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Cystic Fibrosis (CF)

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Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

Cystic fibrosis of the pancreas
Mucoviscidosis

ICD-10 Coding

E84.9, Cystic fibrosis, unspecified

Disorder Category

Genetic disorder

Screening

Abnormal Finding

All 50 states screen newborns for cystic fibrosis (CF), though the method of testing varies. Trypsinogen, which is produced only in the pancreas, is elevated in infants with CF and is tested for by an immunoassay (immunoreactive trypsinogen or IRT). State programs react to a high IRT screening level in several ways: some go directly to genetic testing, some repeat the IRT and, if both tests are abnormal, notify the primary care physician (PCP), some repeat the IRT and then send the blood spot for genetic testing and, if genetic testing shows one of the CFTR mutations, then notify the PCP and family. All positive testing on the newborn screen, whatever the method, should be followed by sweat chloride testing, the gold standard for diagnosis. Infants born, or presenting in the first few days of life, with meconium ileus due to CF, may have normal trypsinogen levels and, therefore, not test positive on newborn screening. Infants with meconium ileus are tested directly with DNA and sweat chloride testing when clinically appropriate.

Tested By

Immunoassay for trypsinogen (immunoreactive trypsinogen test, or IRT); followed by repeat testing and/or CFTR mutation analysis, depending on the state.

Description

CF occurs when a patient carries 2 deleterious mutations for cystic fibrosis transmembrane conductance regulator (CFTR) function (see CFTR Gene (MedlinePlus)). CFTR mutations impair chloride ion channel function and abnormal secretions in sweat glands, lungs, liver, pancreas, digestive system, sinuses, and reproductive system. This accumulation of thick and sticky secretions decreases organ function, especially in the lungs, and makes patients prone to pulmonary infections. In addition, individuals with CF may have difficulty absorbing nutrients, causing malnutrition and fatty stools. With recent advancements in care, individuals with CF are living longer – current life expectancy is around 47 years.

Clinical Characteristics

With treatment, of cystic fibrosis, health complications are reduced and survival into middle adulthood is common. The CF Foundation has established care centers, certified sweat chloride testing, advocated for CF newborn screening, and more, all of which have helped survival in children with CF. [Schechter: 2010]
Without treatment, symptoms may vary. With more severe CFTR mutations, acute and chronic respiratory infections, chronic digestive complications, diabetes, and other symptoms can be expected. Children with two severe mutations generally have malabsorption in the newborn to early childhood. Children with milder mutations could be pancreatic sufficienct and may not need pancreatic enzyme replacement therapy. The presentation of CF-related lung disease cannot always be predicted by the severity of the CFTR mutation.
Initial symptoms may include:
  • Meconium ileus
  • Salty sweat or sweat crystals on the skin
  • Poor weight gain
  • Diarrhea, constipation, or persistent abdominal pain
  • Rectal prolapse
  • Thick phlegm and mucus
  • Recurrent lung and sinus infections
  • Nasal polyps

If not treated, patients may experience:
  • Malnutrition and poor growth
  • Smelly, greasy, bulky, and bright green stools (even in breast fed infants)
  • Electrolyte depletion
  • Pulmonary damage or bronchiectasis
  • Persistent coughing or wheezing
  • Diabetes
  • Pancreatitis
  • Liver disease
  • Death in childhood

Incidence

Cystic fibrosis is the most common life-threatening autosomal recessive disease in the United States, occurring in approximately 1:3500 newborns. [Sontag: 2005] [Parad: 2003] [Comeau: 2004]

Inheritance

Autosomal recessive; CF is caused by one of thousands of possible mutations of the CFTR gene on chromosome 7. Clinical & Functional Translation of CFTR for Clinicians The delta F508 mutation (the most common CF-related mutation) is found in 70-90% of children with CF. CFTR: The Gene Associated with Cystic Fibrosis (NHGRI) Although this mutation is generally associated with severe disease, [Dawson: 2001] [Mickle: 2000] the severity of disease is difficult to predict because it depends on several factors: which two mutations are present, modifier genes, epigenetic factors, and the environment. [Gallati: 2003] Rarely, individuals with two CFTR gene mutations may be asymptomatic.

