Impact of a web-based module on trainees' ability to interpret neonatal cranial ultrasound.

BACKGROUND: Accurate interpretations of neonatal cranial ultrasound (CUS) studies are essential skills for physicians in neonatal intensive care units (NICUs) in order to properly diagnose and manage brain injury. However, these skills are not formally taught to pediatric and neonatal-perinatal medicine (NPM) trainees in Canada. Therefore, our study describes the design, implementation, and evaluation of a new web-based learning (WBL) module that focuses on teaching these skills. METHODS: Trainees' needs assessment survey, sent to all NPM and pediatrics trainees (n = 62), concluded that most of them feel uncomfortable with their ability to interpret CUS, highlighting the need for a new educational intervention. The needs assessment informed the development of the WBL module, which we evaluated using questionnaires and pre-and post-testing methods to measure participants' satisfaction, knowledge gain, skills development, and behaviour changes. Only trainees rotating through the NICU over 6 months (n = 23) were invited to participate in all the evaluation steps. We used the ADDIE instructional design model as a framework for this project. RESULTS: Respondents were very satisfied with the module, and their baseline knowledge increased significantly after studying and engaging with the module. The post-test score was 76% (p < 0.001) compared to the pre-test mean score of 42%. Tests for CUS interpretation skills assessment showed that 49% of pre-test answers were incorrect compared to 8% in the post-test (p < 0.001). Seventy-eight percent of trainees (n = 18) responded to a survey conducted a year after implementation, and 78% of the respondents (n = 14) reported that they still used these skills and shared this knowledge with junior trainees. CONCLUSION: A WBL module for teaching neonatal CUS interpretation considerably improved trainees' knowledge and enhanced their skills in interpreting neonatal CUS.

Effect of oxygen saturation targets on the incidence of bronchopulmonary dysplasia and duration of respiratory supports in extremely preterm infants.

BACKGROUND: Recent clinical practice changes in neonatal care resulted in higher, narrower oxygen saturation target ranges for preterm infants. The effect of targeting higher or lower oxygen saturations on respiratory outcomes of preterm infants and duration of hospitalization has not been extensively reviewed in the context of current care, but could have significant implications. METHODS: A multicentre retrospective cohort of 145 preterm infants was conducted; 105 had lower oxygen saturation targets (88 to 92%), 40 had higher targets (90 to 95%). The primary outcome was bronchopulmonary dysplasia (BPD). Secondary outcomes included duration of invasive/noninvasive respiratory support, oxygen therapy, and hospitalization. The primary outcome was compared using Fisher's exact test. Secondary outcomes were evaluated with survival analysis and Wilcoxon rank sum test. RESULTS: The difference in incidence of BPD in the lower (N=56, 53.3%) and higher saturation groups (N=14, 35.0%) was not statistically significant (relative risk [RR]=0.66 [0.41, 1.04], P=0.06). The difference in duration of mechanical ventilation in the lower (median 7.8 days, interquartile range [IQR] 3.7 to 15.9) and higher saturation groups (median 4.5, IQR 1.9 to 12.3) approached statistical significance (P=0.05). There were no statistically significant differences in the durations of other respiratory supports or hospital stay between the two groups. CONCLUSIONS: The results of this study approached statistical significance and suggest that higher, narrower oxygen saturation targets may result in a clinically important reduction in BPD incidence and duration of mechanical ventilation. These results require validation in a larger sample to refine optimal targets.

Sodium nitrite augments lung S-nitrosylation and reverses chronic hypoxic pulmonary hypertension in juvenile rats.

Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis of chronic neonatal pulmonary hypertension (PHT). Physiological NO signaling is regulated by S-nitrosothiols (SNOs), which act both as a reservoir for NO and as a reversible modulator of protein function. We have previously reported that therapy with inhaled NO (iNO) increased peroxynitrite-mediated nitration in the juvenile rat lung, although having minimal reversing effects on vascular remodeling. We hypothesized that sodium nitrite (NaNO2) would be superior to iNO in enhancing lung SNOs, thereby contributing to reversal of chronic hypoxic PHT. Rat pups were exposed to air or hypoxia (13% O2) from postnatal days 1 to 21. Dose-response prevention studies were conducted from days 1-21 to determine the optimal dose of NaNO2. Animals then received rescue therapy with daily subcutaneous NaNO2 (20 mg/kg), vehicle, or were continuously exposed to iNO (20 ppm) from days 14-21. Chronic PHT secondary to hypoxia was both prevented and reversed by treatment with NaNO2. Rescue NaNO2 increased lung NO and SNO contents to a greater extent than iNO, without causing nitration. Seven lung SNO proteins upregulated by treatment with NaNO2 were identified by multiplex tandem mass tag spectrometry, one of which was leukotriene A4 hydrolase (LTA4H). Rescue therapy with a LTA4H inhibitor, SC57461A (10 mg·kg-1·day-1 sc), partially reversed chronic hypoxic PHT. We conclude that NaNO2 was superior to iNO in increasing tissue NO and SNO generation and reversing chronic PHT, in part via upregulated SNO-LTA4H.

Resolution of refractory hypotension and anuria in a premature newborn with loss-of-function of ACE.

We present the investigation and management of a premature, hypotensive neonate born after a pregnancy complicated by anhydramnios to highlight the impact of early and informed management for rare kidney disease. Vasopressin was used to successfully treat refractory hypotension and anuria in the neonate born at 27 weeks of gestation. Next generation sequencing of a targeted panel of genes was then performed in the neonate and parents. Subsequently, two compound heterozygous deletions leading to frameshift mutations were identified in the angiotensin 1-converting enzyme gene ACE; exon 5:c.820_821delAG (p.Arg274Glyfs*117) and exon24: c.3521delG (p.Gly1174Alafs*12), consistent with a diagnosis of renal tubular dysgenesis. In light of the molecular diagnosis, identification, and treatment of associated low aldosterone level resulted in further improvement in renal function and only mild residual chronic renal failure is present at 14 months of age. Truncating alterations in ACE most often result in fetal demise during gestation or in the first days of life and typically as a result of the Potter sequence. The premature delivery, and serendipitous early treatment with vasopressin, and then later fludrocortisone, resulted in an optimal outcome in an otherwise lethal condition.

Topical nitroglycerin in neonates with tissue injury: A case report and review of the literature.

Peripheral tissue injury is one of the well-described morbidities associated with stays in the neonatal intensive care unit. Despite the potential long-term disability associated with this event, the current available therapeutic options remain very limited. Topical nitroglycerin has emerged as a promising agent for the treatment of tissue injury in infants. The present article includes a review of the currently available evidence on the use of topical nitroglycerin in the neonatal population, and describes a unique case involving successful use of 2% nitroglycerin in the late treatment of prolonged tissue ischemia in a newborn infant.

Les lésions des tissus périphériques font partie des morbidités bien décrites associées à des séjours à l'unité de soins intensifs néonatals. Malgré les invalidités potentielles à long terme qui y sont liées, les possibilités thérapeutiques demeurent très limitées. La nitroglycérine topique a émergé comme un agent prometteur dans le traitement des lésions tissulaires chez les nourrissons. Le présent article contient une analyse des données probantes sur l'utilisation de la nitroglycérine topique dans la population néonatale, ainsi que la description d'un cas unique portant sur l'utilisation réussie de nitroglycérine 2 % dans le traitement tardif d'une ischémie tissulaire prolongée chez un nouveau-né.

Brain Point of Care Ultrasound in Young Children Receiving Computed Tomography in the Emergency Department: A Proof of Concept Study.

