Seminars in neonatology : SN最新文献

Over 400 rare, biochemically diverse genetic metabolic disorders (inborn errors of metabolism) have been described and the list is growing by the month. Although recent advances in the diagnosis and treatment of these disorders have substantially improved the prognosis for many of them, including those presenting in the neonatal period, a proportion of affected individuals die before the diagnosis can be confirmed and, in some cases, before the diagnosis is even considered. This review will provide an outline of the range of clinical presentations seen in neonates with genetic metabolic disorders and provide a practical approach for rapid biochemical screening for these disorders. In addition, suggested guidelines are given for the collection of relevant samples in the perimortem period, the aim being to maximize the chance of identifying any underlying genetic metabolic disorder.

Apnoea is common in the newborn period and especially in preterm newborns. Bradycardia and desaturation of oxyhaemoglobin typically occur with apnoea. These abnormalities reflect an immature cardiorespiratory system and resolution of this immaturity can be expected within a predictable time frame. Infants who have apnoea in the newborn period are thought not to be at higher risk for sudden infant death syndrome (SIDS). Whether apnoea episodes are associated with a higher incidence of long-term handicap for these infants is not yet clear.

Episodes of apnoea, desaturation and bradycardia are a common occurrence in preterm infants and are known to persist after hospital discharge. These events are typically detected by clinical bedside monitoring, but the type and number of events depend on alarm settings, the inclusion of continuous pulse oximetry and the mode of respiratory monitoring used. The long term effects of cardiorespiratory events remain controversial; however, some studies have suggested an association between prolonged apnoea and morbidity such as impaired neurodevelopmental outcome.

Common clinical practice requires an event-free period before hospital discharge, although the specific length of time varies between institutions. Therefore, with the current demand to shorten hospital stay, the possible persistence of cardiorespiratory events after hospital discharge and the potential consequences of these events, cardiorespiratory monitoring remains a subject of considerable interest. Since cardiorespiratory event detection is dependent on the mode of monitoring used, this chapter will focus on both the respiratory patterns and types of cardiorespiratory events that occur in the infant population and the modalities of cardiorespiratory monitoring currently available to detect these events.

This review will focus on the development of behavioural states and breathing during early developmental stages prior to term gestation. Although these behavioural states are immature during early development, their cyclicity is clearly seen. Preterm infants characteristically have a large proportion of indeterminate sleep and small amount of wakefulness. Whereas oxygenation is relatively stable during active and quiet sleep in ventilated preterm infants, indeterminate sleep and arousals are associated with hypoxaemic episodes. Arousals have also been linked to apnoea in spontaneously breathing infants. Since well-defined sleep cycles are beneficial for the oxygenation of preterm infants, we should explore ways to promote their natural sleep while they are exposed to neonatal intensive care. Care practices such as clustering procedures, kangaroo care and optimal positioning have been shown to improve the integrity of sleep. Optimizing the sleep cycling might improve the long-term outcome of preterm infants. More studies in this area are clearly needed.

Up to 50% of apnoeic episodes are obstructive or mixed apnoeas in which, by definition, there is upper airway obstruction. The other 50% of apnoeas are central in origin, but in 40% of these there is evidence of upper airway obstruction, which also occurs in periodic breathing. The obstruction occurs in the upper pharynx. It is due to a failure of activation of the muscles, including the genioglossus, which support the compliant pharynx and normally prevent its collapse. Fibreoptic studies have demonstrated obstruction also at the entrance to the larynx by the arytenoid masses and the aryepiglottic folds. There is some evidence that inspiring against a closed airway can induce central apnoea, possibly via the intercostal-phrenic inhibitory reflex. Upper airway secretions can trigger obstruction. Continuous positive airway pressure distends both the pharynx and laryngeal aperture and so prevents mixed and obstructive apnoeas, but has no effect on central apnoea.

The methylxanthines aminophylline, theophylline and caffeine have been used for more than 30 years to treat apnoea of prematurity. Today, they are among the most commonly prescribed drugs in neonatal medicine. Methylxanthines reduce the frequency of idiopathic apnoea and the need for mechanical ventilation by acting as non-specific inhibitors of adenosine A₁ and A_2a receptors. However, recent and rapidly growing research into the actions of adenosine and its receptors raises concerns about the safety of methylxanthine therapy in very preterm infants. Possible adverse effects include impaired growth, lack of neuroprotection during acute hypoxic–ischaemic episodes and abnormal behaviour. An international controlled clinical trial is underway to examine the long-term efficacy and safety of methylxanthine therapy in very low birth weight babies.

Respiratory control in the fetus and neonate is quite immature when compared to that of adults. This immaturity involves all facets of respiration including respiratory responses to hypoxia, hypercapnia, an exaggerated apnoeic response to laryngeal stimulation and immature responses to activation of pulmonary afferents. The net result of this immaturity of breathing responses is the vulnerability of neonates and especially preterm infants to apnoea and respiratory pauses. The mechanisms behind immature control of breathing are not fully understood, but seem to originate from a predominance of inhibitory input early in life on respiratory centres. The relative contribution of up-regulation of inhibitory pathways versus down-regulation of excitatory ones is not clear. Multiple neurotransmitters have been implicated in the regulation of breathing in mammals and some of them are discussed in this chapter.

Apnoea and periodic breathing are the hallmarks of breathing for the infant who is born prematurely. Sustained respiration is obtained through modulation of respiratory-related neurons with inputs from the periphery. The peripheral arterial chemoreceptors, uniquely and reflexly change ventilation in response to changes in oxygen tension. The chemoreflex in response to hypoxia is hyperventilation, bradycardia and vasoconstriction. The fast response time of the peripheral arterial chemoreceptors to changes in oxygen and carbon dioxide tension increases the risk of more periodicity in the breathing pattern. As a result of baseline hypoxaemia, peripheral arterial chemoreceptors contribute more to baseline breathing in premature than in term infants. While premature infants may have an augmented chemoreflex, infants who develop bronchopulmonary dysplasia have a blunted chemoreflex at term gestation. The development of chemosensitivity of the peripheral arterial chemoreceptors and environmental factors that might cause maldevelopment of chemosensitivity with continued maturation are reviewed in an attempt to help explain the physiology of apnoea of prematurity and the increased incidence of sudden infant death syndrome (SIDS) in infants born prematurely and those who are exposed to tobacco smoke.