PEDIATRICS Vol. 111 No. 3 March 2003, pp. 670-671
COMMENTARY |
Not as Pink as You Think!
Abbreviations: PKU, phenylketonuria
Newborn screening is perceived as a program to identify newborn infants with 1 or more congenital conditions not easily recognized at birth, but requiring immediate medical care. Requisites for newborn screening include available therapy that is most effective when initiated within the first week of life, the condition has a prevalence in the population sufficient to warrant public health attention, there is a marker analyte for the condition in the Guthrie spot (the dried blood specimen taken as part of the discharge process), and there is a test for the analyte with appropriate sensitivity and specificity. Phenylketonuria (PKU) is the classic example of a condition meeting these criteria, and indeed all newborns in the United States are screened for PKU and additionally congenital hypothyroidism. In the nearly 4 decades since its beginnings, newborn screening has expanded to include >30 congenital conditions in the screening panel, all sharing the common link of having a marker in the Guthrie specimen, which can be easily and reliably detected by the screening laboratory.1 With the application of new technology, such as tandem mass spectrometry and DNA analysis, the list of detectable conditions in newborn screening panels is likely to continue to expand, providing even greater opportunity for early and definitive interventions for these inborn errors of metabolism.
The wide adoption of newborn hearing screening in the past decade is the first public health-sponsored screening of newborns to not use the Guthrie specimen. These audiologic tests performed during the nursery stay have a high probability of identifying newborns with hearing defects that otherwise might not become evident until much later in life.1 Interestingly, the same tenets applied to traditional newborn screening were also used to justify hearing screening. In its policy statement on hearing screening the American Academy of Pediatrics cited 5 criteria to "justify universal [hearing] screening."2 Except for the development of a favorable cost-benefit range, these are the same criteria accepted by newborn screening programs for conditions in their screening panels and cited above.
In this issue, Koppel et al3 propose another addition to the newborn screening panel, ie, screening for congenital heart defects, using pulse oximetry measurements coordinated with collection of the Guthrie specimen. As in hearing screening, the procedure is noninvasive, simple to execute, easy to interpret, and can be performed during the nursery stay. The authors offer convincing and compelling evidence that the procedure meets, or exceeds, all criteria now applied to selection of conditions in newborn screening panels. Importantly, the population screened by pulse oximetry in their report excluded infants with cardiac anomalies previously detected by fetal echocardiography. Thus, it was a prescreened population that yielded a prevalence of 4.4 congenital cardiovascular malformations per 10 000, >4 times the prevalence of PKU. In the absence of prescreening, the incidence of congenital cardiovascular malformations is calculated to be 17 per 10 000, a number far exceeding the prevalence of any screened condition in traditional newborn screening panels.
As pointed out by McCabe and McCabe,4 the single best place to screen all neonates is the newborn nursery. After that the population becomes dispersed, with no common point at which to apply a screening procedure. With a potentially fatal condition, such as described by Koppel et al, it seems evident that the entire population should be screened, if the screening test meets the aforementioned criteria. In this case, pulse oximetry performs well. Two recent reports add support to this methodology, although applied in a somewhat different setting and format.5,6 Nevertheless, the conclusions of those authors were the same as that of Koppel: pulse oximetric screening should be carefully considered for neonatal screening.
The false positive rate of pulse oximetry is low, but not nonexistent. However, the "false positive" tests are immediately resolved through echocardiography before discharge from the hospital. This is an option not available in traditional newborn screening in which the laboratory receives the specimen days after the infant has been discharged. A positive screening result in that case requires locating the family and a return to the health care provider. These processes are not 100% effective; thus, some infants with a positive screen are never evaluated for that condition. Some would call this a failure of the system.7 In a systematic evaluation of newborn screening data in the United States, Kwon and Farrell8 reported the ratio of false positives to true positives could be as high as 61:1. The calculated positive predictive value for Guthrie specimen testing was as low as 0.5% compared with the positive predictive value for pulse oximetry screening of 75%. This translates into huge cost savings for pulse oximetric screening in both time, professional intervention, and parental anxiety in the follow-up when compared with procedures effected in traditional Guthrie specimen-based programs. In fact, the anxiety of the frantic return to the emergency department with a cardiovascularly distressed newborn discharged as healthy only a few hours earlier may be avoided entirely with pulse oximetry screening.
The occurrence of false negative results (2 in 11 296 births) in pulse oximetry screening reinforces the need for continued clinical vigilance. Screening programs, whether laboratory analyses (PKU) or physiology measurements (hearing) will have false negative results. As McCabe and McCabe4 emphasized, presence of the clinical signs of a condition should supercede any negative results from a screening program. Numerous factors, biological, analytical, and clerical, can result in an erroneous screening result. Koppel et al3 clearly identify those cardiac malformations that will not be detected by pulse oximetry. This clear demarcation of the limitation of a newborn screening test is not present in the Guthrie spot analytical procedures.
If one accepts the premise that newborn screening should provide a newborn with the maximum advantages for a healthy, productive, disease-free start in life, then one cannot restrict these programs to the traditional analysis of the Guthrie specimen. The demonstration here that pulse oximetry can provide a significantly better beginning for a newborn cannot be overlooked. Expanded trials of these procedures, in nonacademic birthing facilities to assess their applicability in an environment removed from the oversight of cardiovascular specialists are called for, as is the increased vigilance of the pediatrician when performing the initial postnatal examination.
Biggs Laboratory
Wadsworth Center
New York State Department of Health
Albany, NY 12201-0509
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FOOTNOTES
Received for publication Nov 13, 2002; Accepted Nov 13, 2002.
Reprint requests to (K.A.P.) Wadsworth Center, New York State Department of Health, Box 509, Albany, NY 12201. E-mail: kpass{at}wadsworth.org
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REFERENCES |
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 TOP REFERENCES |
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- Levy HL, Albers S. Genetic screening of newborns. Annu Rev Genomics Hum Genet.2000; 01 :139 –177[CrossRef][Web of Science][Medline]
- American Academy of Pediatrics, Task Force on Newborn and Infant Hearing. Newborn and infant hearing loss: detection and intervention (RE9846).
Pediatrics.1999; 103
:527
–530
[Abstract/Free Full Text] - Koppel RI, Druschel CM, Carter T, et al. Effectiveness of pulse oximetry screening for congenital heart disease in asymptomatic newborns. Pediatrics.2002; 111 :451 –455
- McCabe LL, McCabe R. Newborn screening as a model for population screening. Mol Genet Metab.2002; 75 :299 –307[CrossRef][Web of Science][Medline]
- Richmond S, Reay G, Abu Harb M. Routine pulse oximetry in the asymptomatic newborn.
Arch Dis Child Fetal Neonatal Ed.2002; 87
:F83
–F88
[Abstract/Free Full Text] - Hoke TR, Donohue PK, Bawa PK, et al. Oxygen saturation as a screening test for critical congenital heart disease: a preliminary study. Pediatr Cardiol.2002; 23 :403 –409[CrossRef][Web of Science][Medline]
- Holtzman C, Slazyk WE, Cordero JF, Hannon WH. Descriptive epidemiology of missed cases of phenylketonuria and congenital hypothyroidism.
Pediatrics.1986; 78
:553
–558
[Abstract/Free Full Text] - Kwon C, Farrell PM. The magnitude and challenge of false-positive newborn screening test results.
Arch Pediatr Adolesc Med.2000; 154
:714
–718
[Abstract/Free Full Text]
PEDIATRICS (ISSN 1098-4275). ©2003 by the American Academy of Pediatrics
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