Neonatal hypoxic-ischemic encephalopathy (HIE) remains a major cause of death and disability around the world. Therapeutic hypothermia is now established to improve outcomes in term and near-term infants in high-income c...Neonatal hypoxic-ischemic encephalopathy (HIE) remains a major cause of death and disability around the world. Therapeutic hypothermia is now established to improve outcomes in term and near-term infants in high-income countries, but even in this setting, many infants still survive with disability. To further improve outcomes, experimental models are needed to test new interventions before clinical translation. In the present review, we discuss the strengths and weaknesses of a range of near-term and term models and their utility for understanding the pathophysiology of HIE and to test potential treatments. It is important to reflect that the strength of the evidence base for therapeutic hypothermia before it went to trial was that multiple groups using different and complementary models all showed benefit and that these models had been used to define the key parameters needed to achieve neuroprotection. We strongly advocate that this should be the expectation for all new neuroprotective interventions before large pragmatic randomized controlled trials are carried out.
Neonatal encephalopathy of hypoxic-ischemic origin remains a leading cause of global neonatal mortality. Over the past decades, various neuroprotective strategies have been explored; however, therapeutic hypothermia rema...Neonatal encephalopathy of hypoxic-ischemic origin remains a leading cause of global neonatal mortality. Over the past decades, various neuroprotective strategies have been explored; however, therapeutic hypothermia remains the only clinically approved intervention to date. This review outlines emerging and adjunctive treatment modalities beyond therapeutic hypothermia and emphasizes the critical need for robust and reproducible translational research to bridge the gap between preclinical findings and clinical applications.
Brain magnetic resonance imaging (MRI) in neonates with presumed hypoxic-ischemic encephalopathy (HIE) offers a unique window into the extent and timing of injury, providing valuable insights for neuroprognostication. Br...Brain magnetic resonance imaging (MRI) in neonates with presumed hypoxic-ischemic encephalopathy (HIE) offers a unique window into the extent and timing of injury, providing valuable insights for neuroprognostication. Brain MRI refines the prediction of functional outcomes, crucial for guiding family counseling and early interventions. The present article focuses on the role of post-rewarming brain MRI in this context, exploring specific MRI findings associated with diverse neurodevelopmental outcomes and highlights the potential of neuroimaging to improve the understanding and prediction of long-term functional outcomes. Utilizing a framework with likelihood categories, this work aims to enhance the accuracy of prediction of adverse outcomes within specific developmental domains, thereby refining neuroprognostication for informed discussions with caregivers.
Neonatal neurocritical care (NNCC) has emerged as a specialized discipline to address the unique neurological needs of critically ill newborns. However, disparities in access to brain-focused expertise and neuromonitorin...Neonatal neurocritical care (NNCC) has emerged as a specialized discipline to address the unique neurological needs of critically ill newborns. However, disparities in access to brain-focused expertise and neuromonitoring technologies remain a significant global challenge. Remote NNCC, supported by telemedicine and digital health tools, offers a promising approach to extend specialized neurological care beyond tertiary centers, particularly to underserved or resource-limited settings. This review explores the current landscape, opportunities, and limitations of remote NNCC. Key applications include remote consulting and rounding, tele-interpretation of neurophysiological data, integration of multimodal monitoring, remote neuroimaging evaluation, and virtual neurological examinations. Additionally, telehealth platforms are increasingly used to support neurodevelopmental follow-up and therapeutic interventions after NICU discharge. These approaches can enhance diagnostic precision, enable timely intervention, reduce unnecessary transfers, and promote equity in care delivery. Advancements in artificial intelligence, immersive reality, and digital twins modeling may further expand the capabilities of remote NNCC. These emerging technologies hold the potential to optimize real-time decision-making, personalize interventions, and foster large-scale collaboration through cloud-based data integration. However, significant barriers remain, including limitations in infrastructure, interoperability between systems, variability in training, and ethical concerns related to data privacy, algorithmic bias, and equitable access. To ensure the safe and effective adoption of remote NNCC, standardized protocols, robust governance frameworks, and investments in workforce development and infrastructure are essential. Interdisciplinary collaboration and global partnerships will be critical in addressing these challenges and realizing the full potential of remote NNCC in improving neurological outcomes for high-risk neonates worldwide.
