Training in neonatal neurocritical care: A case-based interdisciplinary approach.

Interdisciplinary fetal-neonatal neurology (FNN) training strengthens neonatal neurocritical care (NNCC) clinical decisions. Neonatal neurological phenotypes require immediate followed by sustained neuroprotective care path choices through discharge. Serial assessments during neonatal intensive care unit (NICU) rounds are supplemented by family conferences and didactic interactions. These encounters collectively contribute to optimal interventions yielding more accurate outcome predictions. Maternal-placental-fetal (MPF) triad disease pathways influence postnatal medical complications which potentially reduce effective interventions and negatively impact outcome. The science of uncertainty regarding each neonate's clinical status must consider timing and etiologies that are responsible for fetal and neonatal brain disorders. Shared clinical decisions among all stakeholders' balance "fast" (heuristic) and "slow" (analytic) thinking as more information is assessed regarding etiopathogenetic effects that impair the developmental neuroplasticity process. Two case vignettes stress the importance of FNN perspectives during NNCC that integrates this dual cognitive approach. Clinical care paths evaluations are discussed for an encephalopathic extremely preterm and full-term newborn. Recognition of cognitive errors followed by debiasing strategies can improve clinical decisions during NICU care. Re-evaluations with serial assessments of examination, imaging, placental-cord, and metabolic-genetic information improve clinical decisions that maintain accuracy for interventions and outcome predictions. Discharge planning includes shared decisions among all stakeholders when coordinating primary care, pediatric subspecialty, and early intervention participation. Prioritizing social determinants of healthcare during FNN training strengthens equitable career long NNCC clinical practice, education, and research goals. These perspectives contribute to a life course brain health capital strategy that will benefit all persons across each and successive lifespans.

Neuroprotective therapies in the NICU in preterm infants: present and future (Neonatal Neurocritical Care Series).

The survival of preterm infants has steadily improved thanks to advances in perinatal and neonatal intensive clinical care. The focus is now on finding ways to improve morbidities, especially neurological outcomes. Although antenatal steroids and magnesium for preterm infants have become routine therapies, studies have mainly demonstrated short-term benefits for antenatal steroid therapy but limited evidence for impact on long-term neurodevelopmental outcomes. Further advances in neuroprotective and neurorestorative therapies, improved neuromonitoring modalities to optimize recruitment in trials, and improved biomarkers to assess the response to treatment are essential. Among the most promising agents, multipotential stem cells, immunomodulation, and anti-inflammatory therapies can improve neural outcomes in preclinical studies and are the subject of considerable ongoing research. In the meantime, bundles of care protecting and nurturing the brain in the neonatal intensive care unit and beyond should be widely implemented in an effort to limit injury and promote neuroplasticity. IMPACT: With improved survival of preterm infants due to improved antenatal and neonatal care, our focus must now be to improve long-term neurological and neurodevelopmental outcomes. This review details the multifactorial pathogenesis of preterm brain injury and neuroprotective strategies in use at present, including antenatal care, seizure management and non-pharmacological NICU care. We discuss treatment strategies that are being evaluated as potential interventions to improve the neurodevelopmental outcomes of infants born prematurely.

Relationship Between Neonatal Brain Injury and Objective Measures of Head Trauma: A Case-Control Study.

