A Deep Intronic PKHD1 Variant Identified by SpliceAI in a Deceased Neonate With Autosomal Recessive Polycystic Kidney Disease.

The etiologies of newborn deaths in neonatal intensive care units usually remain unknown, even after genetic testing. Whole-genome sequencing, combined with artificial intelligence-based methods for predicting the effects of non-coding variants, provide an avenue for resolving these deaths. Using one such method, SpliceAI, we identified a maternally inherited deep intronic PKHD1 splice variant (chr6:52030169T>C), in trans with a pathogenic missense variant (p.Thr36Met), in a newborn who died of autosomal recessive polycystic kidney disease at age 2 days. We validated the deep intronic variant's impact in maternal urine-derived cells expressing PKHD1. Reverse transcription polymerase chain reaction followed by Sanger sequencing showed that the variant causes inclusion of 147bp of the canonical intron between exons 29 and 30 of PKHD1 into the mRNA, including a premature stop codon. Allele-specific expression analysis at a heterozygous site in the mother showed that the mutant allele completely suppresses canonical splicing. In an unrelated healthy control, there was no evidence of transcripts including the novel splice junction. We returned a diagnostic report to the parents, who underwent in vitro embryo selection.

Parent Perspectives on Communication Quality in the Neonatal Intensive Care Unit.

BACKGROUND: Though prior literature has demonstrated that communication in the Neonatal Intensive Care Unit (NICU) needs to be improved, in-depth descriptions of parents' views of NICU communication are lacking. PURPOSE: We sought (1) to explore parent perceptions of communication in the NICU and (2) to understand parents' communication needs and preferences. METHODS: We conducted in-depth semi-structured cognitive interviews utilizing concurrent probes with parents of 10 patients in our urban level IV Neonatal Intensive Care Unit over a period of 4 months (July 2021-October 2021). Interview questions were derived from the Quality of Communication scale. We conducted thematic analysis of interview transcripts modeled after work by Braun and Clarke. RESULTS: Four overarching themes were identified: Strengths, Challenges, People, and Coping Strategies. Parents reported a range of communication quality in the NICU. Results revealed that the first 48 hours of NICU hospitalization represent a period of vulnerability and uncertainty for parents. Parents value clear yet hopeful communication about a baby's clinical status and expected course. IMPLICATIONS FOR PRACTICE AND RESEARCH: We hope that the concrete findings from this study can both inform practice in the NICU now and influence practice guidelines to include such components as emphasis on the first 48 hours, desire for proactive information sharing, and the importance of including hope.

Impact of the SARS-CoV-2 pandemic on pediatric subspecialists' well-being and perception of workplace value.

OBJECTIVE: To explore pediatric subspecialist distress and well-being during the pandemic, with a particular focus on relationships between compassion fatigue (CF), burnout (BO), and compassion satisfaction (CS), and physicians' perception of "feeling valued" by their institution. METHODS: The Compassion Fatigue and Satisfaction Self-Test and a questionnaire of personal/professional characteristics were distributed electronically to pediatric subspecialists. Content analysis was performed for responses to the question "How has your institution made you feel valued?" RESULTS: During the 16-month study period, CF and BO scores significantly increased, and CS scores decreased over time. By Epoch 3, 52% of respondents did not feel valued by their employing institution. When controlling for the effect of time, CF and BO scores remained higher, and CS scores lower, in participants who did not feel valued by their institution. Themes from the content analysis of "value" included expressions of gratitude, perks vs. penalties, safety, and leadership. The same overture from leadership provoked disparate responses in recipients, seemingly over the sincerity behind the offering, which may reflect underlying workplace culture. CONCLUSIONS: Increasingly, pediatric subspecialists are not feeling valued for their work. Institutional leadership must prioritize healthy workplace culture, and re-think emotional and mental health support within the health system. IMPACT: A total of 52% of our study population did not "feel valued" by their employing institution by late 2021, which is cause for concern. This is the first longitudinal analysis of distress and well-being in a national cohort of pediatric subspecialists during the COVID-19 pandemic. The same overture or messaging from leadership sparked disparate responses in recipients, seemingly over the sincerity behind the offering, which relates to the underlying workplace culture of the department or institution. Institutional leadership must prioritize a healthy workplace culture, and re-think and re-invent emotional and mental health support within the health system.

