Kwon C, Farrell P M
Department of Pediatrics, University of Wisconsin Medical School, Madison 53706, USA.
Arch Pediatr Adolesc Med. 2000 Jul;154(7):714-8. doi: 10.1001/archpedi.154.7.714.
This study examined for the first time to our knowledge the national data available from newborn screening programs in the United States and determined the salient characteristics of various screening tests for 3 hereditary metabolic disorders and 2 congenital endocrinopathies with emphasis on positive predictive values (PPVs) to delineate the magnitude of false-positive results.
Reports published by the Council of Regional Networks for Genetic Services for 1990 through 1994 were examined carefully, paying particular attention to phenylketonuria, galactosemia, biotinidase deficiency, congenital hypothyroidism, and congenital adrenal hyperplasia (CAH). Because of recent improvements in data collecting, reporting, and tabulating, we used data from 1993 and 1994 to determine the apparent sensitivity, specificity, relative incidence rates, and PPVs for the 5 disorders. For biotinidase deficiency and CAH, we also calculated relative incidence rates and PPVs for 1991 and 1992.
Our analyses revealed the following best estimates for the relative incidence rates of 5 disorders: phenylketonuria, 1:14,000; galactosemia, 1:59,000; biotinidase deficiency, 1:80,000; congenital hypothyroidism, 1:3,300; and CAH, 1:20,000. An apparent sensitivity of 100% has been reported by the various states for most of the disorders, and specificity levels are all above 99%. The PPVs, however, range from 0.5% to 6.0%. Consequently, on average, there are more than 50 false-positive results for every true-positive result identified through newborn screening in the United States.
The magnitude of false-positive results generated in newborn screening programs, particularly for congenital endocrinopathies, presents a great challenge for future improvement of this important public health program. Attention must be given to improved laboratory tests, use of more specific markers, and better risk communication for families of patients with false-positive test results.
据我们所知，本研究首次对美国新生儿筛查项目的全国数据进行了分析，并确定了针对3种遗传性代谢疾病和2种先天性内分泌疾病的各种筛查测试的显著特征，重点关注阳性预测值（PPV），以描述假阳性结果的数量。
仔细研究了遗传服务区域网络理事会1990年至1994年发布的报告，特别关注苯丙酮尿症、半乳糖血症、生物素酶缺乏症、先天性甲状腺功能减退症和先天性肾上腺皮质增生症（CAH）。由于近期在数据收集、报告和制表方面的改进，我们使用1993年和1994年的数据来确定这5种疾病的表观敏感性、特异性、相对发病率和PPV。对于生物素酶缺乏症和CAH，我们还计算了1991年和1992年的相对发病率和PPV。
我们的分析得出了以下5种疾病相对发病率的最佳估计值：苯丙酮尿症，1:14,000；半乳糖血症，1:59,000；生物素酶缺乏症，1:80,000；先天性甲状腺功能减退症，1:3,300；CAH，1:20,000。各州报告的大多数疾病的表观敏感性为100%，特异性水平均高于99%。然而，PPV范围为0.5%至6.0%。因此，在美国，通过新生儿筛查每发现1例真阳性结果，平均会有50多个假阳性结果。
新生儿筛查项目中产生的假阳性结果数量，尤其是针对先天性内分泌疾病的假阳性结果，对这一重要公共卫生项目未来的改进构成了巨大挑战。必须关注改进实验室检测、使用更具特异性的标志物，以及为假阳性检测结果患者的家庭提供更好的风险沟通。
