Xiang Y. Ye

Comparison of Mortality and Morbidity of Very Low Birth Weight Infants Between Canada and Japan

OBJECTIVE: To compare neonatal outcomes of very low birth weight (VLBW) infants admitted to NICUs participating in the Canadian Neonatal Network and the Neonatal Research Network of Japan. METHODS: Secondary analyses of VLBW infants in both national databases between 2006 and 2008 were conducted. The primary outcome was a composite of mortality or any major morbidity defined as severe neurologic injury, bronchopulmonary dysplasia, necrotizing enterocolitis, or severe retinopathy of prematurity at discharge. Secondary outcomes included individual components of primary outcome and late-onset sepsis. Logistic regression adjusting for confounders was performed. RESULTS: A total of 5341 infants from the Canadian Neonatal Network and 9812 infants from the Neonatal Research Network of Japan were compared. There were higher rates of maternal hypertension, diabetes mellitus, outborn, prenatal steroid use, and multiples in Canada, whereas cesarean deliveries were higher in Japan. Composite primary outcome was better in Japan in comparison with Canada (adjusted odds ratio [AOR] 0.87, 95% confidence interval [CI] 0.79–0.96). The odds of mortality (AOR 0.40, 95% CI 0.34–0.47), severe neurologic injury (AOR 0.57, 95% CI 0.49–0.66), necrotizing enterocolitis (AOR 0.23, 95% CI 0.19–0.29), and late-onset sepsis (AOR 0.22, 95% CI 0.19–0.25) were lower in Japan; however, the odds of bronchopulmonary dysplasia (AOR 1.24, 95% CI 1.10–1.42) and severe retinopathy of prematurity (AOR 1.98, 95%CI 1.69–2.33) were higher in Japan. CONCLUSIONS: Composite outcome of mortality or major morbidity was significantly lower in Japan than Canada for VLBW infants. However, there were significant differences in various individual outcomes identifying areas for improvement for both networks.

Prediction of survival without morbidity for infants born at under 33 weeks gestational age: a user-friendly graphical tool

Objective To develop models and a graphical tool for predicting survival to discharge without major morbidity for infants with a gestational age (GA) at birth of 22–32 weeks using infant information at birth. Design Retrospective cohort study. Setting Canadian Neonatal Network data for 2003–2008 were utilised. Patients Neonates born between 22 and 32 weeks gestation admitted to neonatal intensive care units in Canada. Main outcome measure Survival to discharge without major morbidity defined as survival without severe neurological injury (intraventricular haemorrhage grade 3 or 4 or periventricular leukomalacia), severe retinopathy (stage 3 or higher), necrotising enterocolitis (stage 2 or 3) or chronic lung disease. Results Of the 17 148 neonates who met the eligibility criteria, 65% survived without major morbidity. Sex and GA at birth were significant predictors. Birth weight (BW) had a significant but non-linear effect on survival without major morbidity. Although maternal information characteristics such as steroid use, improved the prediction of survival without major morbidity, sex, GA at birth and BW for GA predicted survival without major morbidity almost as accurately (area under the curve: 0.84). The graphical tool based on the models showed how the GA and BW for GA interact, to enable prediction of outcomes especially for small and large for GA infants. Conclusion This graphical tool provides an improved and easily interpretable method to predict survival without major morbidity for very preterm infants at the time of birth. These curves are especially useful for small and large for GA infants.

Adverse Impact of Maternal Cigarette Smoking on Preterm Infants: A Population-Based Cohort Study.

OBJECTIVE The aim of the study is to examine the impact of exposure to maternal cigarette smoking on neonatal outcomes of very preterm infants. STUDY DESIGN A retrospective cohort study examined preterm infants (<33 weeks gestational age) admitted to the Canadian Neonatal Network centers between 2003 and 2011. Mortality and major morbidities (bronchopulmonary dysplasia, severe intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy) were compared between infants exposed and unexposed to maternal smoking during pregnancy after adjusting for confounders. RESULTS Among 29,051 study infants, 4,053 (14%) were exposed to maternal smoking during pregnancy. Multivariable analysis revealed higher odds of grade 3 or 4 intraventricular hemorrhage or periventricular leukomalacia (adjusted odds ratio [OR]: 1.21, 95% confidence interval [CI]: 1.04-1.41) and bronchopulmonary dysplasia (adjusted OR: 1.16, 95% CI: 1.02-1.33) in the smoking group, while mortality, severe retinopathy, and necrotizing enterocolitis were not significantly different. CONCLUSION Maternal smoking during pregnancy is associated with severe neurological injury and bronchopulmonary dysplasia in preterm infants.