Neonatal neuroimaging is essential in research and clinical practice, offering important insights into brain development and neurologic injury mechanisms. Visualizing the brain enables researchers and clinicians to impro...Neonatal neuroimaging is essential in research and clinical practice, offering important insights into brain development and neurologic injury mechanisms. Visualizing the brain enables researchers and clinicians to improve neonatal care and parental counselling through better diagnosis and prognostication of disease. Common neuroimaging modalities used in the neonatal intensive care unit (NICU) are cranial ultrasonography (cUS) and magnetic resonance imaging (MRI). Between these modalities, conventional MRI provides the optimal image resolution and detail about the developing brain, while advanced MRI techniques allow for the evaluation of tissue microstructure and functional networks. Over the last two decades, medical imaging techniques using brain MRI have rapidly progressed, and these advances have facilitated high-quality extraction of quantitative features as well as the implementation of novel devices for use in neurological disorders. Major advancements encompass the use of low-field dedicated MRI systems within the NICU and trials of ultralow-field portable MRI systems at the bedside. Additionally, higher-field magnets are utilized to enhance image quality, and ultrafast brain MRI is employed to decrease image acquisition time. Furthermore, the implementation of advanced MRI sequences, the application of machine learning algorithms, multimodal neuroimaging techniques, motion correction techniques, and novel modalities are used to visualize pathologies that are not visible to the human eye. In this narrative review, we will discuss the fundamentals of these neuroimaging modalities, and their clinical applications to explore the present landscape of neonatal neuroimaging from bench to bedside.
Neurally Adjusted Ventilatory Assist (NAVA) is an innovative ventilation mode that empowers patients to control both the timing and level of ventilatory support. By utilizing the electrical activity of the diaphragm (Edi...Neurally Adjusted Ventilatory Assist (NAVA) is an innovative ventilation mode that empowers patients to control both the timing and level of ventilatory support. By utilizing the electrical activity of the diaphragm (Edi) as the control signal, NAVA enables synchronized non-invasive ventilation (NIV-NAVA) even in the presence of leaks, while also providing continuous monitoring of the patient's respiratory pattern and drive. NIV-NAVA offers several advantages compared to conventional non-invasive ventilation, including enhanced patient-ventilator interaction and synchrony, reliable respiratory monitoring, and self-regulation of respiratory support. These features make NIV-NAVA theoretically ideal for providing effective and tailored non-invasive support to newborns with respiratory insufficiency. In clinical practice, NIV-NAVA has been successfully employed in neonates to prevent intubation, facilitate early extubation, and deliver nasal continuous positive airway pressure in a novel manner. Set up and management of NAVA has unique differences from conventional ventilation and an understanding of these is essential for successful NAVA ventilation. The efficacy of this approach in neonatal care is supported by numerous studies and clinical experiences with NIV-NAVA, demonstrating its potential to improve outcomes for infants with respiratory challenges.
Hypoxic-ischemic encephalopathy (HIE) remains one of the leading causes of neonatal morbidity and mortality despite advancement in care. Over 60 % of infants presenting with phenotypic HIE lack a clear identifiable acute...Hypoxic-ischemic encephalopathy (HIE) remains one of the leading causes of neonatal morbidity and mortality despite advancement in care. Over 60 % of infants presenting with phenotypic HIE lack a clear identifiable acute sentinel event. Clinical genetic testing in neonates with suspected HIE has uncovered an increasing number of genetic conditions and epigenetic modifications that impair their ability to tolerate the stress of labor and delivery or exacerbate the severity of clinical symptoms following a hypoxic-ischemic insult. While most of those conditions are rare, many of the identified alterations involve common biological pathways and organ systems - particularly those affecting energy metabolism or the function of cells and organs of high energy demand such as brain, heart, and skeletal muscle - as well as genetic epilepsies. Here we provide an overview of the genetic makeup and epigenetic signatures associated with HIE and the insights they have provided into distinguishing genetic etiologies from true HIE. By outlining modern genetic testing modalities and their clinical applications, we provide a structured diagnostic approach for clinicians evaluating neonates with phenotypic HIE and highlight the clinical and therapeutic implications of early genetic diagnosis. This review underscores the critical importance of recognizing that HIE may not always represent a purely hypoxic-ischemic etiology, but rather a final common pathway influenced by underlying genetic predisposition and environmental factors that highlight the potential for precision medicine approaches to improve outcomes in this vulnerable population.
The 2023 U.S. Surgeon General's Advisory on the Mental Health and Well-Being of Parents highlights the critical role parents play in family and societal health and underscores the urgent need to address the growing menta...The 2023 U.S. Surgeon General's Advisory on the Mental Health and Well-Being of Parents highlights the critical role parents play in family and societal health and underscores the urgent need to address the growing mental health challenges faced by parents. For parents with an infant in the Neonatal Intensive Care Unit, the key stressors identified in the advisory - such as financial strain, lack of childcare, lack of paid or universal leave from employment, social isolation, and mental health stigma- are often compounded by the trauma, uncertainty, and emotional toll of hospitalization. The advisory calls for coordinated, systemic efforts to support parental mental health, which is critical in the Neonatal Intensive Care Unit where parental well-being directly impacts child outcomes.
