Congenital dyserythropoietic anemia type IV in the genetic era: A rare neonatal case report of rapid identification with a review of the literature.

Congenital dyserythropoietic anemia type IV (CDAIV) is a rare inherited hematological disorder, presenting with severe anemia due to altered erythropoiesis and hemolysis, with variable needs for recurrent transfusions. We present a case of a transfusion-dependent male newborn who presented at birth with severe hemolytic anemia, and required an intrauterine transfusion. Genetic testing rapidly identified a Kruppel-like factor 1 (KLF1) pathogenic variant (c.973G>A, p.E325K), known to be causative for CDAIV. This case highlights the advantages of next-generation sequencing testing for congenital hemolytic anemia: diagnostic speed, guidance on natural history, and optimized clinical management and anticipatory guidance for parents and clinicians. Additionally, we reviewed the literature for all CDAIV cases.

Vulnerabilities in clinician-parent exchanges and the cascade of communication traps: a review.

This review considers parent-clinician interactions that are associated with vulnerabilities in communication and what we refer to as 'communication traps'. Communication traps are defined by high-stress situations with affect-laden subject matter that can lead to progressively dysfunctional communications/exchanges that are avoidable. While this framework was developed in neonatology, it can be applied to other clinical practices.Communication competencies in paediatrics require the rapid development of a therapeutic alliance between parents and clinicians to ensure the provision of best care to their infants. In order to facilitate parent-clinician communication, our framework focuses clinicians' attention on the affective, behavioural and cognitive (ABC) cues that are indicative of real, apparent or potential communication traps. Strategies are provided to slow down clinicians' responses to more effectively consider ABC cues that suggest if patients/parents have failed to engage or disengage from a situation. This framework is illustrated by presenting a narrative synthesised from a number of experiences that clinicians have encountered. This review identifies key decision points in the communication process that, if left unaddressed, can cascade into communication traps which may be difficult to escape.Using results from communication studies and psychological research, our framework was developed to identify key decision points for ABC cues that can be used to prevent falling into communication traps.

Proteomics Profiling of Stool Samples from Preterm Neonates with SWATH/DIA Mass Spectrometry for Predicting Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is a life-threatening condition for premature infants in neonatal intensive care units. Finding indicators that can predict NEC development before symptoms appear would provide more time to apply targeted interventions. In this study, stools from 132 very-low-birth-weight (VLBW) infants were collected daily in the context of a multi-center prospective study aimed at investigating the potential of fecal biomarkers for NEC prediction using proteomics technology. Eight of the VLBW infants received a stage-3 NEC diagnosis. Stools collected from the NEC infants up to 10 days before their diagnosis were available for seven of them. Their samples were matched with those from seven pairs of non-NEC controls. The samples were processed for liquid chromatography-tandem mass spectrometry analysis using SWATH/DIA acquisition and cross-compatible proteomic software to perform label-free quantification. ROC curve and principal component analyses were used to explore discriminating information and to evaluate candidate protein markers. A series of 36 proteins showed the most efficient capacity with a signature that predicted all seven NEC infants at least a week in advance. Overall, our study demonstrates that multiplexed proteomic signature detection constitutes a promising approach for the early detection of NEC development in premature infants.

Medications to manage infant pain, distress and end-of-life symptoms in the immediate postpartum period.

INTRODUCTION: Perinatal palliative care (PnPC) is a growing field where healthcare providers from multiple disciplines are supporting families and providing holistic care for their babies with life-limiting illnesses. It is important to have an approach that includes the standardized management of end-of-life symptoms that are anticipated around the time of birth. AREAS COVERED: A need was identified to develop medication orders for the initial pharmacological management of symptoms at end-of-life for infants with life-limiting conditions intended for use outside of an intensive care setting. The choice of medications was based on a review of the literature, discussion with content experts and guided by their ease of use, accessibility and noninvasive route of delivery. The recommendations can be used as a guide for the initial management of common symptoms encountered in perinatal palliative care. EXPERT OPINION: There are studies looking at many qualitative aspects of perinatal palliative care including perceptions of care, decision-making, and bereavement; however, few specifically focus on symptom management in the delivery room and postpartum ward settings. There is a need for standardization of the medical management of infants born with life-limiting conditions whose parents choose to pursue palliative care.

Lipocalin-2 and calprotectin as stool biomarkers for predicting necrotizing enterocolitis in premature neonates.

