Extremely premature birth bioethical decision-making supported by dialogics and pragmatism.

Moral values in healthcare range widely between interest groups and are principally subjective. Disagreements diminish dialogue and marginalize alternative viewpoints. Extremely premature births exemplify how discord becomes unproductive when conflicts of interest, cultural misunderstanding, constrained evidence review, and peculiar hierarchy compete without the balance of objective standards of reason. Accepting uncertainty, distributing risk fairly, and humbly acknowledging therapeutic limits are honorable traits, not relativism, and especially crucial in our world of constrained resources. We think dialogics engender a mutual understanding that: i) transitions beliefs beyond bias, ii) moves conflict toward pragmatism (i.e., the truth of any position is verified by subsequent experience), and iii) recognizes value pluralism (i.e., human values are irreducibly diverse, conflicting, and ultimately incommensurable). This article provides a clear and useful Point-Counterpoint of extreme prematurity controversies, an objective neurodevelopmental outcomes table, and a dialogics exemplar to cultivate shared empathetic comprehension, not to create sides from which to choose. It is our goal to bridge the understanding gap within and between physicians and bioethicists. Dialogics accept competing relational interests as human nature, recognizing that ultimate solutions satisfactory to all are illusory, because every choice has downside. Nurturing a collective consciousness via dialogics and pragmatism is congenial to integrating objective evidence review and subjective moral-cultural sentiments, and is that rarest of ethical constructs, a means and an end.

Le suivi de l'extrême prématuré après le congé des soins intensifs néonatals.

La survie des extrêmes prématurés (moins de 28 semaines d'âge gestationnel) s'est améliorée au fil du temps. Bon nombre s'en sortent bien et ont une bonne qualité de vie. Ils demeurent toutefois vulnérables à des problèmes de santé, y compris des difficultés neurosensorielles et neurodéveloppementales, que les médecins de première ligne, les pédiatres et les cliniques spécialisées doivent surveiller. Le présent document de principes passe en revue les conséquences médicales et neurodéveloppementales potentielles pour les extrêmes prématurés dans les deux ans suivant leur congé et fournit des stratégies de counseling, de dépistage précoce et d'intervention. Parce qu'ils sont tous liés à l'extrême prématurité, la dysplasie bronchopulmonaire ou les troubles respiratoires, les problèmes d'alimentation et de croissance, le développement neurosensoriel (vision et audition), la paralysie cérébrale et le trouble du spectre de l'autisme doivent faire rapidement l'objet d'une évaluation. Pour évaluer la croissance et le développement, il faut corriger l'âge chronologique en fonction de l'âge gestationnel jusqu'à 36 mois de vie. Par ailleurs, l'attention au bien-être émotionnel des parents et des proches fait partie intégrante des soins de qualité de l'extrême prématuré.

Scandinavian perspectives on life support at the border of viability.

Advances in neonatal medicine have allowed us to rescue extremely preterm infants. However, both long-term vulnerability and the burden of treatment in the neonatal period increase with decreasing gestational age. This raises questions about the justification of life support when a baby is born at the border of viability, and has led to a so-called "grey zone", where many professionals are unsure whether provision of life support is in the child's best interest. Despite cultural, political and economic similarities, the Scandinavian countries differ in their approach to periviable infants, as seen in their respective national guidelines and practices. In Sweden, guidelines and practice are more rescue-focused at the lower end of the border of viability, Danish guidelines emphasizes the need to involve parental views in the decision-making process, whereas Norway appears to be somewhere in between. In this paper, I will give an overview of national consensus documents and practices in Norway, Sweden and Denmark, and reflect on the ethical justification for the different approaches.

The Urinary Metabolomic Fingerprint in Extremely Preterm Infants on Total Parenteral Nutrition vs. Enteral Feeds.

Total Parenteral Nutrition (TPN), which uses intravenous administration of nutrients, minerals and vitamins, is essential for sustaining premature infants until they transition to enteral feeds, but there is limited information on metabolomic differences between infants on TPN and enteral feeds. We performed untargeted global metabolomics on urine samples collected between 23-30 days of life from 314 infants born <29 weeks gestational age from the TOLSURF and PROP cohorts. Principal component analysis across all metabolites showed a separation of infants solely on TPN compared to infants who had transitioned to enteral feeds, indicating global metabolomic differences between infants based on feeding status. Among 913 metabolites that passed quality control filters, 609 varied in abundance between infants on TPN vs. enteral feeds at p < 0.05. Of these, 88% were in the direction of higher abundance in the urine of infants on enteral feeds. In a subset of infants in a longitudinal analysis, both concurrent and delayed changes in metabolite levels were observed with the initiation of enteral feeds. These infants had higher concentrations of essential amino acids, lipids, and vitamins, which are necessary for growth and development, suggesting the nutritional benefit of an enteral feeding regimen.

