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The article presents research experience integrating parents, clinicians, and researchers to identify the selection and reporting of meaningful outcomes after preterm birth. Topics discussed include principles of patient-oriented research, significance of the parents lived exprience to presentations, and impact of the collaborative effort.

Although sucrose is widely administered to hospitalized infants for single painful procedures, total sucrose volume during the entire neonatal intensive care unit (NICU) stay and associated adverse events are unknown. In a longitudinal observation study, we aimed to quantify and contextualize sucrose administration during the NICU stay. Specifically, we investigated the frequency, nature, and severity of painful procedures; proportion of procedures where neonates received sucrose; total volume of sucrose administered for painful procedures; and incidence and type of adverse events. Neonates <32 weeks gestational age at birth and <10 days of life were recruited from four Canadian tertiary NICUs. Daily chart reviews of documented painful procedures, sucrose administration, and any associated adverse events were undertaken. One hundred sixty‐eight neonates underwent a total of 9093 skin‐breaking procedures (mean 54.1 [±65.2] procedures/neonate or 1.1 [±0.9] procedures/day/neonate) during an average NICU stay of 45.9 (±31.4) days. Pain severity was recorded for 5399/9093 (59.4%) of the painful procedures; the majority (5051 [93.5%]) were heel lances of moderate pain intensity. Sucrose was administered for 7839/9093 (86.2%) of painful procedures. The total average sucrose volume was 5.5 (±5.4) mL/neonate or 0.11 (±0.08) mL/neonate/day. Infants experienced an average of 7.9 (±12.7) minor adverse events associated with pain and/or sucrose administration that resolved without intervention. The total number of painful procedures, sucrose volume, and incidence of adverse events throughout the NICU stay were described addressing an important knowledge gap in neonatal pain. These data provide a baseline for examining the association between total sucrose volume during NICU stay and research on longer‐term behavioral and neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long-term neurodevelopmental outcomes in very preterm infants (VPIs), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine the long-term neurodevelopmental outcomes of VPIs with late onset sepsis and meningitis, with and without IVH, in Canada. Methods: We conducted a retrospective cohort study of all infants <29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases, from January 1, 2010, to December 31, 2016. Results: Of the 6,322 infants in the cohort, 4,575 had no infection, 1,590 had late onset culture-positive bloodstream infection (CPBSI) only, and 157 had late onset meningitis. There was a significant (p < 0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment, cerebral palsy, and individual Bayley-III scores <85 for cognitive, language, and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis. Conclusion: There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect. [ABSTRACT FROM AUTHOR]

Exposure to pain‐related stress from frequent invasive procedures in the neonatal intensive care unit (NICU) has been associated with altered physiological stress regulation, neurodevelopment, and behavior in children born very preterm (≤32 weeks gestation). Previously, in a cohort born 2003–2006 (Cohort 1), we found that, at 18 months corrected age (CA), children born extremely low gestational age (ELGA; 24–28 weeks) and very low gestational age (VLGA; 29–32 weeks), had higher pre‐test cortisol levels and a different pattern of cortisol output across a developmental assessment involving cognitive challenge compared to children born full‐term (FT; 39–41 weeks). Also, greater neonatal pain‐related stress exposure among the preterm children was related to higher pre‐test cortisol levels. Given the adverse long‐term effects of neonatal pain in preterm infants and the ensuing rise in clinical concerns to appropriately manage pain in the NICU in recent years, we aimed to examine whether our findings from Cohort 1 would still be evident in an independent cohort (Cohort 2) born 2006–2011 and recruited from the same tertiary NICU in Vancouver, Canada. We also compared the cortisol patterns, clinical and socio‐demographic factors, and their interrelationships between the two cohorts. In Cohort 2, our findings using multi‐level modeling support and extend our earlier findings in Cohort 1, demonstrating that children born ELGA display higher pre‐test cortisol levels than FT. As well, greater cortisol output across assessment was related to more anxiety/depressive behaviors in children born VLGA. Importantly, children born ELGA were exposed to less neonatal pain/stress, mechanical ventilation, and morphine in Cohort 2 than Cohort 1. In both cohorts, however, cortisol levels and patterns were related to neonatal pain/stress and clinical factors (days on mechanical ventilation, overall morphine exposure). Despite less exposure to pain/stress and adverse clinical factors in Cohort 2 compared to Cohort 1, cortisol levels and patterns across cognitive challenge in preterm children at 18‐month CA were consistent across the two independent cohorts. These findings highlight that, despite improvements to neonatal care, children born extremely preterm continue to display altered HPA axis activity, which is associated with their poorer neurodevelopmental and behavioral outcomes. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Preterm infants are at risk for adverse neurodevelopmental outcomes, especially language delay. Preterm infants < 29 weeks' gestational age, cared for in Canadian Neonatal Follow-Up Network affiliated hospitals, were assessed between 18 to 21 months corrected age using the Bayley-III. Bayley-III Language Composite Scores were compared using univariate and multivariate analyses for children in three primary language groups: English, French and other. 6146 children were included. The primary language at home was English, French or another language for 3708 children (60%), 1312 children (21%) and 1126 children (18%), respectively, and overall, 44% were exposed to two or more languages at home. Univariate analysis showed that primary language was associated with lower Bayley-III Language scores; however, multivariate analyses demonstrated that neither primary language nor language of administration were significantly associated with lower language scores when adjusted for gestational age, other developmental delays and sociodemographic factors, but multiple language exposure was. Sociodemographic and other factors are more important in determining language development than primary language at home. Further studies are needed to examine the association between exposure to multiple languages and lower Bayley-III language scores in preterm infants. [ABSTRACT FROM AUTHOR]

