Seminars in Fetal & Neonatal Medicine最新文献

Neonatal encephalopathy (NE) is a diagnosis that is usually unexpected. Though there are many risk factors for the condition and multiple theories as to its genesis, the majority of cases cannot be predicted prior to the occurrence of the clinical syndrome. Indeed, it is common for a pregnant person to have multiple risk factors and a completely healthy child. Conversely, people with seemingly no risk factors may go on to have a profoundly affected child. In this synopsis we review risk factors, potential mechanisms for encephalopathy, the complicated issue of choosing which morbidity to take on and how the maternal level of care may influence outcomes. The reader should be able to better understand the limitations of current testing and the profound levels of maternal intervention that have been undertaken to prevent or mitigate the rare, but devastating occurrence of NE. Further, we suggest candidate future approaches to prevent the occurrence, and decrease the severity of NE. Any future improvements in the NE syndrome cannot be achieved via obstetric intervention and management alone or conversely, by improvements in treatments offered post-birth. Multidisciplinary approaches that encompass prepregnancy health, pregnancy care, intrapartum management and postpartum care will be necessary.

Surfactant is a pivotal neonatal drug used both for respiratory distress syndrome due to surfactant deficiency and for more complex surfactant dysfunctions (such as in case of neonatal acute respiratory distress syndrome). Despite its importance, indications for surfactant therapy are often based on oversimplified criteria. Lung biology and modern monitoring provide several diagnostic tools to assess the patient surfactant status and they can be used for a personalized surfactant therapy. This is desirable to improve the efficacy of surfactant treatment and reduce associated costs and side effects. In this review we will discuss these diagnostic tools from a pathophysiological and multi-disciplinary perspective, focusing on the quantitative or qualitative surfactant assays, lung mechanics or aeration measurements, and gas exchange metrics. Their biological and technical characteristics are described with practical information for clinicians. Finally, available evidence-based data are reviewed, and the diagnostic accuracy of the different tools is compared. Lung ultrasound seems the most suitable tool for assessing the surfactant status, while some other promising tests require further research and/or development.

The introduction of exogenous surfactant in the 1980s has resulted in an improved survival of very preterm infants with respiratory distress syndrome (RDS). Randomized controlled trials conducted before 2000 have shown that the magnitude of this beneficial effect strongly depends on the timing of surfactant treatment, i.e. the earlier surfactant is administered after birth the better. However, the initial mode of respiratory support in infants with RDS has changed dramatically over the last decades, moving from invasive to non-invasive support. Furthermore, new, less invasive techniques to administer surfactant have been introduced to match this non-invasive approach. This review summarizes the evidence on how these practice changes impacted the effect of surfactant timing on mortality and morbidity in preterm infants with RDS.

Surfactant replacement therapy (SRT) has revolutionized the management of respiratory distress syndrome (RDS) in premature infants, leading to improved survival rates and decreased morbidity. SRT may, however, be associated with hemodynamic changes, which can have both positive and negative effects on the immature cardiovascular system, during the transitional adaptation from fetal to extrauterine environment. However, there is a relative paucity of evidence in this domain, with most of them derived from small heterogeneous observational studies providing conflicting results.

In this review, we will discuss the hemodynamic changes that occur with surfactant administration during this vulnerable period, focusing on available evidence regarding changes in pulmonary and systemic blood flow, cerebral circulation and their clinical implications.

Whilst exogenous surfactant therapy is central to the management of newborn infants with respiratory distress syndrome, its use in other neonatal lung diseases remains inconsistent and controversial. Here we discuss the evidence and experience in relation to surfactant therapy in newborns with other lung conditions in which surfactant may be deficient or dysfunctional, including meconium aspiration syndrome, pneumonia, congenital diaphragmatic hernia and pulmonary haemorrhage. We find that, for all of these diseases, administration of exogenous surfactant as bolus therapy is frequently associated with transient improvement in oxygenation, likely related to temporary mitigation of surfactant inhibition in the airspaces. However, for none of them is there a lasting clinical benefit of surfactant therapy. By virtue of interrupting disease pathogenesis, lavage therapy with dilute surfactant in MAS offers the greatest possibility of a more pronounced therapeutic effect, but this has yet to be definitively proven. Lavage therapy also involves a greater degree of procedural risk.

Surfactant replacement therapy (SRT) by nebulization to spontaneously breathing patients has been regarded as the Holy Grail since surfactant deficiency was first identified as the cause for neonatal respiratory distress syndrome. It avoids neonatal endotracheal intubation, a procedure that is often difficult and occasionally harmful. Unapproved alternatives to endotracheal tube placement for liquid surfactant instillation, such as LISA (thin catheter intubation) and SALSA (supraglottic airway insertion) have significant merit but are still invasive, leaving nebulized SRT as the only truly non-invasive method. In the past 60 years, we have learned much about the potential - and limitations - of nebulized SRT. In this review, we examine the promises and pitfalls of nebulized SRT, discuss what we know about neonatal aerosol drug delivery and recap some of the most recent randomized clinical trials of nebulized SRT. We conclude with a discussion of what is known and the next steps needed if this type of SRT is to become a regular part of clinical care.

Drug delivery using a surfactant vehicle has the potential to prevent systemic side effects by delivering therapeutic agents directly to the respiratory system. The inherent chemical properties of surfactant allows it to readily distribute throughout the respiratory system. Therapeutic agents delivered by surfactant can primarily confer additional benefits but have potential to improve surfactant function. It is critically important that additional agents do not interefere with the innate surface tension lowering function of surfactant. Systemic evaluation through benchtop, translational and human trials are required to translate this potential technique into clinical practice.