Case report: Tackling the complexities of an extremely premature newborn with intrauterine growth restriction and congenital metabolic disorders through a multidisciplinary approach.

Background and objectives: The premature birth of a newborn can present a complex challenge for healthcare providers, particularly in cases of extreme prematurity combined with intrauterine growth restriction and multiple metabolic deficiencies. In this report, we aim to shed light on the difficulties and considerations involved in the management of such a case. In addition, our study is aimed to raise awareness of the importance of a multidisciplinary team in managing an extreme premature case with multiple comorbidities. Case presentation and main findings: We present the case of a 28-week premature female newborn with very low birth weight (660 g, percentile <10%) and intrauterine growth restriction. She was born through emergency cesarean delivery due to maternal Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome and had a high-risk pregnancy (spontaneous twin pregnancy, with one fetus stopping development at 16 weeks and maternal hypertension). In the first hours of life, she presented with persistent hypoglycemia requiring progressive glucose supplementation up to 16 g/kg/day to maintain normal blood glucose levels. The baby then showed favorable progress. However, from days 24 to 25, hypoglycemia recurred and did not respond to glucose boluses or supplementation in both intravenous and oral feeds, leading to the suspicion of a congenital metabolic disorder. Endocrine and metabolic screenings led to suspicion of primary carnitine deficiency and a deficiency in hepatic form of carnitine-palmitoyltransferase type I (CPT1) on the second screening. Conclusion and clinical implications: The study highlights rare metabolic anomalies that can be due to both organ and system immaturity and delayed enteral feeding and excessive use of antibiotics. The clinical implications of this study emphasize the need for careful monitoring and comprehensive care of premature infants to prevent and manage potential metabolic abnormalities by neonatal metabolic screening.

Prophylactic Administration of Mesenchymal Stromal Cells Does Not Prevent Arrested Lung Development in Extremely Premature-Born Non-Human Primates.

Premature birth is a leading cause of childhood morbidity and mortality and often followed by an arrest of postnatal lung development called bronchopulmonary dysplasia. Therapies using exogenous mesenchymal stromal cells (MSC) have proven highly efficacious in term-born rodent models of this disease, but effects of MSC in actual premature-born lungs are largely unknown. Here, we investigated thirteen non-human primates (baboons; Papio spp.) that were born at the limit of viability and given a single, intravenous dose of ten million human umbilical cord tissue-derived MSC per kilogram or placebo immediately after birth. Following two weeks of human-equivalent neonatal intensive care including mechanical ventilation, lung function testing and echocardiographic studies, lung tissues were analyzed using unbiased stereology. We noted that therapy with MSC was feasible, safe and without signs of engraftment when administered as controlled infusion over 15 minutes, but linked to adverse events when given faster. Administration of cells was associated with improved cardiovascular stability, but neither benefited lung structure, nor lung function after two weeks of extrauterine life. We concluded that a single, intravenous administration of MSC had no short- to mid-term lung-protective effects in extremely premature-born baboons, sharply contrasting data from term-born rodent models of arrested postnatal lung development and urging for investigations on the mechanisms of cell-based therapies for diseases of prematurity in actual premature organisms.

An assessment of improved outcomes using low-cost bubble CPAP in very low birthweight neonates in a Nigerian tertiary hospital.

Respiratory distress contributes to the high burden of preterm mortality globally. The aim of our study was to evaluate the use of low-cost Bubble Continuous Positive Airway Pressure devices for treating respiratory distress and their outcomes in preterm infants weighing <1500g. Data was extracted from admission records of 211 infants over two distinct 4-year periods before and after introduction of bCPAP. With survival rates of 26.7% and 61.8% in the pre and post bCPAP eras respectively, significantly improved outcomes were found.

Transcatheter patent arterial duct closure in premature infants: A new technique to ease access to the patent arterial duct, with particular benefit for the tricuspid valve.

