Due to the clinical importance of early detection of hemodynamic compromise and the limitations of transthoracic echocardiography (TTE) as an intermittent, operator-dependent assessment, the introduction of non-invasive cardiac output monitoring (NICOM) in the neonatal population has generated considerable interest. Electrical biosensing technology (EBT), one type of NICOM modality, offers non-invasive, continuous, bedside assessment of multiple hemodynamic parameters, yet its clinical utility is limited by variable accuracy and precision, lack of interchangeability with TTE and limited trending studies. Despite this, EBT is progressively being used in research and even clinical domains. Advancing continuous EBT-enabled cardiac output monitoring from technologic promise to clinical accountability requires specific neonatal-based refinements of the technology and a strategic shift in research emphasis, moving from method-comparison studies to rigorously designed, outcome-based trials, in order to determine whether EBT-informed management can meaningfully improve neonatal morbidity and mortality.
Neonatal mortality remains a major global health challenge, disproportionately affecting low-resource settings where access to timely and effective resuscitation is limited. Simulation-based training provides a safe and effective method to develop and sustain the cognitive, technical, and behavioural skills essential for neonatal resuscitation, while improving teamwork, confidence, and patient safety. Despite established evidence of its effectiveness in enhancing these skills, widespread implementation of simulation-based training remains limited in resource-constrained settings due to financial, infrastructural, human resource and organizational barriers. This review proposes simulation as a patient safety intervention that supports the shift from traditional error-focused to system resilience approaches. Scalable innovations including low-cost manikins, in situ simulation, telesimulation, and structured debriefing offer practical and sustainable solutions. Future research linking simulation-based training to measurable improvements in neonatal outcomes is essential to inform policy, guide investment, and promote global health equity.
International collaborations between investigators in low-and-middle-income countries (LMICs) and high-income countries (HICs) in neonatal and fetal medicine have expanded over the past decade. This narrative review documents a rise in HIC-LMIC publications since 2014, with a plateau and transient dip during the COVID-19 pandemic. It analyses leadership, patient recruitment, and how HIC-based technologies and laboratory platforms shape research agendas. Many influential trials are conceived and sponsored by HIC institutions, with recruitment concentrated in LMICs because of higher disease burden, larger eligible populations and lower costs. Meanwhile, LMIC centers report growing readiness to support randomized controlled trials, and LMIC-conceived, led and completed multicentre studies are increasingly reported. Ongoing concerns include misalignment between donor priorities and national agendas, inequities in authorship and leadership, and ethical challenges related to standards of care, post-trial access, consent and compensation. The review compares regulatory, consent and insurance processes in India and the United States, and highlights enabling factors such as harmonised guidelines, global registries, political goodwill and professional networks. It anticipates a doubling of HIC-LMIC collaborative studies over the next decade, rapid growth of South-South partnerships, and gradual, though incomplete, correction of authorship and leadership imbalances in global neonatal and fetal medicine.
Intraventricular hemorrhage (IVH) in newborns is a major cause of mortality and neurodevelopmental morbidity in preterm infants, particularly those with low birth weights. A strong inverse relationship exists between gestational age at delivery and the risk of intraventricular hemorrhage, reflecting the immaturity of the germinal matrix. The germinal matrix is a highly active region of the preterm brain with dense but unstable vasculature that is extremely susceptible to injury. This review examines both the pathogenesis of IVH and evidence-based strategies for its prevention. Antenatal interventions, including prevention of prematurity, maternal transfer to higher-level perinatal centers, treatment of intraamniotic infection, antenatal corticosteroids, and magnesium sulfate for neuroprotection, aid in reducing the incidence and severity of IVH. From a delivery standpoint, route of delivery, careful selection of candidates for operative vaginal delivery based on gestational age, and delayed cord clamping can all influence neonatal cerebral outcomes. Understanding IVH as a multifactorial and potentially preventable injury highlights the importance of coordinated obstetric and neonatal care to improve neurodevelopmental outcomes in preterm infants.
Human milk is universally recognized as the optimal source of nutrition for preterm infants, providing immunologic, bioactive, and enzymatic components that provide health benefits and are associated with decreased morbidities of prematurity. However, fortification of both maternal breast milk (MBM) and donor breast milk (DBM) is needed to meet the elevated metabolic needs and nutrient requirements of preterm infants. This narrative review, reflecting the content presented, audience questions, and the roundtable discussion from the 2025 Neonatal Insights Conference, synthesizes current evidence and literature to evaluate the rationale, composition, and outcomes associated with differing fortification approaches. Randomized controlled trials evaluating fortifier type remain limited to small studies with high MBM usage. Future research must focus on trials evaluating fortifier type in infants who receive MBM and those that receive primarily DBM. Advancing fortification practices requires individualized nutrition planning and maternal breastfeeding support to achieve optimal growth and developmental trajectories for preterm infants.
Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) remains one of the most common neurological conditions in very preterm infants, with the incidence increasing with decreasing gestational age. GMH-IVH is associated with adverse neurodevelopmental outcomes and, for the purpose of prognostication, generally categorized into low-grade, i.e., grade 1 and 2 hemorrhage, and high-grade, i.e., grade 3 hemorrhage and periventricular hemorrhagic infarction. Prognosis, however, depends not only on the grade of GMH-IVH but also on co-occurring preterm brain injuries and downstream effects on brain maturation. In case of low-grade hemorrhage, outcomes are negatively affected by co-occurrence of white matter injury or cerebellar hemorrhage. High-grade hemorrhage, especially periventricular hemorrhagic infarction and when complicated by progressive post-hemorrhagic ventricular dilatation requiring neurosurgical intervention, is associated with a significantly higher likelihood of cognitive, motor, behavioral, and neurosensory impairments. Serial cranial ultrasound throughout the neonatal period is critically important to monitor the evolution of hemorrhage, its complications and overt other brain injury types. Brain MRI has additional value for detecting co-occurring subtle brain lesions and improving neuroprognostication. In this review, we summarize the neurodevelopmental outcomes across GMH-IVH grades and the influence of co-existing preterm brain injuries and secondary changes in brain maturation on outcomes. In addition, we recommend approaches to neurological and neurodevelopmental surveillance of preterm infants during neonatal intensive care admission and after discharge.
Intraventricular hemorrhage (IVH) is a major complication of prematurity and one of the top causes of mortality and neurodevelopmental impairment. We conducted a systematic review of PubMed, Scopus, and Web of Science (From 1980 to 2025), identifying 40 studies evaluating prediction models (regression and machine learning) for risk of IVH occurrence and short- and long-term outcomes in preterm infants with IVH. Across these published studies, IVH risk prediction models included combinations of perinatal clinical variables, physiologic and hemodynamic indices, and serum biomarkers. Outcome-prediction models likewise varied. IVH grade was commonly included, with varying inclusion of comorbidities and neuroimaging-based injury markers. Most models performed acceptably, with machine-learning models showing better discrimination in larger datasets. However, the generalizability of the models is limited by heterogeneity in predictors, limited sample sizes, and inconsistent timing of predictor measurements. IVH severity remained the most consistent predictor across all outcome-prediction models. Despite promising performance assessments, clinical relevance is limited due to the infrequent reporting of model calibration, internal validation, and external validation. Future research that standardizes predictor definitions, leverages multicenter cohorts, and ensures thorough validation can advance early IVH risk and outcome-prediction models, thereby meaningfully improving clinical relevance and neonatal care.
Preterm brain injury is multifactorial and can occur at any point along the continuum from prenatal to postnatal life. Management in the few minutes after birth plays a critical role in mitigating the development of brain injury and subsequent adverse neurodevelopmental outcome in very preterm infants born at < 32 weeks of gestation. Facilitating a smooth transition from intrauterine to extrauterine life is a complex and time-sensitive team sport that requires preparation and training. Delivery room interventions aim is to achieve smooth thermal, respiratory, and circulatory physiological transition that ensures adequate perfusion and oxygenation of vital organs, particularly, the brain. Disruption of cerebral blood flow and oxygen delivery during the first minutes of life is a key mechanistic pathway leading to germinal matrix hemorrhage and white matter injury. Vigorous stimulation, excessive respiratory pressures and volumes, and drastic changes in oxygen delivery should be avoided. In this article, common interventions in the delivery room that may impact the development of brain injury will be discussed.
Intraventricular hemorrhage (IVH) remains one of the most consequential complications facing extremely preterm infants, with enduring effects on survival and neurodevelopment. The first 60 min of life (the Golden Hour) offers a uniquely modifiable window to stabilize physiology, smooth cardio-cerebral transition, and implement neuroprotective strategies that may prevent or decrease the risk of IVH. This review synthesizes randomized trials, observational cohorts, and multicenter quality-improvement (QI) initiatives to define a pragmatic, evidence-based approach to Golden Hour care, and extends that approach through the first few days of life with targeted practices in positioning, handling, respiratory management, hemodynamic intervention, nutrition, blood product transfusions, analgesia/sedation, infection mitigation, and family engagement. We emphasize antenatal corticosteroids and maternal magnesium sulfate, delivery at tertiary centers, delayed umbilical cord clamping, meticulous thermoregulation, early use of continuous positive airway pressure and, if intubated, gentle use of ventilation, head-midline with head-of-bed elevation, early yet judicious cardiovascular support, restricted blood sampling, early parenteral nutrition, cautious oxygen targets with limited FiO2 swings, caffeine therapy, restrictive platelet transfusion thresholds, tight sodium control, and structured nursing rounds with minimal stimulation. Checklists and tables model high-reliability care. While not every component is individually proven to reduce severe IVH, bundled and protocolized adoption has repeatedly improved proximate physiological targets and, in several initiatives, reduced IVH incidence. We propose an integrated, time-phased bundle for the Golden Hour and the following few days of life with implementation checklists.
