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.

Grade 7 school performance of children born preterm: a retrospective Canadian Cohort study.

IMPORTANCE: Data on the middle school outcomes of preterm children are limited and have methodologic issues. OBJECTIVE: To study the association between preterm birth and grade 7 school performance. METHODS: A retrospective population-based cohort study of children born in Manitoba, Canada between 1994 and 2006 using their grade 7 school performance data. A secondary sibling cohort was created comprising children born preterm and their full-term siblings. Primary exposure was preterm birth categorized as <28, 28-33 and 34-36 weeks gestation. The two co-primary grade 7 outcome measures were: not meeting the mathematics competencies, and not meeting the student engagement competencies. Multivariable logistic regression models tested the association between preterm birth and both co-primary outcomes; adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. RESULTS: 7653 preterm (gestational age median [IQR]: 35 weeks [34,36]) and 110,313 term (40 [39,40]) were included. 43% of < 28 weeks, 18% of 28-33 weeks and 17% of 34-36 weeks had the mathematics co-primary outcome compared to 13% of term children. The corresponding % for the student engagement outcome were 42%, 24%, 24% and 24% respectively. Preterm birth was associated with the mathematics (<28 weeks: 5.48, 3.89-7.70; 28-33 weeks: 1.47, 1.27-1.70; 34-36 weeks: 1.26, 1.16-1.35) and student engagement outcomes (<28 weeks: 2.49, 1.76-3.51; 28-33 weeks: 1.21, 1.06-1.39; 34-36 weeks: 1.09, 1.01-1.16). However, there was no difference in outcomes among the sibling cohort. CONCLUSIONS AND RELEVANCE: Children born preterm had lower grade 7 performance compared to children born term in this population-based cohort. Screening and supports for them in their middle school years are warranted.

Mental Disorders Among Adolescents and Young Adults With Cancer: A Canadian Population-Based and Sibling Cohort Study.

PURPOSE: To compare the cumulative incidence of mental disorders among adolescents and young adults (AYAs) diagnosed with cancer with the general population and their unaffected siblings. METHODS: A retrospective, population-based, matched cohort design was used to investigate the impact of cancer diagnosis on mental disorders among individuals age 15-39 diagnosed between 1989 and 2019. Two cancer-free cohorts were identified: matched population-based and sibling cohorts. Outcomes included incidence of mood and anxiety disorders, substance use disorders, suicide outcomes, psychotic disorders, and any of the preceding four categories within 5 years of cancer diagnosis. Competing risk regression was used to estimate adjusted subhazard ratios (aSHR) and 95% CIs. RESULTS: Among 3,818 AYAs with cancer matched to the population-based cancer-free cohort, individuals with cancer were more likely to be diagnosed with incident mental disorders than those without cancer; the risk was highest immediately after a cancer diagnosis and decreased over time with aSHR [95% CI] for mood and anxiety disorders at 0-6 months (11.27 [95% CI, 6.69 to 18.97]), 6-12 months (2.35 [95% CI, 1.54 to 3.58]), and 12-24 months (2.06 [95% CI, 1.55 to 2.75]); for substance use disorders at 0-6 months (2.73 [95% CI, 1.90 to 3.92]); for psychotic disorders at 0-6 months (4.69 [95% CI, 2.07 to 10.65]); and for any mental disorder at 0-6 months (4.46 [95% CI, 3.41 to 5.85]), 6-12 months (1.56 [95% CI, 1.14 to 2.14]), and 12-24 months (1.7 [95% CI, 1.36 to 2.13]) postcancer diagnosis. In sibling comparison, cancer diagnosis was associated with a higher incidence of mood and anxiety and any mental disorder during first 6 months of cancer diagnosis. CONCLUSION: AYAs with cancer experience a greater incidence of mental disorders after cancer diagnosis relative to population-based and sibling cohorts without cancer, primarily within first 2 years, underscoring the need to address mental health concerns during this period.

A Novel Integrated Clinical-Biochemical-Radiological and Sonographic Classification of Necrotizing Enterocolitis.

