Association of 24-Hour In-house Neonatologist Coverage with Outcomes of Extremely Preterm Infants.

OBJECTIVE: This study aimed to assess if 24-hour in-house neonatologist (NN) coverage is associated with delivery room (DR) resuscitation/stabilization and outcomes among inborn infants <29 weeks' gestational age (GA). STUDY DESIGN: Survey-linked cohort study of 2,476 inborn infants of 23 to 28 weeks' gestation, admitted between 2014 and 2015 to Canadian Neonatal Network Level-3 neonatal intensive care units (NICUs) with a maternity unit. Exposures were classified using survey responses based on the most senior provider offering 24-hour in-house coverage: NN, fellow, and no NN/fellow. Primary outcome was death and/or major morbidity (bronchopulmonary dysplasia, severe neurological injury, late-onset sepsis, necrotizing enterocolitis, and retinopathy of prematurity). Multivariable logistic regression analysis was used to assess the association between exposures and outcomes and adjust for confounders. RESULTS: Among the 28 participating NICUs, most senior providers ensuring 24-hour in-house coverage were NN (32%, 9/28), fellows (39%, 11/28), and no NN/fellow (29%, 8/28). No NN/fellow coverage and 24-hour fellow coverage were associated with higher odds of infants receiving DR chest compressions/epinephrine compared with 24-hour NN coverage (adjusted odds ratio [aOR] = 4.72, 95% confidence interval [CI]: 2.12-10.6 and aOR = 3.33, 95% CI: 1.44-7.70, respectively). Rates of mortality/major morbidity did not differ significantly among the three groups: NN, 63% (249/395 infants); fellow, 64% (1092/1700 infants); no NN/fellow, 70% (266/381 infants). CONCLUSION: 24-hour in-house NN coverage was associated with lower rates of DR chest compressions/epinephrine. There was no difference in neonatal outcomes based on type of coverage; however, further studies are needed as ecological fallacy cannot be ruled out. KEY POINTS: · Lower rates of DR cardiopulmonary resuscitation with 24h in-house NN coverage. · The type of 24h in-house coverage was not associated with mortality and/or major morbidity.. · High-volume centers more often have 24h in-house neonatal fellow coverage.

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.

A Comparison of Strategies for Managing the Umbilical Cord at Birth in Preterm Infants.

OBJECTIVE: To evaluate the rates of practice, and the associations between different cord management strategies at birth (delayed cord clamping [DCC], umbilical cord milking [UCM], and early cord clamping [ECC]) and mortality or major morbidity, rates of blood transfusion, and peak serum bilirubin in a large national cohort of very preterm infants. STUDY DESIGN: We retrospectively studied preterm infants <33 weeks of gestation admitted to the Canadian Neonatal Network between January 2015 and December 2017. Patients who received ECC (<30 seconds), UCM, or DCC (≥30 seconds) were compared. Multiple generalized linear/quantile logistic regression models were used. RESULTS: Of 12 749 admitted infants, 9729 were included; 4916 (50.5%) received ECC, 394 (4.1%) UCM, and 4419 (45.4%) DCC. After adjustment for potential confounders identified between groups in univariate analyses, the odds of mortality or major morbidity were higher in the ECC group when compared with UCM group (aOR, 1.18; 95% CI, 1.03-1.35). Mortality and intraventricular hemorrhage were associated with ECC as compared with DCC (aOR, 1.6 [95% CI, 1.22-2.1] and aOR, 1.29 [95% CI, 1.19-1.41], respectively). The odds of severe intraventricular hemorrhage were higher with UCM compared with DCC (aOR, 1.38; 95% CI, 1.05-1.81). Rates of blood transfusion were higher with ECC compared with UCM and DCC (aOR, 1.67 [95% CI, 1.31-2.14] and aOR, 1.68 [95% CI, 1.35-2.09], respectively), although peak serum bilirubin levels were not significantly different. CONCLUSIONS: Both DCC and UCM were associated with better short-term outcomes than ECC; however, the odds of severe intraventricular hemorrhage were higher with UCM compared with DCC.

