Newborn Screening for Cystic Fibrosis: Recommendations from the Centers for Disease Control and Prevention
Am Fam Physician. 2005 Apr 15;71(8):1482-1487.
This article exemplifies the AAFP 2005 Annual Clinical Focus on the legal, social, clinical, and ethical issues of medical genomics.
The Centers for Disease Control and Prevention (CDC) published recommendations for newborn screening for cystic fibrosis in the October 15, 2004, recommendations and reports series of Morbidity and Mortality Weekly Report.1 In this report, the CDC concludes that screening for cystic fibrosis is justified based on evidence of moderate benefit and low risk of harm. The report describes how screening is performed, reviews evidence on the benefits and harms from screening and early detection, and makes recommendations to state health departments. The report was prepared by a writing group of seven persons, five of whom were non-CDC experts. The report followed a November 2003 workshop co-sponsored by the CDC and the Cystic Fibrosis Foundation.
The CDC recommends that states consider including cystic fibrosis in newborn screening panels, although it recognizes that states must consider resource constraints and competing priorities. Currently, 10 states screen newborns for cystic fibrosis. Furthermore, the CDC recommends that states that choose to screen for cystic fibrosis adopt planning and implementation procedures that include primary care physicians and specialists in cystic fibrosis care, and take steps to ensure that children have prompt access to diagnostic and therapeutic services for cystic fibrosis.
In reviewing the scientific evidence, the writing group for the CDC report used the Strength of Recommendation Taxonomy (SORT), endorsed by American Family Physician for evidence-based recommendations.2 SORT distinguishes between disease-oriented outcomes, which consist of surrogate measurements collected during clinical care, and patient-oriented outcomes, which are endpoints that matter to people. Patient-oriented outcomes should be more influential in shaping evidence-based practice recommendations.2
Studies of newborn screening for cystic fibrosis have focused on disease-oriented outcomes, specifically measures of nutritional and pulmonary status. The evidence of nutritional benefit from early identification, including long-term reduction in short stature, is conclusive. However, the evidence for pulmonary benefit is mixed. The CDC review focused on patient-oriented outcomes: survival, cognitive outcomes, hospitalizations, and the use of invasive or burdensome therapies.
Based on the SORT criteria, the report assigned cystic fibrosis newborn screening a moderate (Grade B) recommendation, defined as a recommendation based on “inconsistent or limited-quality patient-oriented evidence.” Unlike any other disorder in newborn screening panels, cystic fibrosis screening is supported by reliable evidence, including a high-quality randomized controlled trial in Wisconsin,3 one other trial,4 and cohort studies.5–8 In particular, the Wisconsin study found evidence of improved cognition functioning.9 In addition, there was evidence of improved child survival from a trial in the United Kingdom4 as well as from several cohort studies.5–8 Evidence from cohort studies of reduced rates of hospitalization and burdensome treatment was not confirmed by the Wisconsin study.
All screening is associated with costs and risks of physical and psychologic harm. Studies10–12 of parents of children who screened positive and either did or did not receive a diagnosis of cystic fibrosis have found low levels of lingering anxiety and concern but no evidence of disturbed parent-child bonding. The Wisconsin study3 found evidence of physical harm in the form of earlier exposure of screened infants in one area to colonization with a serious lung pathogen, Pseudomonas aeruginosa, which was associated with poorer long-term outcomes. The harm to these children was inadvertent, likely associated with person-to-person transmission in a crowded waiting room, and is preventable with proper precautions.13 This is not an inherent risk of newborn screening, and analysis of registry data shows that children with cystic fibrosis identified through newborn screening for cystic fibrosis in the United States are not subject to higher risk of early colonization.
To ensure that screening for cystic fibrosis results in more benefit than harm, the CDC recommends that a deliberative process be followed. First, before implementation of screening, states should consult with other states that have experience in screening for cystic fibrosis as well as cystic fibrosis specialists in their states. Second, they recommend that states carefully address provider and public education, infection control practices among providers of care to persons with cystic fibrosis, and effective communication with families. Third, they propose that state newborn screening programs develop systems in collaboration with specialty care providers to track short-term and long-term child outcomes and identify resources to support this activity.
The process of reviewing scientific evidence and addressing implementation and ethical issues is as important as the specific findings and recommendations of this report. With a wide array of potential new testing technologies and candidate disorders for newborn screening panels, it is more important than ever to establish an objective process for accumulating and interpreting scientific evidence to inform policy decisions.
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