Pediatric residents experience ethical dilemmas and moral distress during training. Few studies have identified meaningful methods in reducing moral distress in pediatric trainees. The authors aimed to determine how residents perceive ethics case discussions, whether such a program affects trainee ethics knowledge and perceived moral distress, and if residents' perceived moral distress changes before, during, and after a discussion series. Participants included pediatric residents in a single residency program. Five separate 1-hour sessions were presented over a 5-month period. Each session consisted of a case presentation by a resident developed under the guidance of an ethicist. Multidisciplinary services and content experts were present during sessions. Baseline, postsession, and final surveys were distributed to resident attendees. Open-ended responses were recorded. When comparing baseline and final responses, the only significance was increased preparedness to navigate ethical decisions (p = 0.004). A 10.2% decline was observed in perceived moral distress. An increase in ethics knowledge was observed. Residents favored case-based, multidisciplinary discussions. Residents desire more sessions, time for small-group discussions, and legal insight. Satisfaction was high with 90.7% of respondents feeling better prepared to address ethical concerns. Pediatric trainees desire case-based ethics training that incorporates small-group discussions and insight from multidisciplinary topic experts.

ImportanceResults of clinical trials can only represent included participants, and many neonatal trials fail due to insufficient participation. Infants not included in research may differ from those included in meaningful ways, biasing the sample and limiting the generalizability of findings.ObjectiveTo describe the proportion of eligible infants included in neonatal clinical trials and the reasons for noninclusion.Evidence ReviewA systematic search of Cochrane CENTRAL was performed by retrieving articles meeting the following inclusion criteria: full-length, peer-reviewed articles describing clinical trial results in at least 20 human infants from US neonatal intensive care units, published in English, and added to Cochrane CENTRAL between 2017 and 2022. Retrieved articles were screened for inclusion by 2 independent researchers.FindingsIn total 120 articles met inclusion criteria and 91 of these (75.8%) reported the number of infants eligible for participation, which totaled 26 854 in aggregate. Drawing from these, an aggregate of 11 924 eligible infants (44.4%) were included in reported results. Among all eligible infants, most reasons for noninclusion in results were classified as modifiable or potentially modifiable by the research team. Parents declining to participate (8004 infants [29.8%]) or never being approached (2507 infants [9.3%]) were the 2 predominant reasons for noninclusion. Other modifiable reasons included factors related to study logistics, such as failure to appropriately collect data on enrolled infants (859 of 26 854 infants [3.2%]) and other reasons (1907 of 26 854 infants [7.1%]), such as loss to follow-up or eligible participants that were unaccounted for. Nonmodifiable reasons, including clinical change or death, accounted for a small proportion of eligible infants who were not included (858 of 26 854 infants [3.2%]).Conclusions and RelevanceThis systematic review of reporting on eligible infants included and not included in neonatal clinical trials highlights the need for improved documentation on the flow of eligible infants through neonatal clinical trials and may also inform recruitment expectations for trialists designing future protocols. Improved adherence to standardized reporting may clarify which potential participants are being missed, improving understanding of the generalizability of research findings. Furthermore, these findings suggest that future work to understand why parents decline to participate in neonatal research trials and why some are never approached about research may help increase overall participation.

Clinicians practicing in a modern NICU are noticing an increase in the proportion of patients who undergo genetic testing as well as changes in the types of genetic testing patients receive. These trends are not surprising given the increasing recognition of the genetic causes of neonatal illness and recent advances in genetic technology. Yet, the expansion of genetic testing in the NICU also raises a number of ethical questions. In this article, we will review the ethical issues raised by genetic testing, with a focus on the practical implications for neonatologists. First, we outline the complexities of measuring benefit, or utility, for neonatal genetic testing. Next, we discuss potential harms such as inequity, unexpected findings, disability biases, and legal risks. Finally, we conclude with a discussion of ethical issues related to consent for genetic testing. Throughout this article, we highlight solutions to challenges toward the ultimate goal of minimizing harms and maximizing the substantial potential benefits of genetic medicine in the NICU.