Background: Point of Care Ultrasound (POCUS) is an important tool in pediatric emergency medicine. In neonatal intensive care medicine ultrasound is often used to evaluate the brains of sick neonates. In theory, POCUS could be used in the ED in young children to evaluate the brain for abnormal pathology. Objectives: To examine the ability of PEM faculty to use brain POCUS to identify clinically significant brain injuries in children with head injuries and/or abnormal neurological exams, and generate sensitivity and specificity of brain POCUS in assessing such findings. Methods: This study used a convenience sample of patients seen in a tertiary care pediatric centre who required a CT head. A team of physicians who were trained at a workshop for brain POCUS were on call to perform the POCUS while being blinded to the results of the CT. Results: 21 children were enrolled in the study. Five (24%) of the patients had a CT that was positive for intracranial bleeds. Of the 5 patients with a positive CT, 3 had a brain POCUS scan that was also positive. The two false negative brain POCUS scans were on patients with small bleeds (no surgical intervention required) on CT, as reported by radiology. The sensitivity of brain POCUS was 60% (CI 15% - 95%) with a specificity of 94% (CI 70%-100%). The diagnostic accuracy of brain POCUS was 86% (CI 64% - 97%). Conclusion: This small proof of concept study shows that brain POCUS is an imaging modality with reasonable sensitivity and specificity in identifying intracranial pathologies that are present on CT. Its use may be most beneficial to expedite definitive imaging and subspeciality involvement.

Risk of Bias Assessment in Non-Randomized Studies of Interventions for Premenstrual Syndrome: A Systematic Review.

Objective: Premenstrual syndrome (PMS) is a very prevalent condition that affects premenopausal women and can result in monthly debilitating emotional and physical symptoms. The objective of this systematic review was to determine which predictive factors were associated with an increased amount of bias in non-randomized studies (NRSs) of PMS. Materials and methods: A search of the EMBASE and Medline electronic databases was completed from January 1, 2010 to December 2021. The methodological quality of the included studies was independently evaluated and critically appraised using the Risk of Bias in Non-Randomized Studies - of Interventions (ROBINS-1) tool. Associations of different factors with the risk of bias levels were assessed using a univariate logistic regression. Odds ratio and 95% confidence interval (CI) were reported. Results: Of the 1668 studies, 38 were determined to be eligible for inclusion. The ROBINS-1 tool identified that 12 studies were of low/moderate risk of bias (31.6%) and 26 were of serious/critical risk (68.4%). Evidence of relationships between the ROBINS-1 score and impact factor (OR=0.20; 95% CI, 0.07 to 0.57; p= 0.003) and number of authors (OR=0.65; 95% CI, 0.43 to 0.99; p= 0.046) were identified, whereas no relationships were found with the number of citations, the sample size, the funding type, or the conflict-of-interest statement. Conclusion: The systematic review concludes that the methodological rigor of non-randomized studies of PMS can vary, with fewer authors and a lower impact factor showing evidence of association with a decreased quality of evidence.

Pulmonary Magnetic Resonance Imaging of Ex-Preterm Children with and without Bronchopulmonary Dysplasia.

Rationale: Children born prematurely, particularly those with bronchopulmonary dysplasia, have persisting lung abnormalities requiring longitudinal monitoring. Pulmonary ultrashort echo time magnetic resonance imaging (MRI) measurements may provide sensitive markers of persisting lung abnormalities and have not been evaluated in school-aged children born prematurely. Objectives: To compare pulmonary MRI and pulmonary function test measurements in preterm-born school-aged children with and without bronchopulmonary dysplasia. Methods: Children aged 7-9 years, born extremely preterm, with and without bronchopulmonary dysplasia, were recruited from three centers. Participants underwent pulmonary ultrashort echo time MRI and pulmonary function tests. Primary outcomes included total proton density and proton density at full expiration, measured using MRI. Multiple linear regression analysis was performed, adjusting for gestational age and bronchopulmonary dysplasia. Associations between MRI and pulmonary function were tested. Results: Thirty-five children were included in the primary analysis (24 with bronchopulmonary dysplasia, 11 without); 29 completed pulmonary function tests, of whom 11 (38%) had airflow limitation. Children with bronchopulmonary dysplasia had 44% (95% confidence interval [CI], 10-66%) lower mean total proton density (mean ± standard deviation, 3.6 ± 2.6) than those without (6.1 ± 4.0). Those with bronchopulmonary dysplasia had 25% (95% CI, 3-42%) lower proton density at full expiration than those without. Lower total proton density and proton density at full expiration were moderately correlated with greater residual volume, residual volume/total lung capacity, and lung clearance index (Spearman correlations for total proton density: -0.42, -0.57, and -0.53, respectively. Spearman correlations for proton density at full expiration: -0.28, -0.57, and -0.45, respectively). Conclusions: School-aged preterm-born children with bronchopulmonary dysplasia have parenchymal tissue abnormalities measured using ultrashort MRI proton density, compared with those without. MRI proton density correlated with pulmonary function measures indicative of gas trapping. Clinical trial registered with www.clinicaltrials.gov (NCT02921308).

