Newborn screening for cystic fibrosis.

As a paediatrician treating children with cystic fibrosis (CF), one of the tasks I fear most is visiting the home of a newly diagnosed CF patient to tell the parents that sweat testing has revealed that one or more of their other children are affected with the disease. A related nightmare is the late diagnosis of CF, at a stage when lung damage is well established. Will plans to introduce a national programme of CF screening in England (screening is already in place in Wales, Northern Ireland and Scotland) abolish these two problems? The answer is that it should. But sceptics of the value of screening have not been won over by anecdotal arguments from clinicians at the coalface and have demanded objective proof. The case made for the national screening programme in England was more political than scientific, and argument continues on the possible harms as well as benefits. One immediate but overcomable challenge is the lack of universal agreement about the best screening protocol. Existing approaches use measurement of immunoreactive trypsin (IRT) in one or more blood samples, coupled with testing for a small number of CF gene mutations, followed by sweat testing. Seemingly the national screening programme will employ a protocol that includes DNA analysis of an initial raised IRT sample and a second IRT on samples when only one CF gene mutation is recognized.1 This two-tier IRT/DNA analysis provides better sensitivity, specificity and positive predictive accuracy than IRT testing alone, and the addition of DNA testing to IRT reduces the need for repeat specimen collection. The most consistently observed benefits of early diagnosis by screening have been nutritional. Infants diagnosed through screening were more likely to have normal height and weight than those identified through traditional diagnosis of symptomatic patients.2 The efficacy of screening in preventing lung damage, probably the single most important aim, has been much harder to demonstrate. One difficulty is that, whereas nutrition is readily assessed from weight gain, we have no means of quantifying lung disease in its early stages. Existing studies comparing the pulmonary outcome in screened versus conventionally diagnosed patients have often been observational and affected by selection bias and lack of standardization of respiratory treatment. A randomized trial in Wisconsin avoided these drawbacks: it showed that, whilst chest radiograph abnormalities were milder at diagnosis in the patients diagnosed by screening, the screened group had worse X-ray scores in the long term, associated with earlier acquisition of Pseudomonas aeruginosa.3,4 Concerns about the presymptomatic diagnosis by screening thus include not only possible harm from aggressive treatment with antibiotics and chest physiotherapy, but also early cross-infection. Any benefits of early diagnosis of CF could be wiped out by mixing these newly diagnosed patients, in the clinic or ward, with others who have established pseudomonas lung infection. Psychosocial harm from diagnosis by screening is a further worry. The way a positive result is handled can have very detrimental effects on parents and families, and great care will be needed when the result is shared and explained. Looking after a newly diagnosed patient and family is a demanding process and requires immense input, mainly educational, from all members of the CF multidisciplinary team including doctor, specialist nurse, physiotherapist, dietitian and psychologist, in close liaison with the primary care and community health team. Alas many CF centres are chronically understaffed—and matters are not likely to improve in the next twelve months as the existing clinical support grants from the CF Research Trust are phased out. Already, specialists in England are having to run some CF clinics without adequate support from essential health professionals such as dietitians and physiotherapists; how will CF centres cope, without additional funding, with the new work that arises from introduction of screening tests? A real worry is the potential adverse effects upon infants who as a result of screening are found to be heterozygote carriers of a CF gene mutation. Although the family may be relieved to hear that the child is not affected by CF, there is concern that anxiety and grief reactions associated with carrier state diagnosis may place families at risk for impaired parent-child bonding, personality problems, disrupted relationships or some variant of the vulnerable child syndrome.2 Other potential drawbacks to the identification of carriers are the recognition of non-paternity (and subsequent family break-up), stigmatization of the child, difficulties with medical or life insurance and employment discrimination (due to a misconception about the potential harm of carrier status), and devaluing of a child as a potential marriage partner. Finally, if an infant's CF gene mutation is not included in the standard CF gene mutation screening panel there is a risk that a negative screening result will be falsely reassuring. In theory, a potential benefit of early diagnosis by screening is the enrolment of newly diagnosed patients into large multicentre randomized controlled trials of existing and new treatments. In practice, the variation in treatment strategies of CF is huge—a legacy of the serious dearth of controlled trials of CF treatments—making large controlled trials hard to perform. Farrell and Farrell2 have concluded that excellent implementation is the key to ensuring that CF screening does more good than harm. As they put it, screening provides an opportunity to achieve good results but does not automatically guarantee a good outcome. Releasing newly diagnosed patients into a poorly resourced and ill-equipped and underfunded treatment programme, with a shortage of staff and a lack of facilities to prevent cross infection, would almost certainly create more problems than it solved. Newborn screening for CF and its implementation in England is one of the topics covered at the most recent CF conference organized by the RSM's Section of Paediatrics, the proceedings of which are published in a Supplement to the JRSM.5