Minesh Khashu ¹ Karel Allegaert ^2,3*

• ¹ University Hospitals Dorset NHS Foundation Trust, Bournemouth, United Kingdom
• ² Department of Development and Regeneration, Faculty of Medicine, KU Leuven, Leuven, Belgium
• ³ KU Leuven, Leuven, Belgium

Neonates and infants are commonly referred to as 'therapeutic orphans' due to the overall scarcity of therapeutic interventions that have been developed and tailored to their needs and specific characteristics (1,2). This is well known by care providers and researchers active in this field, but is perhaps less on the radar of authorities, funding bodies or the broader public.There is significant health inequity when comparing newborns to other age populations in terms of specific drug and device development and therapeutics (1,2). In addition there are health inequities in the provision of neonatal care globally which require special attention in terms of improvement (3).Bronchopulmonary dysplasia, neonatal seizures, poor growth, necrotizing enterocolitis (NEC) and short bowel, hypoxic-ischemic encephalopathy, retinopathy of prematurity (ROP), neonatal infections and sepsis hereby serve as a non-exhaustive list of 'orphan conditions' in need of more equity, through adequately and urgently funded research and improvement.The good news is that there have been increased efforts, in recent years, by researchers and regulatory bodies to focus on the provision of drugs, devices, and treatment modalities tailored for neonatal use, while further advocacy remains an obvious need (2,4,5). This brings perspective and explains the initiative taken to organize a focused research topic on what is on the horizon as well as recent advances. We targeted emerging or new aspects related to monitoring, diagnostics and therapeutics in neonatal care for the current research topic. Fortunately, this research topic was perceived as very relevant by the research community, as 135 authors expressed their interest as contributors, resulting in 20 accepted papers. This serves as a signal of the importance to continue to work on this topic.Post-hoc, and in a somewhat arbitrary way (because of overlap in these subcategories) these papers were subdivided by the editors into different subcategories, with focus on (1, 5 papers) perinatal biomarkers in blood and urine and how these relate to or predict outcomes, (2,6 papers) adaptations of existing and newly emerging equipment in neonatal units, (3, 3 papers) needed advances in pharmacotherapy, (4, 3 papers) machine learning or deep learning applications in neonatal care, and finally, (5, 3 papers) underreported aspects of contemporary NICU care, with a focus on the holistic nature of care for the infant and the family. The currently available medicines and dosing regimens in neonatal care are limited and there is an urgent need for improvement in this domain. This was illustrated by articles on sepsis, septic shock and steroids. Inequity in provision of neonatal care across the globe ought to be a major focus of improvement. Gezahegn et al. described the outcome in neonates admitted with sepsis in Harar (Ethiopia). Low white blood cell count, desaturation, preterm birth, absence of prenatal maternal care, and chorioamnionitis were important risk factors for sepsis-related mortality (Gezahegn et al.). Addressing these prognostic factors hold the promise to act as levelers to improve outcomes. A pilot study compared noradrenaline and adrenaline as first line vasopressor for fluid-refractory sepsis shock (Garegrat et al.). Both interventions were comparable to resolve the septic shock, while the overall mortality (13/42, 30 %) remained significant, highlighting the need for better diagnostic and therapeutic options. Finally, in a systematic review, outcome of postnatal systemic corticosteroids (hydrocortisone to dexamethasone) were compared as reported in randomized controlled trials (Boscarino et al.). The authors concluded that dexamethasone appeared to be somewhat more effective than hydrocortisone in improving respiratory outcomes, but with inconclusive but relevant concerns on the uncertainties on long-term neurodevelopmental outcome, again highlighting the need for better therapies for prevention and management of chronic lung disease of prematurity Artificial intelligence is a rapidly advancing area with fast evolving clinical applications in healthcare, including in the NICU (6). It is no surprise that the current research topic also contains papers illustrating its relevance to improve our practices and outcomes. Two papers hereby focused on NEC, and a 3rd paper on prediction of significant patent ductus arteriosus A prediction model for closure on day 7 included birth weight, mechanical ventilation, left ventricular end-diastolic diameter, and PDA intimal thickness (Hu et al.). Such models can be considered to better target future study, integrated in a precision medicine approach. Use of AI and big data have the potential to significantly improve our understanding of neonatal conditions and also support neonatal researchers in asking better research questions. As part of this research topic, we also accepted papers reporting on the use of music on pain management, on multisensory stimulation to improve maternal milk volume production, and parents' experiences related to congenital cardiac surgery. All these 3 papers reflect the need for holistic care and to further integrate the perspectives of (former) patients and parents into neonatal practice. In our opinion, this research topic nicely illustrates the diversity in ongoing clinical research activities, that all hold the promise to improve our clinical management practices, with the overarching aim to improve neonatal outcomes. There is an urgent need to focus on the current health inequities in the provision of care to neonates (3). The trend towards a 'neuro' dedicated NICU care is an illustration on how relevant progress may occur. This progress is based on improved neuromonitoring techniques (7), improved management and precision medicine in the field of anti-epileptic drugs (8), and integrating families as partners in neonatal neuro-critical care and similar improvement programs (9). The good news is that we are already experiencing a shift in the right direction. The neonatal community and all other relevant stakeholders need to work better together to improve the pace and scale of this improvement.