BACKGROUND: Transcatheter patent arterial duct (PAD) closure in premature infants has been shown to be feasible. Since our early transcatheter PAD closure procedures in premature infants at Hôpital Necker Enfants Malades, we have changed our technique several times to advance the guidewire through the right heart to avoid tricuspid valve damage. AIM: To describe the technique we have been using since May 2019, to report our results with a particular focus on tricuspid leaks and to analyse the potential mechanisms of tricuspid lesion development with previous methods. METHODS: All premature infants weighing<2kg who underwent transcatheter PAD closure with this new technique were included. Demographic data, procedural data, outcome and procedural complications were reviewed, with particular attention to the occurrence of tricuspid regurgitation. RESULTS: Between May 2019 and May 2020, 33 patients were included. Median gestational age was 25 weeks. Median birth weight and procedural weight were 690g (range 490-1065g; interquartile range [IQR] 620-785g) and 1160g (range 900-1900g; IQR 1030-1300g), respectively. Median age at procedure was 35 (IQR 30-46) days. PAD anatomy was evaluated on transthoracic echocardiography only. The median duct diameter was 3 (IQR 2.5-3.2) mm at the pulmonary end. Success rate was 100% (defined as successful closure without residual shunt). One patient had a renal vein thrombosis, which fully resolved with low-molecular-weight heparin anticoagulation. No tricuspid regurgitation or stenosis of the left pulmonary artery or the aorta was seen. One patient died of a superior caval vein obstruction with bilateral chylothorax related to a central catheter thrombosis 56 days after the procedure, unrelated to the catheter procedure. CONCLUSION: In this prospective study, we describe a new technique to avoid tricuspid valve damage and facilitate delivery of the PAD device.

Evaluation of the suitability and clinical applicability of different electrodes for aEEG/cEEG monitoring in the extremely premature infant.

INTRODUCTION: Monitoring of brain function using continuous electroencephalography (aEEG/cEEG) is an essential tool in the standard care of the term infant, and its use is growing in the premature infant as a biomarker of lesion and brain maturity. However, the placing of the electrodes is a great challenge, particularly in the extremely premature infant, which often discourages neuromonitoring. The aim of this study is to assess the different electrodes available, to select the one that best suits the peculiarities of the extremely premature infant, and evaluate its applicability in clinical practice. POPULATION AND METHODS: With the aim of designing a neuromonitoring study protocol using aEEG/cEEG in <28 weeks premature infants, an analysis was made of our experience with the type of electrodes available. The electrode that was considered most suitable for this population was chosen by assessing: the need of preparing the scalp, speed in positioning the electrodes, if the application was invasive or not, the possibility of repositioning, risk of skin injuries, sterility of the technique, and durability. The electrode chosen was used for continuous electroencephalographic monitoring started in the first 24 h of life, and maintained until at least 72 h of life. RESULTS: The electrodes evaluated were: subdermal needles, silver cups, and 2 types of self-adhesive electrodes (solid hydrogel and wet gel). The wet gel electrodes were chosen. They were used on 41 neonates with a mean gestational age of 25.8 ±â€¯1.1 weeks. Good stable impedance was rapidly obtained, without the need of excessive manipulations, and no skin injuries were observed. The satisfaction of the staff involved in positioning them was very high. CONCLUSION: The self-adhesive disposable electrodes with wet gel and integrated cable enabled the electrodes to be positioned rapidly and provided continuous non-invasive and good quality aEEG/cEEG monitoring in the extremely premature infant.

[Evaluation of the suitability and clinical applicability of different electrodes for aEEG/cEEG monitoring in the extremely premature infant]. / Evaluación de la idoneidad y aplicabilidad clínica de diferentes electrodos para la monitorización aEEG/cEEG en el niño prematuro extremo.

INTRODUCTION: Monitoring of brain function using continuous electroencephalography (aEEG/cEEG) is an essential tool in the standard care of the term infant, and its use is growing in the premature infant as a biomarker of lesion and brain maturity. However, the placing of the electrodes is a great challenge, particularly in the extremely premature infant, which often discourages neuromonitoring. The aim of this study is to assess the different electrodes available, to select the one that best suits the peculiarities of the extremely premature infant, and evaluate its applicability in clinical practice. POPULATION AND METHODS: With the aim of designing a neuromonitoring study protocol using aEEG/cEEG in<28 weeks premature infants, an analysis was made of our experience with the type of electrodes available. The electrode that was considered most suitable for this population was chosen by assessing: the need of preparing the scalp, speed in positioning the electrodes, if the application was invasive or not, the possibility of repositioning, risk of skin injuries, sterility of the technique, and durability. The electrode chosen was used for continuous electroencephalographic monitoring started in the first 24h of life, and maintained until at least 72h of life. RESULTS: The electrodes evaluated were: subdermal needles, silver cups, and 2 types of self-adhesive electrodes (solid hydrogel and wet gel). The wet gel electrodes were chosen. They were used on 41 neonates with a mean gestational age of 25.8±1.1 weeks. Good stable impedance was rapidly obtained, without the need of excessive manipulations, and no skin injuries were observed. The satisfaction of the staff involved in positioning them was very high. CONCLUSION: The self-adhesive disposable electrodes with wet gel and integrated cable enabled the electrodes to be positioned rapidly and provided continuous non-invasive and good quality aEEG/cEEG monitoring in the extremely premature infant.

