Newborn screening became practical with the development of a rapid, inexpensive test that could be done in batch format. Robert Guthrie, a microbiologist at the State University of New York at Buffalo, developed a bacterial assay for phenylalanine quantitation in blood dried on filter paper. This test is known as the Guthrie test, and the filter paper cards often are called Guthrie cards. From this beginning in the early 1960s, major strides have been made by public health institutions in preventing mental retardation, death, and disability. All states in the United States have their own or shared newborn screening programs, and private firms also offer primary or supplemental screening tests. A newborn screening program comprises screening and follow-up tests, diagnosis, management, education, and evaluation of these components. Increasing interest is voiced for a national screening policy for the United States, to define minimum standards for all programs.

Screening programs have developed according to criteria set forth in the 1960s, which propose that screening is appropriate if a test is available, feasible, and affordable, and the disorder is difficult to recognize clinically, sufficiently prevalent, and treatable (Box 18.1). Because prevalence varies depending on the disorder and the population, adapting these principles to specific local situations has led to great variation among programs. Phenylketonuria, hypothyroidism, galactosemia, and sickle-cell disease and hemoglobinopathies are tested in all U.S. screening programs. Congenital adrenal hyperplasia and biotinidase are tested in many programs (Box 18.2), and cystic fibrosis (CF) in a few. Required tests are called mandated tests. Expanded newborn screening refers to the use of tandem mass spectrometry (see section, Expanded Newborn Screening Using Tandem Mass Spectrometry and Box 18.3). It is used in about 30 state programs, and several other states are considering it. Maple syrup urine disease, homocystinuria, and tyrosinemia, formerly tested in some states by other methods, are part of most expanded newborn screening programs. For those tests not mandated in a particular jurisdiction, supplemental screening is available on a voluntary basis or through private laboratories. All developed countries have screening programs, and many developing countries have programs available in some locations or hospitals. The current situation for the United States can be found at http://www.genes-r-us.uthscsa.edu/. Screening programs also exist for congenital hearing loss and some infections.

All U.S. jurisdictions require that newborn screening be offered. Some states specify the tests and methods to be used; in others, these are decided by the laboratory or health department, guided by its advisory committee. The number of conditions tested for ranges from four to over 50, if one counts mild and severe forms of several disorders separately. Newborn screening for metabolic diseases and hemoglobinopathies requires a blood sample obtained by heel stick or sometimes by venipuncture. Blood sampling for screening tests has been regarded as within the scope of ordinary neonatal care, but increasingly it is regarded as requiring active informed consent from the parent. Consent should be obtained at a prenatal visit. Some states require a signature for the test to be performed (“opt in”); others require the test, and signature is required to refuse it (“opt out” or “informed dissent”). Refusal of the test must be carefully documented. Funding for newborn screening testing occurs through state legislatures, charges to hospitals, federal block grants to states, and sometimes through direct charges to patients.