Federal regulations and neonatologists' views on care of seriously ill infants: changes over time.

BACKGROUND: The Baby Doe Regulations (BDR) regulate provision of life-sustaining treatment to seriously ill neonates. In 2020, the Trump administration expanded upon these through the Executive Order on Protecting Vulnerable Newborn and Infant Children (EO-PVNIC). Neonatologists were surveyed in 1988 to determine their opinions on the regulations. We sought to compare views of neonatologists from 1988 and 2021 in relation to three hypothetical cases and about the impact of the BDR and to evaluate perceptions of the EO-PVNIC. METHODS: We modified and distributed the 1988 survey to members of the American Academy of Pediatrics Section on Neonatal Perinatal Medicine. We used Chi-squared tests to compare responses in 1988 to responses in 2021. RESULTS: We received 445 survey responses. Neonatologists today felt less compelled to provide aggressive care to the hypothetical patients, felt less constrained by the regulations, and were more likely to report that parental wishes would impact their actions. CONCLUSIONS: There have been shifts in neonatologists' perceptions of the Baby Doe Regulations toward less aggressive medical treatment for seriously ill neonates and more shared decision-making. Further research is required to identify how practices have been impacted over these decades. IMPACT: Neonatologists in the 1980s largely objected to the Baby Doe regulations, fearing the regulations would restrict their ability to provide optimal care to seriously ill neonates. Though still in place, current perceptions of these and newer regulations are unknown. Perspectives on the Baby Doe regulations have changed since their enactment and with the addition of newer, more restrictive regulations. Neonatologists today may favor less aggressive management in the face of poor prognosis. Neonatologists may also favor more shared decision-making now as compared to the past.

Measuring communication quality in the Neonatal Intensive Care Unit.

BACKGROUND: High quality communication between providers and parents of seriously ill neonatal patients is vital and yet poorly understood. Feudtner summarized five challenges and seven priorities to the study and advancement of pediatric palliative care. Improvement of communication is a priority, while lack of specification and measurement of outcomes relevant to the pediatric population remains a challenge. Specifically, measurement of communication quality in pediatrics, and especially neonatology, is problematic. METHODS: We conducted a focused review of this topic which we hope will serve to support further research. We reviewed the current literature in Pubmed and searched the Palliative Care Research Cooperative (PCRC) instrument library. RESULTS: We found five validated instruments which met our criteria, relied on patient or surrogate report, and were developed to measure quality of communication and/or satisfaction with communication with adult patients or their surrogates. Our Pubmed search yielded 249 unique results, only two of which met our inclusion criteria. CONCLUSION: We conclude that development and exhaustive testing of a validated, comprehensive measure of communication quality for the neonatal population is needed. Without such a measure, it will be difficult to advance the field and achieve high quality prognostic communication for the parents of seriously ill babies. IMPACT: Measurement of communication quality in pediatrics, and especially neonatology, is problematic, understudied, and yet critical to the advancement of the field. There has not been an overview of existing measures of communication quality in the NICU published, nor has there been a comprehensive discussion of this important topic. Our paper provides such an overview and initiates such a discussion. We present a narrative review of existing measures of communication quality in the NICU in order to highlight the need for further study.

Compassion fatigue, burnout, and compassion satisfaction in pediatric subspecialists during the SARS-CoV-2 pandemic.

BACKGROUND: The aim of this study was to explore factors contributing to compassion fatigue (CF), burnout (BO), and compassion satisfaction (CS) during the severe acute respiratory syndrome coronavirus-2 pandemic in pediatric subspecialists. METHODS: The Compassion Fatigue and Satisfaction Self-Test (CFST) and a questionnaire of personal/professional characteristics were distributed electronically to pediatric subspecialists. RESULTS: There were no significant differences in pre- and early-pandemic CF, BO, and CS scores. Nearly 40% of respondents felt their contributions to the pandemic were not valued by their institutions. Higher CF scores were significantly associated with: higher BO score; "I have put myself at increased risk through my work"; working in one's specialty >50% of time; distress about mental health and/or future uncertainty. Higher BO scores were significantly associated with: higher CF score; "Self-care is not a priority"; emotional depletion. Higher CS scores were significantly associated with: "My institution values my contribution to the COVID-19 crisis"; workplace debriefs; pet therapy. CONCLUSIONS: The pandemic has only increased the need for physicians to receive social/emotional support from their institution and to feel their workplace contributions are valued. Successful pre-pandemic workplace interventions may not adequately support physicians during the pandemic. Further study is needed to identify supports that best counter the pandemic's unprecedented challenges. IMPACT: The sentiment "My institution has valued my contribution to the Covid-19 crisis" was the only significant factor associated with lower BO scores and was also associated with higher CS scores in pediatric subspecialists. This study is the first comparison of pre- and early-pandemic CF, BO, and CS scores in a national cohort of pediatric subspecialists. When considering interventions to promote CS and mitigate CF and BO for pediatric subspecialists during and after the pandemic, institutional leadership must offer wellness programming focused on social/emotional supports and prioritize a culture that explicitly recognizes and values every physician's contributions.