Primary Care Management

Next Steps After a Positive Screen

  • Contact the family and work with the Newborn Screening Services (see NW providers [1]) to set up further testing.
  • States vary in the screening algorithms they use for testing. For example, infants born in Utah are considered to have a positive screening test if 2 IRT specimens are elevated and if genetic testing for CFTR mutations is positive, while in Idaho, infants are considered to have a positive screen if 2 IRT specimens are elevated, and the medical home is then responsible to ensure the patient receives sweat chloride diagnostic testing, gene analysis, and treatment. In most centers, genetic counseling is scheduled during the sweat chloride test. [Farrell: 2008]

Confirming the Diagnosis

  • To confirm the diagnosis of cystic fibrosis, work with Newborn Screening Services (see NW providers [1]).
  • Sweat chloride testing to confirm/exclude the diagnosis and perform genetic testing as indicated. Sweat testing should be performed by an experienced laboratory, see Cystic Fibrosis Clinics (see NW providers [1]).
  • Sweat chloride testing is the gold standard for identifying children with CF. Children with CF demonstrate high chloride levels in sweat because chloride uptake into the sweat duct is impaired. If the test is equivocal, further testing is indicated, and the child should be evaluated by a cystic fibrosis center. If the test is positive, the infant will receive an appointment in 72 hours (unless extenuating circumstances arise), with treatment started at that time.
  • Though uncommon, DNA testing through newborn screening programs may be falsely negative. If symptoms consistent with CF are present, despite a normal newborn screen result, sweat chloride testing should always be performed.
  • Many patients will already have poor weight gain when a diagnosis is confirmed. Initiation of pancreatic enzyme replacement therapy as early as possible is vital to correcting nutritional deficiencies and reducing morbidity and mortality.
  • Sweat testing is also performed when there is meconium ileus. Because newborn screening genetic testing looks for only a few disease-causing mutations, sweat chloride testing should be performed if a child is symptomatic, regardless of the screening results. Additional and more detailed genetic testing may be needed for positive or borderline sweat test results. The CF Foundation certifies only a limited number of sweat chloride testing sites – see CF Newborn Screening – Info for Parents (CF Foundation).

If the Diagnosis is Confirmed

  • For ongoing collaborative management or consultation, Cystic Fibrosis Clinics (see NW providers [1]).
  • Ongoing education of the family regarding:
    • Signs, symptoms, and the need for urgent care when the infant becomes ill
    • Harmful effects of secondhand smoke
    • Handwashing to prevent infections
    • Need for extra fluids and a high-salt, high-fat, high-calorie diet (caloric intake goal is 110-120% of RDA; 40% of calories should ideally come from fat)
    • Importance of Cystic Fibrosis Center management and follow up
  • Assure completion of routine immunizations, including the 23-valent pneumococcal vaccine and annual influenza vaccines
  • Pancreatic enzymes and vitamin supplements are likely indicated
  • Bronchodilators, mucus thinners, antibiotics, and other medications are likely indicated

Resources

Information & Support

Related Portal Content
Cystic Fibrosis
Assessment and management information for the primary care clinician caring for the child with cystic fibrosis.
Cystic Fibrosis (FAQ)
Answers to questions families often have about caring for their child with cystic fibrosis.
After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.

For Professionals

Cystic Fibrosis (OMIM)CFTR-Related Disorders (GeneReviews)

For Parents and Patients

Health Topic: Cystic Fibrosis (MedlinePlus)Cystic Fibrosis (MedlinePlus)Cystic Fibrosis Information (UDHHS)Cystic Fibrosis (NHLBI, NIH)Cystic Fibrosis - for Kids (KidsHealth.org)

Practice Guidelines

Borowitz D, Parad RB, Sharp JK, Sabadosa KA, Robinson KA, Rock MJ, Farrell PM, Sontag MK, Rosenfeld M, Davis SD, Marshall BC, Accurso FJ.
Cystic Fibrosis Foundation practice guidelines for the management of infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome during the first two years of life and beyond.
J Pediatr. 2009;155(6 Suppl):S106-16. PubMed abstract

Borowitz D, Robinson KA, Rosenfeld M, Davis SD, Sabadosa KA, Spear SL, Michel SH, Parad RB, White TB, Farrell PM, Marshall BC, Accurso FJ.
Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis.
J Pediatr. 2009;155(6 Suppl):S73-93. PubMed abstract

Patient Education

Patient Resources (CF Foundation & Boston Children's Hospital)
Fact sheets covering specific topics related to CF in the areas of nutrition, tests, medications, schools, insurance, and more.

Tools

ACT Sheet for Cystic Fibrosis (ACMG) (PDF Document 59 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Confirmatory Algorithm for Elevated Immunoreactive Trypsinogen (PDF Document 185 KB)
Graphic representation of steps to confirm (or rule out) cystic fibrosis as the cause of a positive IRT test in newborns.