Extreme prematurity is associated with significant risk of mortality and morbidities. Neonatal follow-up assesses health outcomes of babies as they grow older to improve care and contribute to research and quality improv...Extreme prematurity is associated with significant risk of mortality and morbidities. Neonatal follow-up assesses health outcomes of babies as they grow older to improve care and contribute to research and quality improvement initiatives. Recent investigations demonstrate that parents and clinicians/researchers disagree about what is defined as a "severe outcome". Families report they need balanced information about functioning rather than medical diagnoses. Many functional domains other than the presence/absence of impairment are not evaluated during neonatal follow-up. This article recommends how to shift communication with parents of preterm infants throughout the NICU hospitalization - from discussions that are medicalized and deficit-based to those that reflect the processes of growth and development. This includes understanding family-important outcomes and how to communicate with parents using the 'F-words' for child development based on the World Health Organization's integrated biopsychosocial framework for health: Functioning, Family, Fitness, Fun, Friends, and Future.
Semin Perinatol
· 2025 Oct · PMID 40518318
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Full text
Exome or genome sequencing (ES/GS) is increasingly used as the first-line test for postnatal diagnosis of rare genetic conditions, especially in intensive care units (ICUs). Early concerns regarding the use of broad gene...Exome or genome sequencing (ES/GS) is increasingly used as the first-line test for postnatal diagnosis of rare genetic conditions, especially in intensive care units (ICUs). Early concerns regarding the use of broad genetic testing centered on the potential for psychosocial harm, particularly related to unexpected or uncertain findings. As the usage of ES/GS has grown and evolved, the ethical concerns initially raised have not borne out in empirical measurement of patient and family experience. We therefore review the use of diagnostic genomic sequencing in the neonatal intensive care unit with comparison to other standard diagnostic tests that have not elicited similar ethical questioning. We frame this landscape within the concept of genetic contextualism rather than exceptionalism and suggest that this approach may lead to a more productive future for applied genomic medicine, especially for sick neonates and infants in the NICU.
Some life-limiting conditions associated with significant neurodevelopmental impairment, such as trisomy 13/18, have historically been considered lethal, thus medical or surgical treatments would be inappropriate. Evolvi...Some life-limiting conditions associated with significant neurodevelopmental impairment, such as trisomy 13/18, have historically been considered lethal, thus medical or surgical treatments would be inappropriate. Evolving literature has shown that early death is not universal, and though all who survive with trisomy 13/18 will have significant impairments, some experience a positive quality of life. The presence of bias impacts counseling as well as what interventions are offered and/or provided to families of a child with anticipated significant disability. Shared decision-making processes should include parents receiving all relevant information about comfort care as well as available, indicated, and ethically permissible medical/surgical interventions. Ethical frameworks can help clarify which options would be permissible to offer or withhold on an individualized basis. Clinicians are encouraged to be open to revisiting past and sometimes long-established practices regarding patients with disability. A willingness to change should not be perceived as an indictment of past practice.
Climate change has severe consequences for neonatal health. Neonates are uniquely vulnerable to the impacts of climate change due to their developing bodies and immature immune and thermoregulatory systems. Climate chang...Climate change has severe consequences for neonatal health. Neonates are uniquely vulnerable to the impacts of climate change due to their developing bodies and immature immune and thermoregulatory systems. Climate change increases the risk of severe weather events, including extreme heat and natural disasters, as well as pollution and chemical exposures. The physiologic fragility of neonates and dependence on a stable environment require healthcare systems and policymakers to ensure protections are in place to mitigate health risks and potential impacts that will have long-lasting effects on individual development and well-being. The current article details the impacts of climate change on neonatal health across the lifecycle as well as the disproportionate consequences for communities most vulnerable to climate change. We provide evidence as to why this is a bioethical issue and offer recommendations for policies to protect neonatal health and promote environmental and climate justice.
Ableism plays a pervasive yet often unexamined role in decision-making at extreme prematurity. This review examines how ableist assumptions about quality of life, normalcy, and parental burden can shape clinical counseli...Ableism plays a pervasive yet often unexamined role in decision-making at extreme prematurity. This review examines how ableist assumptions about quality of life, normalcy, and parental burden can shape clinical counseling and influence decisions regarding resuscitation and intensive care for extremely preterm infants. Drawing on literature from neonatology, disability studies, and bioethics, the article explores the historical and sociocultural roots of ableist thinking in medicine and its manifestations in prognostic framing, risk communication, and institutional norms. Strategies for recognizing and addressing ableism in clinical practice are reviewed, including approaches to anti-ableist communication, family-centered care, and medical education reform. The article argues that adopting an explicitly anti-ableist stance is essential for promoting ethical, inclusive, and genuinely shared decision-making in the neonatal intensive care unit (NICU) and calls for greater interdisciplinary collaboration to support systemic change.
