ESPE Abstracts (2018) 89 P-P1-249

Neonatal Screening for Congenital Hypothyroidism: Age-dependent Reference Intervals for Dried Blood Spot TSH in the Neonatal Period

Carlo Corbettaa, Simona De Angelisb, Daniela Rotondib, Luisella Albertic, Pamela Cassinic, Tiziana Marianic, Silvana Caiulod, Maria Cristina Vigoned, Giovanna Weberd & Antonella Olivierib


aRegional Reference Laboratory for Neonatal Screening, Children Hospital ‘V. Buzzi’, ASST Fatebenefratelli Sacco, Milan, Italy; bDepartment of Cardiovascular, Dysmetabolic and Ageing-associated Diseases, National Institute of Health, Rome, Italy; cRegional Reference Laboratory for Neonatal Screening, Children Hospital ‘V. Buzzi’, ASST Fatebenefratelli Sacco, Milan, Italy; dVita-Salute San Raffaele University-Pediatric Department San Raffaele Hospital, Milan, Italy


Background: National and international guidelines recommend thyrotropin (TSH) determination as the most sensitive test for detecting primary congenital hypothyroidism (CH) in newborn screening programs. A strategy of a second screening at 2 weeks of age, or 2 weeks after the first screening was carried out, is also recommended in preterm, LBW and VLBW neonates, twins, neonates admitted in NICU, and babies with specimen collection within the first 24 hours of life [1–3]. However specific recommendations on the TSH cut off at 2 weeks of age are lacking, as well as specific reference intervals for TSH at this age. The aim of this study was to determine TSH reference intervals at 2-4 and 14-16 days of age in healthy term newborns.

Methods: Dried blood spot (DBS) samples were obtained from 70,962 healthy term newborns (>37 week Gestational Age) residing in Lombardia region and screened in 2015 at the Lombardia region Reference Laboratory for Neonatal Screening. A time resolved-fluoroimmunoassay (TR-FIA) method was used to detect TSH on DBS at the first (2–4 days) and second screening (14–16 days). STATA 11.0 was used to analyze 2.5th, 50.0th, 97.5th, 99.0th, 99.5th percentiles for DBS-TSH.

Results: No significant difference was found between the 2.5th percentile of DBS-TSH at 2–4 days (0.59 mU/L; 95% CI: 0.59–0.60) and the same percentile at 14–16 days (0.58 mU/L; 95% CI: 0.56–0.59); whereas the 50.0th percentile was significantly higher at 2–4 days (2.06 mU/L; 95% CI: 2.05–2.07) than at 14–16 days of life (1.52 mU/L; 95% CI: 1.51–1.54), as well as the 97.5th percentile (6.24 mU/L; 95% CI: 6.19–6.29 vs 4.04 mU/L; 95% CI: 3.91–4.21), the 99.0th percentile (7.60 mU/L; 95% CI:7.49–7.73 vs 5.10 mU/L; 95% CI: 4.80–5.64), and the 99.5th percentile (8.80 mU/L; 95% CI: 8.65–9.00 vs 6.64 mU/L; 95% CI: 6.11–7.55).

Conclusions: Our data showed that marked changes occur in concentrations of TSH during the first 2 weeks of life with DBS-TSH concentrations significantly higher at 2–4 days than at 14–16 days of life. These results have implications for selection of age-related cut off values of DBS-TSH at screening (2–4 days) and re-screening (14–16 days) to correctly identify newborns at risk for CH.

References: 1. Leger J et al. J Clin Endocrinol Metab 2014, 99:363-384. 2. Cassio A et al. J Endocrinol Invest 2013, 36: 195-203. 3. CLSI document I/LA31-A, Clinical and Laboratory Standards Institute; 2009.