Objective: To 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/methods: Prospective cohort study of infants born <29 weeks' gestational age (GA) who participated in the FICare cluster randomised control trial (cRCT) and were assessed in the Canadian Neonatal Follow-Up Network (CNFUN). The primary outcome measure, Cognitive or Language composite score <85 on the Bayley-III, was compared between FICare exposed and routine care children using logistic regression, adjusted for potential confounders and employing generalised estimation equations to account for clustering of infants within sites.Results: Of 756 infants <29 weeks' GA in the FICare cRCT, 505 were enrolled in CNFUN and 455 were assessed (238 FICare, 217 control). Compared with controls, FICare infants had significantly higher incidence of intraventricular haemorrhage (IVH) (19.5% vs 11.7%, p=0.024) and higher proportion of employed mothers (76.6% vs 73.6%, p=0.043). There was no significant difference in the odds of the primary outcome (adjusted OR: 0.92 (0.59 to 1.42) FiCare vs Control) on multivariable analyses adjusted for GA, IVH and maternal employment. However, Bayley-III Motor scores (adjusted difference in mean (95% CI) 3.87 (1.22 to 6.53) and body mass index 0.67 (0.36 to 0.99) were higher in the FICare group.Conclusions: Very preterm infants exposed to FICare had no significant difference in incidence of cognitive or language delay but had better motor development.Trial Registration Number: Participants in this cohort study were previously enrolled in a registered trial: NCT01852695. [ABSTRACT FROM AUTHOR]

Objectives: Health 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.Methods: Infants 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.Results: Of 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.Conclusion: Most 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. [ABSTRACT FROM AUTHOR]

Objective Survivors of extremely preterm birth are at risk of re-hospitalization but risk factors in the Canadian population are unknown. Our objective is to identify neonatal, sociodemographic, and geographic characteristics that predict re-hospitalization in Canadian extremely preterm neonates. Methods This is a retrospective analysis of a prospective observational cohort study that included preterm infants born 22 to 28 weeks' gestational age from April 1, 2009 to September 30, 2011 and seen at 18 to 24 months corrected gestational age in a Canadian Neonatal Follow-Up Network clinic. Characteristics of infants re-hospitalized versus not re-hospitalized are compared. The potential neonatal, sociodemographic, and geographic factors with significant association in the univariate analysis are included in a multivariate model. Results From a total of 2,275 preterm infants born at 22 to 28 weeks gestation included, 838 (36.8%) were re-hospitalized at least once. There were significant disparities between Canadian provincial regions, ranging from 25.9% to 49.4%. In the multivariate logistic regression analysis, factors associated with an increased risk for re-hospitalization were region of residence, male sex, bronchopulmonary dysplasia, necrotizing enterocolitis, prolonged neonatal intensive care unit (NICU) stay, ethnicity, Indigenous ethnicity, and sibling(s) in the home. Conclusion Various neonatal, sociodemographic, and geographic factors predict re-hospitalization of extremely preterm infants born in Canada. The risk factors of re-hospitalization provide insights to help health care leaders explore potential preventative approaches to improve child health and reduce health care system costs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Hospitalized 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.Methods: An 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.Discussion: This 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 Registration: ClinicalTrials.gov, NCT03825822. Registered 31 January 2019. [ABSTRACT FROM AUTHOR]

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 <29 weeks' gestation and admitted to the neonatal intensive care units contributing data to the Canadian Neonatal Network. Multivariable analysis was performed to examine the primary composite outcome of death or significant neurodevelopmental impairment (sNDI) in infants with various antibiotic utilization rates (AURs). 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. [ABSTRACT FROM AUTHOR]

Objective: To examine the association between the duration of antibiotic exposure and development of stage 2 or 3 necrotizing enterocolitis (NEC) in very preterm neonates. Study Design: A retrospective case–control study was conducted from Canadian Neonatal Network data for preterm neonates born before 29 weeks' gestation and admitted 2010 through 2013. Efforts were made to match each NEC case to two controls for gestational age, birth weight (±100 g) and sex. Results: A total of 224 cases and 447 controls were identified. The incidence of antenatal steroid administration, the number of days nil-per-os and the number of antibiotic days prior to onset of NEC were significantly different in neonates with NEC. A multiple regression analysis revealed that the duration of antibiotic use was higher among NEC cases compared to controls (P<0.01). Empiric antibiotic treatment of 5 or more days was associated with significantly increased odds of NEC as compared with antibiotic exposure of 0 to 4 days (adjusted odds ratio: 2.02; 95% CI 1.55, 3.13). Conclusion: Empiric antibiotic exposure for 5 or more days in preterm neonates born before 29 weeks' gestation was associated with an increased risk of NEC. [ABSTRACT FROM AUTHOR]

Objectives: Identify determinants of neurodevelopmental outcome in preterm children.Methods: Prospective 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.Results: Of 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.Conclusion: Most preterm survivors are free of sNDI. The risk factors, including site, associated with neurodevelopmental status suggest opportunities for improving outcomes. [ABSTRACT FROM AUTHOR]

Background: Administration of magnesium sulphate (MgSO4) to women with imminent preterm birth at <34 weeks is an evidence-based antenatal neuroprotective strategy to prevent cerebral palsy. Although a Society of Obstetricians and Gynaecologists of Canada (SOGC) national guideline with practice recommendations based on relevant clinical evidence exists, ongoing controversies about aspects of this treatment remain. Given this, we anticipated managed knowledge translation (KT) would be needed to facilitate uptake of the guidelines into practice. As part of the Canadian Institutes of Health Research (CIHR)-funded MAG-CP (MAGnesium sulphate to prevent Cerebral Palsy) project, we aimed to compare three KT methods designed to impact both individual health care providers and the organizational systems in which they work.Methods: The KT methods undertaken were an interactive online e-learning module available to all SOGC members, and at MAG-CP participating sites, on-site educational rounds and focus group discussions, and circulation of an anonymous 'Barriers and Facilitators' survey for the systematic identification of facilitators and barriers for uptake of practice change. We compared these strategies according to: (i) breadth of respondents reached; (ii) rates and richness of identified barriers, facilitators, and knowledge needed; and (iii) cost.Results: No individual KT method was superior to the others by all criteria, and in combination, they provided richer information than any individual method. The e-learning module reached the most diverse audience of health care providers, the site visits provided opportunity for iterative dialogue, and the survey was the least expensive. Although the site visits provided the most detailed information around individual and organizational barriers, the 'Barriers and Facilitators' survey provided more detail regarding social-level barriers. The facilitators identified varied by KT method. The type of knowledge needed was further defined by the e-learning module and surveys.Conclusions: Our findings suggest that a multifaceted approach to KT is optimal for translating national obstetric guidelines into clinical practice. As audit and feedback are essential parts of the process by which evidence to practice gaps are closed, MAG-CP is continuing the iterative KT process described in this paper concurrent with tracking of MgSO4 use for fetal neuroprotection and maternal and child outcomes until September 2015; results are anticipated in 2016. [ABSTRACT FROM AUTHOR]

