Seminars in Fetal & Neonatal Medicine

Title Page/Aims and Scope/Editorial Board

2010-08-01

Oxygen as a therapeutic agent in neonatology: a comprehensive approach

Maximo Vento, Ola Didrik Saugstad — 2010-05-24

Oxygen is among the most common elements in nature and probably one of the most frequently employed drugs in neonatology. As a final acceptor of highly energised electrons, oxygen is the key element of aerobic metabolism. Thus, oxidative phosphorylation, which couples the Krebs cycle with the electron transport chain in the mitochondria, allows living organisms to very efficiently extract energy from basic nutrients. However, as by-products of oxidative metabolism, reactive oxygen species (ROS) are produced, some of which are highly reactive free radicals that are capable of causing structural and functional damage to nearby standing molecules. Other ROS will act as signalling molecules implicated in the regulation of metabolic pathways. When the equilibrium between production of free radicals and the enzymatic and non-enzymatic antioxidant defence system is lost in favour of pro-oxidant agents, oxidative stress will ensue with accompanying damage to tissue and enhanced expression of inflammatory transcription factors.

Oxygen toxicity: chemistry and biology of reactive oxygen species

Giuseppe Buonocore, Serafina Perrone, Maria Luisa Tataranno — 2010-05-24

Summary: Oxygen has a central role in the evolution of complex life on Earth mainly because of the biochemical symmetry of oxygenic photosynthesis and aerobic respiration that can maintain homeostasis within our planet biosphere. Oxygen can also produce toxic molecules, reactive oxygen species (ROS). ROS is a collective term that includes both oxygen radicals and certain oxidizing agents that are easily converted into radicals. They can be produced from both endogenous and exogenous substances. ROS play a dual role in biological systems, since they can be either harmful or beneficial to living systems. They can be considered a double-edged sword because on the one hand oxygen-dependent reactions and aerobic respiration have significant advantages but, on the other, overproduction of ROS has the potential to cause damage.

Maturation of the antioxidant system and the effects on preterm birth

Jonathan M. Davis, Richard L. Auten — 2010-05-10

Summary: The study of the interplay of the generation of reactive oxygen and nitrogen species with their related antioxidant enzymes at the maternal–placental–fetal interfaces during normal and abnormal pregnancy is in its ‘infancy’. Our understanding of the role of antioxidant systems during fetal and neonatal development is constantly changing with research better defining the biological roles of these highly reactive species and the maintenance of optimal oxidant/antioxidant balance. The antioxidant enzyme system is upregulated during the last 15% of gestation, a timeframe when non-enzymatic antioxidants are also crossing the placenta in increasing concentrations. These developmental changes provide for the transition from the relative hypoxia of intrauterine development to the oxygen-rich extrauterine environment. Preterm birth is associated with an increased oxidant burden which places these infants at much higher risk of injury. This is especially true since studies have failed to reveal significant induction of antioxidants in response to the increased generation of these reactive species. Improved understanding of these relationships will be necessary for the development of rational treatments aimed at improving pregnancy outcomes and reducing the burden of oxidative stress to premature newborns.

Hypoxia-inducible factor (HIF) and HIF-stabilizing agents in neonatal care

Angela M. Park, Timothy A. Sanders, Emin Maltepe — 2010-07-05

Summary: Oxygen is essential for multicellular existence. Its reduction to water by the mitochondrial electron transport chain forms the cornerstone of aerobic metabolism. Conditions in which oxygen is limiting for electron transport result in bioenergetic collapse in metazoans. However, compared with postnatal existence, all of mammalian development occurs in a hypoxic environment in utero. Not just an epiphenomenon, this ‘physiological hypoxia’ is required for the activation of a transcriptional response mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators that coordinates the expression of hundreds of genes, many with developmentally critical functions. Oxygen tension, therefore, is a morphogen. Understanding the physiological significance of hypoxia responses during human development and the role of the HIF family of transcriptional regulators will have important consequences for the care of preterm neonates. Defining clinical care guidelines for the proper oxygenation of critically ill neonates that take account of these observations is therefore of paramount importance. The pharmacological stabilization of HIF family members may therefore have clinical utility in premature infants in whom this important morphogen has been inactivated by exposure to supraphysiological oxygen levels.