BACKGROUND AND OBJECTIVES: Neonatal brain injury is a common and devastating diagnosis conferring lifelong challenges for children and families. The role of mechanical forces applied to the head, often referred to as "birth trauma," are often considered although evidence for this association is lacking. The objective of this study was to investigate the association between common types of neonatal brain injury and scalp swelling using a novel method to quantify scalp swelling as an unbiased proxy for mechanical forces applied to the head. METHODS: Case-control study using population-based, prospectively collected tertiary care center databases and healthy controls from the Human Connectome Development Project. Included were infants born 32-42 weeks gestational age and MRI in the first 9 days. Outcomes categories included healthy neonates, hypoxic ischemic encephalopathy (HIE) with or without brain injury, or stroke (ischemic or hemorrhagic). Volume of scalp swelling was objectively quantified by a novel imaging method blinded to brain injury. Variables included mode of delivery and use of instrumentation. Statistical tests included Kruskal-Wallis test, chi square, and multivariable and multinomial logistic regression. RESULTS: There were 309 infants included (55% male): 72 healthy controls, 77 HIE without brain injury on MRI, 78 HIE with brain injury, and 82 with stroke (60 ischemic, 22 hemorrhagic). Scalp swelling was present in 126 (40.8%, 95% confidence interval [CI] 35.2%-46.5%) with no difference in proportions between outcome groups. Compared to healthy controls, median volume was higher in those with HIE without brain injury (17.5 mL, 95% CI 6.8-28.2), HIE with brain injury (12.1 mL, 95% CI 5.5-18.6), but not ischemic stroke (4.7 mL, 95% CI -1.2-10.6) nor hemorrhagic stroke (8.3 mL, 95% CI -2.2-18.8). Scalp swelling was associated with instrumented delivery (OR 2.1, 95% CI 1.0-4.1), but not associated with increased odds of brain injury in those with HIE (OR 1.5, 95% CI 0.76-3.30). Scalp swelling measures were highly reliable (ICC = 0.97). DISCUSSION: "Birth trauma" quantified by scalp swelling volume was more common in infants with difficult deliveries, but not associated with greater odds of brain injury due to hypoxia or stroke. These results may help parents and practitioners to dissociate the appearance of trauma with the risk of brain injury.

Prospective assessment of inter-rater reliability of a neonatal adverse event severity scale.

Introduction: To ensure the quality of clinical trial safety data, universal data standards are required. In 2019 the International Neonatal Consortium (INC) published a neonatal adverse event severity scale (NAESS) to standardize the reporting of adverse event (AE) severity. In this study the reliability of AE severity grading with INC NAESS was prospectively assessed in a real-world setting. Methods: Severity of AEs was assessed by two independent observers at each of four centers across the world. In each center two series of 30 neonatal adverse events were assessed by both observers: in a first phase with a generic (Common Terminology Criteria for Adverse Events, CTCAE) severity scale not specific to neonates, and in a second phase with INC NAESS (after a structured training). Intraclass correlation coefficients (ICC) were calculated to express inter-rater agreement in both phases, and bootstrap sampling was used to compare them. Results: 120 AEs were included in each of both phases. The ICC with the use of INC NAESS in phase 2 was 0.69. This represents a significant but modest improvement in comparison to the initial ICC of 0.66 in phase 1 (confidence interval of ratio of ICC in phase 2 to phase 1 = 1.005-1.146; excludes 1). The ICC was higher for those AEs for which a diagnosis specific AE severity table was available in INC NAESS (ICC 0.80). Discussion: Good inter-rater reliability of the INC NAESS was demonstrated in four neonatal intensive care units (NICUs) across the globe. The ICC is comparable to what is reported for scales with similar purposes in different populations. There is a modest, but significant, improvement in inter-rater agreement in comparison to the naïve phase without INC NAESS. The better performance when reviewers use AE-specific NAESS tables highlights the need to expand the number of AEs that are covered by specific criteria in the current version of INC NAESS.

Structured Referral Call Handling Process Improves Neonatal Transport Dispatch Times.

OBJECTIVE: In 2019 the Southern Alberta Neonatal Transport Service adopted a transport call handling process change to expedite transport team mobilization. This study compares the impact of this change on neonatal transport decision to dispatch and mobilization times. STUDY DESIGN: This retrospective cohort study was conducted using a historical cohort of neonates referred for transportation between January 2017 and December 2021. The "dispatch time" (DT) was the time from the start of consultation to the time a decision to dispatch the transport team was made, whereas "mobilization time" (MT) referred to the time from start of consultation to the time the team departed the home base. In 2019, a DT target of <3 minutes was implemented to meet a target MT of <15 and <30 minutes for emergent and urgent high-risk transport referral calls, respectively. In 2021 use of the "Situation" component of the SBAR (Situation, Background, Assessment, Recommendation) communication tool was introduced with the transport team asking five questions to determine need for mobilization. Data between 2017 and 2018 represented the preintervention period, 2019, the "washout" period for implementation, and 2020 to 2021, the postintervention period. Data were analyzed to determine trends in DT and MT. RESULTS: The DT was reduced from a median of 5 to 3 minutes following intervention (p < 0.001). DT target goal of 3 minutes was achieved in 67.08% of calls compared with 26.24% in the preintervention period, (p < 0.001). The team achieved MT target goals in 42.71% of urgent and emergent transfers compared with 18.05% prior to intervention (p < 0.001). CONCLUSION: Introduction of a time-sensitive referral call handling process improved dispatch and mobilization time of the neonatal transport team. KEY POINTS: · Time-sensitive triaging of neonatal transport referrals improves dispatch and mobilization time.. · A structured referral call handling process improves the efficiency of neonatal transport decision-making.. · Dedicated neonatal transport vehicles are likely to improve neonatal transport mobilization time..

