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

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

ObjectiveWe evaluated transport factors and postnatal practices to identify modifiable risk factors for SBI.Study designRetrospective review of Canadian Neonatal Transport Network data linked to Canadian Neonatal Network data for outborns <33 weeks gestational age (GA), during January 2014 to December 2015. SBI was defined as grade 3 or 4 intraventricular hemorrhage or parenchymal echogenicity, including hemorrhagic and/or ischemic lesions.ResultAmong 781 infants, 115 (14.7%) had SBI with range 5.6–40% among transport teams. In multivariable analysis, SBI was associated with GA [0.77 (0.71, 0.85)] per week, receipt of chest compressions and/or epinephrine at delivery [1.81 (1.08, 3.05)] and receipt of fluid boluses [1.61 (1.00, 2.58)].ConclusionsRisk factors for SBI were related to the condition at birth and immediate postnatal management and not related to transport factors. These results highlight the importance of maternal transfer to perinatal centers to allow optimization of perinatal management.

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

ObjectiveTo assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF).MethodsIn this retrospective cohort study, we included neonates born at <29 weeks gestational age (GA) between January 2010 and December 2018 who had a neurodevelopmental assessment at 18–24 months corrected age (CA) at one of the Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment (NDI). We performed propensity score-matched analysis to compare the outcomes of those who received and did not receive iNO.ResultsOf the 5612 eligible neonates, 460 (8.2%) received iNO in the first week of age. Maternal age, receipt of antenatal corticosteroids, GA and birth weight were lower in the iNO group compared with the no-iNO group. Neonates in the iNO group had higher illness severity scores and higher rates of preterm prolonged rupture of membranes and were small for GA. Severe brain injury, bronchopulmonary dysplasia and mortality were higher in the iNO group. Of the 4889 survivors, 3754 (77%) neonates had follow-up data at 18–24 months CA. After propensity score matching, surviving infants who received rescue iNO were not associated with higher odds of NDI (adjusted OR 1.34; 95% CI 0.85 to 2.12).ConclusionsIn preterm neonates <29 weeks GA with HRF, rescue iNO use was not associated with worse neurodevelopmental outcomes among survivors who were assessed at 18–24 months CA.

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.

ObjectiveTo describe the incidence, trends, management’s variability and short-term outcomes of preterm infants with severe post-hemorrhagic ventricular dilatation (sPHVD).MethodsWe reviewed infants <33 weeks’ gestation who had PHVD and were admitted to the Canadian Neonatal Network between 2010 and 2018. We compared perinatal characteristics and short-term outcomes between those with sPHVD and those with mild/moderate PHVD and those with and without ventriculo-peritoneal (VP) shunt.ResultsOf 29,417 infants, 2439 (8%) had PHVD; rate increased from 7.3% in 2010 to 9.6% in 2018 (P = 0.005). Among infants with PHVD, sPHVD (19%) and VP shunt (29%) rates varied significantly across Canadian centers and between geographic regions (P < 0.01 and P = 0.0002). On multivariable analysis, sPHVD was associated with greater mortality, seizures and meningitis compared to mild/moderate PHVD.ConclusionsSignificant variability in sPHVD and VP shunt rates exists between centers and regions in Canada. sPHVD was associated with increased mortality and morbidities.

ObjectiveTo examine the association between probiotic use and antimicrobial utilization.Study designWe retrospectively evaluated very-low-birth-weight (VLBW) infants admitted to tertiary neonatal intensive care units in Canada between 2014 and 2019. Our outcome was antimicrobial utilization rate (AUR) defined as number of days of antimicrobial exposure per 1000 patient-days.ResultOf 16,223 eligible infants, 7279 (45%) received probiotics. Probiotic use rate increased from 10% in 2014 to 68% in 2019. The AUR was significantly lower in infants who received probiotics vs those who did not (107 vs 129 per 1000 patient-days, aRR = 0.89, 95% CI [0.81, 0.98]). Among 13,305 infants without culture-proven sepsis or necrotizing enterocolitis ≥Stage 2, 5931 (45%) received probiotics. Median AUR was significantly lower in the probiotic vs the no-probiotic group (78 vs 97 per 1000 patient-days, aRR = 0.85, 95% CI [0.74, 0.97]).ConclusionProbiotic use was associated with a significant reduction in AUR among VLBW infants.

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

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