Monitoring oxygen saturation and heart rate in the early neonatal period

J.A. Dawson, C.J. Morley — 2010-05-04

Summary: Pulse oximetry is commonly used to assist clinicians in assessment and management of newly born infants in the delivery room (DR). In many DRs, pulse oximetry is now the standard of care for managing high risk infants, enabling immediate and dynamic assessment of oxygenation and heart rate. However, there is little evidence that using pulse oximetry in the DR improves short and long term outcomes. We review the current literature on using pulse oximetry to measure oxygen saturation and heart rate and how to apply current evidence to management in the DR.

Peripheral oxygenation and management in the perinatal period

A. Michael Weindling — 2010-05-21

Summary: The mechanisms for the adequate provision of oxygen to the peripheral tissues are complex. They involve control of the microcirculation and peripheral blood flow, the position of the oxygen dissociation curve including the proportion of fetal and adult haemoglobin, blood gases and viscosity. Systemic blood pressure appears to have little effect, at least in the non-shocked state. The adequate delivery of oxygen (DO2) depends on consumption (VO2), which is variable. The balance between VO2 and DO2 is given by fractional oxygen extraction (FOE=VO2/DO2). FOE varies from organ to organ and with levels of activity. Measurements of FOE for the whole body produce a range of about 0.15–0.33, i.e. the body consumes 15–33% of oxygen transported.

Resuscitation of the term and preterm infant

M. Vento, O.D. Saugstad — 2010-05-07

Summary: Resuscitation is one of the most frequently performed procedures in the neonatal period. Since the most recent guidelines from the International Liaison Committee on Resuscitation (ILCOR) appeared in 2005, experimental and clinical research has introduced changes regarding the different components of the procedure, with the common denominator being the least aggressive to the baby. Babies should be kept warm, avoiding suctioning as a general rule, adjusting pressure, volume and oxygen to the minimum to achieve stabilisation without causing harm to the airways or oxidative stress, and applying all the available technology in the delivery room before transportation to the neonatal intensive care unit. The response to ventilation should primarily be assessed by the heart rate. Babies of gestational age ≥32 weeks should be ventilated initially with 21% oxygen and if <32 weeks with 21–30% oxygen. Intubation, chest compressions, use of drugs or volume therapy are rarely needed in term or near term babies in need of resuscitation. The first minutes of life are decisive, and what we do during these minutes will have unequivocal influence later on.

Hyperoxia-derived lung damage in preterm infants

Vineet Bhandari — 2010-04-30

Summary: Hyperoxia-induced lung injury is characterized by an influx of inflammatory cells, increased pulmonary permeability, endothelial and epithelial cell death. This review highlights the mechanistic aspects of inflammation, vascular leak and cell death. The focus will be on agents that contribute to hyperoxia-induced lung injury in developmentally appropriate animal models, and those that have been detected in human premature neonates.

Long term consequences of oxygen therapy in the neonatal period

Alan H. Jobe, Suhas G. Kallapur — 2010-05-10

Summary: Preterm and term infants are frequently exposed to high concentrations of oxygen for prolonged periods. In experimental models, high and prolonged oxygen exposures cause delayed alveolar septation and a bronchopulmonary dysplasia phenotype. Often, however, the oxygen exposure is tolerated in that the infants recover without severe lung or systemic injury. Multiple exposures change oxygen sensitivity in adult and newborn animals. Examples are antenatal corticosteroids, inflammatory mediators or preconditioning with oxygen, which will increase tolerance to oxygen injury. Intrauterine growth restriction or postnatal nutritional deficits will increase oxygen injury. Different infants probably have quite variable sensitivities to oxygen injury, but there are no biomarkers available to predict the risk of oxygen injury.