The REDUCED trial: a cluster randomized trial for REDucing the utilization of CEsarean delivery for dystocia.

BACKGROUND: To reduce cesarean delivery rates in nulliparous women, guidelines for diagnosing nonprogressive labor have been developed by the National Institute of Child Health and Human Development, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine. These are mainly based on data from the Consortium for Safe Labor study. The guidelines have not been tested in a clinical trial, so the efficacy and safety of this new approach is uncertain. OBJECTIVE: This study aimed to assess whether adoption of new guidelines for diagnosing nonprogressing labor would reduce cesarean delivery rates. STUDY DESIGN: We conducted a cluster randomized controlled trial of a knowledge translation program of the guidelines in 26 Canadian hospitals (13 control sites and 13 intervention sites). The sites included all intrapartum care sites in Alberta that perform cesarean delivery and deliver at least 70 nulliparous women annually. The baseline period started on January 1, 2015. The intervention was initiated at the first intervention site in January 2017. The follow-up period began at the first intervention site in February 2017 and lasted till February 2020. The primary outcome was the rate of cesarean delivery in nulliparous women with vertex presentation in labor at term. The secondary outcomes included spontaneous vaginal birth and maternal and neonatal safety. The main data source for the primary and secondary outcomes was the Alberta Perinatal Health Program database. The cesarean delivery rates were assessed using repeated measures mixed effects logistic regression applied to individual births. RESULTS: The analysis was based on 45,193 deliveries at intervention sites and 43,725 deliveries at control sites. There was no evidence of a decrease in the rate of cesarean delivery in association with the intervention (baseline-adjusted odds ratio, 0.94; 95% confidence interval [0.85-1.05]; P=.259). The rate of spontaneous vaginal delivery increased slightly (baseline-adjusted odds ratio, 1.10; 95% confidence interval, [1.01-1.18]; P=.024). We did not observe any differences in adverse maternal or neonatal outcomes. CONCLUSION: Cesarean delivery rates in nulliparous women were not reduced by the application of recent guidelines for the diagnosis of nonprogressive labor. Spontaneous vaginal delivery-a secondary outcome-was increased in the intervention group. The intervention appears to be safe.

Impact of dexmedetomidine in conjunction with a weaning protocol on post-surgical opioid use in a neonatal intensive care unit.

STUDY OBJECTIVE: To describe the impact of protocol-driven dexmedetomidine (and clonidine) use on opioid exposure in post-surgical neonates. DESIGN: Retrospective chart review. SETTING: A Level III, surgical NICU. PATIENTS: Surgical neonates who received clonidine or dexmedetomidine concomitantly with an opioid for sedation and/or analgesia post-operatively. INTERVENTION: Implementation of a standardized sedation/analgesia weaning protocol. MEASUREMENTS AND MAIN RESULTS: There were clinically, although not statistically, significant reductions in opioid wean duration (240 vs. 227 h, p = 0.82), total opioid duration (604 vs. 435 h, p = 0.23), and total opioid exposure (91 vs. 51 mg ME/kg, p = 0.13), and limited impact on NICU outcomes or pain/withdrawal scores with use of the protocol. Increases in use of medications in alignment with the protocol (e.g., scheduled acetaminophen and opioids weaned first) were noted. CONCLUSIONS: We have been unable to demonstrate a reduction in opioid exposure with use of alpha-2 agonists alone; addition of a weaning protocol showed a reduction in opioid duration and exposure (although not statistically significant). At this point, dexmedetomidine and clonidine should not be introduced outside standardized protocols with scheduled acetaminophen post-operatively.