BACKGROUND: Necrotizing enterocolitis (NEC) is a major challenge for premature infants in neonatal intensive care units and efforts toward the search for indicators that could be used to predict the development of the disease have given limited results until now. METHODS: In this study, stools from 132 very low birth weight infants were collected daily in the context of a multi-center prospective study aimed at investigating the potential of fecal biomarkers for NEC prediction. Eight infants (~6%) received a stage 3 NEC diagnosis. Their stools collected up to 10 days before diagnosis were included and matched with 14 non-NEC controls and tested by ELISA for the quantitation of eight biomarkers. RESULTS: Biomarkers were evaluated in all available stool samples leading to the identification of lipocalin-2 and calprotectin as the two most reliable predicting markers over the 10-day period prior to NEC development. Pooling the data for each infant confirmed the significance of lipocalin-2 and calprotectin, individually and in combination 1 week in advance of the NEC clinical diagnosis. CONCLUSIONS: The lipocalin-2 and calprotectin tandem represents a significant biomarker signature for predicting NEC development. Although not yet fulfilling the "perfect biomarker" criteria, it represents a first step toward it. IMPACT: Stool biomarkers can be used to predict NEC development in very low birth weight infants more than a week before the diagnosis. LCN2 was identified as a new robust biomarker for predicting NEC development, which used in conjunction with CALPRO, allows the identification of more than half of the cases that will develop NEC in very low birth weight infants. Combining more stool markers with the LCN2/CALPRO tandem such as PGE2 can further improve the algorithm for the prediction of NEC development.

Extremely low gestational age infants: Developing a multidisciplinary care bundle.

BACKGROUND: Clinical experience in managing extremely low gestational age infants, particularly those born <24 weeks' gestation, is limited in Canada. Our goal was to develop a bedside care bundle for infants born <26 weeks' gestation, with special considerations for infants of <24 weeks, to harmonize and improve quality of care. METHODS: We created a multidisciplinary working group with experience in caring for preterm infants, searched the literature from 2000 to 2019 to identify best practices for the care of extremely preterm infants and consulted colleagues across Canada and internationally. Iterative improvements were made following the Plan-Do-Study-Act methodology. RESULTS: A care bundle, created in October 2015, was divided into three time periods: initial resuscitation/stabilization, the first 72 hours and days 4 to 7, with each period subdivided in 8 to 12 care themes. Revisions and practice changes were implemented to improve skin integrity, admission temperature, timing of initiation of feeds, reliability of transcutaneous CO2 monitoring and ventilation. Of 127 infants <26 weeks admitted between implementation and end of 2019, 78 survived to discharge (61%). CONCLUSION: It will be important to determine, with ongoing auditing and further evaluation, whether our care bundle led to improvements of short- and long-term outcomes in this population. Our experience may be useful to others caring for extremely low gestational age infants.

Parents' Views to Strengthen Partnerships in Newborn Intensive Care.

Background: Parental involvement in their newborn's neonatal intensive care reduces stress and helps with the parent-child attachment, transition to home, and future development. However, parents' perspectives are not often sought or considered when adapting family-centered care in neonatal intensive care units (NICUs). Aim: To identify what parents believe helps or hinders their involvement in their newborn's care when admitted to our Level 3B NICU. Methods: Between August and October 2018, nine mothers and one father were interviewed during three 60- to 90-min audiotaped focus groups using a semi-structured interview tool. From the content analysis of the verbatims, three reviewers identified key themes that affected how involved parents could be in their newborn's care. Results: Parents provided examples of factors that facilitated or restricted their involvement. The analysis identified themes: (1) parent-staff interactions, (2) supportive/trustworthy healthcare professionals, (3) consistency in care and caring staff, (4) family, couple, and peer support, (5) newborn status, (6) resources and education for parents, (7) the NICU environment, and (8) academic and research participation. Conclusion: We identified a conceptual framework to allow our NICU team to prioritize working strategies to strengthen parental involvement in newborn care. In addition to implementing ways to involve parents, we need to address parents' satisfaction with their participation. These findings may help other investigators explore parents' expectations toward their NICU experience.

"When in Doubt, Ask the Patient": A Quantitative, Patient-Oriented Approach to Formative Assessment of CanMEDS Roles.

