Hanley W B, Demshar H, Preston M A, Borczyk A, Schoonheyt W E, Clarke J T, Feigenbaum A
Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
Early Hum Dev. 1997 Jan 3;47(1):87-96. doi: 10.1016/s0378-3782(96)01846-4.
Recent policies of early discharge of postpartum mothers and their infants has raised concerns of possible decreased sensitivity in Guthrie bacterial inhibition assay (BIA) phenylketonuria (PKU) screening resulting in missed cases. In order to assess the potential impact of early discharge from hospital on neonatal screening for PKU and its variants, we performed 18 standard BIA screening tests on 11 newborn infants with the disease. Blood spot samples were collected from 1 to 24 h after birth and were analyzed at the Ontario Ministry of Health newborn screening laboratory according to the routine screening protocol. Except for one 4-hour postnatal sample from an infant with 'non-PKU mild hyperphenylalaninemia' (MHP) all blood samples showed phenylalanine levels > or = 240 mumol/l, irrespective of the age of the baby. During our 29 year experience with neonatal PKU screening (3.9 million infants tested), employing a cutoff blood phenylalanine of 240 mumol/l in blood spots obtained at > or = 24 h of age, only two biological false negative (one confirmed) tests were discovered in infants subsequently shown to have classical PKU: another three false negative tests were discovered in sibs of infants with MHP. The sensitivity of the screening test was 99.2% for infants with classical and mild PKU. Ascertainment of patients with MHP is unknown and is very likely incomplete. Over a 3-year period (1992-4) the specificity of the test was 99.9% for those screened after 24 h. The positive predictive value was 12.8%. Although early discharge may have an impact on other screened diseases, we conclude, from our studies, that early discharge may not affect the detection of infants with classical and mild (atypical) PKU, but would probably increase the number of infants with MHP missed using the BIA and a cutoff level of 240 mumol/l. Because of our experience and that of others, we recommend that neonates be at least 12 h of age before initial BIA PKU screening be carried out. To confirm this recommendation further prospective studies should be initiated.
近期关于产后母亲及其婴儿早期出院的政策引发了人们对苯丙酮尿症（PKU）筛查中格思里细菌抑制试验（BIA）敏感性可能降低从而导致漏诊病例的担忧。为了评估早期出院对新生儿PKU及其变异型筛查的潜在影响，我们对11例患有该疾病的新生儿进行了18次标准BIA筛查测试。出生后1至24小时采集血斑样本，并按照常规筛查方案在安大略省卫生部新生儿筛查实验室进行分析。除了一名患有“非PKU轻度高苯丙氨酸血症”（MHP）婴儿的产后4小时样本外，所有血样的苯丙氨酸水平均≥240μmol/L，与婴儿年龄无关。在我们29年的新生儿PKU筛查经验（检测了390万例婴儿）中，对于在≥24小时龄采集的血斑，采用240μmol/L的血苯丙氨酸临界值，在随后被证明患有经典PKU的婴儿中仅发现2例假阴性（1例确诊）检测；在患有MHP婴儿的同胞中又发现3例假阴性检测。对于患有经典型和轻型PKU的婴儿，筛查试验的敏感性为99.2%。MHP患者的确诊情况未知且很可能不完整。在3年期间（1992 - 1994年），对于24小时后筛查的人群，该试验的特异性为99.9%。阳性预测值为12.8%。尽管早期出院可能会对其他筛查疾病产生影响，但我们从研究中得出结论，早期出院可能不会影响经典型和轻型（非典型）PKU婴儿的检测，但可能会增加使用BIA和240μmol/L临界值漏诊MHP婴儿的数量。基于我们以及其他人的经验，我们建议在首次进行BIA PKU筛查前，新生儿至少应为12小时龄。为进一步证实这一建议，应开展进一步的前瞻性研究。
