Normal FT4 Reference Range for 1-2 Day Old Newborns
For newborns aged 1-2 days (24-48 hours of life), the normal FT4 reference range is approximately 14.7-53.2 pmol/L (mean ± 2 SD), though this varies significantly by immunoassay platform and must be interpreted using your specific laboratory's assay-specific reference range. 1
Critical Caveats for Neonatal FT4 Interpretation
Always use the reference range established by your specific laboratory using their exact analyzer and reagent system, as reference ranges vary significantly between different immunoassay platforms and manufacturers 2
FT4 must always be interpreted in conjunction with TSH levels for comprehensive assessment—in congenital hypothyroidism of thyroidal origin, TSH is elevated with low FT4, while central hypothyroidism shows low FT4 without clearly elevated TSH 2
Age-Specific Reference Ranges for Days 1-2 of Life
Hour-Based Reference Intervals
For age ≤24 hours: FT4 reference interval is 15.3-43.6 pmol/L (mean ± 2 SD) 1
For age 25-48 hours: FT4 reference interval is 14.7-53.2 pmol/L (mean ± 2 SD) 1
TSH and FT4 are substantially elevated in the first 24 hours after birth, followed by a rapid decline over the subsequent 168 hours, making hour-based reference intervals critical for accurate interpretation 1
Day-Based Reference Intervals (Days 3-7)
For term neonates at day 3-7 of life, the 95% reference interval for FT4 is 20.5-37.1 pmol/L using the Cobas immunoassay (Roche Diagnostics) 3
The lower limit of 20.5 pmol/L at day 3-7 is considerably higher than the adult reference range lower limit for the same assay, emphasizing the importance of age-specific neonatal reference intervals 3
Physiological Changes in Early Neonatal Period
FT4 levels show marked variation in the first week of life, with peak values occurring within the first 48 hours, followed by a gradual decline 1
In term neonates with gestational age 35-41 weeks, FT4 increases postnatally to levels within or above the normal adult range during the first two weeks 4
By day 13-15 of life, the 95% reference interval for FT4 decreases to 15.3-26.5 pmol/L, demonstrating the rapid physiological changes occurring in this period 3
Special Considerations for Preterm Infants
Very preterm neonates (26-31 weeks gestational age) have significantly lower FT4 levels that decline further to values below the range observed in term neonates, with a significant proportion having FT4 levels within the hypothyroid range by day 14 4
For preterm infants with gestational age below 33 weeks, FT4 measurement during the second week of life is recommended due to the high prevalence of transient hypothyroxinemia 4
Comparison Across Different Assay Systems
Reference intervals vary substantially between different manufacturer assays, age groups, and methodologies, making direct comparison between studies challenging 5
One study using the Beckman Coulter DXI 800 immunoassay reported FT4 reference intervals for day 14-21 of 11.59-21.00 pmol/L and for day 22-30 of 10.14-19.60 pmol/L, demonstrating lower values than the Roche Cobas system 5
Another study using the Immulite system (DPC Los Angeles) found median FT4 concentrations were up to 3.2-fold higher during the first 2 weeks of life compared to older children 6
Clinical Application for Diagnosis of Congenital Hypothyroidism
The lower limit of the FT4 reference interval is particularly important for diagnosing central congenital hypothyroidism (CH-C), where FT4 is low without clearly elevated TSH 3
When congenital hypothyroidism is suspected, measure both FT4 and TSH using an assay with an established neonatal reference interval, taking into account the child's age in days 3
In the Netherlands screening program, neonates are screened at day 3-7 of life, with pediatric consultation occurring on average at day 14 for suspected CH-C, highlighting the importance of having reference intervals for both time points 3