Cystic Fibrosis (CF) is a rare genetic condition characterised by a defect in CFTR, an essential gene that encodes a channel protein critical for salt and water regulation. As a result of the defect, the body produces excess mucus that is thick and sticky within the digestive and respiratory systems, causing debilitating issues.

CF is usually detected just after birth during newborn screening programmes. Guidelines for neonatal detection have previously been established, but practice varies between healthcare providers, with many still following outdated protocols.

A study published in the Open Access International Journal of Neonatal Screening by researchers collaborating across the US establishes novel guidelines for screening, ensuring uniform and practice and efficiency across the board.

Newborn screening should be updated and standardised so that it benefits all families equally. All babies deserve early diagnosis and early treatment so they can have the best outcomes. – Dr. Megan McGarry, first author of the study and Associate Professor at UW School of Medicine.

What is Cystic Fibrosis, and how does it impact life?

CF is a serious condition with potentially severe health implications. The thick, excess mucus produced due to the defect causes blockages within internal tubes and ducts affecting the lungs, digestive system, pancreas and other organs, leaving the body prone to infection.

As a result, CF can cause endocrine, reproductive, or digestive disorders. However, it predominantly affects the lungs, which is the most common cause of death in individuals suffering from the disease. Chronic lung infections cause a higher risk of lung damage, resulting in reduced lung function, significantly affecting quality of life.

There is currently no cure for CF, but early diagnosis is critical to ensure early detection and to provide rapid treatment to the patient. Early diagnosis and treatment significantly improves symptoms and quality of life. These life-saving treatments have developed over recent years and include a range of different medications such as bronchodilators, CFTR modulators and mucus thinners. CFTR modulators enhance the function of the CFTR proteins so that salt and water levels are regulated better. To treat the disease as quickly as possible, early and efficient diagnosis is crucial.

Because the disease impairs the newborn’s ability to absorb nutrients, a delay in diagnosis of a week or so can lead to damaging weight loss and other complications. If the diagnosis is missed, you will often see serious growth problems and permanent lung damage as the child grows older. – Dr. McGarry

How is Cystic Fibrosis usually detected?

CF is detected just after a baby is born by screening blood drawn from a heel prick. The amount of immunoreactive trypsinogen (IRT) in the blood is then measured. IRT is a protein normally secreted by the pancreas; however, in the case of CF, these levels are significantly high. Specific mutations associated with CF (and other genetic diseases) are also screened for. Different thresholds in IRT is where differences lie between screening practices.

Furthermore, there are over 40 known mutations that could potentially cause CF; however, not all of these mutations are screened for in every US state. Amongst the recommendations, the authors discuss the limitation in screening for rare mutations that often go amiss in babies from Asian, Hispanic, Black, American Indian and multiracial backgrounds.

Researchers, call for uniform guidelines to ensure more efficient diagnosis for this life-altering disease.

New Cystic Fibrosis screening guidelines

The guidelines published by the United States Cystic Fibrosis Foundation push for more cohesive and consistent screening guidelines across the US and globally. The guidelines are based on data drawn from a systematic review of the available data on CF screening across the US. They cover 5 essential recommendations on screening sensitivity, specificity, and equity and cover these practices in detail.

The authors include recommendations such as increasing the frequency of IRT tests run per week to reduce the potential delay time in CF detection. Furthermore, guidelines highlight the need to take into account variables that may alter IRT results, such as temperature and humidity. Importantly, IRT sensitivities and thresholds are discussed to ensure practices are upheld to the greatest precision.

The guidelines state the importance of immediately screening for CF mutations when high levels of IRT are detected. Researchers of the study also emphasise that a positive or negative test result does not equate to a formal diagnosis. A chloride sweat test is currently used to make a formal diagnosis. This test measures the chloride concentration in the baby’s sweat, where a high level of chloride suggests the presence of CF.

If a baby presents with signs and symptoms of cystic fibrosis, paediatricians should not rule out cystic fibrosis solely based on their normal newborn screening. Families have faced difficulties getting further testing, despite the baby showing classic signs of cystic fibrosis, based on a normal initial screen. – Dr. McGarry

Further research

The authors conclude that more research is needed to refine the CF screening process even further. This encompasses factors such as efficiency in communication, time effectiveness and sensitivity. They also comment on how the detection of very rare mutations more often found in Asian or African populations can improve, as well as questioning how communication with these families can be better dealt with.

The International Journal of Neonatal Screening is an Open Access journal that is owned by the International Society for Neonatal Screening (ISNS), The International Society for Neonatal Screening (ISNS), German Society for Neonatal Screening (DGNS), the Japanese Society for Neonatal Screening (JSNS), the Association of Public Health Laboratories (APHL) and the UK Newborn Screening Laboratory Network (UKNSLN) published by MDPI and supported by the MDPI Societies Team.

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