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.

Quality improvement initiatives in neonatology have yielded positive results; however, few programs have demonstrated sustainability. We evaluated an ongoing, national quality improvement initiative (Evidence-based Practice for Improving Quality Phase 3 (EPIQ-3)) on outcomes of preterm neonates with a gestational age (GA) of 220-286 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 260-286 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.

Neonates born very preterm (before 32 weeks' gestational age), are a significant public health concern because of their high-risk of mortality and life-long disability. In addition, caring for very preterm neonates can be expensive, both during their initial hospitalization and their long-term cost of permanent impairments. To address these issues, national and regional neonatal networks around the world collect and analyse data from their constituents to identify trends in outcomes, and conduct benchmarking, audit and research. Improving neonatal outcomes and reducing health care costs is a global problem that can be addressed using collaborative approaches to assess practice variation between countries, conduct research and implement evidence-based practices. The International Network for Evaluating Outcomes (iNeo) of neonates was established in 2013 with the goal of improving outcomes for very preterm neonates through international collaboration and comparisons. To date, 10 national or regional population-based neonatal networks/datasets participate in iNeo collaboration. The initiative now includes data on >200,000 very preterm neonates and has conducted important epidemiological studies evaluating outcomes, variations and trends. The collaboration has also surveyed >320 neonatal units worldwide to learn about variations in practices, healthcare service delivery, and physical, environmental and manpower related factors and support services for parents. The iNeo collaboration serves as a strong international platform for Neonatal-Perinatal health services research that facilitates international data sharing, capacity building, and global efforts to improve very preterm neonate care.

Background: Use, timing and doses of surfactant in preterm infants are variable in practice in modern NICUs.Objective: The objective of this study is to explore the association between use and timing of surfactant administration and common neonatal adverse outcomes in preterm infants with gestational age (GA)<28 weeks.Material and methods: Neonates admitted to a participating Canadian Neonatal Network NICU between 2013 and 2015 were studied. Infants were divided into three groups based on surfactant administration: none, early (within 30min of life), and late surfactant (>30min). The primary outcome was a composite of 2 predefined outcomes: bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP) and severe neurological injury (intraventricular hemorrhage or intraventricular hemorrhage (IVH) grade III/IVperiventricular leukomalacia).Results: Of 2512 eligible neonates, 430 were in the early, and 1228 were in the late surfactant group. There was no difference in the primary outcome (p=.88). There was a slightly lower risk of late onset sepsis [25% versus 29%, adjusted odds ratio (aOR): 0.8; 95% CI: 0.6-0.9] and ROP (12.4 versus 15%, aOR: 0.7; 95% CI: 0.5-0.9) in the early surfactant group.Conclusions: In preterm neonates, early administration of surfactant within 30min of life was not associated with an increased risk of the primary composite outcome, but did have decreased rates of late onset sepsis and ROP.

OBJECTIVE:To identify predictors of severe retinopathy of prematurity (ROP) in a large population-based cohort and to examine risk-adjusted variations across units.STUDY DESIGN:Retrospective analysis of Canadian Neonatal Network data on neonates with birth weight <1500 g who were screened for ROP between 2003 and 2010. Characteristics of infants with and without ROP were compared and a risk-adjusted model for severe ROP was developed. Rates of severe ROP were compared between sites.RESULTS:1163 of 9187 (12.7%) infants developed severe ROP. Lower gestational age, male sex, small for gestational age, patent ductus arteriosus, late onset sepsis, more than two blood transfusions, inotrope use, and outborn status were associated with an increased risk of severe ROP. Severe ROP rates varied significantly between units.CONCLUSION:Younger, smaller and sicker male infants had higher adjusted risks of severe ROP and rates varied significantly among sites.

