The Trend in Costs of Tertiary-Level Neonatal Intensive Care for Neonates Born Preterm at 220/7-286/7 Weeks of Gestation from 2010 to 2019 in Canada.

OBJECTIVE: To describe the trend in costs over 10 years for tertiary-level neonatal care of infants born 220/7-286/7 weeks of gestation during an ongoing Canadian national quality improvement project. STUDY DESIGN: Clinical characteristics, outcomes, and third-party payor costs for the tertiary neonatal care of infants born 220/7-286/7 weeks of gestation between the years 2010 and 2019 were analyzed from the Canadian Neonatal Network database. Costs were estimated using resource use data from the Canadian Neonatal Network and cost inputs from hospitals, physician billing, and administrative databases in Ontario, Canada. Cost estimates were adjusted to 2017 Canadian dollars (CAD). A generalized linear mixed-effects model with gamma regression was used to estimate trends in costs. RESULTS: Between 2010 and 2019, the number of infants born <24 weeks of gestation increased from 4.4% to 7.7%. The average length of stay increased from 68 days to 75 days. Unadjusted average ± SD total costs per neonate were $120 717 ± $93 062 CAD in 2010 and $132 774 ± $93 161 CAD in 2019. After adjustment for year, center, and gestation, total costs and length of stay increased significantly, by $13 612 CAD (P < .01) and 8.1 days (P < .01) over 10 years, respectively; whereas costs accounting for LOS remained stable. CONCLUSIONS: The total costs and length of stay for infants 220/7-286/7 weeks of gestation have increased over the past decade in Canada during an ongoing national quality improvement initiative; however, there was an increase in the number and survival of neonates at the age of periviability.

Predictors of PDA Treatment in Preterm Neonates Who Had Received Prophylactic Indomethacin.

OBJECTIVE: To identify clinical factors those predict the need for patent ductus arteriosus (PDA) treatment in preterm neonates who had received prophylactic indomethacin. PATIENTS AND METHODS: Preterm neonates with <28 weeks' gestational age admitted to level III neonatal intensive care units (NICUs) in Canada between 2010 and 2015 and who had received prophylactic indomethacin were included. Primary outcome was surgical ligation of PDA, while secondary outcomes were any PDA treatment and common neonatal morbidities. RESULTS: Of the 7,024 eligible neonates, 843 (12%) neonates had received prophylactic indomethacin. Of them, 84 neonates (10%) required surgical ligation while 367 neonates (44%) received medical or surgical treatment for PDA. Logistic regression analyses identified gestational age (odds ratio [OR]: 0.71, 95% confidence interval [CI]: 0.58-0.87) and outborn status (OR: 2.07, 95% CI: 1.09-3.93) as predictors for surgical ligation. Maternal hypertension (OR: 0.57, 95% CI: 0.37-0.89), rupture of membranes (ROM) ≥24 hours (OR: 0.68, 95% CI: 0.48-0.96), and surfactant treatment (OR: 1.70, 95% CI: 1.09-2.66) were predictors for medical or surgical treatment of PDA. CONCLUSION: In extremely preterm neonates who had received prophylactic indomethacin, gestational age and outborn status were predictors for surgical ligation of PDA, while maternal hypertension, ROM ≥24 hours, and surfactant treatment were associated with the medical or surgical treatment of PDA.

Nil-per-os days and necrotizing enterocolitis in extremely preterm infants.

OBJECTIVE: This study aims to evaluate the association between nil-per-os (NPO) days and development of necrotizing enterocolitis (NEC) in extremely preterm neonates (<29 weeks gestational age). STUDY DESIGN: A case-control study of 234 extremely preterm neonates who developed stage II or III NEC and 467 matched control infants admitted to participating sites in the Canadian Neonatal Network between 2010 and 2011 was conducted. The number and percentage of NPO days before the development of NEC was compared with the equivalent period in control infants using logistic regression. RESULTS: Infants with NEC were NPO on average 5.6 days (28% of days before NEC) versus 3.7 days (19% of equivalent days; p < 0.01) among controls. NEC cases required more days of inotropic support, antibiotic use, and had higher rates of patent ductus arteriosus (PDA). After adjusting for inotrope use, PDA, antibiotics, and severity of illness, for each additional NPO day the adjusted odds for NEC increased by 1.08 (95% confidence interval: 1.04-1.12). CONCLUSION: Among extremely preterm neonates, those who developed NEC were NPO for a longer period of time than control infants who were NEC-free. We speculate that delayed initiation or interruption of feeding may be a potent risk factor for NEC.