Objective To develop models and a graphical tool for predicting survival to discharge without major morbidity for infants with a gestational age (GA) at birth of 22-32 weeks using infant information at birth. Design Retrospective cohort study. Setting Canadian Neonatal Network data for 2003- 2008 were utilised. Patients Neonates born between 22 and 32 weeks gestation admitted to neonatal intensive care units in Canada. Main outcome measure Survival to discharge without major morbidity defi ned as survival without severe neurological injury (intraventricular haemorrhage grade 3 or 4 or periventricular leukomalacia), severe retinopathy (stage 3 or higher), necrotising enterocolitis (stage 2 or 3) or chronic lung disease. Results Of the 17 148 neonates who met the eligibility criteria, 65% survived without major morbidity. Sex and GA at birth were signifi cant predictors. Birth weight (BW) had a signifi cant but non-linear effect on survival without major morbidity. Although maternal information characteristics such as steroid use, improved the prediction of survival without major morbidity, sex, GA at birth and BW for GA predicted survival without major morbidity almost as accurately (area under the curve: 0.84). The graphical tool based on the models showed how the GA and BW for GA interact, to enable prediction of outcomes especially for small and large for GA infants. Conclusion This graphical tool provides an improved and easily interpretable method to predict survival without major morbidity for very preterm infants at the time of birth. These curves are especially useful for small and large for GA infants. INSETS: What is already known on this topic;What this study adds. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to evaluate changes over time in the characteristics of permanent hearing impairment (HI) in extremely low-birthweight (ELBW ≤800 g) children. Methods: Data from sequential visits up to 5 years of age assessing hearing and other neurodevelopmental outcomes were extracted from a cohort of ELBW subjects born between 1983 and 2006 at a single Canadian site. Trends in HI incidence, severity and association with other impairments were analysed in three 8-year epochs. Results: Fifty of 586 ELBW children had a HI. HI rates increased from 5% in epoch 1 to 7% in epoch 2-13% in epoch 3 (p = 0.01). Mild HI decreased from 78% in epoch 1 to 35% in epoch 3 (p = 0.03). Median age at diagnosis decreased from 13 to 8 months. Comorbidities were more common in HI children than non-HI children: cerebral palsy (40% vs 14%, p < 0.0001)), cognitive (38% vs 12%, p < 0.0001) and visual impairments (16% vs 6%, p = 0.009). Conclusion: The incidence and severity of hearing impairment in a cohort of extremely low-birthweight children increased significantly from 5% to 13% (p = 0.01) over a 24-year period. Comorbidities were common. Potentially modifiable causes are explored. [ABSTRACT FROM AUTHOR]

Background: 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.Objective: This study aimed to evaluate and compare the neurodevelopmental outcomes of preterm infants born at <29 weeks' gestation at 18 to 24 months' corrected age who were conceived through assisted reproductive technology and those who were conceived naturally.Study Design: This retrospective cohort study included inborn, nonanomalous infants, born at <29 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 of <85; 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.Results: 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 of <85 (adjusted odds ratio, 0.68; 95% confidence interval, 0.48-0.99) and composite language score of <85 (adjusted odds ratio, 0.67; 95% confidence interval, 0.50-0.88).Conclusion: 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 at <29 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. [ABSTRACT FROM AUTHOR]

Objective: To compare mortality and neurodevelopmental outcomes of extremely low gestational age neonates who received delivery room extensive cardiopulmonary resuscitation (DR-CPR) to those who did not require DR-CPR.Methods: Preterm neonates born at <29 weeks' gestational age between January 2010 and September 2011 and assessed at Canadian Neonatal Follow-Up Network centers were studied. Neonates who received DR-CPR were compared to those who did not require DR-CPR using univariate and multivariable analyses. The primary outcome was a composite of mortality or any neurodevelopmental impairment at 18 to 24 months corrected age defined as the presence of any one or more of the following: cerebral palsy; Bayley-III cognitive, language, or motor composite scores <85 on any one of the components; sensorineural/mixed hearing loss or unilateral or bilateral visual impairment. Secondary outcomes were the individual components of the composite outcomes.Results: Of the 2760 neonates born, 173 were excluded and remaining 2587 eligible neonates were included in our study. Of these 2068 had outcome data (80%) of whom 190 (9.2%) received DR-CPR. DR-CPR was independently associated with mortality or neurodevelopmental impairment (adjusted odds ratio [aOR] 1.76; 95% CI 1.21-2.55) and mortality alone (aOR1.94; 95% CI 1.33-2.83). DR-CPR was also associated with increased odds of motor impairment (aOR 2.03; 95% CI 1.28-3.23).Conclusion: In extremely low gestational age neonates, DR-CPR was associated with higher odds of the composite outcome of mortality or neurodevelopmental impairment, mortality alone, and lower motor scores at 18 to 24 months' corrected age. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the association between head growth (HG) during neonatal and postdischarge periods and neurodevelopmental outcomes of preterm neonates of <29 weeks gestational age. METHODS: We conducted a retrospective cohort study of infants <29 weeks gestational age admitted between 2009 and 2011 to participating Canadian Neonatal Network units and followed by Canadian Neonatal Follow-Up Network clinics. Differences in head circumference (ΔHC) z score were calculated for 3 time periods, which include admission to discharge, discharge to follow-up at 16-36 months, and admission to follow-up. These were categorized in 1 reference group (ΔHC z score between -1 and +1) and 4 study groups (ΔHC z score of <-2, between -2 to -1, +1 to +2, and >+2). Neurodevelopmental outcomes were compared with the reference group. RESULTS: 1973 infants met the inclusion criteria. Poor HG occurred frequently during the NICU admission (ΔHC z score <-2 in 24% infants versus 2% infants post-discharge) with a period of "catch-up" growth postdischarge. Significant neurodevelopmental impairment was higher in infants with the poorest HG from admission to follow-up (adjusted odds ratio 2.18, 95% confidence interval 1.50-3.15), specifically cognitive and motor delays. Infants with poor initial HG and catch-up postdischarge have a lower adjusted odds ratio of significant neurodevelopmental impairment (0.35, 95% CI 0.16-0.74). Infants with poor HG received a longer duration of parenteral nutrition and mechanical ventilation and had poor weight gain. CONCLUSIONS: Poor HG during the neonatal and postdischarge periods was associated with motor and cognitive delays at 16 to 36 months. [ABSTRACT FROM AUTHOR]