BACKGROUND Knowledge of neonatal transfusion practices remains limited to local cohorts or survey‐based studies. This study evaluated the pattern and temporal changes in the types and frequency of blood product use among preterm neonates born at less than 30 weeks' gestation in Canada. STUDY DESIGN AND METHODS A retrospective cohort study of preterm neonates born at less than 30 weeks' gestation and admitted to participating neonatal intensive care units in the Canadian Neonatal Network from 2004 to 2012 was conducted to evaluate blood product usage. The temporal change in red blood cell (RBC) use was evaluated by dividing the study period into three epochs: 2004 to 2006, 2007 to 2009, and 2010 to 2012. RESULTS Of 14,868 eligible neonates admitted to participating units in Canada during the overall study period, 8252 (56%) received RBCs, 2151 (15%) platelets, 1556 (11%) fresh‐frozen plasma, 915 (6%) albumin, and 302 (2%) cryoprecipitate. Temporal evaluation over three epochs revealed a trend toward fewer RBC transfusions among neonates born at 26 to 29 weeks' gestation (p = <0.01‐0.04) but use remained unchanged or increased for neonates born at 23 to 25 weeks' gestation (p = 0.02‐0.54). CONCLUSION Blood product use remains at a very high frequency in preterm neonates born at less than 30 weeks' gestation. Evolutionary practice changes and relative high tolerance for anemia may be associated with a reduction in RBC usage in recent years in neonates born at at least 26 weeks' gestation. This contrasts with the ongoing higher usage of blood products observed at extremely low gestational ages.

Objective This study aims to evaluate the association of prophylactic antenatal steroids, indomethacin, and phototherapy with extremely preterm infant outcomes in a pragmatic setting.Study Design Retrospective study of infants born at < 28 weeks gestation and admitted to 26 Canadian Neonatal Network neonatal intensive care units between 2010 and 2012. Mortality, severe neurological injury, retinopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, nosocomial infection, and patent ductus arteriosus ligation rates were compared between infants who received antenatal steroids, prophylactic indomethacin, and/or prophylactic phototherapy and those who did not.Results Of 3,465 eligible infants, 2,900 (84%) received antenatal steroids, 269 (8%) prophylactic indomethacin, and 403 (12%) prophylactic phototherapy. Associations were observed between antenatal steroids and mortality (adjusted odds ration [aOR] 0.47 [0.33-0.66]) and severe neurological injury (aOR 0.60 [0.46-0.77]), indomethacin and ductus arteriosus ligations (aOR 0.52 [0.31-0.87]), but not severe neurological injury (aOR 1.12 [0.81-1.54]), but phototherapy was not associated with any of the neonatal outcomes despite reductions in bilirubin.Conclusion Antenatal steroids were associated with reduced mortality and neurological injury, prophylactic indomethacin was not associated with reduction in neurological injury and phototherapy was not associated with any improvement in neonatal outcomes. In a pragmatic setting, outside randomized controlled trials, the effectiveness and safety of prophylactic interventions in extremely preterm neonates vary; ongoing monitoring is warranted.

The development of clinical practice guidelines involving multiple health care providers presents a challenge in the neonatal intensive care unit (NICU). Implementation and evaluation of the guideline is as important as the development of the guideline itself. We explored the use of a quality improvement approach in the implementation of a feeding framework. A Plan-Do-Study-Act (PDSA) quality improvement cycle model was used to implement and evaluate a stepwise oral infant feeding guideline with emphasis on parent and care provider satisfaction. Three PDSA cycles were conducted, with each cycle resulting in modifications to use of the framework and development of knowledge translation and parent education techniques and tools. A PDSA cycle approach can be used effectively in guideline implementation and evaluation involving multidisciplinary health care professionals. This is Part II of a two-part series. Part I introduced the concept of quality improvement and tools for advancing practice changes.

We describe trends in the rates of admission of preterm twin and triplet infants to neonatal intensive care units (NICUs) across Canada and compare their neonatal outcomes over a 6-year period. Temporal trends of admission rates for 5193 twins and triplets < 33 weeks' gestational age to participating NICUs in the Canadian Neonatal Network between 2003 and 2008 were assessed. Trends in infant outcomes were evaluated using logistic regression. The proportion of twins increased from 26.1 to 28.0 per 100 admissions between 2003 and 2008 (7% increase, p = 0.02). In contrast, the proportion of triplets decreased from 5.0 to 3.3 per 100 admissions (34% reduction, p = 0.04). These trends were significant in mothers ≥ 35 years of age. Neonatal outcomes improved for preterm twins (mortality, p < 0.01; survival without any major morbidity, p < 0.01; severe neurological injury, p = 0.02; and severe retinopathy of prematurity, p = 0.03). Similar improvements were observed for triplets, but the sample size was insufficient to reach statistical significance. The rate of NICU admissions for preterm twins at < 33 weeks' gestation has increased in recent years, whereas for triplets it has gradually declined. Neonatal outcomes of preterm twins improved over the study period.