Red Blood Cell Transfusions at 21 Days of Age or Older in Previously Transfusion-Naive Very Preterm Infants: Association with Neonatal Outcomes.

OBJECTIVE: This study aims to assess the association of red blood cell (RBC) transfusion in a cohort of preterm infants with mortality, retinopathy of prematurity (ROP), and chronic lung disease (CLD) transfused at ≥21 days of life. STUDY DESIGN AND METHODS: This retrospective cohort study included infants born at <30 weeks' gestation who survived ≥21 days, had not received any RBC transfusions before reaching 21 days of age, and were admitted to participating units in the Canadian neonatal network (2003-2009). RESULTS: Out of the 3,799 eligible infants, 3,309 infants did not receive RBC transfusion at ≥21 days of age, whereas 490 received transfusion at ≥21 days of age. Infants who did not receive RBC transfusion/s at ≥21 days of age had higher birth weight (p<0.01) and higher gestational age at the time of birth (p<0.01) as compared with those who received transfusion/s at ≥21 days of age. Receipt of RBC transfusion/s at ≥21 days of age was not associated with mortality (adjusted odds ratio [AOR] 1.20; 95% confidence interval [CI] 0.33-4.34) or severe ROP (AOR 1.02; 95% CI 0.59-1.77) but was associated with increased odds of CLD (AOR 1.78; 95% CI 1.43-2.22). CONCLUSION: RBC transfusion/s at ≥21 days of age in previously transfusion-naive preterm infants was associated with increased odds of CLD but not with ROP or mortality.

CPAP Versus NIPPV Postextubation in Preterm Neonates: A Comparative-Effectiveness Study.

BACKGROUND AND OBJECTIVES: Nasal intermittent positive pressure ventilation (NIPPV) has been shown to be superior to nasal continuous positive airway pressure (CPAP) postextubation in preterm neonates. However, studies have not permitted high CPAP pressures or rescue with other modes. We hypothesized that if CPAP pressures >8 cmH2O and rescue with other modes were permitted, CPAP would be noninferior to NIPPV. METHODS: We conducted a pragmatic, comparative-effectiveness, noninferiority study utilizing network-based real-world data from 22 Canadian NICUs. Centers self-selected CPAP or NIPPV as their standard postextubation mode for preterm neonates <29 weeks' gestation. The primary outcome was failure of the initial mode ≤72 hours. Secondary outcomes included failure ≤7 days, and reintubation ≤72 hours and ≤7 days. Groups were compared using a noninferiority adjusted risk-difference (aRD) margin of 0.05, and margin of no difference. RESULTS: A total of 843 infants extubated to CPAP and 974 extubated to NIPPV were included. CPAP was not noninferior (and inferior) to NIPPV for failure of the initial mode ≤72 hours (33.0% vs 26.3%; aRD 0.07 [0.03 to 0.12], Pnoninferiority(NI) = .86), and ≤7 days (40.7% vs 35.8%; aRD 0.09 [0.05 to 0.13], PNI = 0.97). However, CPAP was noninferior (and equivalent) to NIPPV for reintubation ≤72 hours (13.2% vs 16.1%; aRD 0.01 [-0.05 to 0.02], PNI < .01), and noninferior (and superior) for reintubation ≤7 days (16.4% vs 22.8%; aRD -0.04 [-0.07 to -0.001], PNI < .01). CONCLUSIONS: CPAP was not noninferior to NIPPV for failure ≤72 hours postextubation; however, it was noninferior to NIPPV for reintubation ≤72 hours and ≤7 days. This suggests CPAP may be a reasonable initial postextubation mode if alternate rescue strategies are available.

Transport Risk Index of Physiologic Stability, version II (TRIPS-II): a simple and practical neonatal illness severity score.

OBJECTIVE: Derive and validate a practical assessment of infant illness severity at admission to neonatal intensive care units (NICUs). STUDY DESIGN: Prospective study involving 17,075 infants admitted to 15 NICUs in 2006 to 2008. Logistic regression was used to derive a prediction model for mortality comprising four empirically weighted items (temperature, blood pressure, respiratory status, response to noxious stimuli). This Transport Risk Index of Physiologic Stability, version II (TRIPS-II) was then validated for prediction of 7-day and total NICU mortality. RESULTS: TRIPS-II discriminated 7-day (receiver operating curve [ROC] area, 0.90) and total NICU mortality (ROC area, 0.87) from survival. Furthermore, there was a direct association between changes in TRIPS-II at 12 and 24 hours and mortality. There was good calibration across the full range of TRIPS-II scores and the gestational age at birth, and addition of TRIPS-II improved performance of prediction models that use gestational age and baseline population risk variables. CONCLUSION: TRIPS-II is a validated benchmarking tool for assessing infant illness severity at admission and for up to 24 hours after.

