Vol. 15, Winter, 1998
Issues in Newborn Screening
Top Ten Pitfalls in Newborn Screening
1. Assuming that the result of the newborn screening test is negative (or normal) because you have not heard otherwise.
There are many reasons why the primary care provider may not be notified about an abnormal newborn screening result: difficulty finding and notifying a provider, a test might have never been sent, or an error in delivery of the result to the primary health care provider. The primary care provider of record at the birth of an infant assumes the responsibility to assure that a screen was obtained and that the results are duly recorded in the medical records. In light of the increasing complexity of the health care system, many newborn screening programs are working to facilitate proper dissemination of newborn screening results.
2. Assuming that a negative (or normal) result of newborn screening definitively excludes the conditions screened for.
"False negative" test results may occur for a wide variety of reasons including human error such as sample transposition and the statistically "built in" false negative tests. For example, approximately 30% of hypothyroidism is missed in babies who were tested before the second week of life. If the primary care provider observes symptoms, which could be the result of one of the disorders on the newborn screening panel in your state, it is appropriate to confirm the results.
Any baby with symptoms which might be caused by PKU, hypothyroidism, sickle cell disease, galactosemia, cystic fibrosis or any other disorder for which newborn screening was negative should have specific diagnostic testing performed by an appropriate diagnostic laboratory.
3. Submitting a newborn screening sample with incomplete or illegible information.
All states design the newborn screening forms to suit the specific panel of tests they perform and each piece of requested information is essential. Nevertheless, all newborn screening programs receive samples with inaccurate or incomplete information. The submitter of the sample cannot, of course, be responsible when families deliberately provide misinformation.
The submitter is, however, responsible for providing legible information that is correct so far as she/he is aware. When the screening lab requires multiple copies, all copies must be legible (often a problem with hospital card stamps). When a newborn screening form asks for information about the use of antibiotics, history of transfusion or prematurity - that information is necessary for accurate interpretation of test results. Date of birth is always necessary for proper identification of the newborn, and date of sample for test interpretations. Precise information on age in hours may be necessary for the increasingly complex interpretation of results for early screening.
4. Ordering a solubility test (Sickledex, Sickleprep) as the follow up in an infant with positive newborn screen for hemoglobinopathy.
Diagnostic follow-up testing is required after a positive newborn screen to exclude a false positive result and to define the specific diagnosis. The false positive rate and the differential diagnosis varies with the disease for which screening is performed and with the nature of the test.
Confirmatory testing for infants with abnormal hemoglobinopathy screening tests (hemoglobin Barts excepted) should always include hemoglobin electrophoresis. The solubility test (Sickledex, Sickle-prep) should never be performed in this setting because it is often falsely negative in infants with sickle cell disease, does not define the specific hemoglobinopathy present, and fails to differentiate individuals with disease from those with hemoglobin traits.
Similarly, for other conditions on a newborn screen, specific protocols and policies for confirmatory testing have been developed by each newborn screening program. For example, in Colorado, a result of 4 mg/dl on the screen for PKU should be followed by a repeat screen; while a baby with one level of more than 4 mg/dl or two levels of 4 mg/dl each should have diagnostic testing sent to a specific laboratory for phenylalanine and tyrosine levels.
Consultants are available for each disorder and can assist with routine follow-up and with unusual circumstances in which follow-up might need to be tailored to a particular newborn's situation.
5. Prescribing a PKU treatment formula before confirming the diagnosis of PKU.
A significant number of babies with a positive screening test for PKU ultimately prove to be unaffected. After a positive screen, diagnostic test results can be completed in hours to days and treatment begun in a timely fashion, once the diagnosis is confirmed. If treatment is started after the screen only, this may interfere with subsequent diagnostic testing. Also, the PKU diet may be harmful to a child without PKU.
The diet for PKU needs to be carefully calculated by a trained registered dietitian to give a precise amount of essential amino acids by combination of the metabolic formula with human milk or infant formula. In contrast, if a state screens for galactosemia using a test with a low rate of false-positive results, an immediate diet change might be required while diagnostic tests are pending.