Quality improvement (QI) and patient safety are becoming increasingly powerful drivers for health care planning and delivery. In this two-part series, the concept of QI will be introduced and implications for neonatal nursing care will be discussed. Part I reviews trends in the fields of QI and patient safety and introduces how neonatal practitioners are currently taking up QI and patient safety in their practice. Part II, to come, is titled "Using a Plan-Do-Study-Act Process to Introduce a Step-wise Framework for Establishing Oral Feeds in Premature Infants" will present the QI process "in action" by describing a QI project conducted in a Level III NICU on introducing and testing a new process for improving the transition from tube to oral feeding for preterm infants.

Objective: To determine whether photo-protecting total parenteral nutrition in preterm infants influences arterial blood pressure differently according to gender. Blood pressure is influenced by complex mechanisms of vasomodulation. Oxidants are mediators and effectors in such reactions. Shielding total parenteral nutrition from light contributes to decrease the generation of peroxides. Girls may be better protected against an oxidant load than boys. We questioned whether shielding total parenteral nutrition may have cardiovascular effects that are influenced by gender. Design: A post hoc subgroup analysis of the effect of shielding parenteral nutrition from light. Setting: Neonatal intensive care unit. Subjects: Preterm infants <1000 g with indwelling arterial catheters who received light exposed (n = 20) or light protected (n = 20) parenteral nutrition. Interventions: Invasive monitoring, total parenteral nutrition. Measurements and Main Results: Arterial blood pressure was recorded hourly and compared between light exposed and light protected over the first week of life; timed average maximum velocity (m/s) was measured in the superior mesenteric artery by Doppler; presence of ductus arteriosus was documented by cardiac ultrasound. Data were analyzed by analysis of variance. No differences were noted between light exposed and light protected in clinical determinants that may influence blood pressure. There was an interaction (p < .01) between gender and total parenteral nutrition on blood pressure. In girls (n = 17), systolic and diastolic blood pressures were higher (p < .01) and heart rate lower (p < .01) during light exposed. There was no effect on BP observed in boys (n = 23). The linear correlation between timed average maximum velocity and systolic blood pressure was positive (p < .05). There was no echocardographic difference in hemodynamic variables between boys (n = 21) and girls (n = 9) who had a patent ductus. Conclusion: Failure to shield total parenteral nutrition from light results in higher blood pressure in a selected population of critically ill female infants. This information adds to our understanding of the multiple determinants involved in optimizing arterial blood pressure in a critical care environment.

BACKGROUND:Premature infants are vulnerable to complications related to oxidative stress. Exposure to light increases oxidation products in solutions of total parenteral nutrition (TPN) such as lipid peroxides and hydrogen peroxide. Oxidative stress impairs glucose uptake and affects lipid metabolism.HYPOTHESIS:products of photo-oxidation contaminating TPN affect lipid metabolism.OBJECTIVE:Evaluate the effect of photoprotection of TPN in preterm infants on plasma glucose and triglyceride (TG) concentrations.DESIGN:Secondary analysis of a prospective study allocating preterm infants to light-exposed (LE, n = 32) or light-protected (LP, n = 27) TPN.SETTING:Level III NICU referral centre for patients of British Columbia.PATIENTS:Preterm infants requiring TPN.INTERVENTIONS AND OUTCOME MEASURES:TG and blood glucose measured during routine monitoring while on full TPN were compared between LE and LP.RESULTS:Clinical characteristics were similar between the two groups (gestational age 28+/-1 wk; birth weight: 1.0+/-0.1 kg). Nutrient intakes from TPN and from minimal enteral nutrition were comparable between LE and LP. Blood glucose was higher in preterm infants receiving LE (p<0.001). The accumulation of TG with increasing lipid intake was twice as high with LE accounting for significantly higher TG levels on days 8 and 9 (p<0.05).CONCLUSIONS:Failure to photoprotect TPN may cause alterations in intermediary metabolism. Shielding TPN from light provides a potential benefit for preterm infants by avoiding hypertriglyceridaemia allowing for increased substrate delivery.

