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Issues in Newborn Screening
Vol. 15: Winter, 1998 |
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
