Diagnostic effectiveness of TSH screening and of T4 with secondary TSH screening for newborn congenital hypothyroidism.

We used a receiver operating characteristic (ROC) plot to evaluate the diagnostic accuracy of primary thyrotropin (TSH) screening, and compared it to the primary thyroxine (T4) with secondary TSH screening (T4/TSH) on a certain percentage of the lowest T4 value for newborn congenital hypothyroidism (CH). There were 2198 normal and 117 abnormal CH cases evaluated using both the Wallac Delfia neonatal TSH and neonatal T4 kits. The ROC areas of the primary TSH screening and T4/TSH screening were 0.9841 and 0.9557, respectively. Nine cases (out of 117 cases) of CH would have been misclassified if T4/TSH screening were used. These nine cases, however, were identified using primary TSH screening. We conclude that using primary TSH screening is more effective for mass screening in reducing false-positive and false-negative cases than the combined T4/TSH screening method.

Newborn phenylketonuria (PKU) Guthrie (BIA) screening and early hospital discharge.

Recent policies of early discharge of postpartum mothers and their infants has raised concerns of possible decreased sensitivity in Guthrie bacterial inhibition assay (BIA) phenylketonuria (PKU) screening resulting in missed cases. In order to assess the potential impact of early discharge from hospital on neonatal screening for PKU and its variants, we performed 18 standard BIA screening tests on 11 newborn infants with the disease. Blood spot samples were collected from 1 to 24 h after birth and were analyzed at the Ontario Ministry of Health newborn screening laboratory according to the routine screening protocol. Except for one 4-hour postnatal sample from an infant with 'non-PKU mild hyperphenylalaninemia' (MHP) all blood samples showed phenylalanine levels > or = 240 mumol/l, irrespective of the age of the baby. During our 29 year experience with neonatal PKU screening (3.9 million infants tested), employing a cutoff blood phenylalanine of 240 mumol/l in blood spots obtained at > or = 24 h of age, only two biological false negative (one confirmed) tests were discovered in infants subsequently shown to have classical PKU: another three false negative tests were discovered in sibs of infants with MHP. The sensitivity of the screening test was 99.2% for infants with classical and mild PKU. Ascertainment of patients with MHP is unknown and is very likely incomplete. Over a 3-year period (1992-4) the specificity of the test was 99.9% for those screened after 24 h. The positive predictive value was 12.8%. Although early discharge may have an impact on other screened diseases, we conclude, from our studies, that early discharge may not affect the detection of infants with classical and mild (atypical) PKU, but would probably increase the number of infants with MHP missed using the BIA and a cutoff level of 240 mumol/l. Because of our experience and that of others, we recommend that neonates be at least 12 h of age before initial BIA PKU screening be carried out. To confirm this recommendation further prospective studies should be initiated.

Blood lead screening in Ontario children: blood lead and free erythrocyte protoporphyrin levels.

A blood lead survey was conducted on samples from 2459 children aged 3-6 years to determine the prevalence of lead poisoning in children of this age in the Province of Ontario. Lead poisoning, defined as a blood lead concentration greater than or equal to 1.21 mumol 1-1 (25 micrograms dl-1), was found in 26 subjects (1.1% of the samples). The mean blood lead concentration for children from southern Ontario was 0.50 mumol l-1, and for those from northern Ontario it was 0.37 mumol l-1. Stringent quality controls and independent cross-checks of finger-prick capillary blood sampling were employed in the study. The free erythrocyte protoporphyrin levels were also monitored to detect the presence of iron deficiency in the children.

Aluminum levels in normal human serum and urine as determined by Zeeman atomic absorption spectrometry.

A simple dilution procedure for the determination of aluminum in human serum and urine is described. Serum and urine specimens were analyzed directly after dilution with 0.1% Triton X-100. The matrix-based calibration was used for quantitation with the use of Zeeman background atomic absorption spectrometry. The precision (CV) of the method was from 2.9 to 6.6% for serum concentrations ranging from 3.04 to 0.9 mumol/L. The accuracy of the method was vertified by analyzing U.S. National Bureau of Standards, RM 8419 bovine serum reference material, recovery studies, and comparison with the protein precipitation method. The Quebec Interlaboratory Comparison Program was used for the validation of the analytical performance. The mean value of aluminum in 63 healthy subjects was 0.06 mumol/L for serum and 0.24 mumol/L for urine.

Rapid Zeeman atomic absorption determination of copper in serum and urine.

