Universal newborn screening and adverse medical outcomes: A historical note

Abstract

Universal newborn screening programs for metabolic disorders are typically described as a triumph of medicine and public policy in the US over the last 50 years. Advances in science and technology, including the Human Genome Project, offer the opportunity to expand universal newborn screening programs to include many additional metabolic and genetic conditions. Although the benefits of such screening programs appear to outweigh their costs, some critics have claimed that historical examples of inadvertent harm ensuing from false-positive screening results and subsequent inappropriate medical treatment should make us wary of expanding universal newborn screening. In this essay, we report the results of a review of the published literature to assess whether the extension of screening from at risk populations to all newborns led to substantial morbidity and mortality from misguided medical treatment. We provide a historical overview of universal newborn screening programs in the United States, and then focus on six early NBS programs: congenital hypothyroidism, phenylketonuria, congenital adrenal hyperplasia, galactosemia, sickle cell disease, and maple syrup urine disease. Our comprehensive search of published sources did not reveal a widespread problem of harm ensuing from medical treatment of children with false positive screening test results.

Adverse Medical Outcomes of Early Newborn Screening Programs for Phenylketonuria

“…8,39 However, a close examination also reveals that experts in PKU confronted many problems in the first decade of NBS programs. Diagnostic criteria for PKU were neither clear nor universally shared, and quality standards for laboratory testing on newborn blood samples were not well established.…”

Genetic Screening

“…Advocacy organizations, particularly the National Association for Retarded Children, embraced the potential of diet therapy to prevent the complications of phenylketonuria (26). Political will was spurred by the strong interest of the John F. Kennedy family and presidential administration in the issue (27,29). The result was an alliance among disability advocates, genetics specialists, and political leaders to establish newborn screening state by state.…”

“…A randomized trial established that diet therapy needed to be lifelong rather than limited to a period of neurologic development in childhood (34), and a stringent diet is required in pregnancy to prevent serious problems in children of women with phenylketonuria (35). Also foreshadowing the complexity of many subsequent newborn screening tests, phenylketonuria screening led to the identification of infants with ''physiologic hyperphenylalanemia'' who were not at risk of cognitive impairment and could potentially be harmed by the diet (29,36).…”

“…These cautions were not unreasonable: one historian has estimated that newborn screening for phenylketonuria was promoted on the basis of experience with diet therapy in fewer than 20 infants with the disease (32). In addition, although phenylketonuria screening is considered highly successful, a full understanding of the implications of screening emerged only over time (29,33). A randomized trial established that diet therapy needed to be lifelong rather than limited to a period of neurologic development in childhood (34), and a stringent diet is required in pregnancy to prevent serious problems in children of women with phenylketonuria (35).…”

NAVIGATING the Future Through the Past The Enduring Historical Legacy of Federal Children's Health Programs in the United States

“…US society could thus consider investing large-scale resources in relatively rare conditions of childhood, such as intellectual disability. 49 This epidemiological trend toward lower mortality has continued, and it prompted Robert Haggerty in 1968 to describe the "new morbidity" of childhood as behavior disorders and relatively rare chronic conditions. 50 …”