Relative effectiveness and safety of pharmacotherapeutic agents for patent ductus arteriosus (PDA) in preterm infants: a protocol for a multicentre comparative effectiveness study (CANRxPDA).

INTRODUCTION: Patent ductus arteriosus (PDA) is the most common cardiovascular problem that develops in preterm infants and evidence regarding the best treatment approach is lacking. Currently available medical options to treat a PDA include indomethacin, ibuprofen or acetaminophen. Wide variation exists in PDA treatment practices across Canada. In view of this large practice variation across Canadian neonatal intensive care units (NICUs), we plan to conduct a comparative effectiveness study of the different pharmacotherapeutic agents used to treat the PDA in preterm infants. METHODS AND ANALYSIS: A multicentre prospective observational comparative-effectiveness research study of extremely preterm infants born <29 weeks gestational age with an echocardiography confirmed PDA will be conducted. All participating sites will self-select and adhere to one of the following primary pharmacotherapy protocols for all preterm babies who are deemed to require treatment.Standard dose ibuprofen (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals) irrespective of postnatal age (oral/intravenous).Adjustable dose ibuprofen (oral/intravenous) (10 mg/kg followed by two doses of 5 mg/kg at 24 hours intervals if treated within the first 7 days after birth. Higher doses of ibuprofen up to 20 mg/kg followed by two doses of 10 mg/kg at 24 hours intervals if treated after the postnatal age cut-off for lower dose as per the local centre policy).Acetaminophen (oral/intravenous) (15 mg/kg every 6 hours) for 3-7 days.Intravenous indomethacin (0.1-0.3 mg/kg intravenous every 12-24 hours for a total of three doses). OUTCOMES: The primary outcome is failure of primary pharmacotherapy (defined as need for further medical and/or surgical/interventional treatment following an initial course of pharmacotherapy). The secondary outcomes include components of the primary outcome as well as clinical outcomes related to response to treatment or adverse effects of treatment. SITES AND SAMPLE SIZE: The study will be conducted in 22 NICUs across Canada with an anticipated enrollment of 1350 extremely preterm infants over 3 years. ANALYSIS: To examine the relative effectiveness of the four treatment strategies, the primary outcome will be compared pairwise between the treatment groups using χ2 test. Secondary outcomes will be compared pairwise between the treatment groups using χ2 test, Student's t-test or Wilcoxon rank sum test as appropriate. To further examine differences in the primary and secondary outcomes between the four groups, multiple logistic or linear regression models will be applied for each outcome on the treatment groups, adjusted for potential confounders using generalised estimating equations to account for within-unit-clustering. As a sensitivity analysis, the difference in the primary and secondary outcomes between the treatment groups will also be examined using propensity score method with inverse probability weighting approach. ETHICS AND DISSEMINATION: The study has been approved by the IWK Research Ethics Board (#1025627) as well as the respective institutional review boards of the participating centres. TRIAL REGISTRATION NUMBER: NCT04347720.

Point of care ultrasound (POCUS) in Canadian neonatal intensive care units (NICUs): where are we?