Comparing Three Methods of Therapeutic Hypothermia Among Transported Neonates with Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) and associated multiorgan injury are significant causes of morbidity and mortality in term and near-term neonates. Therapeutic hypothermia (TH) is the current standard of care for neuroprotection in neonates with HIE. In our experience, the majority of babies born with HIE were found in nontertiary care facilities in our region, where effective methods of cooling during transport to tertiary care centers are desirable. Most centers initiate passive TH at referral hospitals, while active cooling is typically initiated during transport. The objective of this study was to evaluate the effectiveness of three methods of cooling during transport of neonates with HIE in southern Alberta. In this prospective cohort study, 186 neonates with HIE were transported between January 2013 and December 2021. Among the 186 neonates, 47 were passively cooled, 36 actively cooled with gel packs, and 103 cooled with a servo-controlled cooling device. The clinical characteristics were comparable for the three groups, with no difference in adverse events. Fifteen neonates (8%) died and 54 neonates (29%) suffered radiologically determined brain injury. Servo-controlled cooling was found to be superior to other methods in maintaining a target temperature without significant fluctuation during transport and with temperature in the target range on arrival at tertiary care facilities. The rate of overcooling was also lower in the servo-controlled group compared with other groups. There were no statistically significant differences between the groups in relation to mortality and brain MRI changes associated with HIE. Adjusting for GA, 10-minute Apgar score, base excess, HIE stage, and need for intubation during transport, passive cooling increased the odds of temperature fluctuation outside the range by 12-fold and gel pack cooling by 13-fold compared with servo-controlled cooling. The use of servo-controlled TH devices should be the preferred practice wherever feasible. (REB17-1334_REN3).

Identifying Genetic Susceptibility in Neonates With Hypoxic-Ischemic Encephalopathy: A Retrospective Case Series.

Neonatal hypoxic-ischemic encephalopathy is a clinical phenomenon that often results from perinatal asphyxia. To mitigate secondary neurologic injury, prompt initial assessment and diagnosis is needed to identify patients eligible for therapeutic hypothermia. However, occasionally neonates present with a clinical picture of hypoxic-ischemic encephalopathy without significant risk factors for perinatal asphyxia. We hypothesized that in patients with genetic abnormalities, the clinical manifestation of those abnormalities may overlap with hypoxic-ischemic encephalopathy criteria, potentially contributing to a causal misattribution. We reviewed 210 charts of infants meeting local protocol criteria for moderate to severe hypoxic-ischemic encephalopathy in neonatal intensive care units in Calgary, Alberta. All patients that met criteria for therapeutic hypothermia were eligible for the study. Data were collected surrounding pregnancy and birth histories, as well as any available genetic or metabolic testing including microarray, gene panels, whole-exome sequencing, and newborn metabolic screens. Twenty-eight patients had genetic testing such as microarray, whole-exome sequencing, or a gene panel, because of clinical suspicion. Ten of 28 patients had genetic mutations, including CDKL5, pyruvate dehydrogenase, CFTR, CYP21A2, ISY1, KIF1A, KCNQ2, SCN9A, MTFMT, and NPHP1. All patients lacked significant risk factors to support a moderate to severe hypoxic-ischemic encephalopathy diagnosis. Treatment was changed in 2 patients because of confirmed genetic etiology. This study demonstrates the importance of identifying genetic comorbidities as potential contributors to a hypoxic-ischemic encephalopathy phenotype in neonates. Early identification of clinical factors that support an alternate diagnosis should be considered when the patient's clinical picture is not typical of hypoxic-ischemic encephalopathy and could aid in both treatment decisions and outcome prognostication.

Variations in care of neonates during therapeutic hypothermia: call for care practice bundle implementation.

