Screening for cystic fibrosis.

Practicable methods are now available for whole population screening of neonates for cystic fibrosis. Although diagnosis and treatment of the disease from birth has not yet been unequivocally shown to improve prognosis, existing evidence suggests that this is likely. Further ethical reasons are proposed in support of neonatal diagnosis and early treatment. The development of tests for prenatal diagnosis and carrier detection is under active investigation, and raises ethical problems for heterozygotes and their medical advisers. The heavy financial and emotional burden this disease imposes on the patient and the family should not be underestimated when policy decisions are made.     

Screening for cystic fibrosis by a stool trypsin method.

Mass screening for cystic fibrosis by a trypsin assay of stool dried on filter paper was evaluated in 20 000 5-day-old babies. Sweat tests were required in only 7 babies. Three of them had cystic fibrosis. The test gave a false-negative result in at least 2 babies, but each had normal pancreatic function. This is not an ideal screening test for cystic fibrosis, as it misses cases with normal pancreatic function, but it is very cheap, highly specific, and appears to be the best currently available screening test.     

Screening for cystic fibrosis. A comparative study

A neonatal screening program for CF by determination of albumin in meconium was performed in the north eastern part of the Netherlands from 1973 to 1979. In this period 94,043 newborns were screened and 116,953 were not. A follow-up study of CF patients in the above cohorts was started in 1980. The purposes of this study were to evaluate the effects of early diagnosis and treatment in CF patients by comparing the outcome in the two groups of patients. Although the results indicate that very early diagnosis and treatment have a beneficial effect on outcome, more studies are needed before a definite answer can be given as to whether or not mass neonatal screening should be started.     

Computerised neonatal case records: a four year experience.

A computerized system for neonatal case records has been used for the last four years at Kasturba Hospital. The software was developed in-house. The data base can be used to generate discharge summaries, neonatal statistics and epidemiological information. For a single patient, entry of data and printing of the discharge summary takes four to five minutes. Consolidated demographic and epidemiological statistics or selective clinical data for clinical research is easily retrievable. The system is efficient, accurate and easy to operate.     

Nutritional rehabilitation in cystic fibrosis: a 5 year follow-up study.

Previously, we reported catch-up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard therapy. To evaluate long-term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV1 and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV1, p less than 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short- and long-term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study.     

Screening for cystic fibrosis in the newborn by meconium analysis.

During a 4-year routine screening programme for cystic fibrosis (CF) 15 464 specimens were examined for raised meconium albumin levels by a test strip method and by electroimmunoassay. The incidence of false-positive results was about 5 per 1000 specimens in either test. This could be reduced by 90% by determining the ratio of albumin : alpha-1-trypsin inhibitor (a ratio below 2.0 being considered as a negative result), and it could be reduced to zero by determining the ratio in subsequent faecal specimens. Three of 12 meconium specimens from infants with proved CF gave false-negative results in all 3 tests. The other 9 specimens had greater than 100 mg albumin/g dry weight and albumin: alpha-1-trypsin inhibitor ratios of greater than 3.0; in subsequent faecal specimens the ratios were over 4.0. 176 meconium specimens from elsewhere in the UK were examined and these included 23 from infants who were subsequently proved to have CF. Six of these 23 CF specimens gave false-negative results, the other 17 being strongly positive. The origins of meconium serum protein suggest that infants with CF in whom meconium gives false-negative results have normal pancreatic functions at birth. The specificity of current meconium tests therefore cannot be improved as they depend on pancreatic dysfunction.     

Comparison of four pancreatic extracts in cystic fibrosis.

Four different pancreatin products, Pancrease, Creon, Pancrex V Forte, and Pancreatin Merck, were compared in a random crossover trial in children with cystic fibrosis. The results of our study showed that patients who received Creon and Pancrease had fewer gastrointestinal symptoms than patients who received Pancrex V Forte and Pancreatin Merck. Fat absorption was significantly improved with Pancrease when compared with Pancrex V forte and Pancreatin Merck. Also the fat absorption with Creon was superior to that with Pancrex V Forte. There was no significant difference in fat absorption between Pancrease and Creon. Pancrex V Forte and Pancreatin Merck, or Pancreatin Merck and Creon. Faecal nitrogen content was less with both Creon and Pancrease compared with Pancreatin Merck. Creon and Pancrease allow the patient with cystic fibrosis to take a high energy diet without any dietary restrictions.     

Screening for cystic fibrosis by examination of meconium

The value of detecting albumin in meconium as a screening procedure for cystic fibrosis (CF) has been assessed on 34,228 samples in South Wales and North Staffordshire over a 4-year period; simultaneously, four methods of detecting albumin were evaluated. 12 cases of CF were detected, detection rate being 60%. The incidence of the disease in the population screened was 1 in 1850, confirmed by clinical and other test procedures. Cases of CF without impairment of pancreatic function are likely to be missed by screening methods which depend on the presence of albumin in meconium.     

Screening for cystic fibrosis by analysis of serum protein in faeces.

Faecal specimens from 51 infants free of cystic fibrosis (CF) and from 9 infants with the disease were analysed for albumin and alpha1-antitrypsin content. Faeces from infants with no CF had a mean albumin content of less than 0-1 mg/g dry weight and a mean albumin: alpha1-antitrypsin ratio value of less than 0-1. Faeces from infants with CF had, with one exception, an albumin content of more than 2-0 mg/g dry weight and a ratio value greater than 3-0. It was subsequently found that the duodenal aspirate from the child with CF but whose faeces had a low albumin content and ratio value, had tryptic activity though at a much reduced level compared to the activity in aspirates from healthy infants.     

Newborn screening for cystic fibrosis in Alberta: Two years of experience

On April 1, 2007, Alberta became the first province in Canada to introduce cystic fibrosis (CF) to its newborn screening program. The Alberta protocol involves a two-tier algorithm involving an immunoreactive trypsinogen measurement followed by molecular analysis using a CF panel for 39 mutations. Positive screens are followed up with sweat chloride testing and an assessment by a CF specialist. Of the 99,408 newborns screened in Alberta during the first two years of the program, 221 had a positive CF newborn screen. The program subsequently identified and initiated treatment in 31 newborns with CF. A relatively high frequency of the R117H mutation and the M1101K mutation was noted. The M1101K mutation is common in the Hutterite population. The presence of the R117H mutation has created both counselling and management dilemmas. The ability to offer CF transmembrane regulator full sequencing may help resolve diagnostic dilemmas. Counselling and management challenges are created when mutations are mild or of unknown clinical significance.