Limite de viabilidade de prematuros extremos atendidos em um hospital universitário / Limit of viability of extremely preterm infants treated at a university hospital / Límite de viabilidad de prematuros extremos atendidos en un hospital universitario

Objetivo: descrever o perfil de recém-nascidos com prematuridade extrema e identificar fatores associados a mortalidade segundo idade gestacional e o limite de viabilidade destes. Método: estudo observacional retrospectivo, com abordagem quantitativa, realizado em um hospital universitário do estado de Minas Gerais, desenvolvido de agosto de 2021 a janeiro de 2022. A amostra foi composta por 39 prontuários de prematuros extremos nascidos vivos. Foi realizada a análise descritiva das variáveis quantitativas usando medidas como média, desvio-padrão e valores mínimo e máximo. As variáveis categóricas foram descritas a partir de suas distribuições de frequência absoluta e percentual. Resultados: a maioria das gestantes são mulheres adultos-jovens, realizaram pré-natal e parto cesárea. Dos prematuros prevalece sexo masculino, idade gestacional de 25 semanas, evoluíram para óbito a maioria destes com idade gestacional de 23 e 24 semanas. Conclusão: o limite de viabilidade nesse serviço situa-se em uma idade gestacional igual ou maior que 25 semanas.

Objective: to describe the profile of newborns with extreme prematurity and to identify factors associated with mortality according to gestational age and their limit of viability. Method: a retrospective observational study, with a quantitative approach, carried out in a university hospital in the state of Minas Gerais, developed from August 2021 to January 2022. The sample consisted of 39 records of live-born extreme preterm infants. Descriptive analysis of quantitative variables was performed using measures such as mean, standard deviation and minimum and maximum values. Categorical variables were described from their absolute and percentage frequency distributions. Results: most pregnant women are young-adult women, who underwent prenatal care and cesarean delivery. Of the preterm infants, the male sex prevails, with a gestational age of 25 weeks, most of whom died at a gestational age of 23 and 24 weeks. Conclusion: the limit of viability in this service is at a gestational age equal to or greater than 25 weeks.

Objetivo: describir el perfil de los recién nacidos con prematuridad extrema e identificar los factores asociados a la mortalidad según la edad gestacional y su límite de viabilidad. Método: estudio observacional retrospectivo, con abordaje cuantitativo, realizado en un hospital universitario del estado de Minas Gerais, desarrollado entre agosto de 2021 y enero de 2022. La muestra estuvo compuesta por 39 prontuarios de prematuros extremos nacidos vivos. El análisis descriptivo de las variables cuantitativas se realizó utilizando medidas como la media, la desviación estándar y los valores mínimo y máximo. Las variables categóricas se describieron a partir de sus distribuciones de frecuencia absoluta y porcentual. Resultados: la mayoría de las gestantes son mujeres adultas jóvenes, que realizaron control prenatal y parto por cesárea. De los prematuros prevalece el sexo masculino, con una edad gestacional de 25 semanas, la mayoría de los cuales fallecieron a las 23 y 24 semanas de edad gestacional. Conclusión: el límite de viabilidad en este servicio es a una edad gestacional igual o mayor a 25 semanas.

Transient Myeloproliferative Disorder and Down Syndrome: Is there a link?

An extremely premature male neonate presented with an unusual multisystem dysfunction within the first 24 to 48 hours of life. The unfolding of clinical events and investigations revealed a transient myeloproliferative disorder (TMD). TMD was the main indication for karyotyping of this premature infant without clinical symptoms of Down syndrome. The awareness of TMD in a newborn warrants karyotype analysis to look for trisomy 21 and a close surveillance because of its potential progression to true leukaemia.