Summary of Recommendation

The U.S. Preventive Services Task Force (USPSTF) recommends screening for phenylketonuria (PKU) in newborns (Table 1). A recommendation.

Rationale

Importance. PKU is an inborn error of phenylalanine metabolism that occurs in 1 in 13,500 to 1 in 19,000 newborns in the United States. In the absence of treatment during infancy, most persons with this disorder will develop severe mental retardation.^1,2

Detection. Two approaches, fluorometry and tandem mass spectrometry, are commonly used. The sensitivity and specificity of fluorometry are 100 and 51 percent, respectively.³ The sensitivity and specificity of tandem mass spectrometry are 100 and 98 percent, respectively.³

Benefits of detection and early intervention. There is good evidence that detection by neonatal screening and early treatment of PKU substantially improve neurodevelopmental outcomes for affected persons.

Harms of detection and early treatment. False-positive tests could generate considerable parental anxiety.

USPSTF assessment. The USPSTF concludes that there is high certainty that the net benefit is substantial for screening for PKU in newborns.

Clinical Considerations

• Patient population. This recommendation applies to newborns.

• Screening tests. Screening for PKU is mandated in all 50 states, although methods of screening vary. There are three principal methods used for PKU screening in the United States: the Guthrie bacterial inhibition assay, automated fluorometric assay, and tandem mass spectrometry. Screening tests are most accurate if performed after 24 hours of life but before seven days of age.

• Treatment. It is essential that phenylalanine restrictions be instituted shortly after birth to prevent the neurodevelopmental effects of PKU.

• Timing of screening. Infants who are tested within the first 24 hours after birth should receive a repeat screening test by two weeks of age. Premature infants and those with illnesses should be tested at or near seven days of age, but in all cases before newborn nursery discharge.

Discussion

In 1996, the USPSTF reviewed the evidence for screening for PKU in newborns and found that the benefits substantially outweighed the harms of screening. The benefits of screening for PKU continue to be well established. This update focused on a search for new and substantial evidence on the benefits and harms of screening.⁴ The USPSTF found no new substantial evidence on the benefits and harms of screening for PKU and, therefore, reaffirms that physicians should screen for PKU in newborns. The 1996 recommendation statement, the 1996 evidence report, and the summary of the updated literature search can be found at http://www.uspreventiveservicestaskforce.org/recommendations.htm.

Recommendations from Other Groups

According to the American Academy of Pediatrics, PKU screening should occur in newborns older than 24 hours and younger than seven days. Infants screened before 24 hours of life should be rescreened by two weeks of age to detect possible missed cases. All infants should be screened at the time of nursery discharge or transfer, regardless of age. Sick infants and premature infants should be screened by seven days of age, regardless of feeding history or antibiotic treatment.⁵ The American Academy of Family Physicians strongly recommends that physicians screen neonates for PKU.⁶ The American College of Medical Genetics recommends that PKU screening be mandated as part of state newborn screening programs.⁷