Thil'en A, Nordenström A, Hagenfeldt L, von Döbeln U, Guthenberg C, Larsson A
Department of Pediatrics, Ryhov Hospital, Jonkoping, Sweden.
Pediatrics. 1998 Apr;101(4):E11. doi: 10.1542/peds.101.4.e11.
The aim of this study was to evaluate the benefits of neonatal screening for congenital adrenal hyperplasia (CAH).
All children with CAH born in Sweden from January 1989 to December 1994 were subjected to a systematic follow-up. Clinical symptoms were recorded and laboratory data collected. The clinical diagnosis versus diagnosis by screening was investigated. The results were compared with those of a retrospective study of all patients diagnosed during 1969-1986 (before the introduction of neonatal screening).
The prevalence of CAH in Sweden was 1:9800 with screening. Patients with CAH were identified earlier by screening. Half of the infants (47%) were not diagnosed at the time of recall, which was 8 days (median). In the study population, 25% of the girls and 73% of the boys were diagnosed by screening alone. The median age at the time of the definite diagnosis in boys was 21 days before screening as compared with 9 days (median) during the last part of the screening period. During the screening period, only 1 boy had a severe salt loss crisis, which occurred at the age of 8 days. Before screening, (1969-1986) 2 boys had died in the neonatal period because of an adrenal crisis. The lowest serum sodium recorded at the time of diagnosis was 124 mmol/L (median; range, 93-148) before, as compared with 134 mmol/L (median; range, 115-148) after the introduction of screening. The number of girls who were initially considered to be boys was not reduced by screening (17% vs 18%). The period of uncertainty regarding gender attributable to virilization was shortened considerably, as well as the time it took to make a correct gender assignment: 23 days (median) before screening versus 3 days (median) with screening. The maximum time it took to make the correct gender assignment was 960 days before screening and 14 days with screening. The number of patients diagnosed late, ie, after the first year of life, decreased considerably after the introduction of screening. The false-positive rate (when a new filter paper blood sample was requested or when a child was referred to a pediatrician for follow-up) was <0.05% and in about 60% of the cases, it was attributable to preterm infants. The cost of screening was US dollar 2.70 per screened infant.
The main benefits of screening were avoidance of serious salt loss crises, earlier correct gender assignment in virilized girls, and detection of patients who would have otherwise been missed in the neonatal period. Deaths in the neonatal period were prevented by screening. The aim of the screening program was to identify patients with the severe forms of CAH. Nevertheless, it must be considered a distinct benefit that a number of patients with milder forms of CAH were detected earlier, because earlier therapy results in decreased virilization, normalized growth and puberty, and, in all probability, an improved psychosocial situation for these children. We conclude that, in the Swedish health care system, the benefits of screening for CAH outweigh the costs.
本研究旨在评估新生儿先天性肾上腺皮质增生症（CAH）筛查的益处。
对1989年1月至1994年12月在瑞典出生的所有CAH患儿进行系统随访。记录临床症状并收集实验室数据。研究临床诊断与筛查诊断情况，并将结果与1969 - 1986年（新生儿筛查引入前）所有确诊患者的回顾性研究结果进行比较。
瑞典CAH的筛查患病率为1:9800。通过筛查能更早识别出CAH患者。半数婴儿（47%）在召回时（中位数为8天）未被诊断出。在研究人群中，25%的女孩和73%的男孩仅通过筛查被诊断出。筛查前男孩确诊时的中位年龄为21天，而在筛查后期中位年龄为9天。在筛查期间，仅1名男孩在8天时发生严重失盐危机。筛查前（1969 - 1986年），有2名男孩因肾上腺危象在新生儿期死亡。诊断时记录的最低血清钠水平，筛查前为124 mmol/L（中位数；范围93 - 148），筛查引入后为134 mmol/L（中位数；范围115 - 148）。筛查并未减少最初被认为是男孩的女孩数量（分别为17%和18%）。因男性化导致的性别不确定期以及做出正确性别认定所需时间大幅缩短：筛查前为23天（中位数），筛查后为3天（中位数）。做出正确性别认定的最长时间，筛查前为960天，筛查后为14天。筛查引入后，一岁后才确诊的患者数量大幅减少。假阳性率（当要求采集新的滤纸血样或儿童被转诊至儿科医生进行随访时）<0.05%，约60%的情况归因于早产儿。筛查成本为每名接受筛查的婴儿2.70美元。
筛查的主要益处包括避免严重失盐危机、更早对男性化女孩做出正确性别认定以及发现新生儿期可能漏诊的患者。筛查预防了新生儿期死亡。筛查项目的目的是识别重症CAH患者。然而，能更早发现一些轻症CAH患者也被认为是一项显著益处，因为早期治疗可减少男性化、使生长和青春期正常化，而且很可能改善这些儿童的心理社会状况。我们得出结论，在瑞典医疗保健系统中，CAH筛查的益处大于成本。
