Cystic fibrosis screening by dried blood spot trypsin assay: results in 75,000 newborn infants.

Seventy-five thousand 5-day-old babies were screened for cystic fibrosis by blood spot immunoreactive trypsin (IRT) assay as part of a statewide screening program. IRT was elevated in 433 babies; retesting revealed persistent elevation in 38. Sweat testing confirmed cystic fibrosis in 35 babies and was normal in two babies, whose IRT remained elevated at the time of the test. Sweat testing was refused by one mother. Of the 35 babies with cystic fibrosis, 13 had meconium ileus or an already diagnosed affected sibling, but the diagnosis was unsuspected in 22, although all but four had some symptoms suggestive of cystic fibrosis. Stool trypsin activity at the time of the diagnostic screen was normal in nine and reduced in seven of the babies with cystic fibrosis. One baby did not have elevated IRT, and the cystic fibrosis was missed by the screening test. In a retrospective study of blood spot samples from 36 newborn infants, who were later diagnosed as having cystic fibrosis, all had IRT levels greater than in matched controls. Our study confirms that elevated IRT is characteristic of newborn babies with cystic fibrosis, and shows that this test is very specific and sensitive when used as a newborn screening test.

Urine screening for aminoacidopathies: is it beneficial? Results of a long-term follow-up of cases detected bny screening one millon babies.

One million 6-week-old infants were screened for aminoacidurias and the long-term follow-up analyzed to assess the benefits of the screening program. Apart from phenylketonuria, now normally detected by blood screening at five days, the most frequent abnormalities identified were cystinuria, histidinemia, Hartnup disease, and iminoglycinuria. Other disorders occurred less frequently than 1:100,000. Early diagnosis provided unequivocal clinical benefit only for phenylketonuria. There was probable benefit to patients with cystinuria, homocystinuria, argininosuccinic aciduria, and to some patients with Hartnup disease. However, benefit of early diagnosis in these disorders, of which the combined incidence was 1:10,000, was not clear-cut; for example, in 68 cystinuric children, four had already developed renal stones despite close medical supervision and a regimen of increased fluid intake to the limits of tolerance. No patient detected with any other condition benefited, either because the condition appeared benign and was not treated, or because the disorder was serious or lethal and there was a bad outcome despite early diagnosis and treatment. Existing urine screening programs should explore the incidence and clinical significance of further biochemical abnormalities detectable in the newborn infant, but there is no indication at present for the initiation of new urine screening programs designed to detect only aminoacidurias.