ABSTRACT. Background. Previous reports of variations in outcomes among neonatal intensive care units (NICUs) examined only specific subpopulations of interest (eg, very low birth weight [VLBW] infants <1500 g of birth weight [BW]). Objectives. We report on current practice and outcomes variations in a population-based national study of Canadian NICUs from January 8, 1996 to October 31, 1997. Method. Information on 20 488 admissions to 17 tertiary level NICUs across Canada was prospectively collected by trained abstractors using a standard manual of operations and definitions. Data were verified and analyzed in concert with a steering committee comprising experienced researchers and neonatologists. Patient information included demographic information, antenatal history, mode of delivery, problems at delivery, status of infant and problems at birth, illness severity (Clinical Risk Index for Babies, Score for Neonatal Acute Physiology, Score for Neonatal Acute Physiology-Version II), therapeutic intensity (Neonatal Therapeutic Intensity Scoring System [NTISS]), selected NICU practices and procedures, use of technology and resources, and selected patient outcomes. Patients were tracked until death or discharge home. Results. The mean number of annual admissions to an NICU was 657, with 26% outborn infants. Fifty-three percent were <2500 g BW, 20% were <1500 g BW (VLBW), and 65% were preterm (<38 weeks' gestational age [GA]). Only 2% of mothers received no prenatal care. Antenatal steroids were given to 58%, but there was wide variation in use (23%-76%). Congenital anomalies were present in 14%, and 4% were small for GA (less than the third percentile). Admission illness severity was lowest among infants 33 to 37 weeks of GA and correlated with risk of death. Ninety-six percent of patients survived until discharge, but fewer survived at lower GA. No infant <22 weeks' GA survived. Seven percent of infants had at least 1 episode of infection, but 75% received ant... [ABSTRACT FROM AUTHOR]

Objective: To evaluate changes in mortality or significant neurodevelopmental impairment (NDI) in children born at <29 weeks of gestation in association with national quality improvement initiatives., Study Design: This longitudinal cohort study included children born at 22 0/7 to 28 6/7  weeks of gestation who were admitted to Canadian neonatal intensive care units between 2009 and 2016. The primary outcome was a composite rate of death or significant NDI (Bayley Scales of Infant and Toddler Development, Third Edition score <70, severe cerebral palsy, blindness, or deafness requiring amplification) at 18-24 months corrected age. To evaluate temporal changes, outcomes were compared between epoch 1 (2009-2012) and epoch 2 (2013-2016). aORs were calculated for differences between the 2 epochs accounting for differences in patient characteristics., Results: The 4426 children included 1895 (43%) born in epoch 1 and 2531 (57%) born in epoch 2. Compared with epoch 1, in epoch 2 more mothers received magnesium sulfate (56% vs 28%), antibiotics (69% vs 65%), and delayed cord clamping (37% vs 31%) and fewer infants had a Score for Neonatal Acute Physiology, version II >20 (31% vs 35%) and late-onset sepsis (23% vs 27%). Death or significant NDI occurred in 30% of children in epoch 2 versus 32% of children in epoch 1 (aOR, 0.86; 95% CI, 0.75-0.99). In epoch 2, there were reductions in the need for hearing aids or cochlear implants (1.4% vs 2.6%; aOR, 0.50; 95% CI, 0.31-0.82) and in blindness (0.6% vs.1.4%; aOR, 0.38; 95% CI, 0.18-0.80)., Conclusions: Among preterm infants born at <29 weeks of gestation, composite rates of death or significant NDI and rates of visual and hearing impairment were significantly lower in 2013-2016 compared with 2009-2012., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To compare neurodevelopmental outcomes of large and appropriate for gestational age (LGA, AGA) infants <29 weeks' gestation at 18-24 months of corrected age., Study Design: Retrospective cohort study using the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network databases. Primary outcome was a composite of death or significant neurodevelopmental impairment (NDI), defined as severe cerebral palsy, Bayley III cognitive, language and motor scores of <70, need for hearing aids or cochlear implant and bilateral visual impairment. Univariate and multivariable logistic analyses were applied for outcomes., Results: The study cohort comprised 170 LGA and 1738 AGA infants. There was no difference in significant NDI or individual components of the Bayley III between LGA and AGA groups. LGA was associated with the increased risk of death by follow-up, 44/170 (25.9%) vs. 320/1738 (18.4%) (aOR: 1.60 95% CI: 1.00-2.54)., Conclusions: Risk of NDI was similar between LGA and AGA infants.

