Seminars in neonatology : SN最新文献

There are numerous pulmonary conditions in which qualitative or quantitative anomalies of the surfactant system have been demonstrated. In premature newborns with immature lungs, a functional deficit in surfactant is the main physiopathologic mechanism of the neonatal respiratory distress syndrome (RDS). Since the landmark pilot study of Fujiwara, published more than 20 years ago, the efficacy of exogenous surfactant for the treatment of neonatal RDS has been established by numerous controlled studies and meta-analyses. Promising results have also been reported in infants suffering from other lung disorders in which endogenous surfactant function is compromised. Enlightened by a growing insight into both the structure and function of the different surfactant components, a new generation of synthetic surfactants has been developed. Various complementary approaches have confirmed the fundamental role of the two hydrophobic proteins, SP-B and SP-C, in the surfactant system, thus opening the way to the design of analogues, either by chemical synthesis or expression in a prokaryotic system. These peptide-containing synthetic surfactant preparations are presently undergoing clinical trials, and may eventually replace the animal-derived surfactants currently used for the treatment of RDS.

Chronic lung disease (CLD) continues to be a significant complication in newborn infants undergoing mechanical ventilation for respiratory failure. Although the aetiology of CLD is multifactorial, specific factors related to mechanical ventilation, including barotrauma, volutrauma and atelectrauma, have been implicated as important aetiologic mechanisms. This article discusses the ways in which these factors might be manipulated by various mechanical ventilatory strategies to reduce ventilator-induced lung injury. These include continuous positive airway pressure, permissive hypercapnia, patient-triggered ventilation, volume-targeted ventilation, proportional assist ventilation, high-frequency ventilation and real-time monitoring.

Prior to 1980, the diagnosis of hypoplastic left heart syndrome (HLHS) was almost uniformly lethal. Over the past 25 years, the development of operative options, including staged surgical palliation and infant heart transplant, have resulted in major improvements in survival and quality-of-life outcomes. Throughout this period, the optimal treatment strategy for children with HLHS has continued to be controversial. Current advances include fetal diagnosis, medical management, catheter intervention and operative techniques, and hold great promise for further improvements. However, as new techniques continue to evolve, controversies will continue to arise. This article will explore the treatment strategies for children with HLHS and review current controversies surrounding this complex congenital cardiac disease.

Systemic hypotension is a common complication of preterm birth affecting approximately one-third of very low-birthweight infants. There is considerable variation between neonatal units in the reported prevalence of hypotension, the threshold for therapeutic intervention and the nature of any cardiovascular support offered. Systemic hypotension is associated with adverse long-term neurodevelopmental outcome. The majority of preterm infants with hypotension have a normal or high left ventricular output, with low systemic vascular resistance often associated with a haemodynamically significant ductal shunt. Historically, volume expansion, dopamine and dobutamine have been the agents most commonly used to treat hypotension. Some hypotensive preterm infants have low cortisol levels, and corticosteroids are being used increasingly to prevent or treat hypotension in these babies.

Necrotizing enterocolitis (NEC) is the most common serious, acquired gastrointestinal disorder in the newborn infant. Although many variables are associated with development of NEC, only prematurity has been consistently identified in case-controlled studies. Traditionally, the diving seal reflex has been invoked as the mechanism responsible for ischaemic injury and necrosis. Intestinal ischaemia is likely to be the final common pathway in NEC; however, it is due to the release of vasoconstricting substances, such as platelet activating factor, rather than perinatal asphyxia. Bacteria and/or bacterial toxins are likely to have a key role in the pathogenesis of NEC by fostering production of inflammatory mediators. The role of feeding practices in the pathogenesis of NEC remains controversial. Treatment of infants with NEC generally includes a regimen of bowel rest, gastric decompression, systemic antibiotics and parenteral nutrition. Infants with perforation are generally operated upon; however, there has been recent interest in primary peritoneal drainage as an alternative. Prevention of NEC still remains elusive. Avoidance of preterm birth, use of antenatal steroids and breast-milk feeding are practices that offer the greatest potential benefits. Use of any other strategy should await further trials.

Survival rates in excess of 25% at 23 weeks' gestation and in excess of 50% at 24 weeks' gestation have been reported among live births in the 1990s within tertiary perinatal care centres in the USA and Australia. Decisions about medical management at these gestational ages can no longer be based merely on whether survival is possible. Relevant moral considerations include the primacy of the newborn's best interests, parental autonomy, physicians' duties of beneficence and non-maleficence, and distributive justice. There is significant variability between developed nations in the survival of extremely premature infants among cohorts born within perinatal tertiary care centres. This is, at least to some degree, the result of differences in the aggressiveness of obstetrical and neonatal management at these gestational ages. There is also great variability in the prevalence of major neurodevelopmental disability among survivors. Moreover, the prevalence of major disabilities does not inform quality-of-life considerations adequately. Despite similar gestational age ranges over which the benefit:burden ratio of aggressive obstetric and neonatal care is questioned in developed countries, there is marked variation in the frequency with which it is provided within these ranges. This is understandable given the relevant moral values and the different ways in which competing values will be balanced by different individuals, cultures and societies; the increasing survival of extremely premature infants, but the persistence of high (but widely variable) prevalences of major disabilities reported among survivors and even higher prevalences of mild-to-moderate neurodevelopmental sequelae; our imperfect ability to estimate an individual extremely premature infant's prognosis; and the complexities of estimating the quality of life from the individual's own perspective.

Patent ductus arteriosus (PDA) continues to be one of the most common problems found in premature infants. The incidence is inversely related to gestation, but may be reduced by use of antenatal steroids, lower volume fluid regimen and judicious use of phototherapy. However, there continues to be controversy as to the appropriate indications for treatment, varying from prophylaxis on the basis of gestation to treatment only when a PDA is demonstrably significant. The situation is further complicated by differing diagnostic criteria for ductal patency or significance. Prophylactic treatment is likely to result in up to 64% of babies being treated unnecessarily. Early treatment of significant or symptomatic PDA depends upon accurate diagnosis. PDA closure can then be achieved using medical means, with surgery reserved for patients in whom this fails or in whom there are contra-indications. However, the optimum timing for intervention remains unknown.

Retinopathy of prematurity (ROP) is a major cause of blindness in children in developed countries. ROP, a two-phase disease, is initiated with delayed retinal vascular growth after premature birth (phase I). Insufficient vascularization of the developing retina creates hypoxia, which precipitates the release of factors stimulating new and abnormal blood vessel growth (phase II). ROP develops because of abnormalities in both oxygen-regulated and non-oxygen-regulated factors, which affect both phases of the disease. Vascular endothelial growth factor (VEGF) is an important oxygen-regulated factor that, if suppressed, inhibits normal vessel growth, but in excess, precipitates retinal neovascularization. A critical non-oxygen-regulated growth factor is insulin-like growth factor (IGF-1). Similar to VEGF, low levels of IGF-1 prevent normal vessel growth (phase I), and higher levels allow neovascularization (phase II). We found that premature infants who develop ROP have low levels of serum IGF-1 compared with age-matched infants without disease. IGF-1 is critical to normal vascular development. Low IGF-1 predicts ROP, and restoration of IGF-1 to normal levels might prevent ROP.