Light-exposed total parenteral nutrition (TPN) generates peroxides that contribute to an oxidant load. Shielding TPN from light protects against lung remodelling. In preterm infants, photoprotection of TPN is associated with a 30% reduction in bronchopulmonary dysplasia, in a post-hoe analysis. This analysis provides justification for a randomized controlled trial.

Background: Failure to protect total parenteral nutrition (TPN) solutions from ambient light induces the generation of peroxides, which contributes to the oxidation of several amino acids. We hypothesized that photo-protection improves the metabolic response to TPN. Aim: To study the effects of photo-protecting TPN on urinary nitrogen and vitamin C excretion and to evaluate in premature infants the influence of sex. Patients and Methods: Premature infants were randomized to receive from birth light-exposed (LE) or light-protected (LP) TPN. Upon reaching full TPN, parenteral nutrient intakes were correlated with normalized urinary nitrogen and vitamin C concentrations. Results: No differences were observed between LE and LP. However, sex-related differences were observed in nitrogen and vitamin C handling. In boys, 50% of the nitrogen loss was explained by parenteral amino acid intake, whereas in girls, no correlation was found. The inverse correlation observed between intake and urinary excretion only in girls suggests a state of greater vitamin C utilization in girls. Conclusions: These results demonstrate that sex-related differences in nitrogen/protein metabolism reported during enteral nutrition are seen during TPN as well. Sex is an important variable that will need to be taken into account in future studies evaluating the potential clinical effects of photo-protecting TPN.

BACKGROUND:Light exposure of TPN generates peroxides which induce vasoconstriction. Mesenteric vasoconstriction may affect feeding tolerance. Since photo-protection of TPN decreases peroxide generation, we hypothesized that shielding TPN from light may improve the establishment of minimal enteral nutrition in preterm infants.METHODS:Infants were randomized to TPN being light exposed (LE) or protected (LP) from birth. Feeding volumes were monitored through 7 days of life in those initiated on minimal enteral nutrition (MEN). Comparisons between LP and LE were performed by ANOVA.RESULTS:Daily increments and cumulative volumes of enteral feeds (mL/kg birth weight/d) during the first week of life were significantly higher in LP (n = 18) than LE (n = 19).CONCLUSION:Photo-protection of parenteral nutrition enhances advancement of MEN in preterm infants. Further research is needed to substantiate these findings and determine whether this confers long-term nutritional advantages.

Background: Very tow birthweight preterm infants receive early total parenteral nutrition (TPN) to optimize protein balance. Adding multivitamins (MVP) to the lipid emulsion (MVP+LIP) rather than to the amino acid+dextrose moiety of TPN (AA+MVP) limits the effects of tight exposure on tipid peroxidation and vitamin loss.Aim: Compare the effects of the mode of delivery of MVP on nutrient handling and indices of oxidant stress.Methods: Three-day old guinea pig pups were assigned to TPN containing MVP+amino acids+dextrose+heparin and electrolytes, with lipids provided separately (AA+MVP). Solutions were tight exposed (LE, n = 8) or light protected (LP, n = 9). In a further group In = 7), MVP was co-administered with the tipid moiety and tight exposed (LP+MVP). Variables measured in urine (creatinine, nitrogen, vitamin Q and in liver (protein, glutathione, isoprostane, vitamins A, E, C) were compared by ANOVA.Results: Urinary nitrogen and vitamin C were higher (P < 0.05) during LE, white hepatic levels of vitamin C were higher (P < 0.05) with LIP+MVR These results were not related to total peroxide levels in TPN or to markers of oxidant stress.Conclusion. Co-administration of MVP with lipid or light protected amino acids offers comparable beneficial effects on nitrogen and vitamin C metabolism. (c) 2004 Elsevier Ltd. All rights reserved.

A triplet pregnancy is described, in which the diagnosis of in utero growth restriction is questioned after postnatal suspicion of superfetation, by using neurosonography and ophthalmic examination to aid gestational age assessment.