IntroductionCare for neonates at the end of life (EOL) is often challenging for families and medical teams alike, performed suboptimally, and requires an experienced and compassionate clinician. Much literature exists on adult and pediatric EOL care, but limited studies examine the neonatal process.MethodsWe aimed to describe clinicians' experiences around EOL care in a single quaternary neonatal intensive care unit as we implemented a standard guideline using the Pediatric Intensive Care Unit-Quality of Dying and Death 20 tool.ResultsSurveys were completed by 205 multidisciplinary clinicians over three time periods and included 18 infants at EOL. While most responses were high, a meaningful minority were below goal (<8 on 0–10 scale) for troubling symptom management, conflict between parents and staff, family access to resources, and parent preparation of symptoms. Comparison between Epochs revealed improvement in one symptom management and four communication categories. Satisfaction scores related to education around EOL were better in later Epochs. Neonatal Pain, Agitation, and Sedation Scale scores were low, with few outliers.DiscussionThese findings can guide those aiming to improve processes around neonatal EOL by identifying areas with the greatest challenges (e.g., conflict management) and areas that need further study (e.g., pain management around death).

Background Pleuropulmonary blastoma (PPB) is a rare mesenchymal malignancy of the lung and is the most common pulmonary malignancy in infants and children. Cystic PPB, the earliest form of PPB occurring from birth to approximately two years of age, is often mistaken for a congenital pulmonary airway malformation, as the two entities can be difficult to distinguish on imaging and pathology. Diagnosis of PPB should prompt workup for DICER1 syndrome, an autosomal dominant tumor predisposition syndrome. We report a newborn with a congenital PPB presenting with tachypnea and hypoxia, who was found to have variant of uncertain clinical significance (VUS) in DICER1 . Case presentation A term female infant developed respiratory distress shortly after birth. Initial imaging was concerning for a congenital pulmonary airway malformation versus congenital diaphragmatic hernia, and she was transferred to a quaternary neonatal intensive care unit for management and workup. Chest CT angiography demonstrated a macrocytic multicystic lesion within the right lower lobe without systemic arterial supply. The pediatric surgery team was consulted, and the neonate underwent right lower lobectomy. Pathology revealed a type I PPB. Oncology and genetics consultants recommended observation without chemotherapy and single gene sequencing of DICER1 , which identified a germline VUS in DICER1 predicted to alter splicing. RNA-sequencing from blood demonstrated that the variant resulted in an in-frame deletion of 29 amino acids in a majority of transcripts from the affected allele. Due to the patient’s young age at presentation and high clinical suspicion for DICER1 syndrome, tumor surveillance was initiated. Renal and pelvic ultrasonography were unremarkable. Conclusion We present the case of a term neonate with respiratory distress and cystic lung mass, found to have a type I PPB with a germline VUS in DICER1 that likely increased her risk of DICER1 -related tumors. Nearly 70% of patients with PPB demonstrate germline mutations in DICER1 . Review of RNA sequencing data demonstrates the difficulty in classifying splice variants such as this. Penetrance is low, and many patients with pathogenic DICER1 variants do not develop a malignancy. Best practice surgical and oncologic recommendations include an individualized approach and tumor board discussion. This case highlights the importance of a multidisciplinary team approach and the utility of international registries for patients with rare diagnoses.