OBJECTIVE: To evaluate the sensitivity and specificity of clinical, laboratory, and radiological markers and the neonatologist-performed intestinal ultrasound (NP-IUS) for treatment interventions in preterm neonates who developed necrotizing enterocolitis (NEC). STUDY DESIGN: This was a case-control study of preterm neonates < 35 weeks with a diagnostic workup for NEC. The diagnostic workup included NP-IUS performed by trained neonatologists using a standard protocol, abdominal roentgenogram (AXR), and laboratory investigations. Intestinal ultrasound (IUS) performed by two neonatologists was standardized to detect 11 injury markers. AXRs were read independently by experienced pediatric radiologists. The investigators who retrospectively interpreted the IUS were blinded to the clinical and treatment outcomes. RESULTS: A total of 111 neonates were assessed. Fifty-four did not require intervention and formed the control group. Twenty cases were treated medically, 21 cases were treated with late surgery for stricture or adhesions, and 16 were treated with early surgery. The integrated model of cumulative severity of ultrasound markers, respiratory and hemodynamic instability, abdominal wall cellulitis, and C- reactive protein > 16 mg/L had an area under the curve (AUC) of 0.89 (95% confidence interval [CI]: 0.83-0.94%, p < 0.0001) for diagnosing NEC requiring surgical intervention. We also investigated the utility of Bell's classification to diagnose either the need for surgery or death, and it had an AUC of 0.74 (95% CI: 0.65-0.83%, p < 0.0001). CONCLUSION: In this cohort, a combination of specific IUS markers and clinical signs of instability, abdominal wall cellulitis, plus laboratory markers were diagnostic of NEC requiring interventions. KEY POINTS: · The diagnosis of necrotizing enterocolitis requires a combination of markers.. · The combination of specific ultrasound markers, clinical signs, and laboratory markers were diagnostic of NEC requiring intervention.. · The intestinal ultrasound performed by a trained neonatologist was the most sensitive diagnostic marker of NEC requiring surgical intervention..

Hyperbilirubinemia Among Infants Born Preterm: Peak Levels and Association with Neurodevelopmental Outcomes.

OBJECTIVE: To describe the distribution of peak bilirubin levels among infants born before 29 weeks of gestation in the first 14 days of life and to study the association between quartiles of peak bilirubin levels at different gestational ages and neurodevelopmental outcomes. STUDY DESIGN: Multicenter, retrospective, nationwide cohort study of neonatal intensive care units in the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network, including neonates born preterm at 220/7 to 286/7 weeks of gestation born between 2010 and 2018. Peak bilirubin levels were recorded during the first 14 days of age. Main outcome was significant neurodevelopmental impairment, defined as cerebral palsy with Gross Motor Function Classification System ≥3, or Bayley III-IV scores of <70 in any domain, or visual impairment, or bilateral hearing loss requiring hearing aids. RESULTS: Among 12 554 included newborns, median gestational age was 26 weeks (IQR 25-28) and birth weight was 920 g (IQR 750-1105 g). The median peak bilirubin values increased as gestational age increased (112 mmol/L [6.5 mg/dL] at 22 weeks and 156 mmol/L [9.1 mg/dL] at 28 weeks). Significant neurodevelopmental impairment was identified in 1116 of 6638 (16.8%) of children. Multivariable analyses identified an association between peak bilirubin in the highest quartile and neurodevelopmental impairment (aOR 1.27, 95% CI 1.01-1.60) and receipt of hearing aid/cochlear implant (aOR 3.97, 95%CI: 2.01-7.82) compared with the lowest quartile. CONCLUSION: In this multicenter cohort study, peak bilirubin levels in neonates of <29 weeks of gestation increased with gestational age. Peak bilirubin values in the highest gestational age-specific quartile were associated with significant neurodevelopmental and hearing impairments.

Mental Disorders Among Mothers of Children Born Preterm: A Population-Based Cohort Study in Canada.

BACKGROUND: Our aim was to examine the association between preterm delivery and incident maternal mental disorders using a population-based cohort of mothers in Canada. METHODS: Retrospective matched cohort study using Manitoba Centre for Health Policy (MCHP) administrative data in Manitoba. Mothers who delivered preterm babies (<37 weeks gestational age) between 1998 and 2013 were matched 1:5 to mothers of term babies using socio-demographic variables. Primary outcome was any incident mental disorder within 5 years of delivery defined as any of (a) mood and anxiety disorders, (b) psychotic disorders, (c) substance use disorders, and (d) suicide or suicide attempts. Multivariable Poisson regression model was used to estimate the 5-year adjusted incidence rate ratios (IRRs). RESULTS: Mothers of preterm children (N = 5,361) had similar incidence rates of any mental disorder (17.4% vs. 16.6%, IRR = 0.99, 95% CI, 0.91 to 1.07) compared to mothers of term children (N = 24,932). Mothers of term children had a higher rate of any mental disorder in the first year while mothers of preterm children had higher rates from 2 to 5 years. Being the mother of a child born <28 week (IRR = 1.5, 95% CI, 1.14 to 2.04), but not 28-33 weeks (IRR = 1.03, 95% CI, 0.86 to 1.19) or 34-36 weeks (IRR = 0.96, 95% CI, 0.88 to 1.05), was associated with any mental disorder. INTERPRETATION: Mothers of preterm and term children had similar rates of incident mental disorders within 5-years post-delivery. Extreme prematurity was a risk factor for any mental disorder. Targeted screening and support of this latter group may be beneficial.

