Seminars in Fetal & Neonatal Medicine

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Lung surfactant is the first drug so far designed for the special needs of the newborn. In 1929, Von Neergard described lung hysteresis and proposed the role of surface forces. In 1955-1956, Pattle and Clements found direct evidence of lung surfactant. In 1959, Avery discovered that the airway's lining material was not surface-active in hyaline membrane disease (HMD). Patrick Bouvier Kennedy's death, among half-million other HMD-victims in 1963, stimulated surfactant research. The first large surfactant treatment trial failed in 1967, but by 1973, prediction of respiratory distress syndrome using surfactant biomarkers and promising data on experimental surfactant treatment were reported...

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...

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...

Safe and effective management of the neonatal airway requires knowledge, teamwork, preparation and experience. At baseline, the neonatal airway can present significant challenges to experienced neonatologists and paediatric anaesthesiologists, and increased difficulty can be due to anatomical abnormalities, physiological instability or increased situational stress. Neonatal airway obstruction is under recognised, and should be considered an emergency until the diagnosis and physiological implications are understood...

Opportunities to learn and maintain competence in neonatal intubation have decreased. As many clinicians providing care to the newborn infant are not skilled in intubation, alternative strategies are critical. Most preterm infants breathe spontaneously, and require stabilisation rather than resuscitation at birth. Use of tactile stimulation, deferred cord clamping, and avoidance of hypoxia can help optimise breathing for these infants. Nasal devices appear a promising alternative to the face mask for early provision of respiratory support...

Endotracheal intubation is a life-saving procedure for many newborns. Historically, it has been achieved by obtaining an airway view through the mouth via direct laryngoscopy. It is a skill that takes time and practice to achieve proficiency. Increasing evidence for the benefit of videolaryngoscopy in adults and the new development of technology has allowed videolaryngoscopy to become a reality in neonatal care. Studies have examined its use as both a technique to improve intubation safety and success, and as a training tool for those learning the skill in this vulnerable population...

The ex-utero intrapartum treatment (EXIT) procedure was originally developed to reverse tracheal occlusion in fetuses with severe congenital diaphragmatic hernia that underwent fetal tracheal occlusion. The EXIT procedure has since been applied to a wide range of indications, but the primary indication remains securing a patent airway and providing respiratory support in fetuses with anticipated difficult airways. The authors review perinatal management of the anticipated difficult airway and their single-institution's experience with the EXIT procedure...

Interest in 'resurrecting' the lifeless by supporting breathing has been described since ancient times. For centuries, methods of resuscitating animals, then humans and specifically the 'lifeless' neonate were debated and discussed. Over time, with experimentation and worldwide collaboration, endotracheal tubes and laryngoscopes specific to the newborn were created and their use refined. This historical work has meant that today, the neonatal community focuses on refining the science and the art of intubation for the benefit of the newborn; who, where, when and how to intubate, with what devices and medications, bringing about significant change in the area of neonatal intubation...

This chapter focuses on the pharmacological management of newborn infants in the peri-extubation period to reduce the risk of re-intubation and prolonged mechanical ventilation. Drugs used to promote respiratory drive, reduce the risk of apnoea, reduce lung inflammation and avoid bronchospasm are critically assessed. When available, Cochrane reviews and randomised trials are used as the primary sources of evidence. Methylxanthines, particularly caffeine, are well studied and there is accumulating evidence to guide clinicians on the timing and dosage that may be used...

'Apnoeic oxygenation' describes the diffusion of oxygen across the alveolar-capillary interface in the absence of tidal respiration. Apnoeic oxygenation requires a patent airway, the diffusion of oxygen to the alveoli, and cardiopulmonary circulation. Apnoeic oxygenation has varied applications in adult medicine including facilitating tubeless anaesthesia or improving oxygenation when a difficult airway is known or anticipated. In the paediatric population, apnoeic oxygenation prolongs the time to oxygen desaturation, facilitating intubation...

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Airway management is one of the most crucial aspects of neonatal care. The occurrence of a difficult airway is more common in neonates than in any other age group, and any neonatal intubation can develop into a difficult airway scenario. Understanding the intricacies of the difficult neonatal airway is paramount for healthcare professionals involved in the care of newborns. This chapter explores the multifaceted aspects of the difficult neonatal airway. We begin with a review of the definition and incidence of difficult airway in the neonate...

Neonatal endotracheal intubation is a challenging procedure with suboptimal success and adverse event rates. Systematically tracking intubation outcomes is imperative to understand both universal and site-specific barriers to intubation success and safety. The National Emergency Airway Registry for Neonates (NEAR4NEOS) is an international registry designed to improve neonatal intubation practice and outcomes that includes over 17,000 intubations across 23 international sites as of 2023. Methods to improve intubation safety and success include appropriately matching the intubation provider and situation and increasing adoption of evidence-based practices such as muscle relaxant premedication and video laryngoscope, and potentially new interventions such as procedural oxygenation...

In neonatal intensive care, endotracheal intubation is usually performed as an urgent or semi-urgent procedure in infants with critical or unstable conditions related to progressive respiratory failure. Extubation is not. Patients undergoing extubation are typically stable, with improved respiratory function. The key elements to facilitating extubation are to recognize improvement in respiratory status, promote weaning of mechanical ventilation, and accurately identify readiness for removal of the endotracheal tube...

In this review, we examine lung physiology before, during and after neonatal extubation and propose a three-phase model for the extubation procedure. We perform meta-analyses to compare different modes of non-invasive respiratory support after neonatal extubation and based on the findings, the following clinical recommendations are made.

Withdrawal of life sustaining medical treatments is a common mode of death in the neonatal intensive care unit. Shared decision making and communication are crucial steps prior to, during and after a withdrawal of life sustaining medical treatments. Discussion should include the steps to occur during the withdrawal. Physicians should recommend appropriate withdrawal steps based on family goals. Stepwise approach should be taken only if a family requests. Care should continue for the family and staff after the withdrawal and the infant's death...

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Studies have clearly shown that development of pain receptors starts as early as 20-weeks' gestation. Despite contrary belief, the human fetus develops a similar number of receptive pain fibers as seen in adults. These receptors' maturation is based on response to sensory stimuli received after birth which makes the NICU a critical place for developing central nervous system's pain perception. In practice, the assessment of pain relies mostly on bedside staff. In this review we will discuss the various developing features of pain pathways in the neonatal brain and the modification of pain perception secondary to various interactions immediately after birth...

While the underlying principles are the same, there are differences in practice in end of life decisions and care for extremely preterm infants compared with other newborns and older children. In this paper, we review end of life care for extremely preterm infants in the delivery room and in the neonatal intensive care unit. We identify potential justifications for differences in the end of life care in this population as well as practical and ethical challenges.