Introduction: Since the introduction of competency-based frameworks into postgraduate medical curricula, educators have struggled to implement robust assessment tools that document the progression of necessary skills. The global movement towards competency-based medical education demands validated assessment tools. Our objective was to provide validity evidence for the Ottawa CanMEDS Competency Assessment Tool (OCCAT), designed to assess clinical performance in the communicator, professional, and health advocate CanMEDS roles. Methods: We developed the OCCAT, a 29-item questionnaire informed by specialty-specific Entrustable Professional Activities and consultation with stakeholders, including patients. Our sample included nine neonatal-perinatal medicine and maternal fetal medicine fellows rotating through antenatal high-risk clinics at the Ottawa Hospital. Following 70 unique encounters, the OCCAT was completed by patients and learners. Generalizability theory was used to determine overall reliability of scores. Differences in self and patient ratings were assessed using analyses of variance. Results: Generalizability analysis demonstrated that both questionnaires produced reliable scores (G-coefficient > 0.9). Self-scores were significantly lower than patient scores across all competencies, F(1, 6) = 13.9, p = .007. Variability analysis demonstrated that trainee scores varied across all competencies, suggesting both groups were able to recognize competencies as distinct and discriminate favorable behaviors belonging to each. Discussion: Our findings lend support to the movement to integrate self-assessment and patient feedback in formal evaluations for the purpose of enriched learner experiences and improved patient outcomes. We anticipate that the OCCAT will facilitate bridging to competency-based medical education.

Review of Methodological Approaches to Human Milk Small Extracellular Vesicle Proteomics.

Proteomics can map extracellular vesicles (EVs), including exosomes, across disease states between organisms and cell types. Due to the diverse origin and cargo of EVs, tailoring methodological and analytical techniques can support the reproducibility of results. Proteomics scans are sensitive to in-sample contaminants, which can be retained during EV isolation procedures. Contaminants can also arise from the biological origin of exosomes, such as the lipid-rich environment in human milk. Human milk (HM) EVs and exosomes are emerging as a research interest in health and disease, though the experimental characterization and functional assays remain varied. Past studies of HM EV proteomes have used data-dependent acquisition methods for protein detection, however, improvements in data independent acquisition could allow for previously undetected EV proteins to be identified by mass spectrometry. Depending on the research question, only a specific population of proteins can be compared and measured using isotope and other labelling techniques. In this review, we summarize published HM EV proteomics protocols and suggest a methodological workflow with the end-goal of effective and reproducible analysis of human milk EV proteomes.

IL-17-related signature genes linked to human necrotizing enterocolitis.

OBJECTIVE: Necrotizing enterocolitis (NEC) is the most frequent life-threatening gastrointestinal disease experienced by premature infants in neonatal intensive care units all over the world. The objective of the present study was to take advantage of RNA-Seq data from the analysis of intestinal specimens of preterm infants diagnosed with NEC. Function enrichments with Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes were used to analyse previous data in order to identify biological and functional processes, which could provide more insight into the pathogenesis of NEC in infants. RESULTS: Gene set enrichment analysis indicated that the most significant biological pathways over-represented in NEC neonates were closely associated with innate immune functions. One of the striking observations was the highly modulated expression of inflammatory genes related to the IL-17 pathway including such as pro-inflammatory cytokines (CXCL8), chemokines (CXCL5 and CXCL10) and antimicrobials (DEF5A, DEF6A, LCN2, NOS2) in the intestine of neonates diagnosed with NEC. Interestingly, the increase in IL-17 expression appeared to be under the IL-17F form, as reported in Crohn's disease, another inflammatory bowel disease. Further investigation is thus still needed to determine the precise role of IL-17F and its downstream targets in NEC.

Fulminant Necrotizing Soft-tissue Infection in an Extremely Low Gestational Age Infant.

We report a case of rapidly progressive necrotizing skin and soft-tissue infection caused by Bacillus cereus in an extremely low for gestational age infant. This case reminds clinicians to consider this opportunistic pathogen as the etiologic agent in fulminant necrotizing infections in vulnerable hosts, and to institute appropriate therapy in a timely fashion.

Case report: necrotizing enterocolitis with a transverse colonic perforation in a 2-day old term neonate and literature review.

BACKGROUND: Necrotizing enterocolitis (NEC), while classically discussed in preterm and low birth weight neonates, also occurs in the term infant and accounts for 10% of all NEC cases. Despite there being fewer reported cases of NEC in term infants, these presentations demonstrate differences in the onset, severity and risk factors from the classic presentation observed in premature infants. We present a novel case of term NEC that contravenes the reported literature making departures from clinical presentation, risk factors and location of perforation in an otherwise healthy term two-day old infant born after an uncomplicated pregnancy who presented with hematochezia. CASE PRESENTATION: A healthy term baby born after an uneventful pregnancy presented with bloody stool at 2 days of life who was otherwise well. Investigations revealed pneumoperitoneum from a large proximal transverse colonic perforation secondary to NEC. No typical risk factors for NEC were found. CONCLUSION: Given the life-threatening potential of an unrecognized perforation we recommend the inclusion of NEC on the differential for neonatal hematochezia.