Purpose: To evaluate neurodevelopment and growth in extremely preterm infants with or without necrotizing enterocolitis or spontaneous intestinal perforation., Methods: 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 infants <29 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., Results: 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., Conclusions: Spontaneous intestinal perforation, necrotizing enterocolitis, or any bowel perforation are risk factors for death or significant neurodevelopmental impairment in extremely preterm infants., Level of Evidence: Study type: prognosis study (cohort study: retrospective) LEVEL OF EVIDENCE RATING: II., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Clinician-initiated deliveries at 34 to 36 weeks gestation have increased in Canada since 2006, but the impacts of clinician-initiated deliveries on the overall preterm birth (PTB) rate and concomitant changes in neonatal outcomes are unknown. This study examined gestational age-specific trends in spontaneous and clinician-initiated PTB and associated neonatal mortality and morbidity., Methods: This population-based study included 1 880 444 singleton live births in Canada (excluding Québec) in 2009-2016, using hospitalization data from the Canadian Institute for Health Information. The primary outcomes were neonatal mortality and a composite outcome mortality and/or severe neonatal morbidity identified by International Statistical Classification of Diseases and Related Health Problems, 10th revision, Canada codes. Outcomes were stratified by spontaneous and clinician-initiated deliveries and gestational age categories. Logistic regression yielded adjusted odds ratios (aORs) per 1-year change and 95% confidence intervals (CIs) (Canadian Task Force Classification II-2)., Results: The PTB rate remained stable (6.2%) and the proportion of clinician-initiated PTBs increased from 31.0% to 37.9% (P < 0.001). Although overall neonatal mortality remained stable (1.1%), mortality declined among infants born spontaneously at 28 to 33 weeks gestation (aOR 0.92; 95% CI 0.87-0.97). The composite mortality and/or severe morbidity declined from 12.7% to 12.2% (aOR 0.98; 95% CI 0.97-0.99). Declines were observed in the rates of sepsis (aOR 0.96; 95% CI 0.95-0.98) and respiratory distress syndrome requiring ventilation (aOR 0.97; 95% CI 0.96-0.98), whereas rates of intraventricular hemorrhage increased (aOR 1.03; 95% CI 1.01-1.05)., Conclusion: With the increase in clinician-initiated deliveries, the stable rates of PTB and neonatal mortality and the decline in composite mortality and/or severe morbidity are encouraging findings. This study adds to clinical understanding of carefully timed and medically justified early interventions., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: The ability to definitively diagnose cerebral palsy (CP) at 18-24 months is unknown., Aims: 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., Study Design and Methods: Longitudinal national cohort study of births <29 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., Results: 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)., Conclusions: 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: 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., Study Design: Preterm infants born at <29 weeks of gestation and evaluated at 18-21 months CA were included. Primary outcome was a composite outcome of death or neurodevelopmental impairment (NDI)., Results: Of a total of 2760 infants, 699 met exclusion criteria. Of the remaining 2061 infants, 280 (13.6%) were exposed to maternal smoking and 1781 (86.4%) were not. The odds of the composite outcome of death or NDI (aOR 1.40; 95% CI: 1.03-1.91), NDI alone (aOR 1.43; 95% CI: 1.01-2.03), and Bayley-III motor score <85 (aOR 1.91; 95% CI: 1.31-2.81) were higher in exposed infants., Conclusions: Exposure to maternal smoking was associated with adverse composite outcome of death or NDI, NDI alone and lower motor scores at 18-21 months CA.

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 22 0 -28 6 weeks (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 22 0 -23 6 weeks 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 26 0 -28 6 weeks, 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.

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 <29 weeks' gestation from the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network databases, we compared mortality and neurodevelopmental outcomes in infants who had neonatal seizures with those without seizures after adjusting for confounders., 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., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Although caffeine use for apnea of prematurity is well studied, the long-term safety and benefit of routine early caffeine administration has not been explored. Our objective was to determine the association between early (within 2 days of birth) versus late caffeine exposure and neurodevelopmental outcomes in preterm infants., Methods: Infants of <29 weeks' gestation born between April 2009 and September 2011 and admitted to Canadian Neonatal Network units and then assessed at Canadian Neonatal Follow-up Network centers were studied. Neonates who received caffeine were divided into early- (received within 2 days of birth) and late-caffeine (received after 2 days of birth) groups. The primary outcome was significant neurodevelopmental impairment, defined as cerebral palsy, or a Bayley Scales of Infant and Toddler Development, Third Edition composite score of <70 on any component, hearing aid or cochlear implant, or bilateral visual impairment at 18 to 24 months' corrected age., Results: Of 2108 neonates who were eligible, 1545 were in the early-caffeine group and 563 were in the late-caffeine group. Rates of bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury were lower in the early-caffeine group than in the late-caffeine group. Significant neurodevelopmental impairment (adjusted odds ratio 0.68 [95% confidence interval 0.50-0.94]) and odds of Bayley Scales of Infant and Toddler Development, Third Edition cognitive scores of <85 (adjusted odds ratio 0.67 [95% confidence interval 0.47-0.95]) were lower in the early-caffeine group than in the late-caffeine group. Propensity score-based matched-pair analyses revealed lower odds of cerebral palsy and hearing impairment only., Conclusions: Early caffeine therapy is associated with better neurodevelopmental outcomes compared with late caffeine therapy in preterm infants born at <29 weeks' gestation., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Background: 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., Methods: 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 born <33 weeks gestation (n = 39,305) during 2003-2013 were compared between neonates diagnosed with an IFI during their stay to infection-free controls., Results: Overall incidence of IFI among all admitted neonates was 0.22% (n = 286), while the incidence of IFI in the group of neonates born <33 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 score <7 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)., Conclusions: 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.

