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Issues in Newborn Screening Vol. 15: Winter, 1998 |
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Issues in Newborn Screening Vol. 15: Winter, 1998 |
For more than three decades, newborn screening has been a successful example of a population-based screening program to detect and treat disorders which cause preventable mental retardation and morbidity. However, some trends in managed care and demand for cost containment are raising concerns for state newborn screening programs across the country, including our region. The greatest impact thus far relates to increasing frequency in early hospital discharge (i.e., hospital stays of 24 hours or less) of healthy infants after birth.
When newborn screening started in 1962, hospital stays allowed for the ideal timing of specimen collection between 48 and 96 hours following birth and for the infants to be monitored. Early newborn screening specimen collection (i.e. before 48 hours of age) is primarily a result of early discharge. This practice affects newborn genetic screening programs in two ways: (1) by decreasing the ability to detect infants with inborn errors of metabolism who have not had adequate nutritional intake, and (2) by not being able to minimize the impact on families that is generated by a high number of false positive test results requiring further testing and follow-up to reach a confirmed diagnosis.
The results of a 1994 study of the impact of early discharge on newborn screening in California showed the following:
The trend toward early hospital discharge in the Mountain States Region is similar to
that of California.
Screening tests for phenylketonuria (PKU) are affected by "too early" specimen collection because there is a physiological rise in phenylalanine levels for the first 10 hours following birth gradually falling back to the level one hour post birth at approximately 24 hours of age. At a cutoff level of 4 mg/dl, a significant number of normal results will be falsely positive if collected during the first 24 hours. California found a false positive rate as high as 11/1000 before 24 hours compared to 1.1/1000 between 24-48 hours. Lowering the cut-off level for specimens collected before 24 hours resulted in more false positives without an increase in confirmed cases.
Early discharge can also result in false negative newborn screening results. For example, discharge of an infant with PKU may occur before blood phenylalanine levels have increased to sufficient levels to be detected by the newborn screen. Hence, the early screen would miss an infant with PKU. This scenario is particularly likely for infants with hyperphenylalaninemia, who do not have classical PKU, but still have an error of phenylalanine metabolism.
The detection of primary hypothyroidism presents a similar problem because of a
thyroid stimulating hormone (TSH) surge at birth which peaks at around six hours
and then gradually declines to reach normal cut-off values by the fifth day of life.
Since the majority of screening programs in the US take the lowest 10% of T4 results
and run TSH analysis to determine a positive screening result for primary
hypothyroidism, specimens collected during the first 24 hours will have a high
false positive rate.
Screening for maple syrup urine disease (MSUD), by detection of elevation of leucine, is optimal at 24-48 hours of age. This elevation is subject to the same considerations as PKU but the medical issues are more complex in that life-threatening symptoms may become evident before screening results are available.
Early specimen collection affects screening for homocystinuria (HCU) by increasing the number of false negative results, since the measured metabolite methionine is often not elevated above normal levels during the first week of life. The optimal time to screen for homocystinuria is actually at 3 to 4 weeks of age.
There are four different forms of congenital adrenal hyperplasia (CAH) that can be detected through newborn screening: salt-wasting, simple virilizing, non-classical late onset, and cryptic. The analyte tested is 17-hydroxyprogesterone (17-OHP). At birth, 17-OHP is normally elevated and undergoes a rapid decline to adult normal levels by one to three weeks of age. During the first week of life, the levels of 17-OHP show marked variation. Thus, early specimen collection is expected to result in an unacceptably high number of false positives.
Other conditions screened for, but not dependent on the time of specimen collection, include tests for sickle cell disease, biotinidase deficiency, and galactosemia. The screening tests for these conditions rely on red cell components. These test results are affected by blood transfusions and specimens must be collected before transfusion for valid results.
It is evident from the above information that early discharge has the potential to adversely affect the accuracy of newborn screening for the majority of conditions included in the panels of most newborn screening programs. Several strategies are being implemented to remedy this problem. The most important of these may be the legislation signed last fall by President Clinton whereby health insurers must cover 48 hour hospital stays for mothers and babies for a normal delivery and 96 hours for Cesarean sections. This will hopefully decrease the number of specimens collected at less than 24 hours. This legislation will go into effect January 1998.
The 1992 AAP and ACOG Guidelines state that all newborns must be screened prior to discharge regardless of age or feeding status of the infant and that the optimal time to collect a sample is at 3 days of age. Most state programs have initiated a routine second screen if the newborn was screened before 24 hours of age. These second screens are collected between 1-2 weeks of age for some programs and 1-4 weeks for others. Some states are narrowing the period of time for the second screen to no later than two weeks of age because of the concern of delayed detection and treatment.
There are seven states that have implemented a routine second screen on the entire screening panel as a safeguard. They include Delaware, Oregon, New Mexico, Nevada, Texas, Colorado, and Utah. All these states consider a routine second screen to be an effective means (both medically and economically) of detecting clinically significant disorders not detected on the original screen.
In the state of Oregon, the routine second screen has resulted in 38 confirmed cases in whom diagnosis would either have been missed or delayed. Since 1991, five PKU cases have been picked up on the second screen. Oregon has also found that the routine second screening enhances practitioners' involvement in the screening process since second screening specimens are collected in their offices. They receive copies of both screening results for all the infants in their care and hopefully discuss these with the parents.
Despite this apparent success in Oregon, there is much controversy in the newborn
screening community concerning the effectiveness of the routine second screen.
The following questions need to be considered in any discussion:
A standard process is needed to incorporate newborn genetic screening into early discharge planning and programmatic changes, including more precise analytical methods, to ensure the integrity of each states' newborn screening program.
For more in-depth discussion of the information presented in this article, consult the Conference Proceedings on "Early Hospital Discharge: Impact on Newborn Screening" held in Washington, D.C. on 3/31/95-4/1/95, available from the National Maternal and Child Health Clearinghouse, 8201 Greensboro Drive, Suite 600, McLean, VA 22102.
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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