Each state has recommendations that take into consideration the specific tests performed in the screening laboratory and the nature of the population served. Guidance regarding any necessary treatment while follow-up screening or diagnostic testing is pursued (also see "pitfall 4") will be provided.
6. Not collecting a newborn screening sample prior to blood transfusion because the baby is "too young" or has not yet been fed.
Transfusion will alter the results of certain newborn screening tests. If a baby is transfused and then screened using an assay affected by transfusion of red cells, the transfusion will affect the test results. For example, when red cells are transfused prior to screening for hemoglobinopathy, the newborn screening laboratory will be testing donor hemoglobins. One test for galactosemia uses the Beutler Assay to measure in red blood cells the activity of galactose-1-phosphate uridyltransferase, the enzyme deficient in galactosemia. The enzyme is present in red cells and thus the transfused red cells will affect the test results. The appropriate strategy always is to collect a newborn screening sample immediately before transfusion in the very young newborn.
7. Not collecting a newborn screening sample prior to transfer of the infant to another institution.
Sick and premature babies, some of whom require transfer for more intensive/specialized care, are at no lower risk than healthy newborns for disorders detected by newborn screening. States may have explicit regulations about responsibility for screening when a baby is transferred from or to a nursery. Regardless of specific regulations, it is appropriate for a newborn screen to be sent by the hospital or institution from which the baby is transferred and for the receiving hospital or institution to verify that screen was sent and subsequently to repeat the screen if appropriate.
8. Not collecting an adequate newborn screening sample.
In each state, a variable percentage of healthy babies are never screened. Reasons for failing to screen a healthy baby vary. A sample may have been collected but failed to reach the laboratory, or the newborn screening laboratory may receive a sample that is inadequate for testing because of insufficient sample, unacceptable collection, or sample contamination. Despite the fact that records will show a sample was collected, that baby was never screened. In other cases, no sample is ever collected. This may be a result of human or system error, and is one reason that the primary care provider must ascertain that each baby has been screened.
Home births present special issues, as the lay midwife or delivering family member who would be responsible to collect and send the screening sample may be uninformed about the purpose and process of newborn screening.
9. Assuming that an abnormal newborn screen is a false positive because the baby is well and/or because one or more factors known to be associated with false positive results are present.
The screening process is successful when affected babies are identified before onset of symptoms. The corollary is that the appearance of good health is not evidence against the presence of the disorder. Even in the presence of special clinical circumstances known to be associated with an increased frequency of physiologic false positive screening tests, a baby who tests positive may be truly affected. For example, the baby who is premature or tested very early, and who has a positive test for thyroid disease, may have real disease and needs prompt confirmatory testing.
10. Referring to the newborn screening test as a "PKU test".
This is a very common practice among hospital staff and practicing physicians. It is misleading to refer to the newborn screen as "a PKU test", because tests for other diseases are included. Parent confusion about the full scope of testing may impact compliance with follow-up should the newborn screen be abnormal. It is good practice to use the term "newborn screen" and to inform the family of the breadth of the newborn screen.
Contributed by Carol Greene, MD (CO)
The Genetic Drift Newsletter is not copyrighted. Readers are free to duplicate all or parts of its contents. The Genetic Drift Newsletter is published semiannually by the Mountain States Genetics Network for associates & those interested in Human Genetics. In accordance with accepted publication standards, we request acknowledgement in print of any article reproduced in another publication. The views expressed in the newsletter do not necessarily reflect local, state, or federal policy. For additional information, contact Carol Clericuzio, M.D., Editor, Department of Pediatrics, The University of New Mexico, Albuquerque, NM, 87131
Table of Contents
Issues in Newborn Screening:
Introduction
Alternative Uses of Guthrie Spots
Impact of Early Hospital Discharge
Screening for Cystic Fibrosis
Hemoglobinopathy Carriers
Pitfalls in Newborn Screening
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