Parental Enrollment Decision-Making for a Neonatal Clinical Trial.

OBJECTIVE: To describe the parental experience of recruitment and assess differences between parents who participated and those who declined to enroll in a neonatal clinical trial. STUDY DESIGN: This was a survey conducted at 12 US neonatal intensive care units of parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and encephaLopathy (HEAL) trial or who were eligible but declined enrollment. Questions assessed 6 factors of the parental experience of recruitment: (1) interactions with research staff; (2) the consent experience; (3) perceptions of the study; (4) decisional conflict; (5) reasons for/against participation; and (6) timing of making the enrollment decision. RESULTS: In total, 269 of 387 eligible parents, including 183 of 242 (75.6%) of those who enrolled their children in HEAL and 86 of 145 (59.3%) parents who declined to enroll their children in HEAL, were included in analysis. Parents who declined to enroll more preferred to be approached by clinical team members rather than by research team members (72.9% vs 49.2%, P = .005). Enrolled parents more frequently reported positive initial impressions (54.9% vs 10.5%, P < .001). Many parents in both groups made their decision early in the recruitment process. Considerations of reasons for/against participation differed by enrollment status. CONCLUSIONS: Understanding how parents experience recruitment, and how this differs by enrollment status, may help researchers improve recruitment processes for families and increase enrollment. The parental experience of recruitment varied by enrollment status. These findings can guide future work aiming to inform optimal recruitment strategies for neonatal clinical trials.

Trends in length of stay for Neonatal Intensive Care Unit patients who die before hospital discharge.

OBJECTIVES: The objectives of this study were to establish days between birth and death for neonates over a 14-year period, determine if days between birth and death have changed over time across gestational age cohorts, and identify diagnoses which may put infants at high risk of prolonged hospitalization leading to death. STUDY DESIGN: This was a single-site, retrospective chart review of inborn infants who died prior to hospital discharge. RESULTS: Two hundred and thirty-nine patients born between 1/1/2006 and 12/31/2020 met inclusion criteria. Days until death ranged from 0 to 300 with a median of 6 days (interquartile range = 23). Median days until death increased over time, with a statistically significant increase between epoch 1 and epoch 2 (p = 0.016) but not between epoch 2 and epoch 3 (p = 0.618). Extremely premature infants died earlier than more mature infants (p < 0.001). In addition, infants with complex congenital heart disease or a gastrointestinal (GI) catastrophe died later (p < 0.001 and p < 0.001, respectively) than newborns without cardiac or GI issues. CONCLUSIONS: Our findings demonstrate an increase in time to death for newborns who did not survive to hospital discharge over a 14-year period. This trend suggests that the dynamics informing Meadows' assertion that "doomed infants die early" may be shifting, with some seriously ill infants who die before hospital discharge surviving longer than previously described. More research is needed to understand how best to care for babies who will not survive to discharge and to explore when supports such as palliative care consultation may be beneficial. KEY POINTS: As per W. Meadow, "Doomed infants die early" · Pre-death length of stay varies with diagnosis.. · Some seriously ill infants who die before hospital discharge are no longer dying early.. · These infants and families may need supports..

NeoTalk: Communication Skills Training for Neonatal Clinicians.

