Effect of specimen collection method on newborn screening for PKU
ABSTRACT Introduction: Although heelstick followed by direct spotting of blood on filter paper is usually the method of choice for routine newborn screening of phenylketonuria (PKU) and other disorders, current National Committee for Clinical Laboratory Standards (NCCLS) recommendations provide guidelines for blood collection by capillary tube and dorsal vein, finding that these methods are acceptable alternatives. These latter methods are used for newborn blood collection by a number of hospitals in the US. In large newborn screening programs, however, standardization and cutoffs are set by large-scale testing of specimens collected by direct spotting on filter paper. Methods: Three separate groups of 21 149, 111 035, and 120 837 newborn filter paper specimens were analyzed for phenylalanine concentration by a fluorometric method to determine the effect of collection method of phenylalanine values. The three methods examined were direct spotting of blood from heelstick on filter paper, collection of blood into capillary tube with transfer to filter paper and dorsal hand venipuncture with transfer to filter paper. Results: The mean phenylalanine levels were 2.63 mg/dl, 2.46 mg/dl, and 2.28 mg/dl for direct spotting, capillary tube, and dorsal hand vein, respectively. Actual presumptive positive rates for the three methods were , and , respectively. These differences were consistent when controlling for laboratory and Area Genetic Center (AGC) origin. Discussion: Since guidelines generally recommend or require direct spotting, values obtained by this method should remain the standard for setting cutoffs; deviations from this method could lead to missed cases, particularly for early-tested infants with borderline elevated values.
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ABSTRACT: A recent study has shown venepuncture to be more effective and less painful than heel-lancing when a single blood test is performed in neonates [Larsson, Pediatrics (in press)]. The aim of the present study was to investigate the value of EMLA applied on the dorsum of the hand when sampling blood in neonates. This was a controlled randomized and double-blinded study. One hundred and twenty neonates were randomly allocated to two groups, EMLA or placebo. Five hundred milligrams (0.5 ml) of EMLA or placebo was placed on the dorsum of the hand, covered with an occlusive dressing, and left in place for 60 minutes. For venepuncture, a needle measuring 0.9 x 40 mm was used. The two groups were also compared as regards the total time needed to complete the PKU test and the number of skin punctures required. The facial reaction was videotaped and later analysed by two blinded observers using the Neonatal Facial Coding System (NFCS). No side effects occurred, except for a temporary blanching or redness of the skin, which disappeared within minutes. Nociceptive response: After skin puncture, the NFCS scores were significantly lower in the EMLA group than in the placebo group (median 287 and 374, respectively). After the first skin puncture, a cry was recorded in 35/55 cases (64%) in the EMLA group and in 38/56 cases (68%) in the placebo group, this difference was not significant. The duration of the first cry was significantly shorter in the EMLA than in the placebo group (median 12 and 31 s, respectively). In comparison with a placebo, EMLA significantly reduces the pain caused by venepuncture on the dorsum of the hand and does not complicate puncture of the vein.Acta Paediatrica 08/1998; 87(7):774-9. · 1.84 Impact Factor
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ABSTRACT: Newborn screening for phenylketonuria (PKU) began in the United States in the early 1960s following development of the Guthrie bacterial inhibition assay that allowed for the easy, rapid screening of elevated blood phenylalanine levels collected on newborn filter paper samples. Since that time, a number of other techniques that screen for PKU, other inborn errors of metabolism, and a variety of nonmetabolic disorders have been developed using newborn blood samples. The most advanced, comprehensive technique available today is tandem mass spectrometry (MS-MS), which simultaneously identifies and measures many compounds of varying structural classes allowing for concurrent screening of many disorders, including aminoacidemias, organic acidurias, and fatty acid disorders.Despite this progress in presymptomatic neonatal detection of PKU, there are some difficulties with newborn screening. These include false-positive results, occasional missed diagnoses, and problems surrounding early discharge. In addition, not all elevated phenylalanine levels are a result of a deficiency of the liver enzyme phenylalanine hydroxylase (PAH). Some infants have transiently elevated levels. Others have defects in the synthesis or recycling of tetrahydrobiopterin (BH4), the cofactor of PAH, and some have secondary phenylalanine elevations due to disorders that affect the liver, such as tyrosinemia or galactosemia. Several of these problems, including the number of false positives, may be eliminated by pattern identification via MS-MS.Once identified with a significant or persistent elevation in phenylalanine, infants and their families are referred to a metabolic center for further evaluation, including repeat quantitative testing and, if necessary, dietary or cofactor therapy. MRDD Research Reviews 1999;5:144–149. © 1999 Wiley-Liss, Inc.Mental Retardation and Developmental Disabilities Research Reviews 05/1999; 5(2):144 - 149. · 3.80 Impact Factor
Article: Genetic screening of newborns.[Show abstract] [Hide abstract]
ABSTRACT: Screening of newborn infants for genetic disease began over 35 years ago as a public health measure to prevent mental retardation in phenylketonuria (PKU). It was so successful that tests for several other genetic disorders were added. We review the current status of this screening, including discussions of the genetic disorders often covered and the results of newborn screening for them. We emphasize recent advances. These include expansion of coverage for genetic disorders with the new methodology of tandem mass spectrometry (MS-MS) and the introduction of molecular (DNA) testing to increase the specificity of testing for several disorders, thereby reducing false-positive rates. These and other advances have also produced issues of criteria for screening, missed cases, and appropriate use of stored newborn specimens.Annual Review of Genomics and Human Genetics 02/2000; 1:139-77. · 9.13 Impact Factor