Although cystic fibrosis (CF) is the most common, potentially fatal genetic disorder of Caucasians, there are often delays in diagnosis, a fact which makes neonatal screening attractive. It has not been established in a controlled study, however, that early treatment achieved by neonatal diagnoses will be medically beneficial, nor have the risks of screening for CF been defined. Furthermore, there has been controversy over the specificity and sensitivity of screening tests. An advance which made CF screening possible during the past decade involves measurement of immunoreactive trypsinogen (IRT) on routinely collected neonatal blood samples. Using the IRT assay as the primary screening test, this project involves a controlled study of both benefits and risks. With a randomized experimental design, half of the newborn population in Wisconsin is being screened in the neonatal period to generate an early diagnosis/treatment group, whereas the other half (control group) is having a """"""""blind"""""""" IRT test performed, with the results not reported until after the child is four years old; prior to that time, CF is diagnosed in the control group based on the standard approach requiring either symptoms or a positive family history. This design allows an unbiased, complete evaluation of the two groups. The project has been underway for 4 1/2 years, and progress has been good, with results thus far indicating a number of potential advantages of CF screening. However, several developments have occurred, as listed below, which make it important for us to continue the project and extend it in the direction of applying new molecular genetics diagnostic techniques. 1. The incidence of CF in Wisconsin, and thus our patient accrual, has been only 1/2- 2/3 of the predicted rate. 2. Meconium ileus has occurred in a surprisingly high proportion of patients (29% overall compared to 10% expected) and by chance has been more prevalent in the control group (42%), thereby causing a significant and disconcerting imbalance in the two groups. 3. Our data indicate that the IRT assay as a sole screening test for CF is not ideal, although it offers promisee as an initial procedure in a two-tiered screening program. 4. Recent identification of the mutant CF gene now makes it feasible to investigate application of this technology to neonatal screening. In order to answer the key questions concerning benefits and risks of CF diagnosis in early infancy, we need continued funding to maintain randomized neonatal screening for 3 more years, particularly to accrue an adequate number of subjects and to both fully develop and apply a second tier test based on molecular genetics. With continuation of funding, we should be able to test the following hypotheses and reach statistically valid conclusions: 1) the majority of CF patients can be diagnosed as neonates; 2) the process of neonatal diagnosis, if implemented appropriately, will not cause harmful effects; and 3) diagnosis in early infancy will enhance nutrition/growth and significantly reduce the chronic pulmonary disease of CF.
Showing the most recent 10 out of 52 publications