Objective: To assess the impact of variations in the definition of severe neurodevelopmental impairment (NDI) on the incidence of severe NDI and the association with risk factors using the Canadian Neonatal Follow-Up Network cohort., Study Design: Literature review of severe NDI definitions and application of these definitions were performed in this database cohort study. Infants born at 23-28 completed weeks of gestation between 2009 and 2011 (n = 2187) admitted to a Canadian Neonatal Network neonatal intensive care unit and assessed at 21 months' corrected age were included. The incidence of severe NDI, aORs, and 95% CIs were calculated to express the relationship between risk factors and severe NDI using the definitions with the highest and the lowest incidence rates of severe NDI., Results: The incidence of severe NDI ranged from 3.5% to 14.9% (highest vs lowest rate ratio 4.29; 95% CI 3.37-5.47). The associations between risk factors and severe NDI varied depending on the definition used. Maternal ethnicity, employment status, antenatal corticosteroid treatment, and gestational age were not associated consistently with severe NDI. Although maternal substance use, sex, score of neonatal acute physiology >20, late-onset sepsis, bronchopulmonary dysplasia, and brain injury were consistently associated with severe NDI irrespective of definition, the strength of the associations varied., Conclusions: The definition of severe NDI significantly influences the incidence and the associations between risk factors and severe NDI. A standardized definition would facilitate site comparisons and scientific communication., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To compare mortality and neurodevelopmental outcomes of outborn and inborn preterm infants born at <29 weeks of gestation admitted to Canadian neonatal intensive care units (NICUs)., Study Design: Data were obtained from the Canadian Neonatal Network and Canadian Neonatal Follow-up Network databases for infants born at <29 weeks of gestation admitted to NICUs from April 2009 to September 2011. Rates of death, severe neurodevelopmental impairment (NDI), and overall NDI were compared between outborn and inborn infants at 18-21 months of age, corrected for prematurity., Results: Of 2951 eligible infants, 473 (16%) were outborn. Mean birth weight (940 ± 278 g vs 897 + 237 g), rates of treatment with antenatal steroids (53.9% vs 92.9%), birth weight small for gestational age (5.3% vs 9.4%), and maternal college education (43.7% vs 53.9%) differed between outborn and inborn infants, respectively (all P values <.01). The median Score for Neonatal Acute Physiology-II (P = .01) and Apgar score at 5 minutes (P < .01) were higher in inborn infants. Severe brain injury was more common among outborn infants (25.3% vs 14.7%, P < .01). Outborn infants had higher odds of death or severe NDI (aOR 1.7, 95% CI 1.3-2.2), death or overall NDI (aOR 1.6, 95% CI 1.2-2.2), death (aOR 2.1, 95% CI 1.5-3.0), and cerebral palsy (aOR 1.9, 95% CI 1.1-3.3)., Conclusions: The composite outcomes of death or neurodevelopmental impairment were significantly higher in outborn compared with inborn infants admitted to Canadian NICUs. Adverse outcomes were mainly attributed to increased mortality and cerebral palsy in outborn neonates., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Competing Interests: Competing interests: Pramod Puligandla received a one-time honorarium, outside the submitted work, for participation in a meeting regarding the use of inhaled nitric oxide in adults and children hosted by Ikaria Canada Inc. Ian Adatia reports a forthcoming grant award from Malinkcrodt. No other competing interests were declared.

Objective: To evaluate the maternal and perinatal outcomes of pregnancies delivered at 23+0 to 23+6 weeks' gestation., Methods: This prospective cohort study included women in the Canadian Perinatal Network who were admitted to one of 16 Canadian tertiary perinatal units between August 1, 2005, and March 31, 2011, and who delivered at 23+0 to 23+6 weeks' gestation. Women were included in the network if they were admitted with spontaneous preterm labour with contractions, a short cervix without contractions, prolapsing membranes with membranes at or beyond the external os or a dilated cervix, preterm premature rupture of membranes, intrauterine growth restriction, gestational hypertension, or antepartum hemorrhage. Maternal outcomes included Caesarean section, placental abruption, and serious complication. Perinatal outcomes were mortality and serious morbidity., Results: A total of 248 women and 287 infants were included in the study. The rate of Caesarean section was 10.5% (26/248) and 40.3% of women (100/248) had a serious complication, the most common being chorioamnionitis (38.6%), followed by blood transfusion (4.5%). Of infants with known outcomes, perinatal mortality was 89.9% (223/248) (stillbirth 23.3% [67/287] and neonatal death 62.9% [156/248]). Of live born neonates with known outcomes (n = 181), 38.1% (69/181) were admitted to NICU. Of those admitted to NICU, neonatal death occurred in 63.8% (44/69). Among survivors at discharge, the rate of severe brain injury was 44.0% (11/25), of retinopathy of prematurity 58.3% (14/24), and of any serious neonatal morbidity 100% (25/25). Two subgroup analyses were performed: in one, antepartum stillbirths were excluded, and in the other only centres that indicated they offered fetal monitoring at 23 weeks' gestation were included and antepartum stillbirths were excluded. In each of these, perinatal outcomes similar to the overall group were found., Conclusion: Pregnant women delivering at 23 weeks' gestation are at risk of morbidity. Their infants have high rates of serious morbidity and mortality. Further research is needed to identify strategies and forms of management that not only increase perinatal survival but also reduce morbidities in these extremely low gestational age infants and reduce maternal morbidity.

Magnetic resonance imaging (MRI) could improve prognostication in neonatal brain injury; however, factors beyond technical or scientific refinement may impact its use and interpretation. We surveyed Canadian neonatologists and pediatric neurologists using general and vignette-based questions about the use of MRI for prognostication in neonates with hypoxic-ischemic injury. There was inter- and intra-vignette variability in prognosis and in ratings about the usefulness of MRI. Severity of predicted outcome correlated with certainty about the outcome. A majority of physicians endorsed using MRI results in discussing prognosis with families, and most suggested that MRI results contribute to end-of-life decisions. Participating neonatologists, when compared to participating pediatric neurologists, had significantly less confidence in the interpretation of MRI by colleagues in neurology and radiology. Further investigation is needed to understand the complexity of MRI and of its application. Potential gaps relative to our understanding of the ethical importance of these findings should be addressed., (© The Author(s) 2014.)

Background: Prematurity and hereditary factors predispose to cerebral palsy (CP). Previously, low cord blood levels of the anti-inflammatory chemokine CCL18 have been found to be associated with risk of CP in preterm children., Objectives: To investigate the association between single nucleotide polymorphisms (SNPs) in CCL18 and susceptibility to CP, as well as the association between the SNPs and cord blood levels of CCL18., Methods: The original population comprised very-low-gestational-age (VLGA; <32 weeks) children from northern and central Finland (25 cases, 195 controls). Five CCL18 SNPs were genotyped and examined for associations with CP and cord blood CCL18. The replication population comprised Caucasian VLGA children from southern Finland and Canada (23 cases, 248 controls)., Results: In the original population, SNP rs2735835 was associated with CP; the minor allele A was underrepresented in cases compared to controls (OR = 0.42, 95% CI: 0.21-0.83, p = 0.01). This association remained significant after adjustment for multiple testing and risk factors of CP, and after combining the original and replication populations (OR = 0.52, 95% CI: 0.33-0.83, p = 0.005). Intraventricular hemorrhage (IVH) additively predicted CP. The Rs2015086 genotype was modestly associated with CCL18 concentration., Conclusions: A common CCL18 polymorphism together with IVH had an additive influence on CP susceptibility. Developmentally regulated CCL18, confined to primates, may be involved in the complex sequence of events leading to brain injury and predisposition to CP phenotype., (© 2015 S. Karger AG, Basel.)