Grade 3 school performance among children born preterm: a population-based cohort study.

OBJECTIVE: To study the association between prematurity and grade 3 school performance in a contemporary cohort of children. METHODS: Population-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. RESULTS: Of 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 RELEVANCE: Children 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.

School Readiness Among Children Born Preterm in Manitoba, Canada.

Importance: Children born preterm may experience learning challenges at school. However, there is a paucity of data on the school readiness of these children as they prepare to begin grade 1. Objective: To examine the association between prematurity and school readiness in a population-based cohort of children. Design, Setting, and Participants: This cohort study was conducted in the province of Manitoba, Canada, and involved 2 cohorts of children in kindergarten at the time of data collection. The population-based cohort included children born between January 1, 2000, and December 31, 2011, whose school readiness was assessed in kindergarten using the Early Development Instrument (EDI) data. The sibling cohort comprised children born preterm and their closest-in-age siblings born full term. Data were analyzed between March 12 and September 28, 2021. Exposures: Preterm birth, defined as gestational age (GA) less than 37 weeks. Main Outcomes and Measures: The primary outcome was vulnerability in the EDI, defined as a score below the tenth percentile of the Canadian population norms for any 1 or more of the 5 EDI domains (physical health and well-being, social competence, emotional maturity, language and cognitive development, and communication skills and general knowledge). Logistic regression models were used to identify the factors associated with vulnerability in the EDI. P values were adjusted for multiplicity using the Simes false discovery method. Results: Of 86 829 eligible children, 63 277 were included, of whom 4352 were preterm (mean [SD] GA, 34 [2] weeks; 2315 boys [53%]) and 58 925 were full term (mean [SD] GA, 39 (1) weeks; 29 885 boys [51%]). Overall, 35% of children (1536 of 4352) born preterm were vulnerable in the EDI compared with 28% of children (16 449 of 58 925) born full term (adjusted odds ratio [AOR], 1.32; 95% CI, 1.23-1.41; P < .001]). Compared with children born full term, those born preterm had a higher percentage of vulnerability in each of the 5 EDI domains. In the population-based cohort, prematurity (34-36 weeks' GA: AOR, 1.23 [95% CI, 1.14-1.33]; <34 weeks' GA: AOR, 1.72 [95% CI, 1.48-1.99]), male sex (AOR, 2.24; 95% CI, 2.16-2.33), small for gestational age (AOR, 1.31; 95% CI, 1.23-1.40), and various maternal medical and sociodemographic factors were associated with EDI vulnerability. In the sibling cohort, EDI outcomes were similar for both children born preterm and their siblings born full term except for the communication skills and general knowledge domain (AOR, 1.39; 95% CI, 1.07-1.80) and Multiple Challenge Index (AOR, 1.43; 95% CI, 1.06-1.92), whereas male sex (AOR, 2.19; 95% CI, 1.62-2.96) and maternal age at delivery (AOR, 1.53; 95% CI, 1.38-1.70) were associated with EDI vulnerability. Conclusions and Relevance: Results of this study suggest that, in a population-based cohort, children born preterm had a lower school-readiness rate than children born full term, but this difference was not observed in the sibling cohort. Child and maternal factors were associated with lack of school readiness among this population-based cohort.

Clinical burden associated with therapies for cardio-pulmonary critical decompensation in preterm neonates across Canadian neonatal intensive care units.

