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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.

Background Admission to the neonatal intensive care unit (NICU) may disrupt parent-infant interaction with adverse consequences for infants and their families. Several family-centered care programs promote parent-infant interaction in the NICU; however, all of these retain the premise that health-care professionals should provide most of the infant’s care. Parents play a mainly supportive role in the NICU and continue to feel anxious and unprepared to care for their infant after discharge. In the Family Integrated Care (FICare) model, parents provide all except the most advanced medical care for their infants with support from the medical team. Our hypothesis is that infants whose families complete the FICare program will have greater weight gain and better clinical and parental outcomes compared with infants provided with standard NICU care. Methods/Design FICare is being evaluated in a cluster randomized controlled trial among infants born at ≤ 33 weeks’ gestation admitted to 19 Canadian, 6 Australian, and 1 New Zealand tertiary-level NICU. Trial enrollment began in April, 2013, with a target sample size of 675 infants in each arm, to be completed by August, 2015. Participating sites were stratified by country, and by NICU size within Canada, for randomization to either the FICare intervention or control arm. In intervention sites, parents are taught how to provide most of their infant’s care and supported by nursing staff, veteran parents, a program coordinator, and education sessions. In control sites standard NICU care is provided. The primary outcome is infants’ weight gain at 21 days after enrollment, which will be compared between the FICare and control groups using Student’s t -test adjusted for site-level clustering, and multi-level hierarchical models accounting for both clustering and potential confounders. Similar analyses will examine secondary outcomes including breastfeeding, clinical outcomes, safety, parental stress and anxiety, and resource use. The trial was designed, is being conducted, and will be reported according to the CONSORT 2010 guidelines for cluster randomized controlled trials. Discussion By evaluating the impact of integrating parents into the care of their infant in the NICU, this trial may transform the delivery of neonatal care. Trial registration NCT01852695 , registered December 19, 2012

ObjectiveTo study the association between prematurity and grade 3 school performance in a contemporary cohort of children.MethodsPopulation-based retrospective cohort study in Manitoba, Canada. Children born between 1999 and 2011 who had their grade 3 school performance data available were eligible. Preterm birth (<37 weeks) was the exposure of interest assessed using multivariable logistic regression models. Our primary outcomes were ‘needs ongoing help’ or ‘outside the range’ in at least two of each of the (1) four numeracy and (2) three reading competencies.ResultsOf the 186 956 eligible children, 101 436 children (7187 preterm (gestational age, median (IQR) 35 weeks (34, 36)) and 94 249 term (40 weeks (39,40)) were included. Overall, 19% of preterm and 14% of term children had the numeracy outcome (adjusted OR (aOR) 1.38; 95% CI 1.29 to 1.47, p<0.001), while 19% and 13% had the reading outcome (aOR 1.38; 1.29 to 1.48, p<0.001). These differences showed a gestational age gradient. Gestational age (for numeracy, <28 weeks aOR 4.93 (3.45 to 7.03), 28–33 weeks 1.72 (1.50 to 1.98), 34–36 weeks 1.24 (1.15 to 1.34); for reading, <28 weeks 3.51 (2.40 to 5.14), 28–33 weeks 1.72 (1.49 to 1.98), 34–36 weeks 1.24 (1.17–1.37)), male sex, small for gestational age and maternal medical and sociodemographic factors were associated with the numeracy and reading outcomes in this cohort.Conclusions and relevanceChildren born preterm had poorer performance in grade 3 numeracy and reading proficiencies than children born full term. All children born preterm, not just those born extremely preterm, should be screened for reading and numeracy performance in school and strategies implemented to address any deficits.

ObjectivesTo identify characteristics and outcomes of infants who received multiple doses of surfactant vs those who received one dose or none.Study designIn this retrospective study, we included neonates of 22–28 weeks’ gestation admitted to NICUs in the Canadian Neonatal Network. Patients were divided into three groups: no surfactant, single dose, and multiple doses. The primary outcome was a composite of mortality or any of the major morbidities, including severe neurological injury, bronchopulmonary dysplasia, or ≥stage 3 retinopathy of prematurity.ResultsOf 8024 eligible neonates, 2461 (31%) did not receive surfactant, 3545 (44%) received one dose, and 2018 (25%) received >1 dose. Receiving one or more doses of surfactant was associated with significantly higher adjusted odds of mortality or major morbidities in a dose-dependent manner.ConclusionsReceiving one or more doses of surfactant was associated with adverse neonatal outcomes. Receipt of more than one dose may reflect underlying severe lung immaturity.

