severe neurological injury when compared to those delivered vaginally, but had an increase in respiratory distress syndrome.

Introduction/Background Bronchopulmonary dysplasia (BPD) is a common complication of extreme prematurity and may require prolonged home respiratory support. BPD is associated with worse neurodevelopmental outcomes but the impact of home respiratory support on neurodevelopmental outcomes, rehospitalization rates and association with caregiver sociodemographics is less well studied. Objectives This study examines the impact of home respiratory support on neurodevelopmental outcomes in very preterm infants at 18-24 months corrected gestational age. Design/Methods This linked Canadian Neonatal Network and Canadian Neonatal Follow-Up Network (CNFUN) multicenter cohort study of infants born April 1, 2009-December 31, 2016 at Results Of the 3918 infants, 622 (15.9%) received home respiratory support. As expected, infants on home respiratory support had a lower gestational age (mean 25.5 vs 26.5 weeks, p < 0.01), lower birth weight (mean 781 vs 955 grams, p < 0.01), longer NICU stay (mean 118 vs 76 days, p < 0.01) and more comorbidities: late onset sepsis (35.1% vs 22.9%, p < 0.01), NEC ≥ stage 2 (8.9% vs 5.9%, p = 0.01), grade 3-4 IVH or PVL (12.7% vs 8.4%, p < 0.01) and ROP ≥ grade 3 (28% vs 10.8%, p < 0.01). Infants on home respiratory support had higher significant neurodevelopmental impairment rates defined as Bayley-III motor, cognitive, language scores 3 rehospitalizations (19.8% vs 5.0%, p < 0.01). With home respiratory support, fewer families had paid employment and more were on social welfare. Conclusion Children born preterm who are discharged home on respiratory support, compared to those without home support, are more likely to experience neurodevelopmental impairment and rehospitalization, and may have an adverse impact on family income. This is important for discharge planning and follow-up care of these high risk children.

BACKGROUND: Preterm birth is the leading cause of morbidity and mortality in children younger than 5 years. We report the changes in neonatal outcomes and care practices among very preterm infants in Canada over 14 years within a national, collaborative, continuous quality-improvement program. METHODS: We retrospectively studied infants born at 23–32 weeks’ gestation who were admitted to tertiary neonatal intensive care units that participated in the Evidence-based Practice for Improving Quality program in the Canadian Neonatal Network from 2004 to 2017. The primary outcome was survival without major morbidity during the initial hospital admission. We quantified changes using process-control charts in 6-month intervals to identify special-cause variations, adjusted regression models for yearly changes, and interrupted time series analyses. RESULTS: The final study population included 50 831 infants. As a result of practice changes, survival without major morbidity increased significantly (56.6% [669/1183] to 70.9% [1424/2009]; adjusted odds ratio [OR] 1.08, 95% confidence interval [CI] 1.06–1.10, per year) across all gestational ages. Survival of infants born at 23–25 weeks’ gestation increased (70.8% [97/137] to 74.5% [219/294]; adjusted OR 1.03, 95% CI 1.02–1.05, per year). Changes in care practices included increased use of antenatal steroids (83.6% [904/1081] to 88.1% [1747/1983]), increased rates of normothermia at admission (44.8% [520/1160] to 67.5% [1316/1951]) and reduced use of pulmonary surfactant (52.8% [625/1183] to 42.7% [857/2009]). INTERPRETATION: Network-wide quality-improvement activities that include better implementation of optimal care practices can yield sustained improvement in survival without morbidity in very preterm infants.

