Context: The Dutch T4-TSH-TBG-based neonatal screening program detects patients with congenital hypothyroidism (CH) of thyroidal (CH-T) as well as central (CH-C) origin. The numbers and characteristics of true-positive and false-positive referrals will differ from other, predominantly TSH-based, screening methods.

Objective: The present study describes the characteristics of the referred neonates, both CH patients and false-positives, and of the reported CH patients with a false-negative screening result born in the study period.

Design/Setting/Patients/Main Outcome Measure: Of each referred child born between April 1^st, 2002 and May 31^st, 2004 screening results and first venous sample results were recorded and classified as transient or permanent CH-T or CH-C, or no CH.

Results: In the study period 430,764 children were screened. Of the 772 children with abnormal screening results 224 (29%) had CH; another 13 CH patients did not have abnormal screening results, giving an overall CH incidence of 1:1,800. Incidences of permanent CH, permanent CH-T, permanent CH-C and transient CH were 1:2,200, 1:2,500, 1:21,000 and 1:12,000, respectively. The most frequent explanations for the 548 false-positive referrals (71% of the referred cohort) were severe illness and TBG deficiency (occurring in 198 and 200 children, respectively).

Conclusions: The Dutch incidence figures for CH belong to the highest worldwide suggesting that the T4-TSH-TBG screening program is an efficient method to detect CH of variable etiology and severity. Still, a small percentage of children with CH escaped detection via this screening approach. Severe illness and TBG deficiency appear to be responsible for the majority of false-positive referrals.