Method- and evidence-based reference intervals for interpretation of thyroid function in the first 168 hours of life.

Introduction: Prompt intervention can prevent permanent adverse neurological effects caused by neonatal hypothyroidism. Thyroid function changes rapidly in the first few days of life but age-related reference intervals (RIs) for TSH, FT4 and FT3 are not available to aid interpretation. This is further complicated by the imprecision of how the days of life are classified, e.g., a neonate who was born just before midnight would be classified as day-1 a few minutes after midnight rather than day-0. We have developed hour-based RIs using data mining. Method(s): All TSH, FT4 and FT3 results (Beckman) with date and time of collection from neonates aged Results: Of the 728 neonates qualifying, 569 had time of birth available. All 569 had TSH, 415 had FT4 and 146 had FT3 results. For age <=24h, 24.1-48.0h, 48.1-72.0h, 72.1-120.0h and 120.0-168.0h of life, the TSH RIs (2.5th-97.5th) (mIU/L) were 4.1-40.2, 3.2-29.6, 2.6-17.3, 1.0-10.3 and 1.0-8.2 respectively; the FT4 RIs (mean +/- 2SD) (pmol/L) were 15.3-43.6, 14.7-53.2, 16.5-45.5, 17.8-39.4, 15.3-32.1, 14.5-32.6, 13.9-30.9 and 14.4-28.6 respectively; and the FT3 RIs (mean +/- 2SD) (pmol/L) were 5.0-9.4, 4.1-9.0, 2.8-7.8, 3.5-7.2, 3.4-8.0, 3.8-7.9 and 3.8-7.2 respectively. Conclusion(s): In most babies, there is a substantial surge in TSH and FT4 shortly after birth followed by a rapid decline over the subsequent 168 hours. The upper limits are manyfold higher than the values for adults. Use of method- and hour-based RIs in newborns allows for correct identification of neonates who are at risk of hypothyroidism. Due to current lack of analytical harmonisation, these RIs must necessarily be method-specific.