BACKGROUND: Therapeutic hypothermia (TH) is the gold-standard treatment for moderate and severe neonatal encephalopathy (NE). Care during TH has implications for long-term outcomes. Outcome variability exists among neonatal intensive care units (NICUs) in Canada, but care variations are not understood well. This study examines variations in care practices for neonates with NE treated with TH in NICUs across Canada. METHODS: A non-anonymous, web-based questionnaire was emailed to tertiary NICUs in Canada providing TH for NE to assess care practices during the first days of life and neurodevelopmental follow-up. RESULTS: Ninety-two percent (24/26) responded. Centres followed national guidelines regarding the use of the modified Sarnat score to assess the initial severity of NE, the need to initiate TH within the first 6 h of birth, and the importance of follow-up. However, other practices varied, including ventilation mode, definition/treatment of hypotension, routine echocardiography, use of sedation, use of electroencephalogram (EEG), MRI timing, placental analysis, and follow-up duration. CONCLUSIONS: NICUs across Canada follow available national guidelines, but variations exist in practices for managing NE during TH. Development and implementation of a consensus-based care bundle for neonates during TH may reduce practice variability and improve outcomes. IMPACT: This survey describes the current HIE care practices and variation among tertiary centres in Canada. Variations exist in the care of neonates with NE treated with TH in NICUs across Canada. This paper Identifies areas of variation that are not discussed in detail in the national guidelines and will help to set up quality improvement initiatives. Elucidating the variation in care practices calls for the creation and implementation of a national, consensus-based care bundle, with the objective to improve the outcomes of these critically ill neonates.

The Utility of Simulation-Based Training in Teaching Frontline Providers Modified Sarnat Encephalopathy Examination: A Randomized Controlled Pilot Trial.

BACKGROUND: Limited training in targeted neurological examination makes it challenging for frontline providers to identify newborns with perinatal asphyxia eligible for therapeutic hypothermia. This training is important in the era of telemedicine, where the experts can remotely guide further care of these newborns. METHODS: This randomized controlled pilot study was conducted in a South Indian tertiary hospital. Neonatal nurses, who had no previous hands-on experience in MSEE, were trained in modified Sarnat staging by a didactic teaching session using online teaching module. The nurses were then randomized into two groups for hands-on demonstration by the same trainer (low-fidelity mannequin versus a healthy term newly born infant). After the training period, MSEEs of a normal newborn were performed independently by nurses and were video recorded and assessed by three blinded neonatologists with expertise in neonatal neurology. A follow-up examination was performed by the same nurses after three months to assess skill retention. RESULTS: The 10 global ratings of the components of the MSEE were comparable among both groups in both initial and follow-up assessments. The overall diagnostic value was comparable between the simulation and traditional groups (93.75%, 94.11%, respectively). Follow-up examination after three months showed better skill retention in the simulation group (84%) compared with the traditional group (66.7%). CONCLUSIONS: Online-based and low-fidelity mannequin training was equally effective as the traditional method of teaching MSEE in term neonates.

Neuroprotective therapies in the NICU in term infants: present and future.

Outcomes of neonatal encephalopathy (NE) have improved since the widespread implementation of therapeutic hypothermia (TH) in high-resource settings. While TH for NE in term and near-term infants has proven beneficial, 30-50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. There is therefore a critical need to find additional pharmacological and non-pharmacological interventions that improve the outcomes for these children. There are many potential candidates; however, it is unclear whether these interventions have additional benefits when used with TH. Although primary and delayed (secondary) brain injury starting in the latent phase after HI are major contributors to neurodisability, the very late evolving effects of tertiary brain injury likely require different interventions targeting neurorestoration. Clinical trials of seizure management and neuroprotection bundles are needed, in addition to current trials combining erythropoietin, stem cells, and melatonin with TH. IMPACT: The widespread use of therapeutic hypothermia (TH) in the treatment of neonatal encephalopathy (NE) has reduced the associated morbidity and mortality. However, 30-50% of infants with moderate-to-severe NE treated with TH still suffer death or significant impairments. This review details the pathophysiology of NE along with the evidence for the use of TH and other beneficial neuroprotective strategies used in term infants. We also discuss treatment strategies undergoing evaluation at present as potential adjuvant treatments to TH in NE.

Placental pathology as a marker of brain injury in infants with hypoxic ischemic encephalopathy.