Services for Patients & Families Nationwide (NW)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Studies

Clinical trial information (CF Foundation)

Helpful Articles

PubMed search for cystic fibrosis in children, last 1 year

Grosse SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M, Rosenfeld M, Wilfond BS.
Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs.
MMWR Recomm Rep. 2004;53(RR-13):1-36. PubMed abstract / Full Text

Castellani C, Southern KW, Brownlee K, Dankert Roelse J, Duff A, Farrell M, Mehta A, Munck A, Pollitt R, Sermet-Gaudelus I, Wilcken B, Ballmann M, Corbetta C, de Monestrol I, Farrell P, Feilcke M, Férec C, Gartner S, Gaskin K, Hammermann J, Kashirskaya N, Loeber G, Macek M Jr, Mehta G, Reiman A, Rizzotti P, Sammon A, Sands D, Smyth A, Sommerburg O, Torresani T, Travert G, Vernooij A, Elborn S.
European best practice guidelines for cystic fibrosis neonatal screening.
J Cyst Fibros. 2009. PubMed abstract

Authors & Reviewers

Initial publication: June 2010; last update/revision: February 2018
Current Authors and Reviewers:
Author: Fadi Asfour, MD, MBBS
Authoring history
2010: first version: Barbara Chatfield, MDA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Borowitz D, Parad RB, Sharp JK, Sabadosa KA, Robinson KA, Rock MJ, Farrell PM, Sontag MK, Rosenfeld M, Davis SD, Marshall BC, Accurso FJ.
Cystic Fibrosis Foundation practice guidelines for the management of infants with cystic fibrosis transmembrane conductance regulator-related metabolic syndrome during the first two years of life and beyond.
J Pediatr. 2009;155(6 Suppl):S106-16. PubMed abstract

Borowitz D, Robinson KA, Rosenfeld M, Davis SD, Sabadosa KA, Spear SL, Michel SH, Parad RB, White TB, Farrell PM, Marshall BC, Accurso FJ.
Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis.
J Pediatr. 2009;155(6 Suppl):S73-93. PubMed abstract

Castellani C, Southern KW, Brownlee K, Dankert Roelse J, Duff A, Farrell M, Mehta A, Munck A, Pollitt R, Sermet-Gaudelus I, Wilcken B, Ballmann M, Corbetta C, de Monestrol I, Farrell P, Feilcke M, Férec C, Gartner S, Gaskin K, Hammermann J, Kashirskaya N, Loeber G, Macek M Jr, Mehta G, Reiman A, Rizzotti P, Sammon A, Sands D, Smyth A, Sommerburg O, Torresani T, Travert G, Vernooij A, Elborn S.
European best practice guidelines for cystic fibrosis neonatal screening.
J Cyst Fibros. 2009. PubMed abstract

Comeau AM, Parad RB, Dorkin HL, Dovey M, Gerstle R, Haver K, Lapey A, O'Sullivan BP, Waltz DA, Zwerdling RG, Eaton RB.
Population-based newborn screening for genetic disorders when multiple mutation DNA testing is incorporated: a cystic fibrosis newborn screening model demonstrating increased sensitivity but more carrier detections.
Pediatrics. 2004;113(6):1573-81. PubMed abstract

Dawson KP, Frossard PM, Al-Awar B.
Disease severity associated with cystic fibrosis mutations deltaF508 and S549R(T-->G).
East Mediterr Health J. 2001;7(6):975-80. PubMed abstract

Farrell PM, Rosenstein BJ, White TB, Accurso FJ, Castellani C, Cutting GR, Durie PR, Legrys VA, Massie J, Parad RB, Rock MJ, Campbell PW 3rd.
Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report.
J Pediatr. 2008;153(2):S4-S14. PubMed abstract / Full Text

Gallati S.
Genetics of cystic fibrosis.
Semin Respir Crit Care Med. 2003;24(6):629-38. PubMed abstract

Grosse SD, Boyle CA, Botkin JR, Comeau AM, Kharrazi M, Rosenfeld M, Wilfond BS.
Newborn screening for cystic fibrosis: evaluation of benefits and risks and recommendations for state newborn screening programs.
MMWR Recomm Rep. 2004;53(RR-13):1-36. PubMed abstract / Full Text

Mickle JE, Cutting GR.
Genotype-phenotype relationships in cystic fibrosis.
Med Clin North Am. 2000;84(3):597-607. PubMed abstract

Parad RB, Comeau AM.
Newborn screening for cystic fibrosis.
Pediatr Ann. 2003;32(8):528-35. PubMed abstract

Schechter MS, Gutierrez HH.
Improving the quality of care for patients with cystic fibrosis.
Curr Opin Pediatr. 2010;22(3):296-301. PubMed abstract

Sontag MK, Hammond KB, Zielenski J, Wagener JS, Accurso FJ.
Two-tiered immunoreactive trypsinogen-based newborn screening for cystic fibrosis in Colorado: screening efficacy and diagnostic outcomes.
J Pediatr. 2005;147(3 Suppl):S83-8. PubMed abstract