Objectives To examine the association between mortality or neurodevelopmental impairment at 18-24 months of corrected age and the Transport Risk Index of Physiologic Stability (TRIPS) score on admission to the neonatal intensive care unit (NICU) in extremely premature infants. Study design Retrospective cohort study of extremely premature infants (inborn and outborn) born at 22-28 weeks of gestational age and admitted to NICUs in the Canadian Neonatal Network between April 2009 and September 2011. TRIPS scores and clinical data were collected from the Canadian Neonatal Network database. Follow-up data at 18-24 months of corrected age were retrieved from the Canadian Neonatal Follow-Up Network database. Neurodevelopment was assessed using the Bayley Scales of Infant and Toddler Development, Edition III. The primary outcome was death or significant neurodevelopmental impairment at 18-24 months of corrected age. The secondary outcomes were individual components of the Bayley Scales of Infant and Toddler Development, Edition III assessment. Results A total of 1686 eligible infants were included. A TRIPS score of ≥20 on admission to the NICU was significantly associated with mortality (aOR 2.71 [95% CI, 2.02-3.62]) and mortality or significant neurodevelopmental impairment (aOR 1.91 [95% CI, 1.52-2.41]) at 18-24 months of corrected age across all gestational age groups of extremely premature infants. Conclusion The TRIPS score on admission to the NICU can be used as an adjunctive, objective tool for counselling the parents of extremely premature infants early after their admission to the NICU.

BackgroundHospitalized infants undergo multiple painful procedures daily. Despite the significant evidence, procedural pain assessment and management continues to be suboptimal. Repetitive and untreated pain at this vital developmental juncture is associated with negative behavioral and neurodevelopmental consequences. To address this knowledge to practice gap, we developed the web-based Implementation of Infant Pain Practice Change (ImPaC) Resource to guide change in healthcare professionals’ pain practice behaviors. This protocol describes the evaluation of the intervention effectiveness and implementation of the Resource and how organizational context influences outcomes.MethodsAn effectiveness-implementation hybrid type 1 design, blending a cluster randomized clinical trial and a mixed-methods implementation study will be used. Eighteen Neonatal Intensive Care Units (NICUs) across Canada will be randomized to intervention (INT) or standard practice (SP) groups. NICUs in the INT group will receive the Resource for six months; those in the SP group will continue with practice as usual and will be offered the Resource after a six-month waiting period. Data analysts will be blinded to group allocation. To address the intervention effectiveness, the INT and SP groups will be compared on clinical outcomes including the proportion of infants who have procedural pain assessed and managed, and the frequency and nature of painful procedures. Data will be collected at baseline (before randomization) and at completion of the intervention (six months). Implementation outcomes (feasibility, fidelity, implementation cost, and reach) will be measured at completion of the intervention. Sustainability will be assessed at six and 12 months following the intervention. Organizational context will be assessed to examine its influence on intervention and implementation outcomes.DiscussionThis mixed-methods study aims to determine the effectiveness and the implementation of a multifaceted online strategy for changing healthcare professionals’ pain practices for hospitalized infants. Implementation strategies that are easily and effectively implemented are important for sustained change. The results will inform healthcare professionals and decision-makers on how to address the challenges of implementing the Resource within various organizational contexts.Trial registrationClinicalTrials.gov,NCT03825822. Registered 31 January 2019.

To develop and validate an itemized costing algorithm for in-patient neonatal intensive care unit (NICU) costs for infants born prematurely that can be used for quality improvement and health economic analyses.We sourced patient resource use data from the Canadian Neonatal Network database, with records from infants admitted to 30 tertiary NICUs in Canada. We sourced unit cost inputs from Ontario hospitals, schedules of benefits, and administrative sources. Costing estimates were generated by matching patient resource use data to the appropriate unit costs. All cost estimates were in 2017 Canadian dollars and assigned from the perspective of a provincial public payer. Results were validated using previous estimates of inpatient NICU costs and hospital case-cost estimates.We assigned costs to 27 742 infants born prematurely admitted from 2015 to 2017. Mean (SD) gestational age and birth weight of the cohort were 31.8 (3.5) weeks and 1843 (739) g, respectively. The median (IQR) cost of hospitalization before NICU discharge was estimated as $20 184 ($9739-51 314) for all infants; $11 810 ($6410-19 800) for infants born at gestational age of 33-36 weeks; $30 572 ($16 597-$51 857) at gestational age of 29-32 weeks; and $100 440 ($56 858-$159 3867) at gestational age of29 weeks. Cost estimates correlated with length of stay (r = 0.97) and gestational age (r = -0.65). The estimates were consistent with provincial resource estimates and previous estimates from Canada.NICU costs for infants with preterm birth increase as gestation decreases and length of stay increases. Our cost estimates are easily accessible, transparent, and congruent with previous cost estimates.