The integration of artificial intelligence (AI) into neonatology offers improved patient care while raising ethical challenges across four principles: beneficence, non-maleficence, justice, and autonomy. AI enhances pred...The integration of artificial intelligence (AI) into neonatology offers improved patient care while raising ethical challenges across four principles: beneficence, non-maleficence, justice, and autonomy. AI enhances prediction and early detection capabilities, but introduces concerns including the "black box" nature of many algorithms, which compromises transparency and may propagate existing biases. Justice considerations arise from potential inequities in AI development and deployment. Autonomy is challenged when clinicians cannot fully explain algorithmic decision-making, affecting shared decision-making with families. These ethical tensions are particularly acute in neonatology, where decisions impact vulnerable patients who cannot advocate for themselves. Mitigating these challenges requires developing transparent AI systems, ensuring diverse training data, maintaining human oversight of clinical decisions, and conducting rigorous validation across diverse healthcare settings. Responsible implementation requires balancing technological benefits with ethical principles.
Perinatal palliative care (PnPC) is a relatively new branch of pediatric palliative care (PPC), which focuses on providing holistic care in the antenatal, delivery, and neonatal settings. In this paper, we address previo...Perinatal palliative care (PnPC) is a relatively new branch of pediatric palliative care (PPC), which focuses on providing holistic care in the antenatal, delivery, and neonatal settings. In this paper, we address previously unexplored justice-based ethical questions related to the provision of PnPC. We examine why some families who receive the diagnosis of a potentially life-limiting condition in their baby before or after birth receive PnPC support whilst others do not. We describe current inequities in the access to, and delivery of, PnPC. Drawing on philosophical theory (the Capabilities Approach) we argue that palliative care represents a valuable capability for babies with life limiting illness and their families. Health professionals should advocate for and promote access to this option for all families, regardless of whether it is ultimately taken up.
There are significant racial and ethnic inequities in neonatal care. These inequities are the result of the multiple levels of racism: structural, institutional, interpersonal, and internalized racism. Recently, there ha...There are significant racial and ethnic inequities in neonatal care. These inequities are the result of the multiple levels of racism: structural, institutional, interpersonal, and internalized racism. Recently, there has been significantly increased attention to measuring and addressing inequities for minoritized infants and their families. One way to support these strategies is to clarify the bioethical justification for allocating clinical, research and educational resources to address inequity. In this narrative review, we describe two bioethical frameworks-the four pillars and the ethics of care-as a foundation to justify equity-focused research, investigation, and interventions. We focus on these two frameworks with specific attention to their application to micro- and macro-level racism. Finally, we conclude with a case example to illustrate how to employ bioethical frameworks in neonatal health equity efforts. Through this narrative review, we demonstrate that pursing neonatal health equity is, in fact, a bioethical imperative.
In medicine, the technological imperative presupposes the inevitable and essential adoption of technologies for the benefit of patients and society. Recent advances in maternal-fetal interventions have followed technolog...In medicine, the technological imperative presupposes the inevitable and essential adoption of technologies for the benefit of patients and society. Recent advances in maternal-fetal interventions have followed technological advances in prenatal diagnostic imaging and genetic testing, anesthesiology, and fetal surgical capabilities. Applied here, the technological imperative raises important ethical questions regarding maternal autonomy, informed consent, and decision-making. The ethical or moral arguments for employing such technology rest with the clinician(s) who offer, use, and state that it is the correct thing to do, and who must also be cognizant of the limits of technology and the assumptions represented by other imperatives. There is a need for the education of ethicists and clinicians about the implications and limitations of the technological imperative in this field. Fetal health centers should collaborate with bioethicists at the patient, committee, and program development levels as the field continues to advance.
Non-invasive ventilation (NIV) commenced soon after birth is highly effective in providing mechanical respiratory support for preterm infants with respiratory distress syndrome (RDS). However, NIV alone frequently fails...Non-invasive ventilation (NIV) commenced soon after birth is highly effective in providing mechanical respiratory support for preterm infants with respiratory distress syndrome (RDS). However, NIV alone frequently fails to provide adequate respiratory support for infants with more significant respiratory compromise due to RDS. Without an endotracheal tube as the conduit to administer exogenous surfactant in such cases, less invasive approaches to surfactant delivery have emerged, with those involving the use of a thin catheter (termed minimally invasive surfactant therapy, MIST) now in the ascendancy. The application of MIST with NIV support continuing allows spontaneous breathing to be harnessed for optimal surfactant dispersal to the distal airspaces. Here we examine the importance of this pairing of NIV with MIST and review the evidence for optimization of NIV before, during and after delivery of surfactant. All evidence points to NIV and MIST being an elegant and synergistic pairing of two therapies for optimal respiratory support of preterm infants in early life. Whilst much of the clinical trial data regarding the pairing of NIV and MIST relates to application of standard continuous positive airway pressure, non-invasive positive pressure ventilation in its various forms may offer additional advantage, and further studies are warranted.