Adele Harrison

Outcomes of preterm infants <29 weeks gestation over 10-year period in Canada: a cause for concern?

Objective:To compare risk-adjusted changes in outcomes of preterm infants <29 weeks gestation born in 1996 to 1997 with those born in 2006 to 2007.Study Design:Observational retrospective comparison of data from 15 units that participated in the Canadian Neonatal Network during 1996 to 1997 and 2006 to 2007 was performed. Rates of mortality and common neonatal morbidities were compared after adjustment for confounders.Result:Data on 1897 infants in 1996 to 1997 and 1866 infants in 2006 to 2007 were analyzed. A higher proportion of patients in the later cohort received antenatal steroids and had lower acuity of illness on admission. Unadjusted analyses revealed reduction in mortality (unadjusted odds ratio (UAOR): 0.83, 95% confidence interval (CI): 0.63, 0.98), severe retinopathy (UAOR: 0.68, 95% CI: 0.50 to 0.92), but increase in bronchopulmonary dysplasia (UAOR: 1.61, 95% CI: 1.39 to 1.86) and patent ductus arteriosus (UAOR: 1.22, 95% CI: 1.07 to 1.39). Adjusted analyses revealed increases in the later cohort for bronchopulmonary dysplasia (adjusted odds ratio (AOR): 1.88, 95% CI: 1.60 to 2.20) and severe neurological injury (AOR: 1.49, 95% CI: 1.22 to 1.80). However, the ascertainment methods for neurological findings and ductus arteriosus differed between the two time periods.Conclusion:Improvements in prenatal care has resulted in improvement in the quality of care, as reflected by reduced severity of illness and mortality. However, after adjustment of prenatal factors, no improvement in any of the outcomes was observed and on the contrary bronchopulmonary dysplasia increased. There is need for identification and application of postnatal strategies to improve outcomes of extreme preterm infants.

Impact of shielding parenteral nutrition from light on routine monitoring of blood glucose and triglyceride levels in preterm neonates

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.

Early life events, sex, and arterial blood pressure in critically ill 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.

Variations in metabolic response to TPN are influenced more by sex than by light exposure.

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.

Prophylactic Interventions in Neonatology: How Do They Fare in Real Life?

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.

Neurodevelopmental Outcomes of Infants Born at <29 Weeks of Gestation Admitted to Canadian Neonatal Intensive Care Units Based on Location of Birth

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.

Use and timing of surfactant administration: impact on neonatal outcomes in extremely low gestational age infants born in Canadian Neonatal Intensive Care Units

Abstract 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 30 min of life), and late surfactant (>30 min). 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/IV ± periventricular 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 30 min 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.