OBJECTIVES: Despite increased evidence that point-of-care ultrasound (POCUS) has the potential to improve patient care in many clinical areas, the extent of use and training in POCUS in Canadian neonatal intensive care units (NICUs) has not been described in the literature. In this study, we aimed to explore the extent to which POCUS is being used and the need for a formal curriculum with defined POCUS competencies in the field of Neonatal-Perinatal Medicine (NPM). METHODS: We sent a cross-sectional electronic survey to all NPM program directors and fellows in Canada. All 13 Canadian NPM programs were invited to participate. Data were analyzed using descriptive statistics and qualitative content analysis. RESULTS: The response rate was 69% (n = 9) from program directors (PDs) and 29% (n = 25) from NPM fellows. Most respondents indicated regular use of POCUS in clinical practice and ready access to a portable ultrasound machine. The most common use for POCUS was targeted assessment of patent ductus arteriosus (PDA) and persistent pulmonary hypertension (PPHN). Only six PDs reported that POCUS skills are taught to trainees in their centers and only two PDs reported that a structured program existed. Barriers to POCUS structured training include a lack of trained personnel as well as insufficient time in the busy NPM curriculum. CONCLUSION: POCUS is widely used in Canadian NICUs. However, a formal curriculum and assessment of competencies in this area of neonatal clinical care are lacking.

Target oxygen saturation and development of pulmonary hypertension and increased pulmonary vascular resistance in preterm infants.

OBJECTIVE: Determine whether higher targeted oxygen levels are associated with reduced incidence of pulmonary hypertension (PH) and elevated pulmonary vascular resistance (PVR) in extremely premature infants. STUDY DESIGN: Retrospective chart review of 252 extremely preterm infants (<29 weeks), who underwent echocardiogram prior to discharge. PH rates were compared during periods (June 2012-May 2015 and June 2015-April 2016) when lower (88-92%) or higher (90-95%) oxygen saturation targets were used. PH was determined on echocardiography. The ratio of pulmonary artery acceleration time to right ventricular ejection time was computed, with values <0.31 indicative of elevated PVR. Survival analysis compared the effects of oxygen saturation group on development/resolution of PH and elevated PVR. RESULTS: The higher saturation group had significantly lower risk of developing PH (hazard ratio (HR) = 0.50, 95%CI 0.26-0.95; P = 0.03) or elevated PVR (HR = 0.55, 95%CI 0.38-0.81; P = 0.002), compared to the lower oxygen saturation group. Median time to PH development was significantly shorter in the lower saturation group than in the higher saturation group (5 days vs 12 days; P = 0.02), as was time to development of elevated PVR (4 days vs 6 days; P < 0.001). Duration of PH (P = 0.12) and elevated PVR (P = 0.86) did not differ significantly between groups. Cumulative incidence of PH (P = 0.04) and elevated PVR (P = 0.01) at 36 weeks post-menstrual age was significantly lower in the high saturation group compared to the lower saturation group. CONCLUSION: Higher targeted oxygen saturation was associated with reduced risk of PH or elevated PVR in extremely preterm infants compared to lower oxygen saturation target.

Influence of timing of initiation of therapeutic hypothermia on brain MRI and neurodevelopment at 18 months in infants with HIE: a retrospective cohort study.

OBJECTIVE: To examine the influence of timing of initiation of therapeutic hypothermia (TH) on brain injury on MRI and on neurodevelopmental outcomes at 18 months. DESIGN: Retrospective cohort study. SETTING: Tertiary neonatal intensive care unit in Ontario, Canada. PATIENTS: Ninety-one patients with hypoxic ischaemic encephalopathy (HIE) were included, 54 in the early TH group and 37 in the late TH group. INTERVENTION: Whole-body hypothermia administered for 72 hours, initiated either before 3 hours of life (early TH) or between 3 and 6 hours of life (late TH). MAIN OUTCOME MEASURES: Brain injury on MRI after TH (assessed by two neuroradiologists), and neurodevelopmental outcomes at 18 months old. RESULTS: TH was initiated at a median time of 1.4 hours (early TH) and 4.4 hours (late TH). Sixty-four neonates (early TH=36, late TH=28) survived and completed neurodevelopmental assessment at 18 months. Neonates in the early TH group received more extensive resuscitation than neonates in the late TH group (p=0.0008). No difference was observed between the two groups in the pattern or severity of brain injury on MRI, or in the neurodevelopmental outcomes at 18 months. The non-survivors (n=16) had lower Apgar scores at 10 min, more extensive resuscitation, suffered from more severe HIE and had significantly more abnormal cerebral function monitoring. CONCLUSION: In this retrospective cohort study, TH initiated early was associated neither with a difference in brain injury on MRI nor better neurodevelopmental outcomes at 18 months.

