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Background We investigated the temporal evolution of post-hemorrhagic ventricular dilatation (PHVD) and compared neurodevelopmental impairments (NDI) in newborns with (Group 1) spontaneous resolution of PHVD, (Group 2) persistent PHVD without neurosurgical intervention, and (Group 3) progressive PHVD receiving neurosurgical intervention. Methods A multicenter retrospective cohort study of newborns born at ≤34 weeks with PHVD (ventricular index [VI] >97th centile for gestational age and anterior horn width [AHW] >6 mm) from 2012 to 2020. Severe NDI was defined as global developmental delay or cerebral palsy GMFCS III–V at 18 months. Results Of 88 survivors with PHVD, 39% had a spontaneous resolution, 17% had persistent PHVD without intervention, and 44% had progressive PHVD receiving intervention. The median time between PHVD diagnosis and spontaneous resolution was 14.0 days (IQR 6.8–32.3) and between PHVD diagnosis and first neurosurgical intervention was 12.0 days (IQR 7.0–22.0). Group 1 had smaller median maximal VI (1.8, 3.4, 11.1 mm above p97; p  < 0.001) and AHW (7.2, 10.8, 20.3 mm; p  < 0.001) than Groups 2 and 3. Neurodevelopmental outcome data were available for 82% of survivors. Group 1 had reduced severe NDI compared to Group 3 (15% vs 66%; p  < 0.001). Conclusion Newborns with PHVD without spontaneous resolution are at higher risk for impairments despite neurosurgical interventions, which may be due to larger ventricular dilatation. Impact The natural evolution of post-hemorrhagic ventricular dilatation (PHVD) and developmental implications of spontaneous resolution are not well established. In this study, approximately one in three newborns with PHVD experienced spontaneous resolution and this subset of newborns had reduced rates of neurodevelopmental impairments. More prominent ventricular dilatation was associated with reduced rates of spontaneous resolution and increased rates of severe neurodevelopmental impairment among newborns with PHVD. Understanding clinically relevant time points in the evolution of PHVD and predictors of spontaneous resolution may help inform the discussion around the optimal timing for intervention and allow for more precise prognostication in this population.

Objective To investigate the association between change in body mass index (BMI) from birth to 36 weeks gestation (ΔBMI) and bronchopulmonary dysplasia (BPD) among infants born <30 weeks gestation. Methods This was a multicenter retrospective cohort study (2015–2018) of infants born <30 weeks gestation and alive at ≥34 weeks corrected. Main exposure was a change in BMI z score from birth to 36 weeks corrected age grouped into quartiles of change. Association between ΔBMI z scores and BPD was assessed using generalized linear mixed models. Results Among 772 included infants, 51% developed BPD. From birth to 36 weeks CGA, the weight z score of infants with BPD decreased less than for BPD-free infants, despite a greater decrease in length z score and similar caloric intake resulting in increases in BMI z score (median [IQR], 0.16 [–0.64; 1.03] vs –0.29 [–1.03; 0.49]; P  < 0.01). In the adjusted analysis, higher ΔBMI z score quartiles were associated with higher odds of BPD (Q3 vs Q2, AOR [95% CI], 2.02 [1.23; 3.31] and Q4 vs Q2, AOR [95% CI], 2.00 [1.20; 3.34]). Conclusion Among preterm infants, an increase in BMI z score from birth to 36 weeks corrected is associated with higher odds of BPD. Impact Preterm infants with evolving lung disease often experience disproportionate growth in the neonatal period. In this multicenter cohort study, increases in BMI z score from birth to 36 weeks CGA were associated with higher odds of BPD. Despite similar caloric intake, infants with BPD had a higher weight- but lower length-for-age, resulting in higher BMI z score compared to BPD-free infants. This suggests that infants with evolving BPD may require different growth and nutritional targets compared to BPD-free infants.

ObjectiveTo assess the association of NICU occupancy with probability of discharge and length of stay (LOS) among infants born <33 weeks gestational age (GA).Study designRetrospective study of 3388 infants born 23–32 weeks GA, admitted to five Level 3/4 NICUs (2014-2018) and discharged alive. Standardized ratios of observed-to-expected number of discharges were calculated for each quintile of unit occupancy. Multivariable linear regression models were used to assess the association between occupancy and LOS.ResultsAt the lowest unit occupancy quintiles (Q1 and Q2), infants were 12% and 11% less likely to be discharged compared to the expected number. At the highest unit occupancy quintile (Q5), infants were 20% more likely to be discharged. Highest occupancy (Q5) was also associated with a 4.7-day (95% CI 1.7, 7.7) reduction in LOS compared Q1.ConclusionNICU occupancy was associated with likelihood of discharge and LOS among infants born <33 weeks GA.