The aim of this retrospective cohort study was to study the clinical burden associated with cardio-pulmonary critical decompensations (CPCDs) in preterm neonates and factors associated with mortality. Through the Canadian Neonatal Network (30 tertiary NICUs, 2010-2017), we identified infants < 32-week gestational age with CPCDs, defined by "significant exposure" to cardiotropes and/or inhaled nitric oxide (iNO): (1) either therapy for ≥ 3 consecutive days, (2) both for ≥ 2 consecutive days, or (3) any exposure within 2 days of death. Early CPCDs (≤ 3 days of age) and late CPCDs (> 3 days) were examined separately. Outcomes included CPCD-incidence, mortality, and inter-site variability using standardized ratios (observed/adjusted expected rate) and network funnel plots. Mixed-effects analysis was used to quantify unit-level variability in mortality. Overall, 10% of admissions experienced CPCDs (n = 2915). Late CPCDs decreased by ~ 5%/year, while early CPCDs were unchanged during the study period. Incidence and CPCD-associated mortality varied between sites, for both early (0.6-7.5% and 0-100%, respectively) and late CPCDs (2.5-15% and 14-83%, respectively), all p < 0.01. Units' late-CPCD incidence and mortality demonstrated an inverse relationship (slope = -2.5, p < 0.01). Mixed-effects analysis demonstrated clustering effect, with 6.4% and 8.6% of variability in mortality after early and late CPCDs respectively being site-related, unexplained by available patient-level characteristics or unit volume. Mortality was higher with combined exposure than with only-cardiotropes or only-iNO (41.3%, 24.8%, 21.5%, respectively; p < 0.01). CONCLUSIONS: Clustering effects exist in CPCD-associated mortality among Canadian NICUs, with higher incidence units showing lower mortality. These data may aid network-level benchmarking, patient-level risk stratification, parental counseling, and further research and quality improvement work. WHAT IS KNOWN: • Preterm neonates remain at high risk of acute and chronic complications; the most critically unwell require therapies such as cardiotropic drugs and inhaled nitric oxide. • Infants requiring these therapies are known to be at high risk for adverse neonatal outcomes and for mortality. WHAT IS NEW: • This study helps illuminate the national burden of acute cardio-pulmonary critical decompensation (CPCD), defined as the need for cardiotropic drugs or inhaled nitric oxide, and highlights the high risk of morbidity and mortality associated with this disease state. • Significant nationwide variability exists in both CPCD incidence and associated mortality; a clustering effect was observed with higher incidence sites showing lower CPCD-associated mortality.

Point of care lung ultrasound service in neonatal intensive care: Five years of experience in Manitoba, Canada.

OBJECTIVE: To evaluate the utility of a point of care lung ultrasound (POC-LUS) on patient management in the Neonatal Intensive Care Unit (NICU). STUDY DESIGN: A retrospective cohort study of neonates who had POC-LUS from 2016 to 2020 in two-level III NICUs in Winnipeg, Manitoba, Canada. The primary outcome was the change in clinical management. The analysis aims mainly to describe the implementation process of the POC-LUS program. RESULTS: A total of 956 neonates underwent 4076 POC-LUS studies during the study period. The number of POC-LUS studies increased significantly every year, from 316 (in 2016) to 1257 (in 2020) (p < 0.001). POC-LUS resulted in a change in clinical management following 2528 POC-LUS studies (62%), while it supported continuing the same management in 1548 studies (38%). CONCLUSION: POC-LUS in Manitoba increased since its inception and led to an alteration in the clinical management in a significant proportion of patients who received the service.

Variations in practices and outcomes of neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia across tertiary NICUs in Canada.

OBJECTIVE: To 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 DESIGN: Retrospective 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. RESULTS: Of 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). CONCLUSION: Significant variations exist in practices and outcomes of HIE neonates treated with hypothermia across Canada.

Neonatal outcomes of twins <29 weeks gestation of mothers with hypertensive disorders of pregnancy.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with dysfunctional placentation and are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancies have a larger placental mass and are a risk factor for HDP. The effect of HDP on neonatal outcomes in twin pregnancies is unknown. METHODS: Retrospective cohort study using the Canadian Neonatal Network database from 2010-2018 of twin infants <29 weeks gestation born to mothers with HDP and normotensive pregnancies. Using multivariable models, we determined adjusted odds ratios (AORs) and 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia, severe neurologic injury, severe retinopathy of prematurity (ROP), necrotizing enterocolitis, and nosocomial infection in twin infants of mothers with HDP compared to twin infants of normotensive mothers. RESULTS: Of the 2414 eligible twin infants <29 weeks gestational age, 164 (6.8%) were born to mothers with HDP and had higher odds of severe ROP (AOR 2.48, 95% CI 1.34-4.59). Preterm twin infants born to mothers with HDP also had higher odds of mortality (AOR 2.02, 95% CI 1.23-3.32). There was no difference in other outcomes. CONCLUSION: Preterm twin infants <29 weeks gestation of HDP mothers have higher odds of severe ROP and mortality. IMPACT: Hypertensive disorders of pregnancy, associated with placental dysfunction, are a major cause of maternal and neonatal morbidity and mortality. Twin pregnancy, associated with a larger placental mass, is a risk factor for hypertensive disorders of pregnancy. The effect of hypertensive disorders of pregnancy on outcomes of preterm twins is unknown. Preterm twins of mothers with hypertensive disorders of pregnancy are at higher risk of severe retinopathy of prematurity and mortality. Our data can be used to counsel parents and identify infants at higher risk of severe retinopathy of prematurity and mortality.