Impact of late preterm and early term infants on Canadian neonatal intensive care units.

OBJECTIVE To examine the short-term morbidities, mortality, and use of neonatal intensive care unit (NICU) resources for late preterm, early term, and term infants. STUDY DESIGN Infants born between 34 and 40 weeks of gestation and admitted to a Canadian NICU in 2010 were designated late preterm (340/7 to 366/7 weeks), early term (370/7 to 386/7 weeks), or term (390/7 to 406/7 weeks). Mortality, short-term morbidities, and resource utilization were compared between the three groups using chi-square tests and analysis of variance. RESULTS Among 6,636 included infants, 44.2% (n = 2,935) were late preterm, 26.2% (n = 1,737) early term, and 29.6% (n = 1,964) term. Term infants were more likely to require resuscitation at birth and had lower Apgar scores than late preterm and early term infants (p < 0.001). Length of stay and need for respiratory support decreased with increasing gestational age; however, the proportion of hospital days that intensive care was required increased. CONCLUSION The greatest impact of late preterm infants is on NICU bed occupancy, whereas for term infants it is on intensity of care. Early term infants experience greater rates of some complications than term, demonstrating that risk persists for these infants. These findings have important implications for NICU resource planning and practice.

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.

First-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis

CONTEXT In the last decade, there has been a proliferation of treatment options for metastatic renal cell carcinoma (mRCC). However, direct comparative data are lacking for most of these agents. OBJECTIVE To indirectly compare the efficacy and safety of systemic therapies used in the first-line treatment of mRCC. EVIDENCE ACQUISITION Medline, EMBASE, Web of Science, and Scopus databases were searched using the OvidSP platform for studies indexed from database inception to October 23, 2017. Abstracts of conferences of relevant medical societies were included, and the systematic search was supplemented by hand search. For the systematic review, we identified any parallel-group randomized controlled trials assessing first-line systemic therapy. For network meta-analysis, we limited these to a clinically-relevant network based on standard practice patterns. Progression-free survival (PFS) was the primary outcome. Overall survival (OS) and grade 3 and 4 adverse events (AEs) were secondary outcomes. EVIDENCE SYNTHESIS In total, 37 trials reporting on 13 128 patients were included in the systematic review. The network meta-analysis comprised 10 trials reporting on 4819 patients. For PFS (10 trials, 4819 patients), there was a high likelihood (SUCRA 91%) that cabozantinib was the preferred treatment. For OS (5 trials, 3379 patients), there was a 48% chance that nivolumab plus ipilimumab was the preferred option. There was a 67% likelihood that nivolumab plus ipilimumab was the best tolerated regime with respect to AEs. CONCLUSIONS Cabozantinib and nivolumab plus ipilimumab are likely to be the preferred first-line agents for treating mRCC; however, direct comparative studies are warranted. These findings may provide guidance to patients and clinicians when making treatment decisions and may help inform future direct comparative trials. PATIENT SUMMARY There are many treatment options for patients diagnosed with metastatic renal cell carcinoma. We indirectly compared the available options and found that cabozantinib and nivolumab plus ipilimumab are likely to be preferable choices as the first-line treatment in this situation.

Outcome comparison of very preterm infants cared for in the neonatal intensive care units in Australia and New Zealand and in Canada

To compare risk‐adjusted neonatal intensive care unit outcomes between regions of similar population demography and health‐care systems in Australia–New Zealand and Canada to generate meaningful hypothesis for outcome improvements.