ObjectiveIn a healthcare system with finite resources, hospital organisational factors may contribute to patient outcomes. We aimed to assess the association of nurse staffing and neonatal intensive care unit (NICU) occupancy with outcomes of preterm infants born <33 weeks’ gestation.DesignRetrospective cohort study.SettingFour level III NICUs.PatientsInfants born 23–32 weeks’ gestation 2015–2018.Main outcome measuresNursing provision ratios (nursing hours worked/recommended nursing hours based on patient acuity categories) and unit occupancy rates were averaged for the first shift, 24 hours and 7 days of admission of each infant. Primary outcome was mortality/morbidity (bronchopulmonary dysplasia, severe neurological injury, retinopathy of prematurity, necrotising enterocolitis and nosocomial infection). ORs for association of exposure with outcomes were estimated using generalised linear mixed models adjusted for confounders.ResultsAmong 1870 included infants, 823 (44%) had mortality/morbidity. Median nursing provision ratio was 1.03 (IQR 0.89–1.22) and median unit occupancy was 89% (IQR 82–94). In the first 24 hours of admission, higher nursing provision ratio was associated with lower odds of mortality/morbidity (OR 0.93, 95% CI 0.89 to 0.98), and higher unit occupancy was associated with higher odds of mortality/morbidity (OR 1.19, 95% CI 1.04 to 1.36). In causal mediation analysis, nursing provision ratios mediated 47% of the association between occupancy and outcomes.ConclusionsNICU occupancy is associated with mortality/morbidity among very preterm infants and may reflect lack of adequate resources in periods of high activity. Interventions aimed at reducing occupancy and maintaining adequate resources need to be considered as strategies to improve patient outcomes.

Abstract Background Post-hemorrhagic ventricular dilatation (PHVD) is a serious complication of intraventricular hemorrhage (IVH) in preterm newborns and is associated with significant impairments. The natural evolution of PHVD and developmental implications of spontaneous resolution are not well established. Objectives To investigate the natural evolution of PHVD and compare neurodevelopmental impairments in newborns with (1) spontaneous resolution of PHVD; (2) persistent PHVD and (3) PHVD who underwent neurosurgical intervention. Design/Methods We conducted a multicenter retrospective cohort study of 5238 newborns born at ≤34 weeks’ gestational age (GA) admitted to two tertiary Neonatal Intensive Care Units (NICU) between 2012 and 2020. Head ultrasounds (HUS) of 476 newborns with IVH grade ≥2 were reviewed to identify PHVD, defined as ventricular index (VI) >97th centile (p97) for GA and anterior horn width (AHW) >6mm on any HUS in the first 6 weeks of life. Newborns with PHVD were divided into three groups, Group 1: newborns with spontaneous resolution of PHVD, defined as the regression of both lateral ventricles below the VI and AHW thresholds, Group 2: newborns with persistent PHVD absent neurosurgical intervention and Group 3: newborns who underwent any neurosurgical intervention. Neurodevelopmental outcomes at 18 months corrected, obtained through chart review, were compared. Results Of 108 newborns with PHVD, 88 survived to NICU discharge (mean GA 28.4 weeks, SD 2.8; median age at PHVD diagnosis 8.0 days, IQR 5.0-12.8). Overall, 34/88 (38.6%) newborns had spontaneous resolution of PHVD (Group 1). The median time between PHVD diagnosis and spontaneous resolution was 14.0 days (IQR 6.8-32.3) (Figure). In Group 3, the median time between PHVD diagnosis and the first neurosurgical intervention was 14.0 days (IQR 7.0-23.0). Group 1 had significantly smaller maximal VI (1.8, 3.4, and 11.1mm above p97, p<0.001) and AHW (7.2, 10.8, and 20.3mm, p<0.001) than Groups 2 and 3, respectively, and were less likely to have bilateral PHVD (OR 0.47, 95% CI 0.33-0.67) than Group 3. Neurodevelopmental outcome data at 18 month were available for 53/88 (60.2%) survivors (Table). Group 1 had lower rates of cerebral palsy (17.4% vs 45.8%; p=0.037), global developmental delay (17.4% vs 50.0%; p=0.018), epilepsy (4.3% vs 29.2%; p=0.048) and involvement of ≥3 allied health professionals (34.8% vs 70.8%; p=0.013) compared to Group 3. Conclusion Newborns with PHVD without spontaneous resolution are at higher risk for significant neurodevelopmental impairments despite neurosurgical interventions, which may be due to more prominent ventricular dilatation. Strategies aimed at mitigating the burden of impairments in patients without spontaneous resolution are needed.