Disseminated Neonatal Herpes Simplex Virus Type 1 After a Water Birth.

Neonatal herpes simplex virus (NHSV) infections are associated with significant morbidity and mortality. Numerous factors influence the transmission of HSV infection to newborns; however, immersion in water during labor has received very little attention as a possible risk factor despite the increasing popularity of water births. We report a case of disseminated NHSV type 1 infection, possibly acquired during a water birth. The purpose of this report is to alert healthcare providers to this potential route of transmission and to highlight the importance of screening guidelines for HSV before a water birth. Furthermore, it is essential to consider NHSV infection in any febrile infant who is not responding to standard empirical antibiotic management, even in the absence of herpetic lesions.

Neonatal Ethics Teaching Program - Scenario-Oriented Learning in Ethics: Announcing the Diagnosis of Trisomy 21.

INTRODUCTION: Delivering unexpected news to families can lead to emotionally charged conversations that cause discomfort and feelings of ineffectiveness in pediatric postgraduate trainees. Although prenatal screening exists, over 80% of trisomy 21 diagnoses continue to be made postnatally to unsuspecting parents who report a desire for better communication from health care professionals when they first receive the news of their child's diagnosis. Recognizing this area for improvement as reported in the literature, as well as the expressed desire from fellows in the University of Ottawa neonatal-perinatal medicine program for additional protected time to preemptively practice such disclosures, this trisomy 21 Scenario-Oriented Learning in Ethics workshop was developed. METHODS: During the workshop, trainees are introduced to an evidence-based communication framework that provides them with strategies to facilitate clear knowledge translation and promote rapport with families for this specific clinical scenario. Participants are divided into small groups and practice disclosing a trisomy 21 diagnosis to a standardized patient in the role of a new mother. Each small group is supported by two trained facilitators who are experts in delivering life-altering news. RESULTS: The pilot workshop was completed by 21 postgraduate trainees from the University of Ottawa. Qualitative evaluations were overwhelmingly positive, with feedback indicating high levels of perceived usefulness for the workshop. DISCUSSION: By preemptively practicing evidence-based communication, we hope to increase trainee confidence and preparation for trisomy 21 disclosures and improve parents' feelings regarding the quality of communication and support provided while receiving real-life trisomy 21 diagnoses.

ASQ3 and/or the Bayley-III to support clinicians' decision making.

BACKGROUND: Appropriate tools are essential to support a clinician's decision to refer very preterm infants to developmental resources. Streamlining the use of developmental assessment or screening tools to make clinical decisions offers an alternative methodology to help to choose the most effective way to assess this very high-risk population. OBJECTIVE: To examine the influence of the Ages and Stages Questionnaire-3rd edition (ASQ3) and the Bayley Scales of Infant Development-3rd edition (Bayley-III) scores within a clinically-based decision-making process. METHODS: This retrospective cohort study includes children born at less than 29 weeks gestation who had completed both psychologist-administered Bayley-III and physician-observed ASQ3 assessments at 18 months corrected age. Theoretical referral decisions (TRDs) based on each assessment results were formulated, using cut-off scores between the lower first and second standard deviation values and below the lower second standard deviation values. TRDs to refer to developmental resources were evaluated in light of the multidisciplinary team's actual final integrated decisions (FID). RESULTS: Complete data was available for 67 children. The ASQ3 and the Bayley-III had similar predictive value for the FID, with comparable kappa values. Comparisons of the physicians' and psychologists' TRDs with the FIDs demonstrated that the ASQ3 in conjunction with the medical and socio-familial findings predicted 93% of referral decisions. CONCLUSION: Taking into consideration potential methodological biases, the results suggest that either ASQ3 or Bayley-III, along with socio-environmental, medical and neurological assessment, are sufficient to guide the majority of clinicians' decisions regarding referral for specialty services. This retrospective study suggests that the physician-supervised ASQ3 may be sufficient to assess children who had been extremely preterm infants for referral purposes. The findings need to be confirmed in a larger, well-designed prospective study to minimize and account for potential sources of bias.