KEY POINTS• The American College of Medical Genetics (ACMG) recommends screening all infants for a standard panel of 29 primary disorders and 25 secondary disorders.
• Initial newborn screening is performed during the first 72 hours of life. Metabolic specimens are typically obtained from a heel stick. Most states do not currently require parental consent to obtain these samples, although some states allow parents to decline screening.
• Primary care PAs should contact the family immediately if any results are abnormal. A screening test is not a definitive diagnostic study, and immediate confirmatory testing is required. Condition-specific algorithms are available from the ACMG.
• Logistical and ethical issues that PAs should take into consideration include genotype-phenotype variability, informed consent, cost
and systems capacity, and newborn profiling.
Newborn screening has long been recognized as one of the success stories in public health. Each year, thousands of infants with congenital conditions are identified, treated, and possibly spared potentially devastating consequences with a minimum of risk.1 This article reviews the changing nature of newborn screening with an emphasis on what the primary care physician assistant needs to know when made aware of an abnormal screening result.
HISTORY
Newborn screening began in the early 1960s, when microbiologist Robert Guthrie, MD, PhD, devised a method of spot-testing dried blood for phenylketonuria (PKU). Screening for congenital hypothyroidism began in the 1970s, and additional tests have been added since that time. Tandem mass spectrometry (MS/MS), developed in the 1990s, provided a leap in technology for newborn screening: Screening for multiple conditions could be accomplished using a single method of biochemical analysis on a drop of blood.1
Historically, little uniformity was seen among the 50 US states with regard to the conditions screened. For example, some states would screen newborns for four medical conditions, whereas other states would screen newborns for as many as 36 medical conditions.2 The decision to screen for certain medical conditions has been influenced by scientific evidence, advocacy groups, financial factors, and other considerations.
This lack of uniformity was an issue of concern, and in 1999, the American Academy of Pediatrics (AAP) recommended developing a national standard for newborn screening.3 In response, the Health Resources and Services Administration commissioned the American College of Medical Genetics (ACMG) to develop a standard screening panel. The ACMG recommendations were officially endorsed by the AAP in 20054 and published in 2006. At that time, ACMG targeted 29 primary disorders and 25 secondary disorders for screening.5 The following rationale was delineated by ACMG for the primary targets:
- [The condition] can be identified at a phase (24-48 hours after birth) when it would not ordinarily be detected clinically.
- A test with appropriate sensitivity and specificity is
available.
- The benefits of early detection, timely intervention, and efficacious treatment have been demonstrated.5
- Screening for the secondary target conditions is recommended because
- These conditions are included in the differential diagnoses of the conditions listed in the core panel.
- They are clinically significant and revealed via MS/MS but lack efficacious treatment.
- They are incidental findings with the potential for clinical significance.5
Although many states now follow the ACMG recommendations, newborn screening programs are managed
at the state level; therefore, significant interstate variability remains. Nonetheless, all states have moved to some form of expanded newborn screening. State panels continue to evolve and are expected to do so for the foreseeable future. The most up-to-date list of state-by-state screening protocols can be found at the National Newborn Screening & Genetics Resource Center Web site at http://genes-r-us.uthscsa.edu/resources/consumer/statemap.htm.