Ranieri E, Lewis B D, Gerace R L, Ryall R G, Morris C P, Nelson P V, Carey W F, Robertson E F
Department of Chemical Pathology, Women's and Children's Hospital, North Adelaide, Australia.
BMJ. 1994 Jun 4;308(6942):1469-72. doi: 10.1136/bmj.308.6942.1469.
To assess the performance and impact of a two tier neonatal screening programme for cystic fibrosis based on an initial estimation of immunoreactive trypsinogen followed by direct gene analysis.
Four year prospective study of two tier screening strategy. First tier: immunoreactive trypsinogen measured in dried blood spot samples from neonates aged 3-5 days. Second tier: direct gene analysis of cystic fibrosis mutations (delta F508, delta I506, G551D, G542X, and R553X) in samples with immunoreactive trypsinogen concentrations in highest 1% and in all neonates with meconium ileus or family history of cystic fibrosis.
South Australian Neonatal Screening Programme, Adelaide.
All 88,752 neonates born in South Australia between December 1989 and December 1993.
Neonates with two identifiable mutations were referred directly for clinical assessment and confirmatory sweat test; infants with only one identifiable mutation were recalled for sweat test at age 3-4 weeks. Parents of neonates identified as carriers of cystic fibrosis mutation were counselled and offered genetic testing.
Identification of all children with cystic fibrosis in the screened population.
Of 1004 (1.13%) neonates with immunoreactive trypsinogen > or = 99th centile, 912 (90.8%) had no identifiable mutation. 23 neonates were homozygotes or compound heterozygotes; 69 carried one identifiable mutation, of whom six had positive sweat tests. Median age at clinical assessment for the 29 neonates with cystic fibrosis was 3 weeks; six had meconium ileus and two had affected siblings. 63 neonates were identified as carriers of a cystic fibrosis mutation. Extra laboratory costs for measuring immunoreactive trypsinogen and direct gene analysis were $A1.50 per neonate screened.
This strategy results in early and accurate diagnosis of cystic fibrosis and performs better than screening strategies based on immunoreactive trypsinogen measurement alone.
基于对免疫反应性胰蛋白酶原的初步评估并随后进行直接基因分析，评估针对囊性纤维化的两层新生儿筛查计划的性能和影响。
对两层筛查策略进行的四年前瞻性研究。第一层：对3至5日龄新生儿干血斑样本中的免疫反应性胰蛋白酶原进行检测。第二层：对免疫反应性胰蛋白酶原浓度处于最高1%的样本以及所有患有胎粪性肠梗阻或有囊性纤维化家族史的新生儿样本进行囊性纤维化突变（ΔF508、ΔI506、G551D、G542X和R553X）的直接基因分析。
阿德莱德南澳大利亚新生儿筛查计划。
1989年12月至1993年12月在南澳大利亚出生的所有88752名新生儿。
具有两个可识别突变的新生儿直接被转诊进行临床评估和确诊性汗液试验；仅具有一个可识别突变的婴儿在3至4周龄时被召回进行汗液试验。对被确定为囊性纤维化突变携带者的新生儿父母进行咨询并提供基因检测。
在筛查人群中识别出所有患有囊性纤维化的儿童。
在1004名（1.13%）免疫反应性胰蛋白酶原≥第99百分位数的新生儿中，912名（90.8%）没有可识别的突变。23名新生儿为纯合子或复合杂合子；69名携带一个可识别的突变，其中6名汗液试验呈阳性。29名患有囊性纤维化的新生儿临床评估的中位年龄为3周；6名患有胎粪性肠梗阻，2名有患病的兄弟姐妹。63名新生儿被确定为囊性纤维化突变携带者。检测免疫反应性胰蛋白酶原和直接基因分析的额外实验室成本为每名筛查新生儿1.50澳元。
该策略可实现对囊性纤维化的早期准确诊断，并且比仅基于免疫反应性胰蛋白酶原检测的筛查策略表现更好。
