Outcomes of lowered newborn screening thresholds for congenital hypothyroidism

Background: Newborn screening (NBS) has largely eliminated the physical and neurodevelopmental effects of untreated congenital hypothyroidism (CH). Many countries, including Australia, have progressively lowered NBS bloodspot thyroid-stimulating hormone (b-TSH) thresholds. The impact of these changes is still unclear. Objectives: To evaluate the performance of CH NBS following the reduction of b-TSH thresholds in New South Wales (NSW) and the Australian Capital Territory (ACT), Australia, from 15 to 8 mIU/L, and to determine the clinical outcomes of cases detected by these thresholds. Methods: NBS data of 346 849 infants born in NSW/ACT, Australia from 1 November, 2016–1 March, 2020 inclusive were analysed. A clinical audit was conducted on infants with a preliminary diagnosis of CH born between 1 January, 2016–1 December, 2020 inclusive. Results: The lowered b-TSH threshold (≥8 mIU/L, ~99.5th centile) detected 1668 infants (0.48%), representing an eight-fold increase in recall rate, of whom 212 of 1668 (12.7%) commenced thyroxine treatment. Of these 212 infants, 62 (29.2%) (including eight cases with a preliminary diagnosis of thyroid dysgenesis) had an initial b-TSH 8–14.9 mIU/L. The positive predictive value for a preliminary diagnosis of CH decreased from 74.3% to 12.8% with the lowered threshold. Proportionally, more pre-term infants received a preliminary CH diagnosis on screening with the lower threshold (16.1% of 62) than with the higher threshold (8.0% of 150). Conclusion: Clinically relevant CH was detected using the lowered threshold, albeit at the cost of an eight-fold increase in recall rate. Further clinical and economic studies are required to determine whether benefits of lowered screening thresholds outweigh potential harms from false-positive results on infants, their families and NBS programs