To detect CH, primary TSH screening is used in most European countries, Japan and Australia. However, using this approach, some forms of CH including delayed TSH elevation in infants with TBG deficiency or low birth weight, central hypothyroidism and hypothyroxinemia are missed. In North America, a T4-based program with additional measurement of TSH in samples with lowest T4 concentration is commonly used . Primary T4 screening with backup TSH measurements has the potential to detect primary hypothyroidism, TBG deficiency and central hypothyroidism. The recall rate for primary hypothyroidism in both approaches is 0.05%, and the rate of false positive results is higher using the primary T4 strategy.
Although both screening strategies detect CH of thyroidal origin, they may miss patients with central CH because T4 may be only moderately decreased and TSH is not elevated. In such patients, however, early diagnosis is crucial not only for early and appropriate thyroxine replacement (fig. 3), but also to detect or rule out CPHD for which adequate and timely treatment is fundamental.
In the Netherlands, a T4-TSH-TBG-based screening strategy has been implemented which has been shown to detect CH of variable origin and severity  with a sensitivity of 95.8% and specificity of 99.9% , associated with the highest incidence rates worldwide. A high rate of false-positive results mainly due to severe illness or TBG deficiency, and occasional false negative cases in very mild forms of CH with normal T4 levels or in premature neonates are pitfalls of this strategy that have to be addressed in the future.
Preterm infants with CH may have a delayed TSH increase owing to the immaturity of the hypothalamic-pituitary-thyroid axis, and may thus be missed by laboratory screening procedures. Therefore, a routine second screening between 2 and 6 weeks of age has been suggested in preterm neonates  leading to a reported additional 10% of cases.
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