Background: This multicenter prospective study of invasive candidiasis (IC) was carried out to determine the risk factors for, incidence of, clinical and laboratory features, treatment and outcome of IC in infants of birth weight <1250 g., Methods: Neonates <1250 g with IC and their matched controls (2:1) were followed longitudinally and descriptive analysis was performed. Survivors underwent neurodevelopmental assessment at 18 to 24 months corrected age. Neurodevelopmental impairment (NDI) was defined as blindness, deafness, moderate to severe cerebral palsy, or a score <70 on the Bayley Scales of Infant Development 2nd edition. Multivariable analyses were performed to determine risk factors for IC and predictors of mortality and NDI., Results: Cumulative incidence rates of IC were 4.2%, 2.2% and 1.5% for birth-weight categories <750 g, <1000 g, <1500 g, respectively. Forty nine infants with IC and 90 controls were enrolled. Necrotizing enterocolitis (NEC) was the only independent risk factor for IC (p=0.03). CNS candidiasis occurred in 50% of evaluated infants, while congenital candidiasis occurred in 31%. Infants with CNS candidiasis had a higher mortality rate (57%) and incidence of deafness (50%) than the overall cohort of infants with IC. NDI (56% vs. 33%; p=0.017) and death (45% vs. 7%; p=0.0001) were more likely in cases than in controls, respectively. IC survivors were more likely to be deaf (28% vs. 7%; p=0.01). IC independently predicted mortality (p=0.0004) and NDI (p=0.018)., Conclusion: IC occurred in 1.5% of VLBW infants. Preceding NEC increased the risk of developing IC. CNS candidiasis is under-investigated and difficult to diagnose, but portends a very poor outcome. Mortality, deafness and NDI were independently significantly increased in infants with IC compared to matched controls.

Objective: The Canadian Perinatal Network (CPN) maintains an ongoing national database focused on threatened very preterm birth. The objective of the network is to facilitate between-hospital comparisons and other research that will lead to reductions in the burden of illness associated with very preterm birth., Methods: Women were included in the database if they were admitted to a participating tertiary perinatal unit at 22+0 to 28+6 weeks' gestation with one or more conditions most commonly responsible for very preterm birth, including spontaneous preterm labour with contractions, incompetent cervix, prolapsing membranes, preterm prelabour rupture of membranes, gestational hypertension, intrauterine growth restriction, or antepartum hemorrhage. Data were collected by review of maternal and infant charts, entered directly into standardized electronic data forms and uploaded to the CPN via a secure network., Results: Between 2005 and 2009, the CPN enrolled 2524 women from 14 hospitals including those with preterm labour and contractions (27.4%), short cervix without contractions (16.3%), prolapsing membranes (9.4%), antepartum hemorrhage (26.1%), and preterm prelabour rupture of membranes (23.0%). The mean gestational age at enrolment was 25.9 ± 1.9 weeks and the mean gestation age at delivery was 29.9 ± 5.1 weeks; 57.0% delivered at < 29 weeks and 75.4% at < 34 weeks. Complication rates were high and included serious maternal complications (26.7%), stillbirth (8.2%), neonatal death (16.3%), neonatal intensive care unit admission (60.7%), and serious neonatal morbidity (35.0%)., Conclusion: This national dataset contains detailed information about women at risk of very preterm birth. It is available to clinicians and researchers who are working with one or more CPN collaborators and who are interested in studies relating processes of care to maternal or perinatal outcomes.

Background: There is limited information in the literature on the presentation and prognosis of candidal urinary tract infection (UTI) in infants in the neonatal intensive care unit (NICU)., Methods: This was a prospective cohort study performed in 13 Canadian NICUs. Infants with candidal UTI without extra-renal candidal infection at presentation were enrolled., Results: Thirty infants fit the study criteria. Median birth weight and gestational age were 2595 grams (range 575-4255) and 35 weeks (range 24-41) with 10 infants being < 30 weeks gestation. The most common primary underlying diagnosis was congenital heart disease (n = 10). The median age at initial diagnosis was 16 days (range 6-84 days). Renal ultrasonography findings were compatible with possible fungal disease in 15 of the 26 infants (58%) in whom it was performed. Treatment was variable, but fluconazole and either amphotericin B deoxycholate or lipid-based amphotericin B in combination or sequentially were used most frequently. Extra-renal candidiasis subsequently developed in 4 infants. In 2 of these 4 infants, dissemination happened during prolonged courses of anti-fungal therapy. Three of 9 deaths were considered to be related to candidal infection. No recurrences of candiduria or episodes of invasive candidiasis following treatment were documented., Conclusion: Candidal UTI in the NICU population occurs both in term infants with congenital abnormalities and in preterm infants, and is associated with renal parenchymal disease and extra-renal dissemination. A wide variation in clinical approach was documented in this multicenter study. The overall mortality rate in these infants was significant (30%). In one third of the deaths, Candida infection was deemed to be a contributing factor, suggesting the need for antifungal therapy with repeat evaluation for dissemination in infants who are slow to respond to therapy.

Background: We developed and tested a new method, called the Evidence-based Practice for Improving Quality method, for continuous quality improvement., Methods: We used cluster randomization to assign 6 neonatal intensive care units (ICUs) to reduce nosocomial infection (infection group) and 6 ICUs to reduce bronchopulmonary dysplasia (pulmonary group). We included all infants born at 32 or fewer weeks gestation. We collected baseline data for 1 year. Practice change interventions were implemented using rapid-change cycles for 2 years., Results: The difference in incidence trends (slopes of trend lines) between the ICUs in the infection and pulmonary groups was - 0.0020 (95% confidence interval [CI] - 0.0007 to 0.0004) for nosocomial infection and - 0.0006 (95% CI - 0.0011 to - 0.0001) for bronchopulmonary dysplasia., Interpretation: The results suggest that the Evidence-based Practice for Improving Quality method reduced bronchopulmonary dysplasia in the neonatal ICU and that it may reduce nosocomial infection.

