Screening

Carrier screening

Routine obstetric practice in the US has included prepregnancy and antenatal carrier screening for CF since 2001.[37]​ Therefore, every pregnant woman or woman considering pregnancy should receive information about genetic carrier screening and be free to make an informed decision after appropriate counselling.[35][38]

Although ethnicity affects the sensitivity of current screening tests, resulting in variation from <50% with Asian ancestry to 94% for the Ashkenazi Jewish population, aim to screen every pregnant woman for cystic fibrosis once during her lifetime, irrespective of their ethnic background.[39][40]​​​​ Expanded panels can improve CF carrier detection rates within specific populations. Routine carrier screening should not include a complete analysis of the CFTR gene by DNA sequencing.[35]

If a woman receives a positive screening result, offer her partner a screening test. If neither is affected, but one or both has a relevant family history, conduct genetic counselling and a medical record review to determine if there has been a CFTR mutation analysis. If a woman’s reproductive partner has CF or apparently isolated congenital bilateral absence of the vas deferens, offer follow-up genetic counselling by a healthcare provider with genetics expertise for mutation analysis and consultation.[35]

Newborn screening

The US Cystic Fibrosis Foundation recommends appropriately performed newborn screening for all infants.[34]​ This should not replace prepregnancy or antenatal carrier screening.[35]

Newborn screening ensures early diagnosis and treatment, providing significant clinical benefits (e.g., improved nutrition and cognition). This approach may decrease lung disease and the amount of hospital admissions. It is performed by quantifying serum immunoreactive trypsinogen (IRT) from a dried heel-stick blood spot. Test results only indicate risk, not a diagnosis, with each laboratory defining a positive IRT test result differently.[29]​ Protocols also differ for the follow-up offered after a positive IRT test, but this usually includes confirmatory testing with a positive sweat test and the identification of two disease-causing mutations on genetic testing. All patients with a positive IRT test should be referred to a CF centre.[41]​ Expanded genetics can be considered when there is more ethnic diversity, depending on the local population (i.e., state or region).

Unintended consequence of CF newborn screening

A positive NBS test may be accompanied by inconclusive diagnostic testing.[29][42]​​

CFTR-related metabolic syndrome (CRMS), also known as a CF screen-positive inconclusive diagnosis (CFSPID) in Europe, refers to infants with a positive newborn screening test for CF and either of the following:[29]

  • A sweat chloride value <30 mmol/L (<30 mEq/L) and two CFTR mutations, at least one of which does not cause any physical symptoms, or

  • An intermediate sweat chloride value (30-59 mmol/L [30-59 mEq/L]) and one or no CF-causing mutations.

It is important to follow these patients closely as the prognosis of CRMS/CFSPID currently remains unclear.[43]​ Certain individuals with CRMS/CFSPID have a higher risk of developing related respiratory, sinus, intestinal, pancreatic, or reproductive pathology similar to CF. In some cases, evolving signs and symptoms, new information about disease-causing CFTR mutations, or changes in sweat chloride concentration levels may ultimately lead to a CF diagnosis.[42][43]

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