Poractant alfa versus bovine lipid extract surfactant: prospective comparative effectiveness study.

OBJECTIVE: To compare short term respiratory outcomes in preterm infants treated with bovine lipid extract surfactant or poractant alfa. STUDY DESIGN: Prospective comparative effectiveness cohort study of infants <32 weeks' gestational age requiring surfactant in thirteen centers. Each center provided bovine lipid extract surfactant for a set period of time in the year 2019 and then changed to poractant alfa for the remainder of the year. The primary outcome was total duration of respiratory support. RESULT: 968 infants were included. 494 received bovine lipid extract surfactant and 474 received poractant alfa. No difference was observed in the total duration of respiratory support (mechanical ventilation or non-invasive) (median 38 vs 40.5 days), need to re-dose surfactant, bronchopulmonary dysplasia, survival to discharge, or length of admission. CONCLUSION: In this pragmatic study, we did not identify any difference in short term outcomes between the groups based on the type of surfactant received.

Vasopressin for refractory persistent pulmonary hypertension of the newborn in preterm neonates - a case series.

OBJECTIVE: To describe the clinical outcomes following treatment with vasopressin for a sub-cohort of critically ill preterm neonates who have refractory persistent pulmonary hypertension of the newborn (PPHN). DESIGN: Case series. SETTING: Tertiary neonatal intensive care unit, Toronto, Canada. POPULATION: Neonates born <37 weeks gestational age (GA) who received vasopressin for refractory PPHN (lack of response to inhaled nitric oxide) over a 4-year period. MEASUREMENTS: Changes in physiological indices of cardio-pulmonary stability during vasopressin therapy were analyzed using one-way repeated measures ANOVA, compared to pretreatment values. Data regarding survival to discharge and neurodevelopmental outcomes at 18-24 months were described. MAIN RESULTS: Thirteen neonates with a mean GA of 31.4 ± 3.3 weeks were included. Vasopressin was initiated at 28.5 ± 4.5 h of age. Overall, oxygenation and hemodynamic variables improved significantly following vasopressin therapy (p < .05 at 24 h vs. pretreatment). Oxygenation failure resolved in 8 cases, of which 7 patients survived (6 without disability). Among the 5 cases where oxygenation failure persisted despite vasopressin, 4 died while one survived with disability. CONCLUSIONS: Vasopressin offers promise as a therapy for preterm neonates with refractory PPHN and hemodynamic instability, but prospective investigation is needed.

Targeted neonatal echocardiography service in neonatal intensive care in Manitoba, Canada.

OBJECTIVE: To evaluate the impact of a targeted neonatal echocardiography (TNE) service on patient management in the neonatal intensive care units (NICU) in Winnipeg, Canada. STUDY DESIGN: Retrospective cohort study of neonates who had TNEs from 2014 to 2019. The primary outcome was the change in clinical management based on TNE recommendation. Multivariate logistic regression analysis was used to identify predictors of the primary outcome. RESULTS: A total of 747 echos were performed on 307 neonates. Patent ductus arteriosus assessment was the most common indication for TNE followed by evaluation of pulmonary hypertension and systemic hemodynamics. TNE led to a change in clinical management following 492 (66%) echos. Mechanical ventilation [Odds ratio (OR) 2.4, 95% CI: 1.7-3.4, P < 0.001) and receiving inhaled nitric oxide (1.9, 95% CI: 1.3-3.0, P = 0.003) were the predictors for the change in clinical management following TNE. CONCLUSION: TNE has enhanced patient care by altering the management of patients in the NICU.

Lung Ultrasound for Prediction of Bronchopulmonary Dysplasia in Extreme Preterm Neonates: A Prospective Diagnostic Cohort Study.