Importance Representativeness of populations within neonatal clinical trials is crucial to moving the field forward. Although racial and ethnic disparities in research inclusion are well documented in other fields, they are poorly described within neonatology.Objective To describe the race and ethnicity of infants included in a sample of recent US neonatal clinical trials and the variability in this reporting.Evidence Review A systematic search of US neonatal clinical trials entered into Cochrane CENTRAL 2017 to 2021 was conducted. Two individuals performed inclusion determination, data extraction, and quality assessment independently with discrepancies adjudicated by consensus.Findings Of 120 studies with 14 479 participants that met the inclusion criteria, 75 (62.5%) included any participant race or ethnicity data. In the studies that reported race and ethnicity, the median (IQR) percentage of participants of each background were 0% (0%-1%) Asian, 26% (9%-42%) Black, 3% (0%-12%) Hispanic, 0% (0%-0%) Indigenous (eg, Alaska Native, American Indian, and Native Hawaiian), 0% (0%-0%) multiple races, 57% (30%-68%) White, and 7% (1%-21%) other race or ethnicity. Asian, Black, Hispanic, and Indigenous participants were underrepresented, while White participants were overrepresented compared with a reference sample of the US clinical neonatal intensive care unit (NICU) population from the Vermont Oxford Network. Many participants were labeled as other race or ethnicity without adequate description. There was substantial variability in terms and methods of reporting race and ethnicity data. Geographic representation was heavily skewed toward the Northeast, with nearly one-quarter of states unrepresented.Conclusions and Relevance These findings suggest that neonatal research may perpetuate inequities by underrepresenting Asian, Black, Hispanic, and Indigenous neonates in clinical trials. Studies varied in documentation of race and ethnicity, and there was regional variation in the sites included. Based on these findings, funders and clinical trialists are advised to consider a 3-point targeted approach to address these issues: prioritize identifying ways to increase diversity in neonatal clinical trial participation, agree on a standardized method to report race and ethnicity among neonatal clinical trial participants, and prioritize the inclusion of participants from all regions of the US in neonatal clinical trials.

AbstractBackgroundMethemoglobinemia can be an acquired or congenital condition. The acquired form occurs from exposure to oxidative agents. Congenital methemoglobinemia is a rare and potentially life-threatening cause of cyanosis in newborns that can be caused by either cytochrome B5reductase or hemoglobin variants known as Hemoglobin M.Case presentationA term male infant developed cyanosis and hypoxia shortly after birth after an uncomplicated pregnancy, with oxygen saturations persistently 70–80% despite 1.0 FiO2 and respiratory support of CPAP+ 6 cm H2O. Pre- and post-ductal saturations were equal and remained below 85%. Initial radiographic and echography imaging was normal. Capillary blood gas values were reassuring with normal pH and an elevated pO2. Investigations to rule out hemolysis and end-organ dysfunction were within acceptable range. Given the absence of clear cardiac or pulmonary etiology of persistent cyanosis, hematologic causes such as methemoglobinemia were explored. No family history was available at the time of transfer to our institution. Unconjugated hyperbilirubinemia > 5 mg/dL (442 μmol/L) interfered with laboratory equipment measurement, making accurate methemoglobin levels unattainable despite multiple attempts. Initial treatment with methylene blue or ascorbic acid was considered. However, upon arrival of the presumed biological father, a thorough history revealed an extensive paternal family history of neonatal cyanosis due to a rare mutation resulting in a hemoglobin M variant. Given this new information, hematology recommended supportive care as well as further testing to confirm the diagnosis of congenital methemoglobinopathy. Whole genome sequencing revealed a likely pathogenic variation in hemoglobin. The neonate was discharged home at 2 weeks of age on full oral feeds with 0.25 L/min nasal cannula as respiratory support, with close outpatient follow-up. By 5 weeks of age, he was weaned off respiratory support.ConclusionCongenital methemoglobinemia should be considered in the differential diagnosis for newborns with persistent hypoxemia despite normal imaging and laboratory values. Accurate quantification of methemoglobin concentrations is challenging in neonates due to the presence of other substances that absorb light at similar wavelengths, including HbF, bilirubin, and lipids.

