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The purpose of this study is to compare the clinical effectiveness of dopamine (DA) versus norepinephrine (NE) as first-line therapy for sepsis-related hypotension in preterm infants. This is a retrospective cohort study over 10 years at two tertiary neonatal units. Preterm infants born < 35 weeks post-menstrual age (PMA), who received DA or NE as primary therapy for hypotension during sepsis, defined as culture-positive or culture-negative infections or necrotizing enterocolitis (NEC), were included. Episode-related mortality (< 7 days from treatment), pre-discharge mortality, and major morbidities among survivors were compared between two groups. Analyses were adjusted using the inverse probability of treatment weighting estimated by propensity score (PS). A total of 156 infants were included, 113 received DA and 43 NE. The mean ± SD PMA at birth and at treatment for the DA and NE groups were 25.8 ± 2.3 vs. 25.2 ± 2.0 weeks and 27.7 ± 3.0 vs. 27.1 ± 2.6 weeks, respectively (p > 0.05). Pre-treatment, the NE group had higher mean airway pressure (14 ± 4 vs. 12 ± 4 cmH2O), heart rate (185 ± 17 vs. 175 ± 17 beats per minute), and median (IQR) fraction of inspired oxygen [0.67 (0.42, 1.0) vs. 0.52 (0.32, 0.82)] (p < 0.05 for all). After PS adjustment, NE was associated with lower episode-related mortality [adjusted odds ratio (95% CI) 0.55 (0.33, 0.92)], pre-discharge mortality [0.60 (0.37, 0.97)], post-illness new diagnosis of significant neurologic injury [0.32 (0.13, 0.82)], and subsequent occurrence of NEC/sepsis among the survivors [0.34, (0.18, 0.65)]. Conclusion: NE may be more effective than DA for management of sepsis-related hypotension among preterm infants. These data provide a rationale for prospective evaluation of these commonly used agents. What is Known: •Dopamine is the commonest vasoactive agent used to support blood pressure among preterm infants. •For adult patients, norepinephrine is recommended as the preferred therapy over dopamine for septic shock. What is New: •This is the first study examining the relative clinical effectiveness of dopamine and norepinephrine as first-line pharmacotherapy for sepsis-related hypotension among preterm infants. •Norepinephrine use may be associated with lower mortality and morbidity than dopamine in preterm infants with sepsis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Acetaminophen use for pharmacological treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants is becoming more popular with emerging evidence that it is effective as well as safe alternative for other agents used to close hsPDA. Data sources: We performed a narrative review of literature about pharmacological treatment of PDA using acetaminophen. Results: Acetaminophen was used as a prophylaxis, symptomatic, targeted, and a rescue approach. Conclusions: It appears that acetaminophen could be used in different approaches to close the hsPDA. Long-term outcomes of acetaminophen exposure early in life still lack certainty. [ABSTRACT FROM AUTHOR]

Objective: Previously conducted cost-effectiveness analyses of pulse oximetry screening (POS) for critical congenital heart defects (CCHDs) have shown it to be a cost-effective endeavour, but the geographical setting of Ontario in relation to its vast yet sparsely populated regions presents unique challenges. The objective of this study was to estimate the cost-effectiveness of POS for CCHD in Ontario, Canada., Methods: A cost-effectiveness analysis, comparing POS to no POS, was conducted from the Ontario healthcare payer perspective using a Markov model. The base case was defined as a well-appearing newborn at 24 h of age. Outcome measures, including quality-adjusted life months (QALMs), lifetime costs, and incremental cost-effectiveness ratios (ICER) [ΔCost/ΔQALMs], were calculated over a lifetime horizon. All outcomes were discounted at 1.5% per year. Cost-effectiveness was assessed using an a priori ICER threshold of CAD$4166.67 per QALM (equivalent to CAD$50,000 per quality-adjusted life year). Deterministic and probabilistic sensitivity analyses were conducted to assess parameter uncertainty., Results: Implementation of POS is expected to lead to timely diagnosis of 51 CCHD cases annually. The incremental cost of performing POS was estimated to be $27.27 per screened individual, with a gain of 0.02455 QALMs. This yielded an ICER of CAD$1110.79 per QALM, well below the pre-determined threshold. The probabilistic sensitivity analysis estimated a 92.3% chance of routine implementation of POS being cost-effective., Conclusion: Routine implementation of POS for CCHD in Ontario is expected to be cost-effective.