Duration of Initial Empirical Antibiotic Therapy and Outcomes in Very Low Birth Weight Infants.

: media-1vid110.1542/5984244681001PEDS-VA_2018-2286Video Abstract BACKGROUND: Overuse of antibiotics can facilitate antibiotic resistance and is associated with adverse neonatal outcomes. We studied the association between duration of antibiotic therapy and short-term outcomes of very low birth weight (VLBW) (<1500 g) infants without culture-proven sepsis. METHODS: We included VLBW infants admitted to NICUs in the Canadian Neonatal Network between 2010-2016 who were exposed to antibiotics but did not have culture-proven sepsis in the first week. Antibiotic exposure was calculated as the number of days an infant received antibiotics in the first week of life. Composite primary outcome was defined as mortality or any major morbidity (severe neurologic injury, retinopathy of prematurity, necrotizing enterocolitis, chronic lung disease, or hospital-acquired infection). RESULTS: Of the 14 207 included infants, 21% (n = 2950), 38% (n = 5401), and 41% (n = 5856) received 0, 1 to 3, and 4 to 7 days of antibiotics, respectively. Antibiotic exposure for 4 to 7 days was associated with higher odds of the composite outcome (adjusted odds ratio 1.24; 95% confidence interval [CI] 1.09-1.41). Each additional day of antibiotic use was associated with 4.7% (95% CI 2.6%-6.8%) increased odds of composite outcome and 7.3% (95% CI 3.3%-11.4%) increased odds in VLBW infants at low risk of early-onset sepsis (born via cesarean delivery, without labor and without chorioamnionitis). CONCLUSIONS: Prolonged empirical antibiotic exposure within the first week after birth in VLBW infants is associated with increased odds of the composite outcome. This practice is a potential target for antimicrobial stewardship.

Racemic epinephrine compared to salbutamol in hospitalized young children with bronchiolitis; a randomized controlled clinical trial [ISRCTN46561076].

BACKGROUND: Bronchiolitis is the most common cause of lower respiratory tract illness in infancy, and hospital admission rates appear to be increasing in Canada and the United States. Inhaled beta agonists offer only modest short-term improvement. Trials of racemic epinephrine have shown conflicting results. We sought to determine if administration of racemic epinephrine during hospital stay for bronchiolitis improved respiratory distress, was safe, and shortened length of stay. METHODS: The study was a randomized, double-blind controlled trial of aerosolized racemic epinephrine compared to salbutamol every one to 4 hours in previously well children aged 6 weeks to < or = 2 years of age hospitalized with bronchiolitis. The primary outcome was symptom improvement as measured by the Respiratory Distress Assessment Instrument (RDAI); secondary outcomes were length of stay in hospital, adverse events, and report of symptoms by structured parental telephone interview one week after discharge. RESULTS: 62 children with a mean age of 6.4 months were enrolled; 80% of children had Respiratory Syncytial Virus (RSV). Racemic epinephrine resulted in significant improvement in wheezing and the total RDAI score on day 2 and over the entire stay (p < 0.05). The mean LOS in the epinephrine arm was 2.6 days (95% CI 2, 3.2) v. 3.4 days in those in the salbutamol group (95% CI 2.6, 4.2) (p > 0.05). Adverse events were not significantly different in the two arms. At one week post-discharge, over half of parents reported that their child still had a respiratory symptom and 40% had less than normal feeding. CONCLUSION: Racemic epinephrine relieves respiratory distress in hospitalized infants with bronchiolitis and is safe but does not abbreviate hospital stay. Morbidity associated with bronchiolitis as identified by parents persists for at least one week after hospital discharge in most infants.

The Pediatric Investigators Collaborative Network on Infections in Canada study of predictors of hospitalization for respiratory syncytial virus infection for infants born at 33 through 35 completed weeks of gestation.

