Effect of specimen collection method on newborn screening for PKU

California Department of Health Services, Genetic Disease Branch, 2151 Berkeley Way, Annex 4, Berkeley, CA, 94704, USA
Screening 08/1994; 3(2):57–65. DOI: 10.1016/0925-6164(94)90001-9

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: 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 01/1999; 5(2):144 - 149. DOI:10.1002/(SICI)1098-2779(1999)5:2<144::AID-MRDD9>3.0.CO;2-B · 3.80 Impact Factor
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    ABSTRACT: IntroductionUsing heel puncture by lancets for the determination of metabolic tests (hypothyroidism and phenylketonuria) using heel puncture is a very painful procedure. Venepuncture can be used as an alternative.Objectives To determine whether venepuncture in the dorsal side of the hand is less painful and more efficient than heel puncture in the screening test for inborn errors of metabolism, as well as comparing false positives in the hypothyroidism test.Material and methodsWe tested 607 consecutives newborns in an observational, randomised study (280 with venepuncture, and 327 with heel puncture). Pain response was assessed using the Neonatal/Infant Pain Scale (NIPS), and the delay and duration of the first cry. We measured the number of punctures needed, and the time taken to complete the test, as well as the number of false positives in the hypothyroidism test.ResultsVenepuncture was less painful than heel prick (NIPS 2 vs 5, P<.001), as well as in the delay (crying in 57.8% vs 90.2%, P<.0001) and duration of the cry (58 vs 104 seconds). Venepuncture was also faster (60 vs 120 seconds), and required less puncture attempts. There were no differences in cases with TSH greater than 5mU/mL, or greater than or equal to 9 mU/mL.Conclusions Venepuncture is associated with less pain, is faster to perform and not is associated with more false positive cases.
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