OBJECTIVES: To evaluate the diagnostic and predictive ability of lung ultrasound at 3 time points in the first 2 weeks after birth for predicting bronchopulmonary dysplasia (BPD) among infants <29 weeks of gestational age. STUDY DESIGN: This was a prospective, diagnostic cohort study. Lung ultrasound was performed on days 3, 7, and 14 after birth and lung ultrasound scores (LUS) were calculated in blinded fashion. Diagnostic test characteristics and area under receiver operating characteristic (AUROC) curves were calculated. RESULTS: A total of 152 infants were enrolled with mean (SD) gestational age of 25.8 (1.5) weeks gestation. Of them, 87 (57%) infants were diagnosed with BPD. The LUS were significantly higher in infants diagnosed with BPD compared with those without BPD at all scan time points (P < .01). The score of >10 at all 3 time points had higher sensitivity (0.89, 0.89, and 0.77), specificity (0.87, 0.90, and 0.92), and corresponding clinically important positive and negative likelihood ratios. The AUROC for LUS at the 3 time points were 0.96, 0.97, and 0.95 on day 3, 7, and 14, respectively. Compared with the model using clinical characteristics, LUS alone had higher AUROC (P < .05 for all 3 time points). CONCLUSIONS: In this cohort, LUS in the first 2 weeks after birth had a very high predictive value for the diagnosis of BPD among infants of <29 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.govNCT04756297.

Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA).

INTRODUCTION: Patent 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 ANALYSIS: A 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). OUTCOMES: The 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 SIZE: The study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years. ANALYSIS: To 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 DISSEMINATION: The 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 NUMBER: NCT04347720.

Effect of Vasopressin on Systemic and Pulmonary Hemodynamics in Neonates.

OBJECTIVE: Despite its increasing use in neonates, the literature on the use of vasopressin (VP) in neonates is limited. The aim of this study is to evaluate the systemic and pulmonary effects of VP in neonates and to assess its safety among them. STUDY DESIGN: This retrospective study enrolled all neonates in two level III neonatal intensive care units in Winnipeg, Manitoba, who had received VP therapy between 2011 and 2016. Infants with congenital malformations/chromosomal disorders were excluded. The changes in cardiovascular and pulmonary parameters were collected from patient charts. The primary outcome was the mean blood pressure (MBP) post-VP initiation. Secondary outcomes included systolic blood pressure (SBP) and diastolic blood pressure (DBP), vasoactive inotropic score (VIS), pH, urine output, lactate, base deficit (BD), mean airway pressure (MAP), and oxygen requirement. RESULTS: A total of 33 episodes from 26 neonates were analyzed. The postnatal age at VP initiation was 14 days (interquartile range [IQR]: 4-25), and the median starting dose was 0.3 mU/kg/min (IQR: 0.2-0.5). MBP improved significantly after VP initiation from 28 to 39 mm Hg 24 hours after VP initiation (p < 0.001). Similar changes are observed with SBP and DBP. VIS declined from 15 to 6 at 24 hours, while pH, lactate, BD, and oxygen requirement improved significantly. While urine output marginally improved, there were no changes to MAP 24 hours post-VP initiation. Hyponatremia was observed in 21 episodes (64%) and severe hyponatremia in 7 episodes (33%). CONCLUSION: VP appears to be a promising rescue therapy in catecholamine resistant shock or refractory pulmonary hypertension in neonates.

Prone versus Supine Position for Lung Ultrasound in Neonates with Respiratory Distress.

OBJECTIVE: To study the feasibility of lung ultrasound (LUS) in prone position and to compare it with supine position in neonates with respiratory distress. STUDY DESIGN: Neonates ≥ 29 weeks of gestational age with respiratory distress requiring respiratory support within first 12 hours of life were enrolled prospectively. First LUS (fLUS) was done in the position infant was nursed (supine or prone), infant's position changed, a second LUS (sLUS) was performed immediately and a third LUS (tLUS) was done 1 to 2 hours later. Primary outcome was the comparison of LUS scores (LUSsc) between fLUS and sLUS. RESULTS: Sixty-four neonates were enrolled. Common respiratory diagnoses were transient tachypnea of newborn (TTN; 53%) and respiratory distress syndrome (RDS; 41%). LUSsc was different between fLUS and sLUS (fLUSsc 6 [interquatile range: 4, 7] vs. sLUSsc 7 [4, 10], p < 0.001), while there was no difference between the fLUS and tLUS (fLUSsc 6 [4, 7] vs. tLUSsc 5 [3, 7], p = 0.43). Subgroup analysis confirmed similar findings in neonates with TTN, while in babies with RDS, all the three LUSsc were similar. CONCLUSION: LUS is feasible in prone position in neonates. LUS scores were higher immediately after a change in position but were similar to baseline 1 hour after the change in position.