Cystic fibrosis - Newcastle Hospitals NHS Foundation Trust

Cystic fibrosis is an autosomal recessive condition. 1 in 25 people of caucasian background carry an altered gene or mutation (less within other ethnic groups).

The condition affects the pancreas / digestive tract and respiratory system by clogging these up with thick sticky mucus. This can lead to recurrent severe chest infections and malnutrition. It can also affect the reproductive organs, nose/sinuses and liver.

Bloodspot screening for cystic fibrosis commenced across the Northern region on 1 November 2006.

Newborn screening enables early detection of pre-symptomatic babies. Early treatment including dietary supplements, antibiotics and physiotherapy may improve health. Screening can be carried out up to 8 weeks of age.

Heel prick test

The screening test looks for raised levels of immuno reactive trypsin within the blood from a heel prick. This is an indirect marker for cystic fibrosis.

If raised levels are detected (>99.5 centile), then genetic testing is performed on the blood sample. This analysis screens for the 50 most common mutations causing CF found in the caucasian population. There are many more mutations in the CF gene, many of which can have little clinical effect.

CF has a significant incidence in non-Europeans, particularly those of Asian ancestry. Some of these cases will have mutations that are not covered by the 30 mutations currently screened for. To compensate for this, babies with no mutation detected but with an initial IRT of >99.9 centile will have a second heel prick to test for IRT levels between days 21 to 28.

False positive IRT screens will arise because of faecal contamination within the blood sample, or transferred by hand, to the sample collection form. It is vital to thoroughly clean the baby’s foot before the heel prick.

If two CF mutations are identified, a presumptive positive diagnosis of CF is made. The parents will be told that the screening test is positive by the designated Health Visitor (HV) and their own HV. An automatic referral is made to the CF team for further assessment. Information will be sent to the GP.

If one CF mutation is identified, and the second heel prick sample remains high, the parents will be told that the baby has a positive screening test and they will automatically be referred to the CF team for evaluation, which may involve a sweat test.

If one CF mutation is identified, but the 2nd IRT level is low, the baby is identified as a ‘carrier’. The parents will be seen in the community by the designated HV and their own HV. They may want to discuss issues with their GP, but can be offered referral to the CF team if they have outstanding issues.

If no mutations are identified, but the baby has two very high IRT levels, they will be classified as having a positive screening test and will automatically be referred to the CF team for further assessment, which may include a sweat test or further mutation testing. This scenario may be the case for non-Caucasian babies.

All screen positive babies are seen by the specialist CF team and started on treatment before 30 days of age.

The screening programme will identify 85-90% of babies affected with CF.

The screening pathway is designed to identify affected babies, but some ‘carriers’ of CF will be identified. Of those carriers identified, most will be healthy, but a small proportion, 1 in 15 of carriers identified by the screening tests, will subsequently prove to have CF clinically.

Because of the possibility of an identified ‘carrier’ actually having CF, or of a false negative screen result, clinicians need to be aware of signs and symptoms which should raise concern and prompt a referral to the CF team. Worrisome signs and symptomsare: persistent cough, poor weight gain/failure to thrive, loose and oily stools, rectal prolapse and nasal polyps in older children.

Genetic Counselling

If a baby is found to have CF, the parents should be offered referral for genetic counselling to discuss options for future pregnancies and cascade testing of other family members.

If the baby is a carrier, the parents should be offered referral for genetic counselling as at least one, and possibly both parents are carriers. If both parents are carriers, there is a 1 in 4 chance in every pregnancy of having a child with CF.

Other family members should be offered carrier status testing. Siblings of these babies will not be offered carrier testing until old enough to understand the implications. Siblings of affected babies or where both parents are carriers will be offered a sweat test by the CF team.