Outcomes of singleton small for gestational age preterm infants exposed to maternal hypertension: a retrospective cohort study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are a major cause of small for gestational age (SGA). Preterm SGA infants have higher rates of adverse outcomes than appropriate for gestational age infants. However, the outcomes are not well established in the setting of HDP. METHODS: Retrospective population-based study using the Canadian Neonatal Network database from January 1, 2010 to December 31, 2016 of SGA infants <33 weeks gestation. Using multivariable models, we determined the adjusted odds ratios (AORs) with 95% confidence intervals (CI) for mortality, bronchopulmonary dysplasia (BPD), severe intraventricular hemorrhage (IVH), severe retinopathy of prematurity, necrotizing enterocolitis, late-onset sepsis, and patent ductus arteriosus (PDA) in infants of HDP mothers and compared them to infants of non-HDP mothers. RESULTS: Of the 2081 eligible SGA infants, 1317 (63%) were born to HDP mothers and had lower odds of mortality (AOR 0.57, 95% CI 0.39-0.83) and BPD (AOR 0.69, 95% CI 0.53-0.90). Sub-group analysis demonstrated decreased mortality in 26-28 and 29-32 weeks gestation groups, decreased BPD in 29-32 weeks gestation group, and decreased PDA in <26 weeks gestation group. CONCLUSION: Preterm SGA infants of HDP mothers have lower odds of mortality and BPD compared to infants of non-HDP mothers.

Outcomes after Neonatal Seizures in Infants Less Than 29 Weeks' Gestation: A Population-Based Cohort Study.

OBJECTIVE: The aim of this study was to evaluate the association between neonatal seizure and neurodevelopmental impairment (NDI) at 18 to 24 months in extremely preterm neonates. The association between anticonvulsants use and NDI was also assessed. STUDY DESIGN: In this retrospective cohort study of infants born at <29 weeks' gestation from the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network databases, we compared mortality and neurodevelopmental outcomes in infants who had neonatal seizures with those without seizures after adjusting for confounders. RESULTS: Of the 2,762 eligible neonates, 133 (4.8%) had seizures. Infants who had seizures were of lower gestation (25.2 vs. 26.2 weeks) and birth weight (819 vs. 920 g) and had higher rates of adverse outcomes. Neonatal seizure was associated with higher odds of composite outcome of death or significant NDI (74 vs. 27%; adjusted odds ratio [OR]: 3.4; 95% confidence interval [CI]: 2.2-5.4). Death or significant NDI was higher in infants with seizures treated with anticonvulsants than those without treatment (89 vs. 70%); however, when adjusted for confounders, it was not significantly different (adjusted OR: 3.5; 95% CI: 0.83-14.6). CONCLUSION: Neonatal seizures were independently associated with higher odds of death or significant NDI at 18 to 24 months of age. Relationship of anticonvulsant and neurodevelopmental outcomes needs further studies.

Comparison of singleton and multiple-birth outcomes of infants born at or before 32 weeks of gestation.

OBJECTIVE: To compare the outcomes of multiple-birth and singleton very preterm infants who were admitted to neonatal intensive care units (NICUs). METHODS: Three-level hierarchical generalized linear and hierarchical linear model analyses were used to compare the risk-adjusted outcomes of 3,242 infants born at or before 32 weeks of gestational age who were admitted to 24 Canadian NICUs in 2005. RESULTS: With the exception of respiratory distress syndrome (RDS), multiple-birth infants were not at a higher risk than singleton birth infants for death, patent ductus arteriosus, necrotizing enterocolitis, chronic lung disease, severe intraventricular hemorrhage, severe (stages 3 or higher) retinopathy of prematurity, or nosocomial infection, after adjusting for perinatal risks and neonatal illness severity. In addition, multiple-birth infants did not have a more prolonged duration of neonatal intensive care unit stay, duration of length of continuous positive airway pressure use, duration of ventilation, or duration of oxygen use than did singletons. Multiple-birth infants had a higher incidence of RDS (adjusted odds ratio 1.3, 95% confidence interval 1.0-1.6) and a lower incidence of severe retinopathy of prematurity (adjusted odds ratio 0.5, 95% confidence interval 0.3-0.9) than did singletons. CONCLUSION: Multiple-birth and singleton very preterm infants had similar outcomes, except for a higher incidence of RDS among multiple-birth infants. LEVEL OF EVIDENCE: II.