Fifty years of newborn screening for congenital hypothyroidism: current status in Australasia and the case for harmonisation.

OBJECTIVES: Since its implementation 50 years ago in Quebec, Canada, newborn screening for congenital hypothyroidism has become one of the most successful public health measures worldwide. Screening programmes across Australia and New Zealand are characterised by significant commonalities in screening algorithms, and a high degree of regional cooperation in harmonisation efforts. We aimed to conduct a comprehensive survey of current performance and practices related to the total testing process for congenital hypothyroidism screening and provide recommendations for harmonisation priorities within our region. METHODS: A survey was conducted involving the six newborn screening laboratories which provide complete geographic coverage across Australasia. Approximately 360,000 newborns are screened annually. Survey questions incorporated pre-analytical, analytical, and post-analytical aspects of the screening programmes and an extensive 5-year (2016-2020) retrospective analysis of individual programme performance data. Responses from individual screening programmes were collated. RESULTS: The uptake of newborn screening was over 98% for the six major jurisdictions. All programmes have adopted a single-tier thyroid stimulating hormone (TSH) strategy using the Perkin Elmer GSP instrument. Significant similarities exist between programmes for recommended age of collection and recollection protocols for low birthweight newborns. The process for the determination of TSH cutoffs varies between programmes. TSH lower cut-offs for borderline-positive and positive notifications between 12-15 and 12-25 mIU/L blood, respectively. Recall rates vary between 0.08 and 0.20%. The case definition for congenital hypothyroidism generally includes biochemical and radiological parameters in addition to the commencement of thyroxine. All programmes reported collecting biochemical and clinical data on infants with positive screening tests, and positive predictive values vary between 23.6 and 77.3%. Variation in reported incidence (1:1,300-2,000) cannot be entirely explained by cutoff or recall rate (although one programme reporting fewer cases includes only permanent disease). CONCLUSIONS: Despite similarities between newborn screening algorithms for congenital hypothyroidism across Australia and New Zealand, differences in reported programme performance provide the basis for further harmonisation. Surveillance of a large population offers the potential for the ongoing development of evidence-based screening guidelines.

Managing Newborn Screening Repeat Collections for Sick and Preterm Neonates.

Some preterm and sick neonates have altered biochemical profiles and follow-up newborn screening (NBS) collections are recommended. The Victorian NBS program historically recommended repeat collections for babies with birth weight < 1500 g (managed by the maternity service provider) and 3 weeks post-transfusion (managed by the laboratory). We aimed to determine adherence to current guidelines and review the guidelines to improve NBS performance. To do this, we audited data from 348,584 babies between January 2018 and June 2022. Babies with a recorded birth weight of <1500 g were filtered for inclusion. For the overall review and visualization of the protocol, we sourced information from the literature, our professional society and tertiary hospital services. A total of 2647 babies had a birth weight recorded between 200 and 1499 g. Of these, 2036 (77%) had a second sample collected, indicating that >1 in 5 babies were not receiving a follow-up collection. Our timing of repeat collections for transfused babies, requiring a 3-week follow-up collection, was longer than in other Australasian jurisdictions. A new combined "sick-prem protocol" was launched to support repeat collections and after a 1-year review achieved 95% compliance. We recommend NBS laboratories audit preterm and sick neonate repeat collections to ensure appropriate follow-up. This should be supported with a visual process map to aid education and compliance.

Best Practice for Identification of Classical 21-Hydroxylase Deficiency Should Include 21 Deoxycortisol Analysis with Appropriate Isomeric Steroid Separation.

There are mixed reports on the inclusion and use of 21 deoxycortisol (21DF) as the primary decision marker for classical 21-hydroxylase deficiency. We hypothesize that this may be due to insufficient recognition of the presence and chromatographic separation of isomeric steroids. The aim of this study was to determine the comparative utility of 21DF for screening and diagnosis of CAH due to classical 21-hydroxylase deficiency using a second-tier LC-MS/MS method that included the separation of isomeric steroids to 17OHP and 21DF. For each baby sample, one 3.2 mm dried blood spot was eluted in a methanolic solution containing isotopically matched internal standards. Data were interrogated by univariate and receiver operator characteristic analysis. Steroid profile results were generated for 924 non-CAH baby samples (median gestational age 37 weeks, range 22 to 43 weeks) and 17 babies with 21-hydroxylase deficiency. The ROC curves demonstrated 21DF to have the best sensitivity and specificity for the diagnosis of classical 21-hydroxylase deficiency with an AUC = 1.0. The heatmap showed the very strong correlation (r = 0.83) between 17OHP and 21DF. Our data support 21DF as a robust marker for CAH due to 21-hydroxylase deficiency. We recommend that 21DF be incorporated into routine newborn screening panels as part of the second-tier LC-MS/MS method, follow-up plasma steroid panels, and external quality assurance material.