Repository hosted by TU Delft Library

The Dutch neonatal screening scheme for Congenital Hypothyroidism (CH) is primarily based on the determination of thyroxine (T4) in filter paper blood spots. In the lowest 5% of T4 values, thyroxine binding globulin (TBG) is measured in order to be able to correct for occasional low TBG levels. However, because the commercial TBG kit has been withdrawn from the market, alternative strategies are needed to be explored including the assessment of free T4.We evaluated the Neonatal Free Thyroxine (fT4) enzyme immunoassay (EIA) kit of Bio-Rad.FT4 as measured in a daily run of random samples correlated with T4. We also observed a correlation between fT4 and T4, and between fT4 and T4/TBG ratio in blood spots with low T4 concentrations. The correlation between fT4 and T4 in blood spots of proven CH-patients was highly significant. ROC curves were constructed for the fT4 assay and the T4/TBG ratio based on 27 CH patients and 215 controls with a complete set of data. The curves of both assays seemed to be rather similar.We conclude that the validity of the fT4 and the T4/TBG-approach seems to be the same. A study with a larger sample size giving the same or even more favorable results for the fT4-approach is necessary before we will change the present CH protocol. •The paper describes the evaluation of a free T4 enzyme immunoassay in blood spots.•The aim is to replace total T4 and TBG for a single fT4 measurement.•Despite a correlation between fT4 and T4 in CH-patients, no cut-off value can be established.•Determination of fT4 levels in blood spots was inferior to the present CH-protocol. © 2013 Elsevier B.V.

Objective: In newborn screening programs for congenital adrenal hyperplasia, 17-α-hydroxyprogesterone (17OHP) cutoff levels are based on birth weight (BW) or on gestational age (GA). We investigated which approach would result in the greatest specificity and sensitivity. Study design: For the determination of 17OHP, a neonatal 17OHP assay was used in filter paper blood of 9492 newborns. The relationships between 17OHP and BW and between 17OHP and GA were studied by regression analysis. Reference curves with a specificity of 99.95% were constructed with the method that summarizes the distribution by three smoothed curves representing the skewness (L curve), the median (M curve), and the coefficient of variation (S curve). Median cutoff levels for BW and for GA according to the 99.95% reference curves were calculated. Results: Regression analysis showed that GA is a better predictor of 17OHP than BW (R2 was 50.6 vs. 35.8%, respectively). At a specificity of 99.95%, the calculated median 17OHP cutoff level was lower for GA [12.6 μg/liter (38 nmol/liter)] than for BW [17.6 μg/liter (54 nmol/liter)], thus leading to a greater sensitivity. Conclusion: This study demonstrates that GA is a better predictor of 17OHP in newborns and will result in greater specificity than BW despite the fact that the determination of GA might be less reliable than BW. Copyright © 2005 by The Endocrine Society.

Context: Newborn screening for cystic fibrosis (CF) is included in many routine programmes but current strategies have considerable drawbacks, such as false-positive tests, equivocal diagnosis and detection of carriers. Objective: To assess the test performance of two newborn screening strategies for CF. Design, setting and participants: In 2008 and 2009, CF screening was added to the routine screening programme as a prospective study in part of the Netherlands. Interventions: Two strategies were performed in all newborns. In the first strategy, concentrations of immunoreactive trypsinogen (IRT) and pancreatitis-associated protein (PAP) were measured. In the second method, samples with IRT ≥60 μg/litre were analysed for 36 CFTR mutations, followed by sequencing when a single mutation was detected. Tests were positive only with two identified CFTR mutations. Main outcome: Sensitivity, specificity and positive predictive value (PPV) of both screening strategies. Results: 145 499 infants were screened. The IRT/PAP approach showed a sensitivity of 95.0%, a specificity of 99.897% and a PPV of 12.3%. Test properties for the IRT/DNA/sequencing strategy were respectively 100%, 100% and 64.9%. Combining both strategies (IRT/PAP/DNA/sequencing) led to a sensitivity of 95.0%, a specificity of 100% and a PPV of 87.5%. Conclusion: In conclusion, all strategies performed well. Although there was no statistically significant difference in test performance, the IRT/DNA/sequencing strategy detected one infant that was missed by IRT/PAP (/DNA/sequencing). IRT/PAP may be the optimal choice if the use of DNA technology must be avoided. If identification of carriers and equivocal diagnosis is considered an important disadvantage, IRT/PAP/DNA/sequencing may be the best choice.