Intrapartum Asphyxiated Newborns Without Fetal Heart Rate and Cord Blood Gases Abnormalities: Two Case Reports of Shoulder Dystocia to Reflect Upon.

Our report covers two cases of severe hypoxic-ischemic encephalopathy in newborns whose birth was complicated by shoulder dystocia. In both cases, there were inconsistencies observed among cardiotocographic traces, baby's clinical conditions at birth, and umbilical cord blood gases. Namely, normal cardiotocographic monitoring and cord pH > 7, in spite of the fact that the newborns were severely depressed at birth and their blood gases evaluated within 1 h from birth showed a severe metabolic acidosis. Moreover, one of the two newborns displayed moderately low hemoglobin levels. Metabolic and infectious causes were ruled out. Both newborns developed severe hypoxic-ischemic encephalopathy and received therapeutic hypothermia for 72 h. Both survived, one with a severe dystonic cerebral palsy whereas the other developed only a mild developmental delay in language. Cardiac asystole theory could explain these two cases, reinforcing the need for specific resuscitation guidelines for infants experiencing a birth complicated by shoulder dystocia.

Economic Analysis of Exclusive Human Milk Diets for High-Risk Neonates, a Canadian Hospital Perspective.

Background: There is increasing evidence that premature newborns and infants with low birth weight can benefit substantially from an exclusive human milk-based diet (EHMD), consisting of human milk supplemented with a pasteurized donor human milk-derived fortifier. However, compared with the standard infant diet, EHMD also represents a significant added cost to the hospital and/or health system, thereby raising important questions about the economic feasibility of incorporating EHMD into newborn care. Design: We conducted a cost analysis and estimated the potential cost savings to a Canadian tertiary hospital based on the attributable complications averted from EHMD among low-weight neonates. A meta-analysis was performed to derive input parameters. A probabilistic analysis was conducted to determine the probability that EHMD is cost saving and 95% confidence interval (CI) around our estimates. Results: Our findings show that providing EHMD to preterm infants under 750 g at birth and at the highest risk of developing major complications is likely to be cost saving in the amount of $107,567 (95% CI: -145,229 to 360,362) per year. Extending EHMD to higher weight classes may be economically feasible depending on the pricing of the human milk-derived fortifier and the baseline risk of complications in the hospital setting. Conclusions: This comprehensive study provides critical insight for hospital-based decision makers to evaluate the potential gains and uncertainties associated with improved nutritional care for neonatal patients.

Neonatal necrotizing enterocolitis: a case series examining clinical diagnosis with discrepant versus concordant autopsy results.

OBJECTIVE: The objective of this study is to determine whether rapidity of death in necrotizing enterocolitis (NEC) increased odds of discordance between clinical and pathological diagnosis. STUDY DESIGN: Retrospective case-series study including preterm infants admitted to the NICU. RESULTS: Twenty-two infants met the selection criteria. Gross pathologic evidence of NEC was present in 1/6 cases (17%) where demise occurred <12 h after onset of symptoms, 3/5 cases (60%) within 12-24 h, and 8/11 cases (73%) in >24 h. Histological evidence of necrosis was present in 4/6 (67%) cases when death occurred <12 h, 4/5 (80%) in 12-24 h, and 9/11 (82%) in >24 h. The percentage with gross pathologic evidence showed a monotonic trend (P = 0.031), while the trend was less clear for histologic findings (P = 0.496). CONCLUSION: Pathologic features of cell death may not have had sufficient time to develop. This study could reassure both healthcare providers and families when pathologic and clinical diagnoses are not consistent.

Needs assessment of ethics and communication teaching for neonatal perinatal medicine programs in Canada.

OBJECTIVE: To explore ethics education needs in Canadian Neonatal Perinatal Medicine (NPM) training programs. METHODS: A retrospective review of NPM trainees' performance at the National NPM Objective Structured Clinical Examination (OSCE) was undertaken for 2012 to 2017 and two distinct cross-sectional online surveys were carried out. One survey targeted recently graduated neonatologists (RGNs) who completed 2 years' training in a Canadian NPM program between 2010 and 2015; the other survey was sent to Canadian NPM training program directors (PDs). The domains of interest were: perception of education, ethics and communication topics, educational strategies, assessment of trainees' competencies, and barriers to neonatal ethics education. RESULTS: NPM trainees generally performed less well in stations involving ethics and communication relative to other domains on the National OSCE. Forty-seven RGNs (44.3%) and 12 PDs (92.3%) completed the survey. Over 90% of PDs and RGNs agreed on the importance of training in ethics and communication. Both groups highly valued training on topics related to communication. Preferred teaching strategies were experiential: observation and feedback. PDs mentioned the importance of using validated tools to regularly and formally assess trainees. They recognized challenges in regard to financial resources, physical space, and faculty training in patient-physician communication. CONCLUSIONS: National OSCE results indicate the need to improve neonatal ethics and communication training in Canadian NPM programs. RGNs and PDs identified important topics, as well as teaching and evaluation strategies. These results can be used to develop a training program for ethics and communication in NPM.