BACKGROUND: Hypoxic Ischemic Encephalopathy (HIE) can lead to devastating consequences for the affected infant. Although therapeutic cooling benefits infants with moderate and severe HIE, differentiating mild from moderate-severe HIE may be challenging. The placenta reflects the fetal intrauterine environment and may reveal underlying processes that affect brain injury. AIM: To describe placental histopathology using the Amsterdam Placental Workshop Group Criteria in different grades of HIE. STUDY DESIGN: Retrospective cohort. SUBJECTS: Infants admitted to a tertiary care neonatal intensive care unit with a diagnosis of HIE between 2011 and 2016. OUTCOME MEASURE: Maternal and neonatal clinical variables and placental histopathology using the Amsterdam Placental Workshop Group Criteria were compared between mild and moderate-severe HIE. Mann-Whitney or t-test or ꭓ2 were performed for bivariate associations as appropriate. To explain the relationship between placental pathology and severity of HIE odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using logistic regression models. RESULTS: Of the 73 infants in the study, 23 had mild and 50 moderate-sever HIE. There was no difference in maternal and neonatal characteristics except for sentinel events which were higher in the moderate- severe group. On placental histopathology, acute inflammation, including fetal inflammatory reaction (FIR) were significantly higher in the moderate-severe group. After adjusting for confounders, FIR remained significantly associated with moderate-severe HIE, ORs 6.29, 95 % CI 1.5-25. CONCLUSION: Our study demonstrates FIR in the placenta is associated with severity of HIE.

Neuroprotection care bundle implementation is associated with improved long-term neurodevelopmental outcomes in extremely premature infants.

OBJECTIVE: To study the impact of an evidence-based neuroprotection care (NPC) bundle on long-term neurodevelopmental impairment (NDI) in infants born extremely premature. STUDY DESIGN: An NPC bundle targeting predefined risk factors for acute brain injury in extremely preterm infants was implemented. We compared the incidence of composite outcome of death or severe neurodevelopmental impairment (sNDI) at 21 months adjusted age pre and post bundle implementation. RESULTS: Adjusting for confounding factors, NPC bundle implementation associated with a significant reduction in death or sNDI (aOR, 0.34; 95% CI 0.17-0.68; P = 0.002), mortality (aOR, 0.31; 95% CI (0.12-0.79); P = 0.015), sNDI (aOR, 0.37; 95% CI: 0.12-0.94; P = 0.039), any motor, language, or cognitive composite score <70 (aOR, 0.48; 95% CI: 0.26-0.90; P = 0.021). CONCLUSION: Implementation of NPC bundle targeting predefined risk factors is associated with a reduction in mortality or sNDI in extremely preterm infants.

Outcomes of infants with hypoxic-ischemic encephalopathy during COVID-19 pandemic lockdown in Canada: a cohort study.

PURPOSE: To evaluate change in the severity of hypoxic-ischemic encephalopathy (HIE) and associated morbidities between pre- and during COVID-19 pandemic periods in Canada. METHODS: We conducted a retrospective cohort study extracting the data from level-3 NICUs participating in Canadian Neonatal Network (CNN). The primary outcome was a composite of death in the first week after birth and/or stage 3 HIE (Sarnat and Sarnat). Secondary outcomes included rate and severity of HIE among admitted neonates, overall mortality, brain injury on magnetic resonance imaging (MRI), neonates requiring resuscitation, organ dysfunction, and therapeutic hypothermia (TH) usage. We included 1591 neonates with gestational age ≥ 36 weeks with HIE during the specified periods: pandemic cohort from April 1st to December 31st of 2020; pre-pandemic cohort between April 1st and December 31st of 2017, 2018, and 2019. We calculated the odds ratio (OR) and confidence intervals (CI). RESULTS: We observed no significant difference in the primary outcome (15% vs. 16%; OR 1.08; 95%CI 0.78-1.48), mortality in the first week after birth (6% vs. 6%; OR 1.10, 95%CI 0.69-1.75), neonates requiring resuscitation, organ dysfunction, TH usage, or rate of brain injury. In the ad hoc analysis, per 1000 live births, there was an increase in the rate of infants with HIE and TH use. CONCLUSIONS: Severity of HIE, associated morbidities, and mortality were not significantly different during the pandemic lockdown compared to a pre-pandemic period in Canada. Anticipated risks and difficulties in accessing healthcare have not increased the mortality and morbidities in neonates with HIE in Canada.

Variations in practices and outcomes of neonates with hypoxic ischemic encephalopathy treated with therapeutic hypothermia across tertiary NICUs in Canada.

OBJECTIVE: To 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 DESIGN: Retrospective 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. RESULTS: Of 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). CONCLUSION: Significant variations exist in practices and outcomes of HIE neonates treated with hypothermia across Canada.

