ESPE Abstracts

Background: Congenital hypothyroidism (CH) is a common and preventable cause of mental retardation in children, and is detected using dried blood spots in many neonatal screening programs. Upon suspicion of CH, plasma free thyroxine (FT4) and thyroid stimulating hormone (TSH) concentrations are measured. CH can be of thyroidal or central origin (CH-T and CH-C, respectively). While CH-T diagnosis is based on an elevated plasma TSH in combination with a low FT4, CH-C diagnosis is based solely on a low plasma FT4.

Currently, reliable neonatal reference intervals (RIs) for plasma FT4 and TSH are lacking. Age-specific neonatal RIs would greatly improve the diagnostic process for CH, especially for CH-C.

Objectives: To establish neonatal RIs for plasma FT4 and TSH concentrations in healthy, term neonates during the Dutch neonatal screening at day 3-7 (t=1) and at day 13-15 (t=2; day of birth is day 0). The current study was particularly designed to provide a reliable FT4 lower limit to facilitate the diagnosis CH-C. In the Netherlands, children with an abnormal screening result suggestive for CH-C are referred for pediatric consultation on average on day 14; time point for measurement t=2 was chosen accordingly.

Methods: Venous blood collection (heparin plasma) was performed in 120 healthy neonates at two time points. If plasma was missing for one time point, another participant was recruited for replacement (total number of participants >120). Here, we report our first 200 measurements. FT4 and TSH concentrations were measured using an electrochemiluminescence immunoassay (Cobas, Roche Diagnostics, Switzerland; adult RI for FT4 12-22 pmol/L, TSH 0.5-5.0 mU/L). RIs were calculated with MedCalc for Windows (version 18.5, Belgium). If data were not normally distributed, the non-parametric percentile method was used.

Results: From 122 participants (53% female) ≥1 measurement was available. FT4 concentrations were normally distributed at both time points, while TSH concentrations were positively skewed. 95% RIs for FT4 were 20.1-37.5 pmol/L (day 3-7, n=104) and 15.0-26.9 pmol/L (day 13-15, n=96). 95% RIs for TSH were 0.8-8.4 mU/L (day 3-7) and 1.3-8.2 mU/L (day 13-15).

Conclusion: In this study, neonatal RIs for plasma FT4 and TSH were determined using the Cobas (Roche) immunoassay. Preliminary results indicate a FT4 lower limit of 20.1 pmol/L during the first week of life, and 15 pmol/L at the age of two weeks. This is considerably higher than the assay's lower limit of the adult RI for FT4.