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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
E84.0, Cystic fibrosis with pulmonary manifestations
E84.8, Cystic fibrosis with pancreatic insufficiency

Disorder Category

Genetic disorder

Screening

Abnormal Finding

All 50 states screen newborns for cystic fibrosis (CF), though the testing method varies. Trypsinogen, produced only in the pancreas, is elevated in infants with CF and is tested for by an immunoassay (immunoreactive trypsinogen or IRT). State programs address an elevated IRT screening level in several ways: some go directly to genetic testing, while others repeat the IRT. The PCP and family will be notified if tests are abnormal. All positive testing on the newborn screen should be followed by sweat chloride testing (sweat test), 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 may not test positive on newborn screening. Infants with meconium ileus should be 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. Positive findings are followed by a sweat test that confirms the diagnosis.

Description

CF occurs when a patient carries 2 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene (see CFTR Gene (MedlinePlus)). CFTR mutations impair chloride ion channel function and cause abnormal secretions in sweat glands, lungs, liver, pancreas, digestive system, sinuses, and reproductive system. This accumulation of thick secretions impairs organ function, especially in the lungs, and makes patients prone to pulmonary infections. Individuals with CF also commonly have pancreatic insufficiency. This causes difficulty absorbing nutrients, which may lead to malnutrition and fatty stools. With recent advancements in care, individuals with CF live longer, with life expectancy in the early 50s.

Clinical Characteristics

With treatment, 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 of children with CF. [Schechter: 2010]
Some children are pancreatic insufficient based on their mutations and need PERT (pancreatic enzyme replacement therapy), and some are pancreatic sufficient, although they can convert to insufficient during childhood.
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 breastfed infants)
  • Electrolyte depletion
  • Pulmonary inflammation or bronchiectasis
  • Persistent coughing or wheezing
  • Cystic fibrosis-related diabetes
  • Chronic or recurrent pancreatitis
  • Liver disease
  • Digital clubbing
  • 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. [Dickinson: 2021] [Polgreen: 2022]

Inheritance

Autosomal recessive - CF is caused by one of thousands of possible mutations of the CFTR gene on chromosome 7. [CF: 2023] The delta F508del mutation (the most common CF-related mutation) is found in 70-90% of children with CF. Although this mutation is generally associated with severe disease [Rafeeq: 2017], the severity of disease is difficult to predict because it depends on several factors: which 2 mutations are present, modifier genes, epigenetic factors, and the environment. [Bell: 2020] [Goss: 2019] Rarely, individuals with 2 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 RI providers [2]) 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. In Idaho, infants are considered to have a positive screen if 2 IRT specimens are elevated. The newborn screen refers all positive tests to the CF Center where all treatment is coordinated. In most centers, genetic counseling is scheduled during the sweat chloride test. [Farrell: 2017]

Confirming the Diagnosis

  • To confirm the diagnosis of cystic fibrosis, work with Newborn Screening Services (see RI providers [2]).
  • Sweat chloride testing to confirm/exclude the diagnosis and perform genetic testing as indicated. Sweat testing should be performed by a CF-Foundation accredited laboratory. See Cystic Fibrosis Clinics (see RI providers [2]).
  • Sweat chloride testing is the gold standard for identifying people with CF. People 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 a cystic fibrosis center should evaluate the child. 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.

If the Diagnosis is Confirmed

  • For ongoing collaborative management or consultation, Cystic Fibrosis Clinics (see RI providers [2]).
  • Ongoing education of the family regarding:
    • Signs, symptoms, and the need for urgent care when the infant becomes ill
    • Harmful effects of secondhand smoke and vape aerosol
    • 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
  • Ensure completion of routine immunizations, including the 23-valent pneumococcal vaccine, annual influenza vaccines, and the COVID-19 vaccine if available for that age group.
  • Pancreatic enzymes, vitamin supplements, and salt supplementation are likely indicated
  • Bronchodilators, routine airway clearance, 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)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

CFTR-Related Disorders (GeneReviews)
Detailed information addressing clinical characteristics, diagnosis/testing, management, genetic counseling, and molecular pathogenesis; from the University of Washington and the National Library of Medicine.

For Parents and Patients

Health Topic: Cystic Fibrosis (MedlinePlus)
An overview of the condition with links to other organizations providing more information; National Library of Medicine and National Institutes of Health.

Cystic Fibrosis (MedlinePlus)
Detailed review of CF genetics aimed at patients and families; National Library of Medicine and National Institutes of Health.

Cystic Fibrosis (NHLBI, NIH)
Information about the causes, prevalence, signs and symptoms, diagnostic tests, and treatments for CF; National Heart Lung and Blood Institute and National Institutes of Health.

Cystic Fibrosis - for Kids (KidsHealth.org)
Information for kids from a national site, sponsored by Nemours Foundation. Also provides pages for parents and teens (see tabs at the top of the page).