Impact of quality improvement outreach education on the incidence of acute brain injury in transported neonates born premature.

OBJECTIVE: To evaluate impact of a quality improvement (QI) outreach education on incidence of acute brain injury in transported premature neonates. STUDY DESIGN: Neonates born at <33 weeks gestation outside the tertiary center were included. The QI intervention was a combination of neuroprotection care bundle, in-person visits, and communication system improvement. Descriptive and regression (adjusting for Gestational Age, Birth Weight, Gender, and antenatal steroids, Mode of delivery, Apgars at 5 minutes, Prophylactic indomethacin, PDA, and Inotropes use) analyses were performed. The primary outcome was a composite of death and/or severe brain injury on cranial ultrasound using a validated classification. RESULTS: 181 neonates studied (93 before and 88 after). The rate and adjusted odds of death and/or severe brain injury reduced significantly post intervention (30% vs 15%) and (AOR 0.36, 95%CI, 0.15-0.85, P = 0.02) respectively. CONCLUSION: Implementation of outreach education targeting neuroprotection can reduce acute brain injury in transported premature neonates.

Hemodynamic Quality Improvement Bundle to Reduce the Use of Inotropes in Extreme Preterm Neonates.

BACKGROUND: We evaluated the effect of the quality improvement (QI) bundle on the rate of inotrope use and associated morbidities. METHODS: We included inborn preterm neonates born at < 29 weeks admitted to level III NICU. We implemented a QI bundle focusing on the first 72 h from birth which included delayed cord clamping, avoidance of routine echocardiography, the addition of clinical criteria to the definition of hypotension, factoring iatrogenic causes of hypotension, and standardization of respiratory management. The rate of inotropes use was compared before and after implementing the care bundle. Incidence of cystic periventricular leukomalacia (cPVL) was used as a balancing measure. RESULTS: QI bundle implementation was associated with significant reduction in overall use of inotropes (24 vs 7%, p < 0.001), dopamine (18 vs 5%, p < 0.001), and dobutamine (17 vs 4%, p < 0.001). Rate of acute brain injury decreased significantly: acute brain injury of any grade (34 vs 20%, p < 0.001) and severe brain injury (15 vs 6%, p < 0.001). There was no difference in the incidence of cPVL (0.8 vs 1.4%, p = 0.66). Associations remained significant after adjusting for confounding factors. CONCLUSIONS: A quality improvement bundled approach resulted in a reduction in inotropes use and associated brain morbidities in premature babies.

Feeding during therapeutic hypothermia is safe and may improve outcomes in newborns with perinatal asphyxia.

OBJECTIVE: We assessed the impact of early enteral feeding introduction during therapeutic hypothermia on time to reach full enteral feeding (FEF) and other feeding related outcomes in infants born at ≥35 weeks gestational age and diagnosed with moderate to severe Hypoxic-Ischemic Encephalopathy. METHODS: A prospective cohort with historical control study, conducted on infants admitted to the Alberta Children's Hospital level III NICU in Calgary between January 2013 and December 2018. Infants were divided into 2 groups: (1) unfed group (UG), which was kept nil per os during the 72 h of therapeutic Hypothermia (TH), with subsequent introduction of feeding and gradual increase to FEF; (2) fed group (FG), which received feeding at 10 mL/kg/day during TH then increased gradually to FEF. Groups were compared for time to FEF and the type of milk they were being fed on discharge. Other gut related health risks such as NEC and sepsis were examined. RESULTS: During the study period, 146 infants received therapeutic hypothermia, of whom 75 in the UG and 71 in the FG. The FG compared to the UG received the first feed sooner after TH initiation (median 57 vs. 86.5 h, p < .001), reached FEF earlier (median 6 vs. 8 days, p = .012), had a higher rate of being fully fed in the first week of life (70 vs. 53%, p < .035), was kept NPO for shorter duration (median 2 vs. 4 days, p < .001), and had a higher rate of breast milk feeding at discharge (41 vs. 13%, p < .001). There were no cases of necrotizing enterocolitis or late onset sepsis in either group during the hospital stay. CONCLUSION: Minimal enteral feeding during therapeutic hypothermia appears to be safe and leads to a shorter time to FEF and higher rates of breast milk feeding at discharge.