Sinclair Graham, McMahon Vanessa, Schellenberg Amy, Nelson Tanya N, Chilvers Mark, Vallance Hilary
Department of Pathology and Laboratory Medicine, BC Children's Hospital, University of British Columbia, Vancouver, BC V6H 3N1, Canada;
Department of Pediatrics, BC Children's Hospital, Vancouver, BC V6H 3N1, Canada;
Int J Neonatal Screen. 2020 Jun 2;6(2):46. doi: 10.3390/ijns6020046. eCollection 2020 Jun.
Newborn screening for Cystic Fibrosis has been implemented in most programs worldwide, but the approach used varies, including combinations of immunoreactive trypsinogen (IRT) and CFTR mutation analysis on one or more specimens. The British Columbia (BC) newborn screening program tests ~45,000 infants per year in BC and the Yukon Territory, covering almost 1.5 million km in western Canada. CF screening was initiated using an IRT-DNA-IRT approach with a second bloodspot card at 21 days of age for all CFTR mutation heterozygotes and any non-carriers in the top 0.1% for IRT. This second IRT was implemented to avoid sweat testing of infants without persistent hypertrypsinemia, reducing the burden of travel for families. Over nine years (2010-2018), 401,977 infants were screened and CF was confirmed in 76, and a further 28 were deemed CF screen positive inconclusive diagnosis (CFSPID). Day 21 IRT was normal in 880 CFTR mutation carriers who were quoted a very low CF risk and offered optional sweat testing. Only 13% of families opted for sweat testing and a total of 1036 sweat tests were avoided. There were six false negative CF cases (and three CFSPID) due to a low initial IRT or no CFTR mutations. Although one CFSPID case had a normal repeat IRT result, the addition of the day 21 IRT did not contribute to any CF false negatives.
全球大多数筛查项目都已开展了针对囊性纤维化的新生儿筛查,但所采用的方法各不相同,包括对一个或多个样本进行免疫反应性胰蛋白酶原(IRT)检测和CFTR基因突变分析。不列颠哥伦比亚省(BC)的新生儿筛查项目每年对BC省和育空地区约45,000名婴儿进行检测,覆盖加拿大西部近150万平方公里的区域。CF筛查最初采用IRT-DNA-IRT方法,在所有CFTR基因突变杂合子以及IRT检测结果处于前0.1%的非携带者的21日龄婴儿中,使用第二张血斑卡进行检测。实施这第二次IRT检测是为了避免对没有持续性高胰蛋白酶血症的婴儿进行汗液检测,从而减轻家庭的出行负担。在九年时间(2010 - 2018年)里,共筛查了401,977名婴儿,确诊76例CF,另有28例被判定为CF筛查阳性但诊断不确定(CFSPID)。880名CFTR基因突变携带者的21日龄IRT检测结果正常,这些携带者被告知CF风险极低,并可选择进行汗液检测。只有13%的家庭选择了汗液检测,总共避免了1036次汗液检测。由于初始IRT检测值低或无CFTR基因突变,出现了6例假阴性CF病例(以及3例CFSPID)。尽管有1例CFSPID病例的重复IRT检测结果正常,但增加21日龄IRT检测并未导致任何CF假阴性结果。