Practice Guidelines

Farrell PM, White TB, Ren CL, Hempstead SE, Accurso F, Derichs N, Howenstine M, McColley SA, Rock M, Rosenfeld M, Sermet-Gaudelus I, Southern KW, Marshall BC, Sosnay PR.
Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation.
J Pediatr. 2017;181S:S4-S15.e1. 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 in Rhode Island (RI)

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 Finder for Cystic Fibrosis (CF Foundation)

Helpful Articles

PubMed search for cystic fibrosis in children, last 1 year

Martiniano SL, Wu R, Farrell PM, Ren CL, Sontag MK, Elbert A, McColley SA.
Late Diagnosis in the Era of Universal Newborn Screening Negatively Affects Short- and Long-Term Growth and Health Outcomes in Infants with Cystic Fibrosis.
J Pediatr. 2023;262:113595. PubMed abstract

Rock MJ, Baker M, Antos N, Farrell PM.
Refinement of newborn screening for cystic fibrosis with next generation sequencing.
Pediatr Pulmonol. 2023;58(3):778-787. PubMed abstract

McGarry ME, Ren CL, Wu R, Farrell PM, McColley SA.
Detection of disease-causing CFTR variants in state newborn screening programs.
Pediatr Pulmonol. 2023;58(2):465-474. PubMed abstract / Full Text

Polgreen PM, Comellas AP.
Clinical Phenotypes of Cystic Fibrosis Carriers.
Annu Rev Med. 2022;73:563-574. PubMed abstract / Full Text

Authors & Reviewers

Initial publication: June 2010; last update/revision: December 2023
Current Authors and Reviewers:
Author: Hannah Holik, MD
Senior Author: Kimberly Stowers, MD
Reviewer: Kristen N. Ameel, MD
Authoring history
2018: update: Fadi Asfour, MD, MBBSA
2010: first version: Barbara Chatfield, MDA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Bell SC, Mall MA, Gutierrez H, Macek M, Madge S, Davies JC, Burgel PR, Tullis E, Castaños C, Castellani C, Byrnes CA, Cathcart F, Chotirmall SH, Cosgriff R, Eichler I, Fajac I, Goss CH, Drevinek P, Farrell PM, Gravelle AM, Havermans T, Mayer-Hamblett N, Kashirskaya N, Kerem E, Mathew JL, McKone EF, Naehrlich L, Nasr SZ, Oates GR, O'Neill C, Pypops U, Raraigh KS, Rowe SM, Southern KW, Sivam S, Stephenson AL, Zampoli M, Ratjen F.
The future of cystic fibrosis care: a global perspective.
Lancet Respir Med. 2020;8(1):65-124. PubMed abstract / Full Text

CF Foundation, Johns Hopkins, Sequenom.
Clinical and Functional Translation of CFTR.
(2023) https://cftr2.org/.

Dickinson KM, Collaco JM.
Cystic Fibrosis.
Pediatr Rev. 2021;42(2):55-67. PubMed abstract / Full Text

Farrell PM, White TB, Ren CL, Hempstead SE, Accurso F, Derichs N, Howenstine M, McColley SA, Rock M, Rosenfeld M, Sermet-Gaudelus I, Southern KW, Marshall BC, Sosnay PR.
Diagnosis of Cystic Fibrosis: Consensus Guidelines from the Cystic Fibrosis Foundation.
J Pediatr. 2017;181S:S4-S15.e1. PubMed abstract

Goss CH.
Acute Pulmonary Exacerbations in Cystic Fibrosis.
Semin Respir Crit Care Med. 2019;40(6):792-803. PubMed abstract / Full Text

Martiniano SL, Wu R, Farrell PM, Ren CL, Sontag MK, Elbert A, McColley SA.
Late Diagnosis in the Era of Universal Newborn Screening Negatively Affects Short- and Long-Term Growth and Health Outcomes in Infants with Cystic Fibrosis.
J Pediatr. 2023;262:113595. PubMed abstract

McGarry ME, Ren CL, Wu R, Farrell PM, McColley SA.
Detection of disease-causing CFTR variants in state newborn screening programs.
Pediatr Pulmonol. 2023;58(2):465-474. PubMed abstract / Full Text

Polgreen PM, Comellas AP.
Clinical Phenotypes of Cystic Fibrosis Carriers.
Annu Rev Med. 2022;73:563-574. PubMed abstract / Full Text

Rafeeq MM, Murad HAS.
Cystic fibrosis: current therapeutic targets and future approaches.
J Transl Med. 2017;15(1):84. PubMed abstract / Full Text

Rock MJ, Baker M, Antos N, Farrell PM.
Refinement of newborn screening for cystic fibrosis with next generation sequencing.
Pediatr Pulmonol. 2023;58(3):778-787. 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