Newborn screening perspective.

The four traditional criteria for newborn screening originated in 1963 with the development of the Guthrie test for phenylketonuria (PKU). The first criterion was that there be a disease, not simply a laboratory variation; for example, PKU and congenital hypothyroidism are examples of laboratory abnormalities which are associated with pathological states. The second criterion was that the disease should cause significant problems, such as mental retardation and early death. The third criterion has been that the problems caused by the disease be amenable to treatment directed at preventing symptoms. The fourth criterion was that a marker for the disease be identifiable in the newborn prior to the appearance of symptoms and before the biochemical abnormalities of the disease produce irreversible damage. Over time, the strict application of those classical criteria has been compromised, so that we no longer require that the intervention totally eliminate the appearance of symptoms. Instead, it is acceptable if there are some benefits from early detection even if complete prevention of disease is not possible. Based on the new relaxed treatment criterion, we are now screening for cystic fibrosis and sickle-cell disease in many states. The course of both diseases many, however, be dramatically changed by newborn screening. In patients with cystic fibrosis, severe morbidity and mortality within the first year of life may be avoided through early intervention with antibiotics and pancreatic enzymes. Similarly, for sickle-cell patients, early initiation of antibiotic therapy can prevent death from overwhelming bacterial infection during infancy. These diseases illustrate the importance of newborn screening even for diseases in which symptoms cannot be completely prevented by early detection and intervention. Although the long-term consequences of these disorders are not altered by early identification and treatment, the benefits are considered adequate reasons for screening. Newborn screening is not conducted in a vacuum. We must be conscious of the negative effects of the screening process. One of the most troubling effects for the family is anxiety, which is generated by identification in the newborn of diseases for which there may be no effective treatment. Anxiety is also generated by the false-positive results which inevitably occur in newborn screening. Is this consequence counterproductive, relative to the overall benefits to be obtained from newborn screening? What about the family's perception of the child who is identified by newborn screening as suffering from a disorder, particularly when the infant does not truly have the disorder? Is the family's perception of the child changed in a way that will have serious negative consequences for the child? One can certainly ask this question with regard to carrier identification. Children known to be sickle-cell carriers may be viewed quite differently from children who do not carry the sickle globin gene. This attitude may also be true for identification of other, seemingly benign carrier states, such as that for PKU. The situation could result in stigmatization of the child, not only by the family but also by society. Such