In this simple, quick procedure for determining copper in human serum and urine, the serum and urine specimens were analyzed directly after dilution with a solution of HNO3 and Triton X-100, 1 mL/L each. We calibrated with aqueous standards for quantitation in Zeeman background atomic absorption spectrometry. By modifying the drying and pyrolysis stages of the graphite furnace atomic absorption spectrometer, we reduced the analytical time to 30 s per determination. The within-run imprecision (CV) is 2.6% and 3.4% and the between-run imprecision is 0.9% and 2.5% for serum and urine copper at concentrations of 30.4 and 2.70 mumol/L, respectively. The accuracy of this fast method was verified by analyzing the National Institute of Standards and Technology Standard Reference Materials SRM 1598 bovine serum and SRM 2670 urine (agreement with certified values within 0.1 mumol/L for serum and within 0.02 mumol/L for urine), by analytical recovery studies (98% recovered in serum, 100% recovered in urine), and by comparison with our normal routine method. We also used the Quebec Interlaboratory Comparison Program to validate the analytical performance. From the precision and accuracy studies, we conclude that this fast-furnace program is a rapid, simple, and reliable method for determining copper in serum and urine.

Determination of blood lead in dried blood-spot specimens by Zeeman-effect background corrected atomic absorption spectrometry.

A simple procedure for the determination of blood-lead levels in dried blood-spot filter-paper specimens is described. A 3/16 inch dried blood spot was analysed by a method involving extraction of the lead into 1.25% (NH4)2HPO4-0.5% Triton X-100 solution. A matrix-based calibration was used for analysis, with use of a Zeeman-effect background corrected atomic absorption spectrometer. The within-run precision (% relative standard deviation) of the method at the low end of the analytical range was 19% at 0.36 mumol dm-3 and 14% at 0.60 mumol dm-3. The accuracy of the method was verified by recovery tests and by comparison with a routine whole-blood method. The mean blood lead level of 425 Toronto newborns was 0.19 mumol dm-3 (range 0-0.75 mumol dm-3).

Receiver operating characteristic plots to evaluate Guthrie, Wallac, and Isolab phenylalanine kit performance for newborn phenylketonuria screening.

We used ROC plots to evaluate the clinical performance of the Guthrie, Wallac, and Isolab assays for newborn phenylketonuria (PKU) screening and assessed the screening discriminatory power of these three assays by the area under the ROC plot, Youden's J index, and the likelihood ratio. The use of these plots not only allows us to pinpoint the exact cutoff value in screening, but also provides a direct comparison of these three different assays in clinical outcome performance. The optimum cutoff for the newborn PKU screening is a blood phenylalanine concentration of 0.30, 0.27, and 0.18 mmol/L for the Guthrie, Wallac, and Isolab assays, respectively. We conclude that the Wallac and Isolab kits, like the Guthrie assay, are suitable for newborn PKU screening.

Lead exposure among mothers and their newborns in Toronto.

Recent studies have suggested that a fetal blood lead level of 0.48 mumol/L (much lower than 1.21 mumol/L, which is the level previously believed to be toxic to the developing brain) may impair brain development permanently. We measured the maternal and umbilical cord blood levels of lead and free erythrocyte protoporphyrin (FEP) among 95 consecutive mother-infant pairs to determine whether neonates in Toronto are in the high-risk group. There was a significant correlation between the maternal and the cord blood lead levels (r = 0.59, p less than 0.0001). Most (99%) of the infants had cord blood lead levels below 0.34 mumol/L; in 11 cases the levels were below the detection limit of 0.01 mumol/L. The cord blood FEP levels were higher than the maternal levels. The US Centers for Disease Control, Atlanta, currently finds acceptable a blood FEP level of 0.62 mumol/L among children up to 10 years of age; however, this is not applicable to newborns since their higher FEP levels apparently reflect immature heme synthesis and increased erythrocyte volume rather than lead poisoning. Our data suggest that living in Toronto does not impose increased teratogenic risk from intrauterine exposure to lead; however, residents in high-risk areas should be followed up.

The Ontario HIV seroprevalence study of childbearing women: results from the first year of testing.

The Ontario HIV Seroprevalence Study of Childbearing Women is an unliked anonymous seroprevalence study designed according to the well-established ethical and legal guidelines for such studies. Commencing in November, 1989, randomly selected neonatal heelprick specimens were tested for the presence of HIV antibodies after all identifying information had been permanently and irrevocably unlinked from the specimens. During the first year of the study 94,119 (approximately 60% of all submitted specimens) were tested. Twenty-six specimens which were repeatedly reactive by EIA were confirmed as positive for an overall crude seroprevalence rate of 2.8 per 10,000 women having live births (95% CI: 1.8-4.1). Twenty-five of the 26 confirmed seropositive results came from babies born in hospitals in the Metropolitan Toronto, Ottawa-Carlton, or Hamilton-Peel-Halton regions.