BACKGROUND: Infants born at 33 through 35 completed weeks of gestation (33-35GA) are at risk for severe respiratory syncytial virus (RSV) infection, and palivizumab prophylaxis lowers hospitalizations for RSV infection by as much as 80%. The 33-35GA cohort comprises 3-5% of annual births; thus expert panels recommend limiting prophylaxis to situations in which frequency or health care impact of RSV infection is high. This study sought to identify independent risk factors for hospitalization for RSV infection. METHODS: This was a multicenter, prospective, observational cohort study of 33-35GA infants followed through their first RSV season (2001/2002 or 2002/2003). Baseline data were collected by interview with parents and review of medical records. Respiratory tract illnesses were identified by monthly phone calls, and medical records were reviewed for emergency room visits or hospitalizations. Risk factors were determined by stepwise logistic regression. RESULTS: Of 1,860 enrolled subjects, 1,832 (98.5%) were followed for at least 1 month, and 1,760 (94.6%) completed all follow-ups. Of 140 (7.6%) subjects hospitalized for respiratory tract illnesses, 66 infants had proven RSV infection. Independent predictors for hospitalization for RSV infection were: day-care attendance (odds ratio, 12.32; 95% confidence interval, 2.56, 59.34); November through January birth (odds ratio, 4.89; 95% confidence interval, 2.57, 9.29); preschool age sibling(s) (odds ratio, 2.76; 95% confidence interval, 1.51, 5.03); birth weight <10th percentile (odds ratio, 2.19; 95% confidence interval, 1.14, 4.22); male gender (odds ratio, 1.91; 95% confidence interval, 1.10, 3.31); > or = 2 smokers in the home (odds ratio, 1.87; 95% confidence interval, 1.07, 3.26); and households with >5 people, counting the subject (odds ratio, 1.79; 95% confidence interval, 1.02, 3.16). Family history of eczema (odds ratio, 0.42; 95% confidence interval, 0.18, 0.996) was protective. CONCLUSIONS: Specific host/environmental factors can be used to identify which 33-35GA infants are at greatest risk of hospitalization for RSV infection and likely to benefit from palivizumab prophylaxis.

Neighbourhood income level and outcomes of extremely preterm neonates: protection conferred by a universal health care system.

OBJECTIVES: To determine the impact of neighbourhood income and maternal residence population density on mortality and various morbidities at discharge or transfer from the NICU among extremely preterm neonates (<27 weeks gestation) in Canada. METHODS: Neighbourhood income level and residential status was derived using a postal code conversion file and census data. Multivariable logistic regression analysis was used to estimate the risk-adjusted odds ratio (AOR) of mortality and survival without major morbidities (chronic lung disease, necrotizing enterocolitis, severe intraventricular hemorrhage, and retinopathy of prematurity) among 2,752 extremely preterm infants admitted to 25 tertiary level neonatal intensive care units in Canada between 2007 and 2008. RESULTS: There were no significant differences between mothers from different neighbourhood income quintiles (Q1 = low; Q5 = high) and neonatal mortality AOR (95% confidence interval): Q1: 1.10 (0.74-1.62), Q2: 1.00 (0.67-1.49), Q3: 1.39 (0.93-2.07), Q4: 1.01 (0.67-1.52), Q5: 1 (reference); or survival without major morbidity: Q1: 1.01 (0.70-1.44), Q2: 0.84 (0.58-1.23), Q3: 0.85 (0.58-1.24), Q4: 0.92 (0.63-1.35), Q5: 1 (reference). There were no significant differences in mortality (AOR 1.14 [0.83-1.57]) or in survival without major morbidity (AOR 0.92 [0.67-1.26]) between infants of mothers residing in sparsely populated areas compared to densely populated areas. CONCLUSION: Maternal residence in a low-income neighbourhood or sparsely populated area was not associated with higher odds of mortality or survival free of major morbidities in extremely preterm infants.

Comparison of the safety and immunogenicity of concomitant and sequential administration of an adult formulation tetanus and diphtheria toxoids adsorbed combined with acellular pertussis (Tdap) vaccine and trivalent inactivated influenza vaccine in adults.

The annual contact for influenza vaccination provides an opportunity to ensure that adults have received other recommended vaccines such as Tdap. Healthy 19-64 year-olds were randomized to receive concomitant administration of Tdap and influenza vaccines or influenza vaccine followed (in 4-6 weeks by) Tdap. 720 participants were enrolled. No clinically relevant between-group differences were observed in the rates or severities of erythema, swelling, or pain at the Tdap injection site. Injection-site pain was the most commonly reported adverse event (66.6% concomitant administration group versus 60.8% sequential administration group); most pain was graded as mild and resolved by day 3. Seroprotection and seroresponse rates for all influenza strains were comparable between the two groups. For diphtheria and tetanus, seroprotection rates and post-vaccination GMTs were non-inferior in the concomitant administration group compared to the sequential administration group. A trend for lower antibody responses to pertussis antigens PT, FHA, and FIM was observed after concomitant administration and, for PRN, this difference failed the non-inferiority criteria. While there is a small diminution in antibody response to tetanus and pertussis antigens, concomitant administration of Tdap and influenza vaccine was well tolerated and immunogenic and may offer practical advantages including convenience, compliance, and cost-savings.