Background: More mothers are choosing to return to work during the first 2 years of their child's life with an uncertain impact on early developmental outcomes., Aims: To determine the association between duration of maternity leave and motor and social development of toddlers., Study Design: Population-based, retrospective cohort study., Subjects: The Canadian National Longitudinal Survey on Children and Youth (NLSCY) Cycle 3 provides data on the characteristics and life experience of Canadian children. For sampled households, the person most knowledgeable about the child completed a survey on demographics, parent characteristics and family environment. The analysis was limited to 6664 families with children up to 2 years., Outcome Measures: Logistic regression was used to assess the association between duration of maternity leave and impaired performance (<-1 SD below the mean) on the Motor and Social Development (MSD) scale adjusted for multiple covariates including maternal age, gender, breastfeeding and socioeconomic status., Results: One month of maternity leave increased the odds of impaired performance on the MSD by 3% (OR 1.03, 95% CI 1.02, 1.04). This was also seen with categorized maternity leave duration. Being male (OR 1.53, 95% CI 1.35, 1.74) and having a younger mother (OR 1.48, 95% CI 0.98, 2.23) increased the risk of impaired performance on the MSD while being of higher SES reduced the risk (OR 0.96, 95% CI 0.93, 1.00)., Conclusions: There is an association between duration of maternity leave and impaired performance in motor and social development in children up to 2 years.

Background: The increased survival of preterm and very low birth weight infants in recent years has been well documented but continued surveillance is required in order to monitor the effects of new therapeutic interventions. Gestation and birth weight specific survival rates most accurately reflect the outcome of perinatal care. Our aims were to determine survival to discharge for a large Canadian cohort of preterm infants admitted to the neonatal intensive care unit (NICU), and to examine the effect of gender on survival and the effect of increasing postnatal age on predicted survival., Methods: Outcomes for all 19,507 infants admitted to 17 NICUs throughout Canada between January 1996 and October 1997 were collected prospectively. Babies with congenital anomalies were excluded from the study population. Gestation and birth weight specific survival for all infants with birth weight < 1,500 g (n = 3419) or gestation < or = 30 weeks (n = 3119) were recorded. Actuarial survival curves were constructed to show changes in expected survival with increasing postnatal age., Results: Survival to discharge at 24 weeks gestation was 54%, compared to 82% at 26 weeks and 95% at 30 weeks. In infants with birth weights 600-699, survival to discharge was 62%, compared to 79% at 700-799 g and 96% at 1,000-1,099 g. In infants born at 24 weeks gestational age, survival was higher in females but there were no significant gender differences above 24 weeks gestation. Actuarial analysis showed that risk of death was highest in the first 5 days. For infants born at 24 weeks gestation, estimated survival probability to 48 hours, 7 days and 4 weeks were 88 (CI 84, 92)%, 70 (CI 64, 76)% and 60 (CI 53, 66)% respectively. For smaller birth weights, female survival probabilities were higher than males for the first 40 days of life., Conclusion: Actuarial analysis provides useful information when counseling parents and highlights the importance of frequently revising the prediction for long term survival particularly after the first few days of life.

Objective: The objective of this study was to examine survival, morbidity, and resource use in a large cohort of extremely preterm infants., Study Design: We examined all (n = 754) neonatal intensive care unit admissions born at < or =25 weeks' gestation and inborn deliveries (n = 949) between 22 and 25 weeks' gestation at 17 Canadian neonatal intensive care units., Results: The overall survival rate was 63%, with a range from 14% at 22 weeks' gestation to 76% at 25 weeks' gestation. There was a high incidence of chronic lung disease (33%-51%), > or =grade 3 intraventricular hemorrhage (0%-16%), necrotizing enterocolitis (0%-14%), > or =stage 3 retinopathy of prematurity (27%-55%), nosocomial infection (25%-39%), and multiple gestation (18%-46%). Extremely preterm infants comprise 4% of neonatal intensive care unit admissions but account for 22% of deaths, 20%-60% of major morbidities, 11% of patient days, and 10%-35% of major procedures. Outborn infants had a higher incidence of chronic lung disease, severe retinopathy of prematurity, and intraventricular hemorrhage., Conclusion: Extremely preterm infants have a high incidence of mortality and morbidity and consume disproportionate amounts of neonatal intensive care unit resources.

Objectives: To examine the variation in intraventricular hemorrhage (IVH) incidence among neonatal intensive care units and identify potentially modifiable risk factors., Study Design: Multiple logistic regression analysis was used to examine variations in > or =grade 3 IVH, adjusting for baseline population risk factors, admission illness severity, and therapeutic risk factors. Subjects were born at <33 weeks' gestational age, admitted within 4 days of life to 1 of 17 participating Canadian NICU network sites in 1996-97, and had neuroimaging in the first 2 weeks of life., Results: Of 5126 subjects <33 weeks' gestational age, 3806 had neuroimaging reports. Five of 17 sites had significantly (P <.05) different crude incidence rates of grade 3-4 IVH (odds ratios [OR] 0.2, 3.2, 2.6, 2.1, 1.9) than the hospital with median incidence. With adjustment for baseline population risk factors, perinatal risks, and admission illness severity, IVH incidence rates remained significantly (P <.05) higher at 3 sites (OR 2.9, 2.3 and 2.1). Inclusion of therapy-related variables (treatment of acidosis and vasopressor use on the day of admission) in the model eliminated all site differences., Conclusions: IVH incidence rates vary significantly. Patient characteristics explain some of the variance. Early treatment of hypotension and acidosis and mode of delivery are potentially modifiable factors and warrant further study in IVH prevention.

The objective of this survey was to describe assessment and treatment approaches commonly used by occupational therapists for children exhibiting handwriting and related fine motor difficulties. Secondarily, the application of weights as a treatment modality was also explored. Fifty experienced paediatric occupational therapists from Ontario (46%), Quebec (22%) and six other Canadian provinces, were surveyed by telephone. The majority of therapists indicated that they evaluated gross/fine motor and perceptual skills, motor planning, quality of movement and sensory functioning for this population, while psychosocial and environmental factors were often not formally evaluated. Evaluations most commonly utilized included the Beery, Bruininks-Oseretsky and Gardner Tests. Standardized handwriting assessments were rarely employed. All used an eclectic treatment approach with sensorimotor most frequently selected (90%). Work setting and years of experience did not influence the treatment approach favoured.