An early term female neonate is born at 37 weeks, 2 days of gestation with a birthweight of 3.1 kg. She is delivered vaginally by a 26-year-old woman after induction of labor for preeclampsia with severe features; magnesium sulfate was given during labor. Prenatal history is significant for late prenatal care (14 weeks) and fetal diagnosis of right-sided ventriculomegaly noted on serial ultrasonography, first at 20 weeks of gestation and confirmed on fetal magnetic resonance imaging (MRI) at 27 weeks. All prenatal serologic findings were negative, a 1-hour oral glucose tolerance test result was within normal limits, and cell-free fetal DNA was negative for trisomies 13, 18, and 21. Maternal-fetal medicine, neonatal-perinatal medicine, and pediatric neurosurgical physician teams were involved in the prenatal care, and a plan was developed to admit the infant to the level III NICU after birth for further brain imaging. At delivery, the infant is vigorous, with Apgar scores of 9 and 9 at 1 and 5 minutes, respectively. Birthweight is at the 50th percentile, length is greater than the 97th percentile, and occipitofrontal circumference …

A 2-day-old, 2.68-kg term male neonate is brought to the emergency department with lethargy, poor feeding, and significant generalized jaundice. He was born via spontaneous vaginal delivery at home to a gravida 4, para 3 Amish woman under the supervision of a midwife, at an estimated gestational age of 39 weeks after an uncomplicated pregnancy with scant prenatal care. Jaundice was noticed 7 hours after birth. The neonate has only breastfed 5 to 6 times since birth, and passed a normal-colored stool at home. Prenatal laboratory findings are unavailable because of limited prenatal care. The mother’s blood type is AB, Rh negative. The mother’s obstetric history includes a previous miscarriage (4 years earlier), a previous stillbirth at 30 weeks’ gestation (3 years earlier), and a term pregnancy (2 years earlier). She had received Rho(D) immune globulin 3 weeks after the miscarriage, 2 weeks after the stillbirth delivery, and 2 weeks after the most recent pregnancy. The mother, father, and 2-year-old brother are reportedly healthy. Review of systems at admission is significant for decreased activity, poor feeding, and generalized, intense yellow discoloration of the skin. The infant has no fever, vomiting, diarrhea, constipation, bloody stools, seizures, or hypertonia. Physical examination reveals a weak cry, lethargy, scleral icterus, soft liver edge 3 cm below the right costal margin, and significant generalized jaundice of the entire body. No dysmorphic features are appreciated. Initial evaluation revealed a total serum bilirubin (TB) of 49.4 mg/dL (845 μmol/L), conjugated bilirubin of 42 mg/dL (718 μmol/L), unconjugated bilirubin of 10.7 mg/dL (183 μmol/L), reticulocyte count greater than 23, and hemoglobin of 12.6 g/dL (126 g/L). Urinalysis demonstrated dark brown urine. Serum aspartate aminotransferase (AST) was elevated at 239 U/L (4 μkat/L), serum alanine …

Tamm-Horsfall protein (THP) is a glycoprotein uniquely expressed in the kidney. We recently showed an important role for THP in mediating tubular cross-talk in the outer medulla and in suppressing neutrophil infiltration after kidney injury. However, it remains unclear whether THP has a broader role in neutrophil homeostasis. In this study, we show that THP deficiency in mice increases the number of neutrophils, not only in the kidney but also in the circulation and in the liver, through enhanced granulopoiesis in the bone marrow. Using multiplex ELISA, we identified IL-17 as a key granulopoietic cytokine specifically upregulated in the kidneys but not in the liver of THP-/- mice. Indeed, neutralization of IL-17 in THP-/- mice completely reversed the systemic neutrophilia. Furthermore, IL-23 was also elevated in THP-/- kidneys. We performed real-time PCR on laser microdissected tubular segments and FACS-sorted renal immune cells and identified the S3 proximal segments, but not renal macrophages, as a major source of increased IL-23 synthesis. In conclusion, we show that THP deficiency stimulates proximal epithelial activation of the IL-23/IL-17 axis and systemic neutrophilia. Our findings provide evidence that the kidney epithelium in the outer medulla can regulate granulopoiesis. When this novel function is added to its known role in erythropoiesis, the kidney emerges as an important regulator of the hematopoietic system.