Newborn screening
Newborn screening
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DOI：
10.1080/00313020701813743
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发表时间：
2008-01-01
期刊：
影响因子：
4.5
通讯作者：
Wiley, Veronica
中科院分区：
文献类型：
--
作者：
Wilcken, Bridget;Wiley, Veronica
新生儿筛查的目的是发现患有严重、可治疗疾病的新生儿，以便采取适当的干预措施，避免或改善不良后果。新生儿的大规模生化测试是在20世纪60年代开创的，当时引入了苯丙酮尿症筛查，这是一种罕见的先天性代谢缺陷，通过使用干血斑样本进行测试。下一个被引入筛查项目的疾病是先天性甲状腺功能减退症，一些更罕见的疾病也逐渐被纳入筛查项目。最近的两项进展极大地改变了这一步伐：串联质谱法的改进和新生儿筛查干血斑的DNA提取和分析。这两项技术使得新生儿筛查的未来可能性几乎是无限的。新生儿筛查测试通常是在干血斑样本上进行的，对此有特殊的分析考虑。需要在同一批号滤纸上制备的干血斑校准品和质控品。由于干燥的滤纸样品与其他生物化学样品相比的可变性增加，因此方法具有约10%的变异系数。红细胞压积是一个无法测量的额外变量。同样重要的是获得每个测定的灵敏度和特异性之间的平衡。确定行动的截止点需要考虑什么是可接受的人口百分比，以回忆起进一步的测试。很少有检测方法是100%有区别的，澳大拉西亚的项目目前筛查至少30种疾病。这些的检测不仅需要主要标志物的测定，而且通常需要测定该标志物与另一个标志物的比率，或者可能需要替代测定，例如DNA突变。最重要的疾病筛查简要描述：苯丙酮尿症，原发性先天性甲状腺功能减退症，囊性纤维化，半乳糖血症，中链酰基辅酶A脱氢酶缺乏症，戊二酰辅酶A脱氢酶缺乏症和先天性肾上腺增生症，连同其他几个疾病检测串联质谱。新生儿筛查处理罕见的疾病，没有非常大的试点研究，不能轻易显示的好处。已经有了囊性纤维化筛查的随机对照试验，现在有几项研究开始确立串联质谱筛查脂肪酸和氨基酸代谢紊乱的益处。两件事将影响新生儿筛查的新方向：开发有效治疗迄今无法治疗的疾病的方法，以及先进的技术，使新的检测策略得以开发。对于许多离散的疾病，新的治疗方法即将出现。药敏试验最近被认为是新生儿筛查的应用，但更有争议。新生儿筛查已经进入了一个新的和令人兴奋的阶段，新的治疗方法，新的技术，并可能在未来，新的预防策略爆炸。
The aim of newborn screening is to detect newborns with serious, treatable disorders so as to facilitate appropriate interventions to avoid or ameliorate adverse outcomes. Mass biochemical testing of newborn babies was pioneered in the 1960s with the introduction of screening for phenylketonuria, a rare inborn error of metabolism, tested by using a dried blood spot sample. The next disorder introduced into screening programs was congenital hypothyroidism and a few more much rarer disorders were gradually included.Two recent advances have greatly changed the pace: modification of tandem mass spectrometry and DNA extraction and analysis from newborn screening dried blood spot. These two technologies make the future possibilities of newborn screening seem almost unlimited.Newborn screening tests are usually carried out on a dried blood spot sample, for which there are special analytical considerations. Dried blood spot calibrators and controls, prepared on the same lot number of filter paper, are needed. Methods have a co-efficient of variation of about 10% due to the increased variability of a dried filter paper sample compared with other biochemical samples. The haematocrit is an additional variable not able to be measured. Also of importance is obtaining a balance between the sensitivity and specificity of each assay. Fixing cut-off points for action needs consideration of what is an acceptable percentage of the population to recall for further testing. Few assays are 100% discriminatory.Programs in Australasia currently screen for at least 30 disorders. Detection of these requires not only the assay of a primary marker but often determination of a ratio of that marker with another, or possibly an alternative assay, for example a DNA mutation. The most important disorders screened for are described briefly: phenylketonuria, primary congenital hypothyroidism, cystic fibrosis, the galactosaemias, medium-chain acyl-CoA dehydrogenase deficiency, glutaryl-CoA dehydrogenase deficiency and congenital adrenal hyperplasia, together with several other disorders detectable by tandem mass spectrometry.Newborn screening deals with rare disorders and benefit cannot be shown easily without very large pilot studies. There have been randomised controlled trials of screening for cystic fibrosis, and now several studies are beginning to establish the benefit of tandem mass spectrometry screening for disorders of fatty acid and amino acid metabolism.Two things will influence the new directions for newborn screening: the development of effective treatments for hitherto untreatable disorders, and advancing technology, enabling new testing strategies to be developed. There are novel treatments on the horizon for many discrete disorders. Susceptibility testing has recently been considered for newborn screening application, but is more controversial. Newborn screening has entered a new and exciting phase, with an explosion of new treatments, new technologies, and, possibly in the future, new preventive strategies.