Intraventricular hemorrhage (IVH) is a major cause of mortality and morbidity in preterm infants. As there are no curative treatments for IVH, prevention is the cornerstone of management. A review of the pathogenesis of IVH suggests that interventions that limit disruptions in cerebral blood flow in the first week after birth are the most effective. Evidence-base strategies to prevent IVH after admission to the nursery include: (1) management of preterm respiratory distress syndrome with less invasive surfactant administration, permissive hypercapnia, and volume-targeted ventilation; (2) systematic screening of at-risk preterm infants with targeted neonatal echocardiography for early detection of hemodynamic impairment and provision of individualized cardiovascular support; (3) prophylactic indomethacin; (4) multifaceted approach to prevention of physiologic stressors including early and routine use of kangaroo care. Although reducing rates of IVH may be desirable, the overall benefits and risks need to be considered before implementing any strategy routinely.
Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) continues to be a common form of brain injury in very preterm infants. Cranial ultrasonography (cUS) is the most widely used neuroimaging modality for the diagnosis of GMH-IVH, and serial cUS enables early detection, accurate grading, and monitoring of complications. Brain magnetic resonance imaging (MRI) is being used more commonly in neonates and is superior to cUS for detecting subtle hemorrhages in the temporal and occipital regions, concurrent white matter injury, and cerebellar hemorrhage, as well as for providing prognostic information. Despite major advances in perinatology and neonatology, GMH-IVH remains associated with high rates of neurodevelopmental impairment, especially when complicated by progressive post-hemorrhagic ventricular dilatation or periventricular hemorrhagic infarction. In this review, we present the neuroimaging modalities used in the neonatal intensive care unit and their role in the detection of GMH-IVH, with a focus on preterm infants.
Germinal matrix-intraventricular hemorrhage (GM-IVH) is a major complication of prematurity that contributes significantly to mortality and long-term neurodevelopmental impairments. There are no established treatments to reverse or directly treat the established brain injury resulting from IVH. This review examines the growing evidence that IVH is not simply local destruction of tissue, but that it also triggers a long-lasting cascade of secondary events that may be mitigated with targeted interventions. Strategies may include acute interventions to enhance clot clearance and restore cerebrospinal fluid flow, followed by pharmacological and cellular therapies to mitigate secondary neurotoxicity and the progression to post-haemorrhagic hydrocephalus, by targeting iron overload, oxidative stress, and inflammation, or promoting neurorepair. Finally, we critically evaluate the translational potential of these therapies and outline future directions for research and clinical application.
Posthemorrhagic ventricular dilatation (PHVD) and posthemorrhagic hydrocephalus (PHH) remain major complications of intraventricular hemorrhage in extremely preterm infants. These conditions reflect multifactorial disturbances in cerebrospinal fluid dynamics, involving impaired resorption, obstruction of flow, and inflammation-mediated injury. Advances in neuroimaging and early intervention strategies have improved recognition and management; however, significant variability persists among centers regarding the timing and thresholds for treatment. This review summarizes current understanding of PHVD pathophysiology, brain maturation effects, and evidence-based monitoring and medical management, with particular emphasis on randomized controlled trials and meta-analyses. We emphasize the pivotal role of quantitative cranial ultrasonography and early, individualized intervention in mitigating progressive brain injury and optimizing neurodevelopmental outcomes.
This chapter traces the evolution of intraventricular hemorrhage in the premature infant highlighting the importance of the germinal matrix, a critical role for cerebral blood flow perturbations in the genesis of hemorrhage, clinical factors that increase bleeding risk, and potential preventative strategies. In the 1970`s a neuropathological study demonstrated capillary rupture within the germinal matrix as the source of hemorrhage; loss of cerebral autoregulation in the sick infant was demonstrated. In 1980`s the introduction of cranial ultrasound facilitated diagnosis of hemorrhage. Experimental and clinical studies demonstrated the importance of intravascular perturbations in provoking hemorrhage. Specifically, the association of cerebral blood flow velocity fluctuations and subsequent hemorrhage was demonstrated. Surfactant introduction was not associated with a reduction in hemorrhage. In the 1990`s antenatal steroids use to accelerate lung development was recommended; this was associated with an unanticipated reduction in hemorrhage. Early indomethacin administration was associated with a reduction of severe hemorrhage.
Red blood cell transfusions from adult donors can be lifesaving for neonates with severe anemia or acute massive hemorrhage but can be associated with specific and significant risks. Infectious transmission, acute lung injury, and circulatory overload are well known risks and are part of blood transfusion informed consent. Less well-described, but more common, are the risks that occur when transfusing the smallest and most immature neonates, those less than 1000 g. Repeated adult red cell transfusions may worsen inflammatory conditions, such as pulmonary inflammation, and they can increase the incidence and severity of retinopathy of prematurity and neurodevelopmental delay. In this review, we will provide an overview of neonatal transfusion stewardship including instituting both non-pharmacological transfusion-avoidance techniques and pharmacologic strategies to reduce transfusion rates. Erythropoiesis-stimulating agents like erythropoietin and darbepoetin further reduce and can eliminate the need for a transfusion. Instituting non-pharmacologic and pharmacologic strategies will increase the number of NICU infants who remain transfusion free, even those born weighing less than 1000 g.