ObjectiveTo 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 designRetrospective 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.ResultsOf 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).ConclusionSignificant variations exist in practices and outcomes of HIE neonates treated with hypothermia across Canada.

ObjectiveTo assess the neurodevelopmental outcomes of preterm neonates who received inhaled nitric oxide (iNO) in the first week of age for hypoxaemic respiratory failure (HRF).MethodsIn this retrospective cohort study, we included neonates born at <29 weeks gestational age (GA) between January 2010 and December 2018 who had a neurodevelopmental assessment at 18–24 months corrected age (CA) at one of the Canadian Neonatal Follow-Up Network clinics. The primary outcome was neurodevelopmental impairment (NDI). We performed propensity score-matched analysis to compare the outcomes of those who received and did not receive iNO.ResultsOf the 5612 eligible neonates, 460 (8.2%) received iNO in the first week of age. Maternal age, receipt of antenatal corticosteroids, GA and birth weight were lower in the iNO group compared with the no-iNO group. Neonates in the iNO group had higher illness severity scores and higher rates of preterm prolonged rupture of membranes and were small for GA. Severe brain injury, bronchopulmonary dysplasia and mortality were higher in the iNO group. Of the 4889 survivors, 3754 (77%) neonates had follow-up data at 18–24 months CA. After propensity score matching, surviving infants who received rescue iNO were not associated with higher odds of NDI (adjusted OR 1.34; 95% CI 0.85 to 2.12).ConclusionsIn preterm neonates <29 weeks GA with HRF, rescue iNO use was not associated with worse neurodevelopmental outcomes among survivors who were assessed at 18–24 months CA.

ObjectiveTo describe the incidence, trends, management’s variability and short-term outcomes of preterm infants with severe post-hemorrhagic ventricular dilatation (sPHVD).MethodsWe reviewed infants <33 weeks’ gestation who had PHVD and were admitted to the Canadian Neonatal Network between 2010 and 2018. We compared perinatal characteristics and short-term outcomes between those with sPHVD and those with mild/moderate PHVD and those with and without ventriculo-peritoneal (VP) shunt.ResultsOf 29,417 infants, 2439 (8%) had PHVD; rate increased from 7.3% in 2010 to 9.6% in 2018 (P = 0.005). Among infants with PHVD, sPHVD (19%) and VP shunt (29%) rates varied significantly across Canadian centers and between geographic regions (P < 0.01 and P = 0.0002). On multivariable analysis, sPHVD was associated with greater mortality, seizures and meningitis compared to mild/moderate PHVD.ConclusionsSignificant variability in sPHVD and VP shunt rates exists between centers and regions in Canada. sPHVD was associated with increased mortality and morbidities.

ObjectiveTo examine the association between probiotic use and antimicrobial utilization.Study designWe retrospectively evaluated very-low-birth-weight (VLBW) infants admitted to tertiary neonatal intensive care units in Canada between 2014 and 2019. Our outcome was antimicrobial utilization rate (AUR) defined as number of days of antimicrobial exposure per 1000 patient-days.ResultOf 16,223 eligible infants, 7279 (45%) received probiotics. Probiotic use rate increased from 10% in 2014 to 68% in 2019. The AUR was significantly lower in infants who received probiotics vs those who did not (107 vs 129 per 1000 patient-days, aRR = 0.89, 95% CI [0.81, 0.98]). Among 13,305 infants without culture-proven sepsis or necrotizing enterocolitis ≥Stage 2, 5931 (45%) received probiotics. Median AUR was significantly lower in the probiotic vs the no-probiotic group (78 vs 97 per 1000 patient-days, aRR = 0.85, 95% CI [0.74, 0.97]).ConclusionProbiotic use was associated with a significant reduction in AUR among VLBW infants.