Review of neonatal screening programme for phenylketonuria.

OBJECTIVE--To review the neonatal screening programme during 1984-8. DESIGN--Analysis of data from screening laboratories and paediatricians. SUBJECTS--All live births in United Kingdom. MAIN OUTCOME MEASURES--Structure of programme; number of infants tested and number with phenylketonuria; number of infants missed; ages at testing and treatment. RESULTS--The proportion of infants tested approached 100%. The incidence of phenylketonuria was 11.7/100,000 births (445 subjects): 273 had classic phenylketonuria and three had defects of cofactor metabolism. One child with phenylketonuria was known to have been missed compared with three in 1979-83 and six in 1974-8. Seven subjects had been missed over the 15 years due to negative test results. All seven had been tested with the bacterial inhibition assay, although only 53% of infants had been so tested; the difference between the expected and observed proportion was significant (Fisher''s exact test, p = 0.017). Eleven infants with classic phenylketonuria were not tested by 14 days of age and 23 (8%) did not start treatment until after 20 days, an improvement compared with 36 (15%) in 1979-83. There were, however, wide regional variations (0% to 27% treated after 20 days). CONCLUSION--The screening programme achieves high coverage and effectiveness, although some children are still missed. A national practice for screening may help reduce regional variations.     

Carrier screening for phenylketonuria: comparison of two discriminant analysis procedures

Absence of a convenient, direct enzyme assay for detecting phenylketonuria (PKU) heterozygotes has resulted in continued effort to develop an accurate and reliable procedure to discriminate the heterozygous individual from the homozygous normal. Our study compares two statistical procedures that combine the semifasting plasma phenylalanine and tyrosine concentrations with the individuals' prior probability of being a heterozygous carrier in order to discriminate carriers from noncarriers. The results of this comparison indicate that the quadratic discriminant function is superior to the linear discriminant function as a method of carrier testing both in theory and in practice. An interactive computer system is described that facilitates the clinical utilization of the quadratic discriminant function.     

Neonatal screening for sickle haemoglobinopathies in Birmingham.

During 1978-81 there were about 43,500 births in Birmingham, of which 10.3% were to Negroes and 22.6% to Asians. Cellulose acetate electrophoresis of red cell haemolysates from capillary specimens collected for phenylketonuria screening was performed for these babies to assess the feasibility, cost, and benefits of detecting sickle haemoglobinopathies early. Eight babies had important haemoglobinopathies; four were homozygotes for haemoglobin S (HbS), three were mixed heterozygotes for HbS and haemoglobin C (HbC), and one had haemoglobin E (HbE) and beta-thalassemia. Also, 534 (1.19%) were heterozygotes for HbS or haemoglobin D (HbD) and 205 (0.46%) for HbC or HbE, 453 (1.01%) were heterozygotes with a fast-moving band, one was a heterozygote for haemoglobin Norfolk, and one a heterozygote for both HbS and haemoglobin G Philadelphia. The cost of neonatal screening for haemoglobinopathies was 12.5 p per baby (705 pounds for each serious abnormality).     

Fifteen-year experience with screening for phenylketonuria with an automated fluorometric method.

An automated fluorometric method, rather than the Guthrie test, has been used in North Carolina for neonatal screening for phenylketonuria (PKU). Although there is no testing law, 97% of newborn infants are screened. Twelve children with PkU, not referred for dietary management, were born before the screening program was established, were born elsewhere, or were successfully identified at birth but not referred for treatment. None was missed because of laboratory error or because of the lack of a testing law. Positive skewing was noted among initial blood phenylalanine levels of 49 infants with PKU and severe hyperphenylalaninemia. Log transformations caused the values to be normally distributed and permitted the calculation of tolerance and confidence limits. These provided estimates of the percentage of phenylketonuric infants whose initial blood levels might fall below any given cutoff value.     

Reasons for variation in coverage in the NHS cervical screening programme

In order to investigate reasons for variation in coverage of cervical screening, data from standard Department of Health returns were obtained for all Health Authorities for 1998/1999. Approximately 80% of the variation between health authorities is explained by differences in age distribution and area classification. Considerable differences between Health Authority and Office of National Statistics (ONS) population figures in City and Urban (London) areas for the age group 25-29 years and for City (London) for age group 30-34 years, suggest an effect of list inflation in these groups. Coverage as a performance indicator may be more accurately represented using the age range 35-64 years. Using this narrower age range, the percentage of health authorities meeting the 80% 5-year coverage target increases from 87% to 90%.