brand logo

Am Fam Physician. 2005;71(8):1605-1610

The Centers for Disease Control and Prevention (CDC) released recommendations on the screening of newborns for cystic fibrosis. The report includes an evaluation of the benefits and risks of this type of screening. It also provides recommendations on how to effectively implement screening programs for states that choose to routinely screen newborns for cystic fibrosis. The recommendations were published in the October 15, 2004, recommendations and reports series of Morbidity and Mortality Weekly Report. The full report is available online at An editorial discussing these guidelines also appears in this issue of American Family Physician onpage 1482.

In November 2003, the CDC and the Cystic Fibrosis Foundation (CFF) cosponsored a workshop to examine the benefits and risks of newborn screening for cystic fibrosis. The three objectives of the workshop were: (1) to review and evaluate the scientific evidence on the benefits and risks of newborn screening for cystic fibrosis; (2) to review screening, diagnostics, and follow-up concerns when making decisions about newborn screening for cystic fibrosis; and (3) to disseminate information about models and best practices for states that choose to adopt newborn screening for cystic fibrosis.

Evidence presented at the workshop supported the clinical utility of this type of screening. Demonstrated benefits include improved growth and cognitive development, reduced hospitalizations, and improved survival. Risks include psychosocial effects for carrier children and their families, and exposure of children to infectious agents through person-to-person transmission in clinical settings.


Cystic fibrosis is the second most common life-shortening, childhood-onset inherited disorder in the United States, behind sickle cell disease. Annually, about 1,000 persons in the United States are diagnosed with cystic fibrosis. In 1979, a test to measure the levels of immunoreactive trypsinogen (which is substantially elevated in newborns with cystic fibrosis) in dried blood spots was introduced and made universal newborn screening for cystic fibrosis possible. This test is now the basis for newborn screening protocols.

In 15 to 20 percent of children with cystic fibrosis, the first symptom is meconium ileus; adverse outcomes include malnutrition, lung disease, and mortality. Because meconium ileus is diagnostic for cystic fibrosis, screening does not increase early detection for these children.

Early recognition of cystic fibrosis based on symptoms often is difficult because the majority of symptoms are not specific to the condition. Therefore, affected children are often diagnosed with celiac disease, food allergies, asthma, or bronchitis. The consequences of misdiagnosis include unnecessary diagnostic tests and hospitalizations, multiple office visits, cost to the health care system, and anxiety for parents.

The median age at diagnosis for all persons with cystic fibrosis in the United States is 5.3 months. The overall median age at diagnosis includes infants diagnosed soon after birth based on newborn screening, prenatal screening, family history, or the presence of meconium ileus. The median age at diagnosis based on signs and symptoms other than meconium ileus is 14.5 months, compared with 0.2 months in those with meconium ileus and 0.5 months for those receiving newborn screening. A diagnosis based on symptoms is associated with a more than twofold greater risk of medical complications before diagnosis than a diagnosis resulting from screening. Adverse psychosocial effects for the child's family also may result during the delay between the appearance of cystic fibrosis–related symptoms and diagnosis.

In 1999, a CFF consensus panel developed a new case definition for cystic fibrosis based on the following criteria: the presence of at least one characteristic phenotypic feature or a history of cystic fibrosis in a sibling or a positive newborn screening test, together with laboratory evidence of an abnormality in the gene that regulates expression of the cystic fibrosis transmembrane conductance regulator protein as documented by (1) elevated sweat chloride concentrations, (2) identification of two mutations associated with cystic fibrosis, or (3) in vivo demonstration of characteristic abnormalities in ion transport across the nasal epithelium. Sweat testing can be performed accurately on most infants at two to three weeks of age, but not all infants have sufficient quantities of sweat for reliable testing. Although a sweat chloride level of 60 mEq per L is diagnostic of cystic fibrosis, infants with cystic fibrosis often have initial sweat values of 30 to 59 mEq per L.

In 2000, approximately 400,000 children (10 percent) born in the United States were screened for cystic fibrosis, and this number was expected to increase to 800,000 in 2004. Screening protocols for cystic fibrosis are listed in the accompanying table.

ProtocolAction after elevated IRT on first specimenResult of DNA assay on first specimenActionResult of repeat DNA assay on first specimenActionResult of IRT assay on second specimenAction
IRT-repeat IRTTest second specimen for IRTExceeds cutoffRefer to sweat test
IRT-DNA (ΔF508)DNA assay for ΔF508 allelesOne to two mutations detectedRefer to sweat test
No mutation detectedExceeds cutoffRefer to sweat test
IRT-DNA (multiple mutations)DNA assay for multiple mutationsOne to two mutations detectedRefer to sweat test
IRT-DNA (ΔF508, multiple mutations)DNA assay for ΔF508 allelesTwo mutations detectedRefer to sweat test or treatmentTwo mutations detectedRefer to sweat test or treatment
One mutation detectedDNA assay for multiple mutationsOne mutation detectedInconclusive result reported

Scientific Evidence

The CDC performed a search of the MEDLINE database for articles on newborn screening for cystic fibrosis published since 1997. Relevant articles had to measure patient-oriented outcomes (either health outcomes or psychosocial outcomes) in groups of children identified with cystic fibrosis through newborn screening compared with children identified through other means. The group also included findings from previously published studies that were identified in reference lists. The report summarizes current knowledge concerning the strength of evidence for health benefits of newborn screening for cystic fibrosis, including assessments of the strengths and limitations of study designs and the consistency and magnitude of reported benefits.



