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ObjectiveTo compare the characteristics and outcomes of neonates with mild hypoxic-ischemic encephalopathy (HIE) who received hypothermia versus standard care.Study designWe conducted a retrospective cohort study of neonates ≥35 weeks’ gestation and ≥1800 g admitted with a diagnosis of Sarnat stage 1 encephalopathy. We evaluated length of hospital stay, duration of ventilation, evidence of brain injury on MRI, and neonatal morbidities.ResultsOf 1089 eligible neonates, 393 (36%) received hypothermia and 595 (55%) had neuroimaging. The hypothermia group was more likely to be outborn, born via C-section, had lower Apgar scores, and required extensive resuscitation. They had longer durations of stay (9 vs. 6 days, P < 0.001), respiratory support (3 vs. 2 days, P < 0.001), but lower odds of brain injury on MRI (adjusted odds ratio 0.33, 95% CI: 0.22–0.52) compared with standard care group.ConclusionDespite prolongation of hospital stay, hypothermia may be potentially beneficial in neonates with mild HIE; however, selection bias cannot be ruled out.

ObjectiveTo compare neurodevelopmental outcomes of large and appropriate for gestational age (LGA, AGA) infants <29 weeks’ gestation at 18–24 months of corrected age.Study designRetrospective cohort study using the Canadian Neonatal Network and Canadian Neonatal Follow-Up Network databases. Primary outcome was a composite of death or significant neurodevelopmental impairment (NDI), defined as severe cerebral palsy, Bayley III cognitive, language and motor scores of <70, need for hearing aids or cochlear implant and bilateral visual impairment. Univariate and multivariable logistic analyses were applied for outcomes.ResultsThe study cohort comprised 170 LGA and 1738 AGA infants. There was no difference in significant NDI or individual components of the Bayley III between LGA and AGA groups. LGA was associated with the increased risk of death by follow-up, 44/170 (25.9%) vs. 320/1738 (18.4%) (aOR: 1.60 95% CI: 1.00–2.54).ConclusionsRisk of NDI was similar between LGA and AGA infants.

ObjectiveTo evaluate outcomes of preterm infants <26 weeks gestational age (GA) following postdelivery extensive cardiopulmonary resuscitation (ECPR) compared with airway and breathing support (ABS).Study designRetrospective review of Canadian Neonatal Network data during January 2010 to December 2016. The primary outcome was death or severe morbidity (intraventricular hemorrhage ≥grade 3 or periventricular leucomalacia, retinopathy of prematurity ≥stage 3, bronchopulmonary dysplasia, or necrotizing enterocolitis).ResultAmong 3633 infants analyzed, 433 (11.9%) received ECPR. In multivariable analysis, death or severe morbidity was higher in the ECPR versus ABS group [adjusted odds ratio 2.26 (95% confidence interval 1.49, 3.43)]. The majority of the difference was due to increased mortality, which occurred mostly during the first week of life.ConclusionThese data from a recent cohort of infants near the limits of viability may be useful for prognostication for health care providers and counseling of parents.

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.

Abstract Objective To examine the association between the duration of antibiotic exposure and development of stage 2 or 3 necrotizing enterocolitis (NEC) in very preterm neonates. Study Design A retrospective case–control study was conducted from Canadian Neonatal Network data for preterm neonates born before 29 weeks’ gestation and admitted 2010 through 2013. Efforts were made to match each NEC case to two controls for gestational age, birth weight (±100 g) and sex. Results A total of 224 cases and 447 controls were identified. The incidence of antenatal steroid administration, the number of days nil-per-os and the number of antibiotic days prior to onset of NEC were significantly different in neonates with NEC. A multiple regression analysis revealed that the duration of antibiotic use was higher among NEC cases compared to controls (P<0.01). Empiric antibiotic treatment of 5 or more days was associated with significantly increased odds of NEC as compared with antibiotic exposure of 0 to 4 days (adjusted odds ratio: 2.02; 95% CI 1.55, 3.13). Conclusion Empiric antibiotic exposure for 5 or more days in preterm neonates born before 29 weeks’ gestation was associated with an increased risk of NEC.