Catch the moment: The power of turning mistakes into 'precious' learning opportunities.

We developed a series of small group workshops that aim to facilitate communication during very challenging ethically sensitive scenarios within a Neonatal-Perinatal Medicine (NPM) postgraduate curriculum at the University of Ottawa. These workshops are called Scenario-Oriented Learning in Ethics (SOLE). This educational intervention aims to focus attention on the learner's needs and to help them recognize, define, and view each communicative or behavioural mistake as an occasion to achieve a personal-defined learning goal in a controlled environment free of judgement. The goal of this commentary is to describe the importance of timely interruptions during the scenarios allowing mini concurrent-guided debriefing-feedback by focusing upon trainees' communication mistakes, utilizing them as valuable learning opportunities.

Testing a Communication Assessment Tool for Ethically Sensitive Scenarios: Protocol of a Validation Study.

BACKGROUND: Although well-designed instruments to assess communication during medical interviews and complex encounters exist, assessment tools that differentiate between communication, empathy, decision-making, and moral judgment are needed to assess different aspects of communication during situations defined by ethical conflict. To address this need, we developed an assessment tool that differentiates competencies associated with practice in ethically challenging situations. The competencies are grouped into three distinct categories: communication skills, civility and respectful behavior, clinical and ethical judgment and decision-making. OBJECTIVE: The overall objective of this project is to develop an assessment tool for ethically sensitive scenarios that measures the degree of respect for the attitudes and beliefs of patients and family members, the demands of clinical decision-making, and the success in dealing with ethical conflicts in the clinical context. In this article, we describe the research method we will use during the pilot-test study using the neonatal context to provide validity evidence to support the features of the Assessment Communication Tool for Ethics (ACT4Ethics) instrument. METHODS: This study is part of a multiphase project designed according to modern validity principles including content, response process, internal structure, relation to other variables, and social consequences. The design considers threats to validity such as construct underrepresentation and factors exerting nonrandom influence on scores. This study consists of two primary steps: (1) train the raters in the use of the new tool and (2) pilot-test a simulation using an Objective Structured Clinical Examination. We aim to obtain a total of 90 independent assessments based on the performance of 30 trainees rated by 15 trained raters for analysis. A comparison of raters' responses will allow us to compute a measure of interrater reliability. We will additionally compare the results of ACT4Ethics with another existing instrument. RESULTS: This study will take approximately 18 months to complete and the results should be available by September 2019. CONCLUSIONS: ACT4Ethics should allow clinician-teachers to assess and monitor the development of competency of trainees' judgments and communication skills when facing ethically sensitive clinical situations. The instrument will also guide the provision of meaningful feedback to ensure that trainees develop specific communication, empathy, decision-making, and ethical competencies. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/12039.

Early Onset Allergic Proctitis in a Preterm Neonate-A Case Report and Review of the Literature.

Cow's milk protein allergy/intolerance (CMPA/CMPI) is a common entity in the pediatric population with a nonspecific presentation ranging from gastrointestinal symptoms to systemic manifestations. Most infants with CMPI are term, and symptoms often appear in the week following the introduction of cow's milk-based formula. There is typically a significant delay in the onset of milk allergy in premature infants compared to full term. We report a rare case of a premature neonate who presented with symptoms of CMPA within the first 2 days of life.

A Newborn with Simmering Bleeding after Circumcision.

We present a case of a healthy male neonate born at term, circumcised on Day 1 of life. Facing ongoing bleeding at the incision site, the baby was transferred to a level III neonatal intensive care unit for further investigation and management. His family history was unremarkable for bleeding disorders. On arrival, the baby was hemodynamically stable with abnormal coagulation values. Further investigations revealed a diagnosis compatible with severe hemophilia A. He deteriorated on Day 2, developing acute severe anemia which required two red blood cell transfusions. This rare but potentially fatal event reminds clinicians to remain extremely vigilant with minor surgical procedures such as circumcision even in the absence of family history.