Abstract The American Academy of Pediatrics and until recently the Canadian Paediatric Society recommend preterm infants undergo an Infant Car Seat Challenge test prior to discharge to rule out systemic oxygen desaturation when placed at a 45-degree angle in a car seat. Near-infrared spectroscopy (NIRS) provides objective measurements of the impact of systemic oxygen (SO2) desaturation, bradycardia, or both on cerebral regional oxygen saturation (rSO2). Objective To characterize baseline cerebral rSO2 during a car seat trial in preterm infants ready for discharge. Design/Methods A prospective observational study was performed in 20 infants (32 ± 5 weeks [mean] at a postmenstrual age 37 ± 6 weeks [mean]). Cerebral rSO2 was continuously monitored by placing a NIRS transducer on head during Infant Car Seat Challenge (ICSC). Failure of an ICSC was defined as two SO2 desaturation events below 85% for more than 20 seconds or one event below 80% for 10 seconds. Results The lowest SO2 was 70% with a lowest NIRS recording of 68%. Three infants failed their ICSC, with the lowest rSO2 in these three infants being 68%, above the lowest acceptable limit of 55%. Heart rate but not SO2 appears to influence rSO2 over the range of cerebral oxygenation seen. Conclusions Baseline cerebral rSO2 during ICSC oscillates between 68 and 90%. There were no episodes of significant cerebral oxygen desaturation in studied infants regardless of whether they passed or failed the ICSC. We postulate that former preterm infants are capable through cerebral autoregulation, of maintaining adequate cerebral blood flow in the presence of either systemic oxygen desaturation or bradycardia when they are otherwise ready for discharge.

IntroductionPatent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants.Methods and analysisA multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born <29 weeks gestational age with an echocardiography confirmed PDA will be conducted. All participating sites will self-select and adhere to one of the following primary pharmacotherapy protocols for all preterm babies who are deemed to require treatment.Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3–7 days.Intravenous indomethacin (0.1–0.3 mg/kg intravenous every 12–24 hours for a total of three doses).OutcomesThe primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment.Sites and sample sizeThe study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years.AnalysisTo examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student’s t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach.Ethics and disseminationThe study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres.Trial registration numberNCT04347720.

Objective:To study the outcomes of extremely preterm infants of hypertensive mothers who smoke.Study design:This retrospective cohort study included infants born between 2003 and 2012 at <29 weeks’ gestation and admitted to neonatal intensive care units participating in the Canadian Neonatal Network. Infants were divided into four mutually exclusive groups. Infants of hypertensive mothers who smoked; infants of hypertensive, non-smoking mothers; infants of normotensive mothers who smoked; and infants of normotensive, non-smoking mothers. Using infants of normotensive, non-smoking mothers as the reference group, neonatal outcomes were compared between the groups. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated using univariate and multivariate regression analysis.Results:Of the 12,307 eligible infants, 172 had hypertensive mothers who smoked, 1689 had hypertensive non-smoking mothers, 1535 had normotensive mothers who smoked, and 8911 had normotensive non-smoking mothers. Compared to infants of normotensive non-smoking mothers, infants of hypertensive mothers, regardless of smoking status, had higher odds of developing bronchopulmonary dysplasia (AORs of smokers 1.62; 95% CI 1.12–2.35 and of non-smokers 1.43; 95% CI 1.24–1.64). There was no difference in the odds of mortality and retinopathy of prematurity stage ≥3 between the groups. Infants of hypertensive, non-smoking mothers had decreased odds of intraventricular hemorrhage >grade 2 and higher odds of necrotizing enterocolitis. There was decreased odds of hypertension if the mother was a smoker (AOR 0.71; 95% CI 0.59–0.85).Conclusion:Maternal hypertension is associated with increased rates of bronchopulmonary dysplasia, irrespective of smoking status.

ObjectiveTo compare neurodevelopmental outcomes of large and appropriate for gestational age (LGA, AGA) infants <29 weeks’ gestation at 18–24 months of corrected age.Study designRetrospective 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.ResultsThe 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).ConclusionsRisk of NDI was similar between LGA and AGA 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 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 designPreterm 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).ResultsOf 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.ConclusionsExposure to maternal smoking was associated with adverse composite outcome of death or NDI, NDI alone and lower motor scores at 18–21 months CA.