Background Systemic hypertension (SH) has been reported in 0.2–3% of Neonatal Intensive Care Unit (NICU) patients. The epidemiology of the disease in preterm infants needs further exploration. Objectives To assess the incidence, temporal trend, risk factors, clinical characteristics, management and associated outcomes of preterm infants with SH. Design/Methods A retrospective population-based study including all infants born between January 2002 and December 2016 at < 31 weeks gestation in Nova Scotia. Patients diagnosed with SH (systolic blood pressure > 100mmHg requiring treatment, before discharge from NICU, or on 3 consecutive occasions during outpatient follow-up), were identified from the Provincial Perinatal Follow-up Database and patients’ charts. All SH patients were compared with matched controls (for gestational age, sex and birth weight). Perinatal data, details of SH and neonatal course were reviewed. Infants who died < 7 days of age were excluded. Results Out of 935 infants who met inclusion criteria, 109 (13.1%) had SH. Mean gestational age was 27.2 weeks (±1.9) and mean birth weight was 1039.3 g (±281.9) Table 1. Median post-menstrual age at diagnosis was 40 weeks Table 2. There was no significant difference in the temporal trend between the three study epochs (Figure 1). On logistic regression analysis, presence of major congenital anomaly was the only risk factor for SH (aOR 14.7, 95% CI:1.54, 141.2). Antenatal magnesium sulfate was protective (aOR 0.39, 95% CI: 0.20,0.75). 64 SH infants (59%) had nephrocalcinosis at time of diagnosis and the majority (79, 72.5%) were treated with ACE inhibitors. There was no significant difference in mortality (p=1.0) but the median length of stay was higher in the SH patients (p <0.01). Table 1: Maternal, Delivery Room, and infantile characteristics for infants with HTN and matched controls Variable Systemic HTN N=109 Matched Controls N=109 p-value Maternal Age, mean (SD) 29.4 (5.4) 29 (5.9) 0.62 Maternal smoking, n (%) 36/102 (34.6) 32/102 (31.4) 0.62 Maternal Diabetes, n (%) 6 (5.5) 8 (7.3) 0.58 Maternal hypertension, n (%) 1 (0.9) 2 (1.8) 1.0 Preeclampsia, n (%) 15 (13.8) 27 (24.8) 0.04 Antenatal steroids, n (%) 96 (88.1) 98 (89.9) 0.67 Magnesium sulfate, n (%) 23 (21.1) 50 (45.9) <0.001 Gestational age in weeks, mean (SD) 27.2 (1.9) 27.2 (1.9) 1.0 Mean birth weight, kg (SD) 1039.3 (281.9) 1038 (269.9) 0.97 Male, n (%) 73 (67) 73 (67) 1.0 BPD, n (%) 82 (75.2) 66 (60.6) 0.02 Duration of mechanical ventilation in hours mean (SD) 581.7 (5969) 412.4 (630) 0.04 Use of Caffeine, n (%) 101 (92.7) 100 (91.7) 0.80 PDA, n (%) 47 (43.1) 32 (29.4) 0.04 IVH (gr III and IV), n (%) 16 (14.4) 12 (11.0) 0.42 Umbilical artery catheterization, n (%) 77 (70.6) 67 (61.5) 0.15 NEC, n (%) 9 (8.3) 6 (4.6) 0.27 Sepsis, n (%) 32 (29.4) 29 (26.6) 0.65 ROP, n (%) 52 (47.7) 51 (46.8) 0.89 Median length of stay, days (IQR) 100 (7, 130) 73 (64, 100) 0.001 Death, n (%) 2 (1.8) 3 (2.8) 1.0 BPD: bronchopulmonary dysplasia| PDA: patent ductus arteriosus| IVH: intraventricular hemorrhage| NEC: necrotizing enterocolitis| ROP: retinopathy of prematurity Table 2: Clinical Data of infants with systemic hypertension Variable Systemic hypertension N=109 Postnatal age at diagnosis in weeks, median (IQR) 13 (9.5, 30) Postmenstrual age at diagnosis in weeks, median (IQR) 40 (37, 57) Diagnosed during NICU stay, n (%) 77 (70.6%) Diagnosed after discharge, n (%) 32 (29.4%) Anatomical abnormality on renal ultrasound, n (%) 5 (4.6%) Nephrocalcinosis on renal ultrasound, n (%) 64 (59.3%) Abnormal renal function at time of diagnosis, n (%) 0 Treated with diuretics, n (%) 45 (41.3%) Treated with ACE-Inhibitor, n (%) 79 (72.5%) Treated with > 1 medication, n (%) 17 (15.6%) ACE: angiotensin-converting-enzyme Conclusion The incidence of SH in preterm infants < 31weeks gestation was 13.1% with no significant change in trend over the study years. Administration of antenatal magnesium sulfate was protective. More than half of SH patients had nephrocalcinosis. Patients with SH had longer hospital stay without increase in mortality.

Background Systemic hypertension (SH) is not uncommon in ex-preterm infants. There is little data in literature about its impact on neurodevelopmental outcomes. Objectives To evaluate the neurodevelopmental outcomes at 18 months corrected age of preterm infants with SH as compared with their matched controls. Design/Methods Preterm infants born < 31 weeks’ gestation to mothers living in Nova Scotia between January 2002 and December 2016 and diagnosed with SH (systolic blood pressure > 100mmHg requiring treatment, before discharge from NICU or on 3 consecutive occasions, 1–2 weeks apart, during outpatient follow-up), were identified through the provincial Perinatal Follow-up Program Database. Neonates who died < 7 days of age and those with major congenital anomalies were excluded. Perinatal data and neonatal course were reviewed. Neurodevelopmental outcomes were assessed at 18 months of age using Bayley Scales of Infant and Toddler Development and cognitive adaptive test/clinical linguistic auditory milestone scale (CAT/CLAMS). Outcomes of patients with SH were compared with matched controls (for gestational age, sex and birth weight). Results 100 (98%) infants out of 102 infants diagnosed with SH were assessed at 18 months corrected age. Baseline clinical characteristics are noted in Table 1. Median post-menstrual age at SH diagnosis was 40 weeks. There were no significant differences in mean Mental Development Index, cognitive, language, motor, or CAT/CLAMs scores between SH patients and their matched controls -Table 2. Similarly, rates of neurodevelopmental impairments, cerebral palsy, deafness, and blindness were not significantly different. Conclusion Systemic hypertension does not appear to be negatively associated with long-term neurodevelopmental outcomes at 18 months corrected age in ex-preterm infants.

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.