Balsamo A, Cacciari E, Piazzi S, Cassio A, Bozza D, Pirazzoli P, Zappulla F
First Pediatric Clinic, University of Bologna, Italy.
Pediatrics. 1996 Sep;98(3 Pt 1):362-7.
Comparative study of the incidence of classic 21-hydroxylase deficiency congenital adrenal hyperplasia (21ase-def CAH) and clinical findings of affected infants diagnosed via newborn screening versus case survey only in the Emilia-Romagna region of Italy.
Neonatal mass screening (from March 1980 to September 1983-Period A, and from March 1991 to August 1995-Period C) and case survey study (from 1980 to June 1995; case survey alone from October 1983 to February 1991--Period B) were performed by the Regional Referral Center for Neonatal Screening for Endocrine-Metabolic Disease with a laboratory (Central Laboratory, S. Orsola Hospital, Bologna) and clinical (First Pediatric Clinic, University of Bologna, S. Orsola Hospital, Bologna) component. A population-based sample of 420 960 newborns consecutively born in the Emilia-Romagna region from March 1980 to August 1995 were studied. Spot 17-OH-progesterone (nmol/L blood) was tested by the radioimmunoassay method after sample extraction during Period A and by fluoroimmunometric time resolved method without sample extraction during Period C. Serum 17-OH-progesterone (ng/dL or nmol/L) was tested by the radioimmunoassay method (Diagnostic Product Corporation Kit, Los Angeles, CA). The case survey was performed by means of a questionnaire sent to all regional centers dealing with pediatrics, neonatology, endocrinology, and pediatric surgery.
Thirteen classic 21ase-def CAH were diagnosed by means of neonatal screening (combined A and C periods). One true and one questionable false-negative cases were identified. The incidence of classical 21-hydroxylase deficiency for the white population was 1:15 518 (95% confidence limits 1:9249-1:28 400) by neonatal screening plus case survey, 1:18 105 (95% confidence limits 1:10 365-1:35 041) by neonatal screening alone and 1:25 462 (95% confidence limits 1:12 925-1:59 043) by case survey alone. The sensitivity and specificity of screening for classic CAH were 83% and 99.8% for Period A and 90% and 99.2% for Period C, respectively. The percentage of salt-wasting forms and the male/female ratio were higher during the neonatal screening period than during the case survey only. Sixty-one percent of classic CAH patients benefited from a prompt diagnosis. Nonclassical 21ase-def CAH cases detected via screening and case survey were also reported.
Even in a region with adequate neonatal services, clinical diagnosis alone of classic CAH might be delayed or misinterpreted and salt-wasting crises could cause neonatal deaths. CAH screening is thus an effective tool for diagnosing affected male infants without a family history of CAH and for preventing salt loss. However, to achieve maximal benefit from screening, quick procedures are necessary for notification of positive results and beginning prompt treatment. The possibility of false-negative cases indicates that clinical observation should never be abandoned, even with ongoing screening programs.
比较意大利艾米利亚 - 罗马涅地区通过新生儿筛查与仅通过病例调查诊断的经典型21 - 羟化酶缺乏先天性肾上腺皮质增生症（21ase - def CAH）的发病率及患病婴儿的临床特征。
由内分泌 - 代谢疾病新生儿筛查区域转诊中心开展新生儿群体筛查（1980年3月至1983年9月——A期，以及1991年3月至1995年8月——C期）和病例调查研究（1980年至1995年6月；1983年10月至1991年2月仅进行病例调查——B期），该中心有实验室（博洛尼亚圣奥索拉医院中央实验室）和临床（博洛尼亚大学第一儿科诊所，博洛尼亚圣奥索拉医院）两个部门。对1980年3月至1995年8月在艾米利亚 - 罗马涅地区连续出生的420960名新生儿进行基于人群的抽样研究。A期在样本提取后通过放射免疫分析法检测血斑17 - 羟孕酮（nmol/L血液），C期通过荧光免疫时间分辨法在不进行样本提取的情况下检测。血清17 - 羟孕酮（ng/dL或nmol/L）通过放射免疫分析法（诊断产品公司试剂盒，加利福尼亚州洛杉矶）检测。病例调查通过向所有涉及儿科、新生儿科、内分泌科和小儿外科的区域中心发送问卷来进行。
通过新生儿筛查（A期和C期合并）诊断出13例经典型21ase - def CAH。发现1例真阴性和1例可疑假阴性病例。通过新生儿筛查加病例调查，白人人群中经典型21 - 羟化酶缺乏的发病率为1:15518（95%置信区间1:9249 - 1:28400），仅通过新生儿筛查为1:1810（%置信区间1:1036 = 1:35041），仅通过病例调查为1:25462（95%置信区间1:12925 - 1:59043）。A期筛查经典型CAH的灵敏度和特异度分别为83%和99.8%，C期分别为90%和99.2%。新生儿筛查期间失盐型的比例和男/女比例高于仅病例调查期间。61%的经典型CAH患者因早期诊断而受益。还报告了通过筛查和病例调查检测出的非经典型21ase - def CAH病例。
即使在一个具备完善新生儿服务的地区，仅靠临床诊断经典型CAH可能会延迟或误诊，失盐危象可能导致新生儿死亡。因此，CAH筛查是诊断无CAH家族史的患病男婴以及预防失盐的有效工具。然而，为了从筛查中获得最大益处，需要快速程序来通报阳性结果并开始及时治疗。假阴性病例存在的可能性表明，即使有正在进行的筛查项目，临床观察也绝不能放弃。