The most clearly defined benefit of newborn screening for cystic fibrosis is improved growth in affected children. One study found long-term improvements in height-for-age measures and reductions in chronic malnutrition. Results of another study demonstrated that the height advantage in children who were screened persisted through at least 10 years of age.


Newborn screening has been shown to positively influence neurodevelopment in a subset of children with cystic fibrosis. A study of school-age children and adolescents found moderate, clinically significant improvements in general cognitive ability in those with vitamin E deficiency at the time of diagnosis.


Studies have shown a substantial benefit of newborn screening in reducing the days of hospitalization for children with cystic fibrosis. However, the authors state that a preliminary analysis of retrospectively collected data from a randomized controlled trial did not show this to be the case. Studies also have shown that newborn screening can reduce costs to the health care system with regard to hospitalizations and reduced ordering of sweat tests.


Several studies have reported proportional reductions of at least 50 percent in mortality rates among children with cystic fibrosis who are diagnosed by newborn screening. However, the authors point out that child mortality as a result of cystic fibrosis is low in absolute terms and the majority of findings from individual studies lack statistical significance.


The effect of newborn screening on pulmonary status among patients with cystic fibrosis as measured by chest radiography and lung function is uncertain. Three studies have shown evidence of less severe lung damage among children identified by newborn screening; no difference in lung function was demonstrated in two of those studies. One Australian study reported evidence of better lung function and less lung damage among children with cystic fibrosis who were born after screening was implemented.


Evidence is lacking for improved health-related quality of life as a patient-oriented outcome measure for the efficacy of newborn screening for cystic fibrosis. Differences in health-related quality of life may be related directly to the frequency of pulmonary exacerbations and treatment interventions, including hospitalization, and not to nutritional status or lung function.


The benefits of screening are more significant for certain children. For example, greater growth is primarily of benefit to children who would have been below the normal range in the absence of screening. The cognitive benefits from screening are greater among children who are at risk for micronutrient deficiency. Newborn screening for cystic fibrosis is most likely to be helpful for children who do not receive a prompt diagnosis despite severe disease manifestations. Although child mortality from cystic fibrosis is low, early detection may save an infant from a life-threatening event, such as hyponatremic dehydration. However, persons with pancreatic sufficiency may not benefit from newborn screening. Also, the 20 percent of patients with meconium ileus do not appear to benefit from newborn screening for cystic fibrosis because they generally receive a diagnosis at birth.


In addition to the health benefits for the children, the families may benefit from the elimination of diagnostic concerns, the value of the genetic risk information gained, and the potential for identifying older siblings who are symptomatic but have not received a diagnosis of cystic fibrosis.


The potential for harm from person-to-person transmission can be avoided through involvement of newborn screening programs with cystic fibrosis care centers and adoption of infection control practices. Other potential negative outcomes from screening include the psychological and social effects of carrier identification for parents and children and the effects of false-positive results. Screening programs should focus on ways to minimize parental anxiety and misunderstanding through better communication of screening results and provision of information about newborn screening.


From the preponderance of evidence, the authors conclude that the health benefits of screening newborns for cystic fibrosis outweigh the risk of harm. They recommend that states consider routine newborn screening for cystic fibrosis in conjunction with systems to ensure access to high-quality care. The following is a list of the specific recommendations from the report:

• When deciding whether to add newborn screening for cystic fibrosis, states should consider available state resources and priorities as well as available national guidelines regarding cystic fibrosis screening, diagnosis, and treatment.

• States that implement newborn screening for cystic fibrosis should collect follow-up data in collaboration with cystic fibrosis care centers and should analyze this information to monitor and improve the quality of cystic fibrosis newborn screening. In particular, states should collect, share, and analyze data by using standard protocols to evaluate and optimize laboratory algorithms used to screen for cystic fibrosis and refer for diagnosis. States seeking guidance on optimal laboratory protocols might wish to consult with states that have more experience in screening for cystic fibrosis in newborns.

• Newborn screening for cystic fibrosis should be accompanied by rigorous infection control practices to minimize the risk to children with cystic fibrosis detected at an early age of acquiring infectious organisms associated with lung disease from older patients. Further research is needed to evaluate and optimize these practices.

• Newborn screening systems should ensure education of parents and health care professionals and communication of screening results to primary care physicians in a manner that will ensure prompt referral to diagnostic centers. For cystic fibrosis, these should be centers skilled in providing sweat tests to young, presymptomatic children with cystic fibrosis and accurate and effective counseling to families, including those with infants identified as carriers. States are encouraged to work with each other and with professional organizations and federal agencies to develop approaches to provide newborn screening information to parents during the prenatal and perinatal periods on all conditions, including cystic fibrosis, to facilitate informed choices and appropriate responses to positive screening results.

Continue Reading

More in AFP

Copyright © 2005 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See for copyright questions and/or permission requests.