BACKGROUND: Despite proven benefit, pediatric subspecialists often have not been offered formal serious illness communication skills training. We sought to: 1) develop and evaluate the impact of a communication skills course, based on the VitalTalk framework, on Neonatal Intensive Care Unit (NICU) clinicians; 2) evaluate provider comfort with key serious illness communication skills and frequency of use of those skills, before and after "NeoTalk" and; 3) explore differences and similarities between adult and pediatric serious illness communication skills courses. METHODS: We developed a NICU specific communication skills course and surveyed course participants to evaluate comfort with key communication skills before and after course participation, and frequency of use of key skills before and 2 months after our course. Wilcoxon signed rank tests and Kruskal-Wallis tests were performed to compare participant responses across time points. RESULTS: 34 providers completed NeoTalk training. Complete pre- and post-course data was available for 29 participants. Participants reported increased comfort with skills including 'sharing difficult news' (P = .018), and 'responding to emotion' (P = .002). Participants did not report increased frequency in using target skills 2 months after training. CONCLUSIONS: A multi-disciplinary cohort of NICU providers endorsed increased confidence in key communication skills but not increased skill application 2-months post-course completion. While a single course can successfully teach skills, additional exposure may be necessary to build new communication habits. Our experience developing NeoTalk helped elucidate some of the ways in which conversations about seriously ill infants may be different from conversations about seriously ill adults.

Parent Perspectives on Defining Neonatal Serious Illness.

Objectives: We hoped to understand (1) how parents of seriously ill neonatal intensive care unit patients conceptualize neonatal serious illness, and (2) how parent and physician perspectives on neonatal serious illness might differ. Design: This was a prospective survey study. Setting/Subjects: Parent members of the Courageous Parents Network. Measurements: We circulated a modified version of a previously developed survey. Participants were presented with a list of potential definition components and asked to rank components by importance and suggest modifications to the definition as needed. Thematic analysis of free-text responses was conducted to identify key themes in parent responses Results: Eighty-eight percent of parent participants agreed or strongly agreed with our working definition of neonatal serious illness. Parents agreed with the content of the definition but suggested using different language (especially less jargon) when using the definition to inform conversations with parents. Conclusions: The majority of parents surveyed for this study supported our definition of neonatal serious illness, which suggests that it may be useful for clinical and research applications. At the same time, parent responses revealed important differences in perceptions about serious illness between parents and physicians. In addition, parents will likely use any definition of neonatal serious illness differently than clinicians. We therefore propose that our definition be used to identify neonates with serious illness for the purposes of research and clinical care, but should not be used verbatim for communication with parents.

Defining Neonatal Serious Illness: Perspectives of Nurses and Social Workers.

Objectives: To explore (1) how neonatal nurses (NN) and social workers (SW) define serious illness and (2) how physician, nurse, and SW perceptions of serious illness differ. Design: Prospective survey study. Setting/Subjects: Members of the National Association of Neonatal Nurses or the National Association of Perinatal Social Workers. Measurements: We circulated a modified version of a previously developed survey. Participants were given a list of definition components and asked to rank components by importance and to suggest modifications. Results: Eighty-eight percent of participants agreed with our definition of neonatal serious illness. NN and SW differ in important ways in their views of neonatal serious illness when compared with physicians and parents. Conclusions: Our definition of neonatal serious illness has broad acceptability and may be useful for clinical care and research. Future work should prospectively identify patients with neonatal serious illness and establish the usefulness of our definition in real time.

PedsTalk: A Pilot Communication Skills Education Course for Pediatric Residents.

OBJECTIVE: Communication skills are critical to pediatric practice, but few pediatric residency programs provide formal communication skills education. Pediatric residents often lack confidence in these skills. We hypothesized that a simulation-based communication skills course would improve resident confidence in the skills required for serious illness conversations with patients/families. METHODS: In collaboration with multidiscipline VitalTalk-trained faculty, we developed PedsTalk, a communication skills course for pediatric residents based on the VitalTalk framework. In PedsTalk, faculty/peers offered real-time coaching during simulation sessions with actors. Resident participants self-rated confidence in 9 communication skills using a 5-point Likert scale before, immediately after, and 4 months after course participation, with course nonparticipants serving as controls. Responses were analyzed by using Friedman tests and Wilcoxon rank tests. Thematic analysis was conducted to identify themes among free-text responses. RESULTS: Twenty-seven pediatric residents participated in PedsTalk, 11 of whom completed survey assessments at all timepoints. Eleven course nonparticipants served as controls. Over time, participants' confidence in the following communication skills was retained or significantly improved: "difficult conversations" (P < .001), "recognizing emotion" (P < .01), "using silence" (P < .008), "headline statements" (P < .001), eliciting "VALUES" (P < .001), and asking "permission to continue" (P < .001). Over time, controls had significant improvements in confidence in 2 skills: headline statements (P < .014) and eliciting "VALUES" (P < .031). CONCLUSIONS: PedsTalk is a novel approach to communication skills education in pediatric residency. Participation improved residents' confidence in 6 communication skills, including overall confidence in having difficult conversations. Although confidence in some skills may naturally develop through clinical experiences, PedsTalk further enhances communication skills education among trainees.