SNAP-II for prediction of mortality and morbidity in extremely preterm infants

Abstract Objective: To determine the specific Score of Neonatal Acute Physiology (SNAP-II) cut-off scores associated with outcomes in extremely preterm infants, and to examine its contribution to predictive models that include nonmodifiable birth predictors. Study design: Retrospective observational study of 9240 infants born at 22–28 weeks’ gestation and admitted to the Canadian Neonatal Network from 2010 to 2015. Outcomes included early and hospital mortality, composite of mortality/morbidity and individual morbidities. The SNAP-II cut-off to predict each outcome was determined using the Youden index. Additional contributions were evaluated using a base model that adjusted for gestational age, birth weight z-score and sex and by comparing the area under the curve (AUC). Results: The mortality/morbidity rate was 63% (5859/9240). Specific SNAP-II cut-offs ranged from 12 to 20 and were associated with each adverse outcome. Adding SNAP-II cut-offs to predictive models that included birth variables significantly improved (p < .05) the prediction of early mortality (AUC 0.84 versus 0.79), hospital mortality (AUC 0.80 versus 0.78), mortality/morbidity (AUC 0.76 versus 0.75), and severe neurological injury (AUC 0.69 versus 0.66) but had little or no effect on predictive models for retinopathy of prematurity, bronchopulmonary dysplasia, necrotizing enterocolitis, and nosocomial infection. Conclusions: SNAP-II cut-offs were independently associated with each adverse outcome and using the proposed SNAP-II cut-offs improved the performance of predictive models for certain short-term outcomes.

Chronic lung disease in preterm infants receiving various modes of noninvasive ventilation at ≤ 30 weeks’ post menstrual age

Abstract Objective: To determine the incidence of chronic lung disease (CLD) in mechanically ventilated infants who were born at <29 weeks’ gestational age (GA), extubated to continuous positive airway pressure (CPAP) or nasal intermittent positive pressure ventilation (NIPPV), and treated with CPAP/NIPPV alone, changed to heated humidified high flow nasal cannula (HHHFNC), or exposed to a combination of CPAP/NIPPV and HHHFNC at ≤30 weeks’ postmenstrual age (PMA). Study design: Retrospective cohort study of infants born at <29 weeks’ GA admitted to tertiary Canadian neonatal intensive care units between 2011 and 2015. Infants were grouped according to the type of noninvasive ventilation they received at ≤30 weeks’ PMA: CPAP/NIPPV alone, HHHFNC alone, or a combination of both. Results: Of the 2378 eligible infants, 1091 (46%) were on CPAP/NIPPV alone, 173 (7.3%) were on HHHFNC alone, and 1114 (47%) were on a combination of CPAP/NIPPV and HHHFNC at ≤30 weeks’ PMA until weaned to room air or low flow nasal cannula. After adjustment for confounders, infants in both the CPAP/NIPPV (odds ratio [95% confidence interval]; 2.37 [1.18, 4.79]) and Combination (3.47 [2.06, 5.86]) groups had higher odds of developing CLD than infants in the HHHFNC group. Conclusions: Our results demonstrate that infants transitioned to HHHFNC ≤30 weeks’ PMA after extubation to CPAP/NIPPV were associated with a lower odds of CLD than infants maintained on CPAP/NIPPV or a combination of CPAP/NIPPV and HHHFNC.

Admission Systolic Blood Pressure and Outcomes in Preterm Infants of ≤ 26 Weeks' Gestation

Objective To examine the relationship between admission systolic blood pressure (SBP) and adverse neonatal outcomes. Specifically, we aimed to identify the optimal SBP that is associated with the lowest rates of adverse outcomes in extremely preterm infants of ≤ 26 weeks’ gestation. Methods In this retrospective study, inborn neonates born at ≤ 26 weeks’ gestational age and admitted to tertiary neonatal units participating in the Canadian Neonatal Network between 2003 and 2009 were included. The primary outcome was early mortality (≤ 7 days). Secondary outcomes included severe brain injury, late mortality, and a composite outcome defined as early mortality or severe brain injury. Nonlinear multivariable logistic regression models examined the relationship between admission SBP and outcomes. Results Admission SBP demonstrated a U‐shaped relationship with early mortality, severe brain injury, and composite outcome after adjustment for confounders (p < 0.01). The lowest risks of early mortality, severe brain injury, and composite outcome occurred at admission SBPs of 51, 55, and 54 mm Hg, respectively. Conclusion In extremely preterm infants of ≤ 26 weeks’ gestational age, the relationship between admission SBP, and early mortality and severe brain injury was “ U‐shaped.” The optimal admission SBP associated with lowest rates of adverse outcome was between 51 and 55 mm Hg.