Factors That Impact Hospital-Specific Enrollment Rates for a Neonatal Clinical Trial: An Analysis of the HEAL Study.

Inconsistent enrollment among hospitals for neonatal clinical trials may lead to study populations that are not representative of the patient population in the neonatal intensive care unit. The High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial was a multisite randomized clinical trial investigating erythropoietin as a neuroprotective treatment for term infants (those born between 37 and 42 complete weeks) with hypoxic ischemic encephalopathy. Substantial variability was noted in enrollment rate by hospital. We developed survey questions across five conceptual domains to understand systems-level issues that might contribute to variation in enrollment rate by hospital. Our study found that hospitals varied in their responses across these five domains. We propose three potential reasons that we found a lack of identifiable hospital-level factors that correlated with enrollment rates: sample-size limitations, methodological concerns, and confounding factors. Future studies with a larger sample size should be considered to evaluate contributors to hospital-level variability. This will lead to more robust recruitment strategies, improved enrollment, and decreases in the waste of research resources.

Parental Factors Associated With the Decision to Participate in a Neonatal Clinical Trial.

Importance: It remains poorly understood how parents decide whether to enroll a child in a neonatal clinical trial. This is particularly true for parents from racial or ethnic minority populations. Understanding factors associated with enrollment decisions may improve recruitment processes for families, increase enrollment rates, and decrease disparities in research participation. Objective: To assess differences in parental factors between parents who enrolled their infant and those who declined enrollment for a neonatal randomized clinical trial. Design, Setting, and Participants: This survey study conducted from July 2017 to October 2019 in 12 US level 3 and 4 neonatal intensive care units included parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial or who were eligible but declined enrollment. Data were analyzed October 2019 through July 2020. Exposure: Parental choice of enrollment in neonatal clinical trial. Main Outcomes and Measures: Percentages and odds ratios (ORs) of parent participation as categorized by demographic characteristics, self-assessment of child's medical condition, study comprehension, and trust in medical researchers. Survey questions were based on the hypothesis that parents who enrolled their infant in HEAL differ from those who declined enrollment across 4 categories: (1) infant characteristics and parental demographic characteristics, (2) perception of infant's illness, (3) study comprehension, and (4) trust in clinicians and researchers. Results: Of a total 387 eligible parents, 269 (69.5%) completed the survey and were included in analysis. This included 183 of 242 (75.6%) of HEAL-enrolled and 86 of 145 (59.3%) of HEAL-declined parents. Parents who enrolled their infant had lower rates of Medicaid participation (74 [41.1%] vs 47 [55.3%]; P = .04) and higher rates of annual income greater than $55 000 (94 [52.8%] vs 30 [37.5%]; P = .03) compared with those who declined. Black parents had lower enrollment rates compared with White parents (OR, 0.35; 95% CI, 0.17-0.73). Parents who reported their infant's medical condition as more serious had higher enrollment rates (OR, 5.7; 95% CI, 2.0-16.3). Parents who enrolled their infant reported higher trust in medical researchers compared with parents who declined (mean [SD] difference, 5.3 [0.3-10.3]). There was no association between study comprehension and enrollment. Conclusions and Relevance: In this study, the following factors were associated with neonatal clinical trial enrollment: demographic characteristics (ie, race/ethnicity, Medicaid status, and reported income), perception of illness, and trust in medical researchers. Future work to confirm these findings and explore the reasons behind them may lead to strategies for better engaging underrepresented groups in neonatal clinical research to reduce enrollment disparities.